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3894707
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In a prospective, single-blind, randomized study, a single 2-g dose of metronidazole was compared with a seven-day course of 500 mg given twice daily in the treatment of symptomatic vaginal discharge associated with Gardnerella vaginalis. Based on resolution of symptoms and on cultures negative for G vaginalis, 86% (40/46) of women treated with the single dose and 97% (35/36) of women treated with the seven-day course were considered cured at seven to ten days after treatment. Evaluation at 21 days after treatment, however, indicated that only 46% (16/34) of patients treated with the single 2-g dose were considered cured compared with 86% (26/30) of those treated with the seven-day course. Treatment of sexual contacts did not significantly improve cure rates in either group.
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3894717
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We studied the production and secretion of immunoglobulin by tumor cells in two patients with nonsecretory myeloma, by means of an immunoperoxidase technique and plaque-forming cell assay. Immunoperoxidase staining of bone marrow cells revealed monoclonal proliferation of immunoglobulin-containing cells, and the plaque-forming cell assay of peripheral mononuclear cells and bone marrow cells showed secretion of monoclonal immunoglobulin from the myeloma cells. These observations suggest that the secreted protein disappears as a result of enhanced catabolism or rapid deposition. There has been speculation as to the existence of this type of nonsecretory myeloma, but there had been no evidence. We were able to demonstrate it with the plaque-forming cell assay.
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3894732
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Pathophysiology, outcome and some therapeutic problems of hypertension were described. Frequency of secondary hypertension and its underlying diseases in a hypertensive population greatly varied by study population. In the adult general population (Hisayama study) it was estimated to be 3.8%. Significance of various tests was evaluated in the diagnosis of renovascular hypertension and primary aldosteronism. Consideration of sodium balance in the evaluation was very necessary. The usefulness of captopril test was emphasized. Blood pressure was tended to decrease in upright posture and ambulation in cases with essential hypertension responding to acute sodium depletion by a significant reduction in blood pressure. In the observation of diurnal rhythm of urinary sodium excretion, the peak phase appeared about 3 hours earlier in essential hypertension than in normal control and 5 to 6 hours later in primary aldosteronism and Cushing syndrome. Sympathoadrenal function was activated in young borderline hypertensives but not in middle-aged ones. Outcome of hypertension accompanying diabetes mellitus was poor. Cardiovascular disease and renal failure occurred much frequently. Significance of hypertension as a risk factor of cardiovascular disease was described based on the data obtained through prospective epidemiological study (Hisayama Study). Hypertension was significantly correlated with stroke but not with myocardial infarction. Serum cholesterol level did not significantly correlate with both stroke and myocardial infarction. Reduction in stroke incidence in recent years was described in relation to the changes in risk factors of cardiovascular diseases. Pathophysiology and outcome of malignant hypertension (KW III-IV) were described in relation to underlying disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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3894751
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Glycoproteins binding to Ulex europaeus agglutinin-I (UEA-I) lectin, which recognizes the terminal alpha-L-fucose residue, were analyzed in 18 cases of human colorectal carcinoma by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by the Western blotting method. In the distal large bowel (descending and sigmoid colon and rectum), high-molecular-weight glycoproteins binding to UEA-I existed in carcinoma tissue but not in normal mucosa. In the proximal large bowel (ascending and transverse colon), high-molecular-weight glycoproteins binding to UEA-I were found both in normal mucosa and in carcinoma tissue, whereas those from the carcinoma tissue had an apparently lower molecular weight as compared to the weight of those from the normal mucosa. Thus there is a biochemical difference in UEA-I binding glycoproteins between the normal mucosa and the carcinoma tissue, although in our previous histochemical study no difference was observed in UEA-I binding glycoproteins of the proximal large bowel between the carcinoma tissue and the normal mucosa. Furthermore, carcinoembryonic antigen from the carcinoma tissue was found to have the same electrophoretical mobility as the UEA-I binding glycoproteins.
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3894752
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Clones of the T10 sarcoma, originated in a (H-2b X H-2k)F1 mouse, differ in their metastatic competence, correlated with differences in the expression of antigens of the two parental haplotypes. In fact, the metastatic phenotype is determined by the H-2Dk antigen. Whether the different major histocompatibility complex gene products control the metastatic phenotype via their different immunogenic properties was tested. The involvement of the immune system in controlling the development of metastases was inferred from experiments in which nonmetastatic T10 cloned cells were found to produce both experimental and spontaneous metastases in syngeneic immune-suppressed mice. After the testing of T-cell-mediated immune responses, metastatic T10 cloned cells, which expressed the H-2Db and H-2Dk antigens, were nonimmunogenic in their syngeneic hosts, whereas nonmetastatic T10 cloned cells, which expressed predominantly the H-2Db antigens, evoked a strong T-cell response. H-2Db and H-2Dk antigens expressed on T10 cells appeared to differ in their immunogenicity. This was further supported by the observation that whereas a good antibody response was elicited by H-2Db antigens expressed on T10 cells, only a low anti-H-2Dk antibody was produced. The different T10 cloned cells were not susceptible to natural killer (NK) activity in an in vitro assay, yet in vivo studies suggested the participation of NK activity in controlling T10 metastasis. In animals with depressed NK activity, metastases were generated even by nonmetastatic clones, whereas in animals in which NK activity was elevated, even metastatic clones failed to generate metastases. Both T-cell-mediated immune responses, probably restricted by the H-2D products and NK reactivity, appeared to participate in controlling the development of metastases by T10 cells.
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3894753
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Hematopoietic stem cells of W/Wv mice failed to produce macroscopically visible hematopoietic spleen colonies in irradiated recipient mice. Infection of W/Wv mice of the spleen focus-forming virus-susceptible genotype Fv-2ss (DBA/2) or Fv-2rs (BD2F1) with Rauscher leukemia virus (RLV) restored the spleen colony-forming capacity of the stem cells. The resulting spleen colonies had normal size and cellularity; the frequency of and ratio between granulocyte-macrophage and erythroid progenitor cells were also normal, without excessive production of erythroid cells. The frequency of spleen colony-forming units (CFU-S) appeared to be strongly reduced in W/Wv mice. The seeding fraction of RLV-infected W/Wv stem cells in the recipient spleens did not differ from that of uninfected or RLV-infected +/+ stem cells. At equivalent numbers of CFU-S, spleen suspensions of RLV-infected W/Wv mice were equally effective as +/+ control suspensions in protecting irradiated mice from death due to bone marrow failure. Thus the number of CFU-S observed appeared to be predictive for the number of W/Wv cells required for effective radioprotection. In irradiated W/Wv mice that received transplants of RLV-infected W/Wv cells, circulating erythrocyte numbers approached those of control mice; the erythrocytes were of normal size, in contrast to the macrocytic red cells of untreated W/Wv mice. The reduced frequency of CFU-S in RLV-infected W/Wv mice can be readily explained by a reduced self-replicating capacity, attributable to the W/Wv genes, which was not reconstituted by infection with RLV. The data indicate a direct involvement of pluripotent stem cells upon infection with RLV.
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3894758
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Using an information system, the authors compared the results of the examination of 169 patients with coronary heart disease and left coronary artery trunk lesions and of 605 patients without such lesions. The functioning of the system was controlled by a complex of programmes designed according to the modular principle. It comprises the following modules: modules of the formation and control of the data pool, modules of the formation of sub-pools according to a given set of signs and modules of data processing. The patients with coronary heart disease and a lesion of the left coronary artery trunk had a number of clinical characteristics including frequent and severe anginal attacks, a large zone of myocardial ischemia, a low exercise tolerance and a considerable depression of the ST segment on the ECG, as well as a long rehabilitation period.
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3894761
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A new in vitro system was developed in which renin release was studied in the absence of tubules, glomeruli, and macula densa. Rabbit afferent arterioles were isolated by microdissection and incubated in medium 199 for consecutive 15-min periods. Renin concentration of incubation media and arteriolar tissue was measured using partially purified rabbit angiotensinogen. Basal renin release rate was 0.68 +/- 0.06 ng of angiotensin I (AI) X hr-1 X arteriole-1/hr incubation of arterioles (x +/- SEM, N = 29), and remained stable for 60 min. The renin release rate was 2.76 +/- 0.22% of arteriolar renin content each hour, and there was a significant correlation between the two (r = 0.73, P less than 0.01). Renin release increased from 0.56 +/- 0.07 to 1.71 +/- 0.17 ngAI X hr-1 X arteriole-1/hr (P less than 0.01, N = 6) during exposure to isoproterenol (8.1 X 10(-5) M) and returned to basal values during the recovery period. Dietary sodium depletion resulted in a significantly greater arteriolar renin content (86.1 +/- 17.5 ngAI X hr-1/arteriole) compared with that from rabbits on a normal sodium diet (26.8 +/- 2.51 ngAI X hr-1/arteriole). However, sodium depletion did not alter the basal renin release rate suggesting that sodium depletion increased renin content in a storage pool rather than a pool contributing to basal release. It is concluded that the isolated afferent arteriole is a good model for the study of renin release in the absence of tubules, glomeruli, and macula densa.
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3894762
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It is now well established that longstanding human uremia is associated with impaired in vivo insulin action on glucose utilization of peripheral target tissues. In an attempt to define the cellular basis of the uremic insulin resistance we studied insulin action in adipocytes from eight patients with undialyzed chronic uremia and from eight matched healthy controls. (125I)-Insulin binding to fat cells from uremic patients was normal. In contrast (14C)-D-glucose transport exhibited decreased sensitivity to insulin. The concentrations of insulin that elicited half-maximal response was 422 +/- 95 pmoles/liter in uremic patients and 179 +/- 38 pmoles/liter in normal subjects (P less than 0.01). The noninsulin- and the maximal insulin-stimulated glucose transport of adipocytes from uremic patients with normal. (14C)-D-glucose conversion to total lipids was also measured in these cells in the absence and presence of various insulin concentrations. Similar to the findings in transport studies the lipogenesis of fat cells from uremic patients had depressed sensitivity to insulin (half-maximal stimulation at 38 +/- 8 pmoles/liter in uremic patients and at 11 +/- 3 pmoles/liter in normal subjects, P less than 0.01) with unchanged noninsulin and maximal insulin-stimulated lipogenesis. Taken together these results suggest that the insulin resistance of adipocytes from patients with chronic uremia may be accounted for primarily by postbinding defects localized to glucose transport and metabolism.
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3894763
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The study was undertaken to redefine morphological appearance and clinical implications of the diagnosis of transplant glomerulopathy (TGP). Fifty-seven renal transplant biopsy specimens from thirty patients with the diagnosis of TGP were evaluated. Multiple repeat biopsies in several cases enabled us to follow the pattern of the evolution of the changes. Transplant dysfunction manifested itself 8 days to 13 years post-transplantation by proteinuria and/or elevated creatinine level. The earliest recognizable morphological change was the swelling of endothelial and mesangial cells. This stage was called evolving TGP. The intermediate stage was characterized by enlarged glomeruli with lobular simplification, spongy matrix, and glomerular basement membrane (GBM) deformities. The advanced stage of TGP showed pronounced GBM changes (reduplication, interposition). These light microscopic changes were associated with vascular rejection. Immunofluorescence showed significant glomerular deposition of IgM (83% of biopsies) and fibrinogen (66%). Electron microscopy at an early stage showed subendothelial widening with cellular debris and focal endothelial damage with fibrin deposition. In the advanced stage, complex GBM changes developed as a reparative response to the capillary wall injury. Effacement of foot processes was a constant finding at all stages. In follow-up, twenty-three allografts failed (77%), five patients are stable, and two died due to other causes. TGP has specific morphology with an attendant poor long-term prognosis for the allograft.
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3894764
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A 61-year-old female patient accidentally aspirated liquid mercury during a medically ordered diagnostic procedure. To develop animal-based guidelines, liquid mercury was introduced into the lungs of four dogs. Based on the study of these animals, a method of predicting the kidney inorganic mercury burden was developed using radioactive isotope dilution techniques. It was further demonstrated in dogs that oral administration of dimercaptopropane sulfonate (DMPS) increased mercury excretion and reduced the kidney burden. A rat experiment was performed permitting a statistical evaluation of the assumptions basic to the use of the method. The method was applied to the patient with the result that the kidney inorganic mercury burden was predicted to be 28.1 mg, 8 months after the accident. Treatment with DMPS increased urinary excretion and the post-treatment kidney burden was estimated at 19.6 mg Hg. Inasmuch as the radioactive dose to the subject may be kept at a negligible level and because sensitive methods exist for measurement of radioactive and stable mercury concentrations, the technique may be applicable in special cases to the estimation of kidney inorganic mercury burdens incurred by industrial exposure.
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3894765
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To determine if the site of immune reaction could influence the mediation and morphological expression of glomerular injury in experimental anti-glomerular basement membrane (anti-GBM) nephritis and membranous nephropathy, we studied the events that followed the in situ reaction of rat antibody with antigen planted in either the GBM (especially the lamina rara interna) or in the subepithelial space (SE). Non-nephritogenic amounts of noncomplement-fixing sheep anti-GBM or anti-tubular brushborder antibody were injected into separate groups of rats to plant sheep IgG in the GBM and SE, respectively. Kidneys containing sheep IgG were then transplanted into naive recipients that were passively immunized with rat anti-sheep IgG. There was marked proteinuria after 2 days (antigen in GBM: 226 +/- 50.7; antigen in SE: 69 +/- 50.7 mg/24 hr) that was abrogated by prior depletion of complement in both groups (antigen in GBM: 10.2 +/- 1.7; antigen in SE: 14.3 +/- 8.7 mg/24 hr). When antigen was planted in SE, inflammatory-cell depletion with either anti-neutrophil (PMN) serum or lethal irradiation had no effect on proteinuria. In contrast, anti-PMN abolished proteinuria (12.0 +/- 5.6 mg/24 hr) and irradiation reduced it by 60% when antigen was in GBM. Glomeruli of kidneys with antigen in GBM were significantly larger and more hypercellular than those with antigen in SE after transplantation into immunized recipients. Endothelial cell injury and adherence of inflammatory cells to denuded GBM were prominent in the former (antigen in GBM), while glomeruli with antigen in SE showed only subepithelial deposits, adjacent slit-diaphragm displacement, and epithelial cell foot-process effacement. Thus, the reaction of antigen and antibody in glomeruli produced complement-mediated injury which was cell-independent when complex formation occurred on the outer aspect of the GBM but was cell-dependent when the same reagents reacted more proximally to the circulation. We therefore conclude that antigen distribution can critically influence the mediation and morphologic expression of immune glomerular injury and may, in part, account for variations in the clinical and histological manifestations of antibody-induced glomerular disease in humans.
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3894786
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The ferret (Mustela putorius furo) is proving to be an excellent experimental animal for many anatomical and physiological studies of the adult and developing visual system. As a result, the amount of data available on the ferret's visual system is increasing at a rapid rate. The purposes of this paper are to briefly review some of those data and to present some of the reasons why the ferret is an appropriate choice as an experimental animal for visual system studies.
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3894787
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The basic neuroanatomy of the forebrain, mainly of the telencephalon, of the adult ferret (Mustela furo), is reviewed and illustrated with special references to the features that distinguish this animal from other carnivores. References to the pertinent literature describing similar regions of other carnivores are cited.
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3894788
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Young adult male ferrets were inoculated intracerebrally (i.c.) with a cell-associated encephalitogenic subacute sclerosing panencephalitis (SSPE) virus strain to study the pathogenesis of the disease at the ultrastructural level. Most became acutely ill in 8-13 days. Areas of the brain were examined with indirect immunoperoxidase labeling techniques to detect measles antigen. None of these animals showed the characteristic viral nucleocapsids or marked inflammatory response associated with SSPE. However, all had positive immunolabeling of unstructured virus antigen, especially in post-synaptic regions in all areas of the brain that were examined. One ferret, immunized with measles vaccine 40 days prior to challenge with SSPE, became ill 18 days post inoculation (p.i.). Perivascular cuffings of inflammatory cells and large cytoplasmic inclusions of fuzzy nucleocapsids were found in the brain and spinal cord. The study indicates that ferrets which become acutely ill after inoculation with cell-associated SSPE virus do so before there is a marked cellular immune response or formation of virus nucleocapsids.
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3894789
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A behavioral profile of the ferret is presented for those who would like to use this animal in behavioral teratology and toxicology, or other disciplines involving behavior. We have reviewed neurobehavioral teratology of lisencephalic ferrets and neuropsychology of ferrets sustaining frontal lesions, as well as most of the studies of "normal" ferret behavior that have appeared in the research literature. Emphasis is placed on discussion of the tests used and how ferrets behaved on them. The behaviors discussed include spatial (maze) learning, delayed response, visual discrimination learning, discrimination learning sets, schedule maintained behavior, shock avoidance learning and spontaneously occurring behaviors, such as ambulation in open field, spontaneous alternation and species specific behaviors. Although the use of the ferret in behavioral experiments is not yet extensive and large gaps exist in our knowledge about the basic functional capacities of this animal, the ferret is unquestionably well suited for behavioral studies.
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3894790
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Ferrets have become an increasingly important animal in biological research. This paper discusses unique aspects of the ferret's anatomy, reproductive behavior, husbandry, and diseases as they relate to the research use of this animal.
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3894791
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A survey of research publications since 1977 indicated that the ferret is a rather popular research animal. Using the BIOSIS and MEDLINE data bases, 569 citations of research involving the ferret were identified. Over 27% of these citations involved the use of ferrets in the field of physiology, and an additional 24% of the citations were in virology and immunology. The areas of pharmacology, toxicology and teratology accounted for 10.4, 8.4 and 4.0% of the citations, respectively.
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3894792
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Glomerular cell culture has now become a widely used research technique. At the present time procedures are available to obtain isolated glomeruli from nearly all species. The isolation of individual cells has proven problematical. This is due to the lack of defined markers. Thus, it is not yet possible to determine the presence and relative degree of contamination by other glomerular or even nonglomerular, cell types. The importance of dealing with individual cell types, or defined mixtures, is exemplified by the variable results obtained in the assessment of prostaglandin synthesis within and between species. Several important bits of information have, nevertheless, evolved from glomerular cell culture experiments. The sites of synthesis of basement membrane components, as well as their composition, have been determined. Confirmation of the existence of a bone marrow-derived mesangial cell population and some of their properties has been obtained. The response of mesangial cells to, as well as their production of, various mediators has been shown. Finally, clear evidence for interspecies differences and similarities has been documented. Areas of controversy remain, including whether contractile mesangial cells are phagocytic, the presence of C3b receptors on epithelial cells, the amounts and types of certain extracellular matrix products synthesized by the various cell types, and the best methods for separation and culture of the individual glomerular cell types. There remain many fruitful areas for research. Fundamental questions such as the appropriate basal medium and supplements, the type of substrate, and the means to separate the individual cell types remain as unanswered or partially answered questions. When isolated cells are reliably obtained, the study of biosynthetic products in the resting and stimulated states must be again addressed. At that point, the effect of various and deliberate combinations of the glomerular cell types on the biosynthetic or proliferative responses will require further studies. For instance, although contractility mediated by receptors for angiotensin II has been assumed to be a specific property of mesangial cells, recent work shows that epithelial cells also respond to angiotensin II. In addition, the handling of immune complexes by various cells needs to be further investigated (43). Similarly, the pharmacologic response of the diverse populations of glomerular cells represents another area of study that has just begun. Finally, these data will provide the backdrop on which the analysis of various induced and genetic diseases can be performed.(ABSTRACT TRUNCATED AT 400 WORDS)
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3894794
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Monospecific antibodies against collagen types I, IV, fibronectin, and laminin were used to characterize the hepatic extracellular matrix in CCl4-induced cirrhosis. Of the four antigens studied, fibronectin was the first (2 weeks) to be deposited in Disse's space. Synthesis of fibronectin by hepatocytes was demonstrable by 3 weeks. This increased synthesis and deposition of fibronectin continued throughout the cirrhotic process. Type I collagen was deposited in the same areas as fibronectin, but there was a delay of 2 weeks between fibronectin deposition and the subsequent type I collagen deposition. Like fibronectin, type I collagen was localized in the rough endoplasmic reticulum of hepatocytes, but unlike fibronectin type I collagen synthesis was restricted to hepatocytes near zones of necrosis. Type I collagen and fibronectin synthesis were demonstrable only in hepatocytes. Type IV collagen deposition was noticeable after 3 to 4 weeks of CCl4 administration and continued throughout the cirrhotic process. Laminin deposition was delayed, with regard to type IV collagen, by 1 to 2 weeks. Except for this time lag, both basement membrane components codistributed in the space of Disse and were synthesized by the same cells: endothelial, smooth muscle, and Ito cells. The deposition of these two basement membrane components culminated with the formation of continuous endothelial basement membranes. The four extracellular matrix components studied were synthesized and secreted by resident cells of the normal liver. It is proposed that fibronectin deposition in the space of Disse, modulating collagen deposition, may be the crucial event in the cirrhotic process. The interposition of basement membranes between plasma and hepatocytes may have profound effects on hepatic systemic functions.
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3894793
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Four patients with type 1 diabetes mellitus received segmental pancreatic grafts. The donors were HLA-identical twins in three patients and an HLA-identical sibling in one. Each patient had normal glucose metabolism in the posttransplantation period but impaired graft function developed after 6 to 12 weeks. Complete loss of function developed in three patients. The fourth patient received immunosuppressive therapy but continues to require a low dose of insulin 15 months following transplantation. Pancreatic graft biopsy at the time of declining graft function in three patients revealed a mononuclear cell infiltrate centered upon islets consisting of variable numbers of T11 (pan T), OKT8 (suppressor-killer), OKT9 (transferrin receptor), OKT10 (activated), and HLA-DR-reactive mononuclear cells, as well as 63D3 and OKM1 reactive monocytes. Biopsies obtained following loss of graft function revealed resolution of the inflammatory process and selective destruction of all islet beta-cells in two patients, whereas graft biopsy in one patient demonstrated a mononuclear cell infiltrate in islets containing demonstrable beta-cells but no infiltrate in islets without beta-cells. Following immunosuppressive therapy the fourth patient showed resolution of the insulitis and destruction of beta-cells in 70% of the islets. The variable numbers of beta-cells observed in the remaining islets likely account for the relatively low amount of exogenous insulin required by this patient. There was no immunohistologic evidence of humoral mediated immune reaction in any of the biopsies. It is postulated that selective beta-cell destruction was a consequence of cell-mediated immunity leading to recurrent diabetes mellitus.
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3894795
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Implantation of a sterile rigid sheet of polyethylene into the right patellofemoral rabbit joint caused changes that resemble those found in human osteoarthritis. Initial synovial proliferation resulted in the isolation of the implant. Marginal osteophytes developed from soft cellular tissue which later underwent chondrification and finally became ossified. Articular cartilage under the area in contact with the implant showed early cell necrosis and diffuse loss of metachromasia. Focal superficial fibrillation followed and later developed into deep erosions and bone exposure. The first clefts appeared tangentially to the surface within an acellular electron-dense material. In spite of numerous mitotic divisions of viable chondrocytes, mainly in clusters or clones, cell density progressively decreased in every layer of articular cartilage beneath the implant. The present study suggests that necrosis of chondrocytes, and the later failure of viable cells to respond adequately to the altered environment, can lead to cartilage fibrillation and then to more severe lesions.
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3894796
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The thesis is developed that therapy and research are not necessarily the same activity and that clinicians are not necessarily researchers. Though there are commonalities between research and therapy, especially as the use of single-subject research designs has increased, using the scientific method to guide therapy is not the same as doing science. The requirements of good therapy and good research are often different in critical ways. Both research and therapy are important to the vitality of the profession, and the profession is strengthened when the differences are acknowledged.
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3894799
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The ability of an organism to distinguish self from nonself is determined by a cluster of genes located in the major histocompatibility complex. Recent advances in molecular genetics and cellular immunology have begun to elucidate the mechanisms responsible for immune response regulation. In this review article, the genetic organization of the murine and human major histocompatibility complexes and the manner by which their gene products modulate immune responsiveness are discussed.
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3894800
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A procedure is described for separating guinea-pig prostatic tissue into viable epithelial and stromal fractions. Epithelial cells were isolated using 0.1% protease, but this method resulted in significant damage to the stromal cells. However, using a mechanical tissue fractionation technique, a viable stromal matrix consisting predominantly of confluent sheets of smooth muscle cells and intervening collagen fibres was obtained. Although this method selectively spilled-out the epithelial cells, the majority were non-viable and therefore not suitable for receptor studies. Electron microscopy confirmed that cell architecture and organelle morphology were well preserved in both the enzymatic epithelial preparation and the mechanically prepared stroma. Saturation analysis studies indicated that the concentration of high affinity (Kd approximately 0.15 nM) oestrogen receptors was approx. 10-times greater in the separated stroma than in the epithelial fraction. In contrast, the concentration of androgen receptors (Kd approximately 2.2nM) was almost 2-fold greater in the epithelial than in the stromal fraction. These findings suggest that oestrogen, either independently or in association with androgen, may play a role in the growth and development of the stromal component of the guinea-pig prostate.
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3894801
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Specific binding of steroid hormones to microsomes has been reported for several tissues. In the hen oviduct, this receptor appears to be very similar to activated cytosolic receptor. The microsomal receptor is readily solubilized, and resembles the cytosolic receptor in all physico-chemical characteristics: sedimentation coefficient approximately 4 S, Stokes radius 5.5 nm, slow dissociation rate of the complex, adsorption to polyanions. It is precipitated by an antibody to the cytosolic receptor. Microsomes display saturable binding of cytosolic receptor, with a Bmax of approximately 300 fmol/mg protein. This binding is also observed using microsomes from non-target tissues, and is decreased by treatment with RNase. It seems likely that microsomal binding is due to the high affinity of activated cytosolic receptor for RNA.
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3894802
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Ischemia of the donor bronchus, perfused solely by retrograde collaterals from the pulmonary circulation, is an important factor in the impaired healing of the bronchial anastomosis of transplanted lungs. The healing of two experimental models of bronchial anastomotic ischemia, the bronchial segmental autograft and the postpneumonectomy bronchial autograft, was assessed in dogs. The application of a polytetrafluoroethylene wrap to the bronchial segmental autograft and the application of an intercostal pedicle flap to the postpneumonectomy bronchial autograft, with and without concomitant administration of corticosteroids, were also studied to elucidate factors that affect bronchial anastomotic healing. The bronchial segmental autograft healed normally without stricture, but isolation of this autograft from the mediastinum and lung by the polytetrafluoroethylene wrap resulted in necrosis of the autograft. All dogs that had a postpneumonectomy bronchial autograft died of bronchopleural fistulas due to autograft necrosis. Application of an intercostal pedicle flap to the autograft resulted in healing in all animals. Arteriography and Microfil injection demonstrated revascularization of the postpneumonectomy bronchial autograft by the pedicled intercostal artery. Several conclusions can be drawn: With the lung in situ the bronchial segmental autograft survives, probably as a free composite graft. In contrast, the postpneumonectomy bronchial autograft is an excellent model of bronchial anastomotic ischemia. The intercostal pedicle flap is a reliable method for providing neovascularity and mechanical reinforcement to an ischemic bronchial anastomosis. Its effect on bronchial anastomotic healing was not diminished by administration of corticosteroids. The intercostal pedicle flap may be useful in preventing bronchial anastomotic complications in clinical lung transplantation.
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3894803
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The percentage of total 125I-labeled insulin specifically bound to lymphoblasts was measured in 46 children with leukemia. Among 35 children with newly diagnosed acute lymphoblastic leukemia (ALL), specific insulin binding ranged from 0.09 to 14.8% per 10(6) blasts. A lower level of insulin binding was correlated with T-cell surface markers (P less than 0.003), higher hemoglobin level (P less than 0.005), presence of a mediastinal mass (P less than 0.01), lower glucocorticoid receptor level (P less than 0.02), higher platelet count (P less than 0.04), age less than 2 or greater than 10 yr (P less than 0.05), white blood cell count greater than or equal to 100 X 10(3)/mm3 (P less than 0.06) and higher labeling index (P less than 0.07). It was not correlated with the presence of central-nervous-system disease, FAB classification, or sex. With a follow-up of 24 to 33 + months, insulin binding was not correlated with treatment outcome. Six patients with relapsed ALL and three with acute nonlymphoblastic leukemia showed insulin binding levels similar to those in newly diagnosed ALL patients. Blasts from one patient with B-cell ALL and one with chronic myelogenous leukemia were characterized by lower insulin binding, while lymphoblasts from a patient with T-cell lymphoma bound insulin at marginally detectable levels. In vitro studies with IM-9, NALM-1 and NALM-16 cell lines showed that changes in insulin binding caused by dexamethasone treatment were not correlated with hormone-induced cell death. Although study of insulin binding by malignant lymphoid cells may be important in understanding the biology of leukemic cells, it does not appear to have any obvious clinical utility.
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3894804
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A double immunofluorescence assay for terminal transferase (TdT) and surface membrane T-cell differentiation markers, defined by monoclonal antibodies, was used to analyse peripheral blood and bone marrow from patients with mediastinal T-cell lymphoma with clinically localized disease. In 2 patients, at diagnosis and during two subsequent relapses, cells with abnormal immunological phenotype were detected in low numbers in the peripheral blood, which contained no morphologically abnormal cells on any occasion. Bone marrow was uninvolved by immunological criteria on 3 of 4 examinations. The findings suggest that morphologically undectable T-lymphoblasts escape from the site of disease origin in the thymus in patients with lymphoblastic lymphoma, leading to "seeding" of sites such as bone marrow and central nervous system. Furthermore, the techniques described appear to be potentially very useful for the monitoring of lymphoblastic lymphoma patients for early prediction of disease relapse.
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3894805
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Leukemic cells from 124 acute lymphoblastic leukemia (ALL) and 31 chronic lymphatic leukemia (CLL) were examined for sheep erythrocyte receptor (E), surface immunoglobulin (SIg) and their reactivity with a panel of monoclonal antibodies recognizing specific surface antigens including pan-T, Common ALL and Ia antigens. In acute lymphatic leukemia, 33% of patients reveal T-cell receptor associated with higher age group, mediastinal mass and high WBC count. Common ALL was predominant between 2 and 9-yr age group. Among chronic lymphatic leukemia, 2 patients were found to be T-CLL while 29 revealed presence of SIg. Ia antigen was detected in 44.4% of ALL and 64% fo CLL patients. The pattern of surface marker observed in our series may be related to our life style, socio-economic and environmental factors.
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3894814
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Adjuvant chemotherapy consisting of 5-fluorouracil and semustine was given to 26 patients who had undergone resection (with curative intent) of hepatic metastatic lesions from a primary colorectal carcinoma. Our objective was to obtain preliminary observations regarding the effectiveness of this regimen for improving the long-term survival associated with hepatic resection alone in these patients (the overall 5-year survival after hepatic resection is 25% at our institution). At the time of analysis, the malignant disease had progressed in 19 of our patients, and 17 patients had died. For all patients who receive adjuvant chemotherapy, the median duration of survival is 34 months, and the estimated 5-year survival is 15%. Statistical analysis indicated no significant advantage in survival for the study patients in comparison with 26 control patients who were treated with hepatic resection only and were closely matched for prognostic factors. Because 5-fluorouracil plus semustine conferred no apparent beneficial effects as an adjuvant treatment in this exploratory study, we do not recommend a definitive randomized trial of this regimen.
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3894816
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Pseudallescheria boydii is a recognized cause of mycetoma, a chronic fungal disease that usually affects the extremities. Isolated case reports have also implicated P. boydii in infections of other sites. We report the first large series (83 isolates) of P. boydii in 46 patients, including the second report of P. boydii brain abscess and disseminated infection in a noncompromised host. Between 1974 and 1984 at our institution, P. boydii was cultured from a variety of sites: respiratory tract, 36; soft tissue, 25; bone, 9; gastric aspirate, 4; maxillary sinus, 2; wound, 2; urine, 2; brain abscess, 1; ear, 1; and toenail, 1. Pulmonary colonization proved to be the most common form of pseudallescheriasis of the lung (34 of 36 cultures in this category); 28 of the 32 patients with pulmonary infections had received immunosuppressive therapy or had an underlying disorder. The importance of isolation of P. boydii from bone and soft tissue is supported in this series because all 9 cultures from bone and 21 of 25 cultures from soft tissue were associated with infection. Of 10 cases of infection, 5 were osteomyelitis and 2 were infected wounds; in addition, maxillary sinusitis, disseminated infection, and a lung abscess occurred in 1 patient each.
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3894818
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In the electron microscopic investigation of the secretory cells of adenohypophysis, adrenal cortex, adrenal medulla and pancreatic islets from the adult and old Wistar male rats, certain age-related ultrastructural features have been found. Age changes appeared to be more pronounced in the thyrotrophs, somatotrophs and gonadotrophs of the adenohypophysis and in zona glomerulosa and zona reticularis spongiocytes of the adrenal cortex. They consisted of atrophy of the Golgi apparatus, appearance of the cytoplasmic vacuoles, lipid and lipofuscin granules, secondary lysosomes and damage of the inner mitochondrial membrane. Parallel to these, hypertrophy of the Golgi apparatus and rough endoplasmic reticulum, formation of giant mitochondria and presence of a great number of secretory cells in the cellular cytoplasm were noted in zona fasciculata spongiocytes and chromaffin cells of the adrenal medulla, and in beta cells of the pancreatic islets during aging thus evidencing for the adaptive changes in the ultrastructure of these cells. However, no appreciable age changes have been observed in the ultrastructure of the adrenocorticotropic cells of the adenohypophysis.
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3894817
|
In this second segment of our article on pulmonary disease in the immunocompromised host (ICH), we review the infections associated with pulmonary infiltrates in the ICH and the diagnostic approaches for both infectious and noninfectious conditions. Although certain immunologic defects may predispose patients to specific infectious agents, virtually any infectious agent can cause pulmonary disease in any ICH. Physical findings and laboratory observations may give the clinician clues about probable causes of infection. Nevertheless, invasive diagnostic procedures-in particular, open-lung biopsy-are often necessary to diagnose pulmonary disease in the ICH. The relatively new technique of bronchoalveolar lavage is useful in diagnosing pulmonary disease in the patients with acquired immunodeficiency syndrome (AIDS). Further studies are necessary to confirm the reliability of this procedure as a diagnostic method in the ICH who does not have AIDS.
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3894822
|
The effects of financial coverage, education, race, age, and marital status on the start of prenatal care was studied in this analysis of 85,000 live births that occurred in New York City in 1981. Log-linear models were selected for the three variables prenatal care, coverage, and education after the data had been partitioned by race, age, and marital status. An overall model for the six variables was also selected to determine the relationship between race, age, and marital status and the three principal variables named above. Late or no prenatal care was found to be associated with Medicaid and an education of less than 12 years. For the most part, the association of race and age with late or no prenatal care was mediated by coverage and education. Hispanics, blacks, and teenagers who experienced greater odds of incomplete education and Medicaid insurance experienced greater odds of late or no prenatal care.
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3894813
|
Twenty patients have undergone a total of 47 charcoal haemoperfusions without the use of prostacyclin. A fall in platelet numbers and evidence of platelet activation have been found during haemoperfusion but few clinical complications have been observed. Therefore, we believe that the clinical value of the addition of prostacyclin during charcoal haemoperfusion has not been proven. Nevertheless, its apparent protective effect on platelet numbers and activation indicates that further controlled trials of the use of prostacyclin during charcoal haemoperfusion are required.
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3894839
|
According to the present situation of nonrenal organ transplantation there is an urgent need for heart, liver and pancreas grafts. To confront the steadily widening gap between cadaveric organ demand and supply the introduction of a multiorgan procurement protocol is mandatory. This protocol that is described in detail should regulate the collaboration between donor hospitals, the Eurotransplant Foundation, and transplant centers. On the basis of general, specific, and organspecific criteria potential donors can be evaluated, selected and accepted, then being followed by a well organized combined organ retrieval. The application of the proposed procurement protocol is expected to contribute significantly to the frequency and success rate of organ transplantation in Europe.
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3894840
|
After a brief historical outline of the radical operation of the ear, the possibilities are presented which are at our disposal to construct a mastoid cavity after removal of the posterior bony wall of the auditory canal, thus keeping the problems for the patient at a minimum. At best, a small self-cleansing well-designed cavity is formed under favourable conditions. Important prerequisites for the construction of such a cavity are: A good overview obtained by smoothening of the cavity walls; widening of the auditory canal entrance (cartilage excision); removal of excess bone covering the facial nerve; and reducing the size of the cavity by means of a Palva flap while preserving the postauricular artery and its larger branches. Postoperative management (and cleansing) must be done with an operation microscope.
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3894841
|
The efficacy of treatment of Menière's disease was investigated in 2 double blind study versus placebo. Forty patients were given 36 mg betahistine dimesilate daily for at least six weeks. The course of disease and findings one year before and one year after the treatment were noted and compared for assessing the therapeutic success. The findings on threshold audiograms, spontaneous and provoked nystagmus and caloric tests did not show any significant changes. A slight improvement was noted in the low frequency range of threshold audiograms. Dizziness, tinnitus and disturbances of walking were significantly improved. The incidence of vertigo attacks was reduced to 64%. In 89% of the patients no further vertigo attacks were seen after the treatment. The best results of betahistine dimesilate treatment were observed in the early stages of Menière's disease.
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3894843
|
Tracheostomy tube fracture with subsequent migration of the proximal fragment down the tracheobronchial tree is an almost unheard of cause of tracheal foreign bodies. Most such occurrences have been reported outside the United States, and only six previous reports have been filed. We report an additional case of fractured tracheostomy tube and review the literature.
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3894842
|
A review of 34 patients presenting with acute mastoiditis was undertaken. Prior treatment was noteworthy for lack of medical or surgical drainage at the time of initial otitis media. Typical findings, in hospital, included postauricular edema and tenderness, displaced auricle, and distorted tympanic membrane. X-rays were not diagnostic, nor were they helpful in determining who was a surgical candidate. Treatment was individualized. Patients with obvious subperiosteal abscesses, and those who did not respond rapidly to enteric antibiotics, underwent early mastoid surgery. The remaining patients received enteric antibiotics, had drainage established, and were carefully followed. Most resolved without mastoid surgery. Patients with a history of antecedent ear disease were examined separately from those without such history. The former group required mastoid surgery more often than the latter and had poorer outcome.
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3894844
|
Thermal biofeedback and general relaxation procedures were employed to treat 32 patients with subjective tinnitus. Each patient received eight 1-hour biofeedback sessions over an eight-week period, while listening to standard Jacobsonian type relaxation tapes. Sixty-five percent of the patients experienced a reduction of their symptoms. While none reported worsening of their symptoms, only two reported total symptom abatement. Findings suggest relaxation and peripheral vascular circulation are inversely related to the intensity of tinnitus symptoms. The probability that an individual will benefit from biofeedback appears related to his/her ego strength (Es). No differences were noted between the performance of male and female patients. Although not fail-safe, biofeedback and relaxation treatment are excellent management tools in the treatment of tinnitus.
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3894845
|
There is no agreement upon the number of punctions guided by ultrasonography needed to establish cytologically the diagnosis of pancreas carcinoma. Therefore reliability of the method as being dependent upon the number of punctions in 43 maligne tumors of the pancreas was evaluated. Performing two to five punctions yielded significantly better results than just one. In addition the macroscopic aspect of the aspirate is important.
|
3894853
|
It has been demonstrated in a variety of experiments that ORF 18260 inhibits (ED100) spontaneous and LHRH-induced ovulation in rats (10 micrograms/kg s.c.; 10 mg/kg i.g.) and hamsters (100 micrograms/kg s.c. and 100 mg/kg i.g.). Inhibition of LHRH induced ovulation appears to be competitive in nature. In normally cycling animals, efficacy varies with time of administration. In the spontaneously ovulating rat, the most effective time is 15.00 hr of proestrus; in the hamster it is 10.00 hr. Continuous administration inhibits ovulation in rats, and ORF 18260 has contragestational activity in rats and hamsters but not in guinea pigs and mice. Prostate growth in rats is inhibited at a dose of 100 micrograms/kg (s.c.). Our studies also suggest that ORF 18260 can also induce cutaneous anaphylactoid-like reactions in rats. When compound is administered intradermally in rats, ORF 18260 causes a dose-related whealing response, noticeable from the 0.01 micrograms/rat dose level.
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3894852
|
Naloxone produces large increases in serum luteinizing hormone (LH) levels in normal males and females, supporting a role for endogenous opioids (EOP) in the tonic inhibition of LH. Since the antagonist apparently exerts no important effects on the pituitary, the reasonable assumption has been made that it elevates gonadotropin levels by affecting the release of LH-releasing hormone (LHRH) from the hypothalamus. However, at present there is no direct in vivo evidence supporting this widely-held view. In an attempt to directly demonstrate that naloxone increases the secretion of LHRH, and thereby elevates serum LH levels, we examined whether a potent synthetic antagonist of LHRH ( [D-p Glu1, D-Phe2, D-Trp3,6]-LHRH, GPT-LHRH) blocked the effects of naloxone in male rats with a normal response to naloxone and in those with a markedly enhanced sensitivity to the drug induced by a brief period of morphine pellet implantation. Our results demonstrated that GT-LHRH antagonized equipotent doses of LHRH (100 ng/kg) and naloxone (0.5 mg/kg) over a similar time course with approximately the same AD50. Most importantly, however, we showed that the GPT-LHRH produced equivalent, parallel shifts to the right in the dose-response curves for LHRH and naloxone, indicative of competitive inhibition. We also found that GPT-LHRH completely abolished the enhanced response to naloxone's effects on LH which occurs in morphine-pretreated rats. Since we observed no competition between LHRH and naloxone for their binding sites in pituitary or brain, the only viable interpretation of our results is that naloxone increases LH by inducing the release of LHRH.
|
3894854
|
Comprehensive radiobiological studies of the relative biological and genetic efficacy (RBE and RGE) of powerful 252Cf radiation (the ANET-B unit) were conducted using research tools of various radiosensitivity (bacteria, Drosophila, Chinese hamster cells, murine thymocytes, human and murine bone marrow stem cells, human peripheral blood lymphocytes, Lewis lung carcinoma cells). It was shown in the tests of reproductive or interphase death and chromosome aberrations that the RBE and the RGE values of a 252Cf new source varied within the same limits from 1.3 to 3.0 whereas in the tests of gene mutations the RGE of the source did not exceed the efficacy of 60Co gamma-radiation and in some cases it was much lower. Thus the RBE of the new source in induced lethal and chromosome damages was 2-4 times lower than the efficacy of a low-activity 252Cf source used now in radiotherapy.
|
3894866
|
Athletic injuries to the cervical spine associated with quadriplegia most commonly occur as a result of axial loading. Whether it be a football player striking an opponent with the top or crown of his helmet, a poorly executed dive into a shallow body of water where the subject strikes his head on the bottom, or a hockey player pushed into the boards head first, the fragile cervical spine is compressed between the rapidly decelerated head and the continued momentum of the body. Appropriate rule changes recognizing this mechanism have resulted in a reduction of football quadriplegia by two-thirds. Presumably, educational efforts designed to inform the public of the dangers of diving would have a similar effect. The predominance of the axial loading mechanism is not as clearly defined in trampoline and minitrampoline injuries. However, both of these devices are dangerous when used in the best of circumstances, and their use has no place in recreational, educational, or competitive gymnastics. The emergence of severe cervical spine injuries resulting from ice hockey is recognized. Methods, based on sound scientific evidence, to modify the games so as to prevent these injuries are lacking.
|
3894868
|
The physiological energy expenditure involved in common activities such as running, walking, or cycling can be influenced by a variety of biomechanical factors. In evaluating changes in mechanical energy in order to derive a measure of mechanical power which is more directly related to metabolic energy cost, it is necessary to be able to identify the source of these changes. Factors such as concentric and eccentric muscular contractions, transfer of energy, elastic storage and reuse of energy, and joint range of motion limitations can all change the mechanical energy of a segment, but each involves a different metabolic energy expenditure. While a number of computational methods have been suggested for the calculation of mechanical power, each incorporates a different set of assumptions involving the factors just mentioned, and widely varying results for mechanical power have been obtained. The lack of definitive information concerning the relationship between mechanical and physiological energy changes limits the accuracy, meaningfulness, and usefulness of measures of mechanical power and muscular efficiency.
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3894867
|
It has been recognized for many years that factors of a psychogenic nature can influence resting as well as exercise metabolism, and the primary purpose of the present review was to summarize existing evidence dealing with this topic. The review is focused primarily upon experimental evidence involving the hypnotic manipulation of metabolism, since most of the relevant literature has relied upon utilization of the hypnotic tool. Several investigations involving non-hypnotic manipulations are directly related to the general research theme, and these reports are also included in the review. Following a general overview, research involving the influence of cognition and affect on heart rate, cardiac output, forearm blood flow, respiration rate, ventilatory minute volume, and oxygen consumption at rest is considered. The following section deals with the influence of cognition and affect, as well as perception on these same physiological parameters during exercise. It is concluded that psychogenic factors representing the cognitive, affective, and perceptual domains can significantly influence resting as well as exercise metabolism.
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3894869
|
This paper reviews specific examples of how energy expenditure during submaximal exercise is affected by mechanical and muscular factors. Structural biomechanical variables are discussed as a possible reason for economy differences between individuals. The practical question, "Can economy of performing a certain task be modified?" is posed. Examples of how the manipulation of a particular movement pattern results in an energetic minimum (optimal phenomena) are presented. The physiological mechanisms for these phenomena are summarized. The influence of positive vs negative work and storage of elastic energy in relation to the topic of economy and muscular efficiency is considered. The effects of athletic equipment such as footwear, track surfaces, and bicycle components on economy and muscular efficiency are presented. The prospects for improving athletic performance by improving economy are evaluated, and recommendations for future directions are made.
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3894870
|
The relationship between VO2 and velocity of running (running economy) has been rather casually dealt with until very recently, and there still remains considerable disagreement as to the importance of this variable. Various factors which have been shown, or appear, to affect running economy include environment (temperature, altitude, running surface), fatigue, age, weight, state of fitness, and inherent differences. That differences between individuals and within individuals can and do exist seems clear; the questions which need to be addressed in future research are: (1) What type of training is most effective in bringing about changes in running economy? and (2) How much change in economy can be expected with optimum training? Furthermore, it is suggested that running economy be investigated as an entity, so that changes that may take place with time or training can be more accurately related to their cause.
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3894871
|
Eight healthy males were studied to compare the effects of preexercise fructose and glucose ingestion on muscle glycogen usage during exercise. Subjects performed three randomly assigned trials, each involving 30 min of cycling exercise at 75% VO2max. Forty-five min prior to commencing each trial, subjects ingested either 50 g of glucose (G), 50 g of fructose (F), or sweet placebo (C). No differences in VO2 or respiratory exchange ratio were observed between the trials. Blood glucose was elevated (P less than 0.05) as a result of the glucose feeding. With the onset of exercise, blood glucose declined rapidly during G, reaching a nadir of 3.18 +/- 0.15 (SE) mmol X 1(-1) at 20 min of exercise. This value was lower (P less than 0.05) than the corresponding values in F (3.79 +/- 0.20) and C (3.99 +/- 0.18). No differences in exercise blood glucose levels were observed between F and C. Muscle glycogen utilization was greater (P less than 0.05) during G (55.4 +/- 3.3 mmol X kg-1 w.w.) than C (42.8 +/- 4.2). No difference was observed between F (45.6 +/- 4.3) and C. There was a trend (P = 0.07) for muscle glycogen usage to be lower during F than G. These results suggest that the adverse effects of preexercise glucose ingestion are, in general, not observed with either fructose or sweet placebo.
|
3894872
|
Ten experienced male marathon runners ran 20 miles (32.18 km) on an outdoor course in a warm climate to measure responses in selected physiological variables as a result of drinking water, an electrolyte-glucose solution (ERG), or a caffeine solution (5 mg X kg-1 body weight) before and during the run. The caffeine solution and water were colored and flavored to resemble the electrolyte-glucose solution so that a double-blind condition could be maintained. Subjects ingested a different fluid in each of the three trials in a counterbalanced design. Parameters studied were: heart rate; rectal temperature; body weight; hemoglobin and hematocrit; serum glucose, sodium, potassium, chloride, and free fatty acids; perceived exertion; respiratory exchange ratio (R); and fractional utilization of VO2max (percentage of VO2max). Both R and percentage of VO2max were higher in subjects who drank the caffeine solution compared to those who drank water. Although post-run free fatty acid mean values were significantly higher than pre-run levels, there were no statistically significant differences among the fluid treatments. Since no other differences were observed, we concluded that, under the outdoor road-running conditions encountered here, these fluid replacement treatments did not differ in their effects on the parameters studied.
|
3894874
|
We developed a new technique of venous interposition graft where the principle of sleeve anastomosis was applied at the proximal suture site and fibrin glue was used at both suture sites to prevent leakage. An advantage of this procedure was a reduction in the number of stitches, which reduced operative time and obtained good vascular healing. Since in an animal experiment a high patency rate of 97% was obtained, we applied the procedure to a clinical case with complete amputation at the PIP joint level of a long finger. Good recirculation was seen on angiography 6 weeks postoperatively.
|
3894875
|
The historical development of vascular surgery is reviewed from ancient times (Ruphus of Ephesus, Aëtius of Amida) to recent developments (sutured anastomosis by Carrel). Attempts to anastomose blood vessels by means of nonsuturing technique, using a ring or short tube of diverse materials called prostheses, were undertaken at the start of this century and continued until shortly after World War II. With the advent of modern polymeric materials, prostheses of different types, sizes, structures, and fabrics have been used to substitute for blood vessels, both experimentally and clinically. Recently, blood vessel prostheses with small (1-1.5 mm) internal diameters became available and have been implanted experimentally. Patency rates, biophysical and structural properties, the re-endothelialization and the neointima formation of several types of microvascular prostheses are briefly reviewed.
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3894876
|
To study the role of pancreatic beta-cell function in glucose intolerance and frank diabetes that sometimes develops in cirrhosis, the C-peptide response to a bolus IV injection of 1 mg of glucagon was measured in nine controls and in two groups of patients with cirrhosis. The first group comprised nine subjects with normal or high-normal fasting plasma glucose and no glycosuria; five of them had impaired glucose tolerance. The second group consisted of eight cirrhotics in whom frank diabetes had developed six to 48 months after the diagnosis of cirrhosis. They were characterized by fasting plasma glucose greater than 140 mg/dL and permanent glycosuria. No differences in the degree of liver impairment or portal-systemic shunting were observed between the two groups. Plasma glucose response to glucagon was similarly reduced in cirrhotic subjects. Basal C-peptide was high normal in patients with cirrhosis, and significantly increased in nondiabetic subjects. By contrast peak C-peptide levels and total C-peptide responses to glucagon were low normal in cirrhotics and significantly reduced in patients with cirrhosis and diabetes. In 14 patients the C-peptide response to a standard meal was also measured. It was significantly reduced in patients with cirrhosis and diabetes (six cases), as compared to cirrhotic subjects without diabetes. Peak C-peptide after IV glucagon significantly correlated with peak C-peptide after the meal (r = .927), or total C-peptide response to meal (r = .871). Impaired insulin secretion may add to insulin resistance in patients with liver cirrhosis, leading to the development of frank diabetes, characterized by fasting hyperglycemia and glycosuria.
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3894877
|
Serum lipids and lipoproteins were measured in 170 insulin-treated diabetics (90 females, 80 males) and in 124 nondiabetic control subjects (59 females, 65 males) aged 45 to 64 years. Plasma C-peptide response to intravenous (IV) glucagon was measured in order to classify the patients according to their capacity of endogenous insulin secretion. In both sexes, HDL and HDL2 cholesterol were higher in diabetics with no C-peptide response than in controls, whereas diabetics with high C-peptide response (postglucagon C-peptide level greater than 0.60 nmol/L) showed lower levels of HDL and HDL2 than nondiabetic controls. When adjustment for age, alcohol consumption, physical activity, body mass index, and insulin dose was made by analysis of covariance, the highly significant difference in HDL and HDL2 cholesterol level between diabetics with no C-peptide response and diabetics with high C-peptide response still remained in both sexes. This study gives support to the hypothesis that elevated HDL and HDL2 cholesterol levels in insulin-treated diabetics are not explained by effects of treatment with exogenous insulin, but rather are associated with the type of diabetes characterized by deficient endogenous insulin secretion.
|
3894887
|
The initial Laser Doppler Flux (LDF) values and skin temperature in the first, third, and fifth finger were evaluated as well as the postocclusion reactive hyperemia (PORH) response to a 4-min suprasystolic compression. The mean values varied from 276.5 to 335.3 mV while the skin temperature ranged from 32.5 to 34.2 degrees. The LDF-monitored PORH response was very reproducible with an average increase of 144.7 +/- 63.6 mV (from an initial LDF value of 327.1 +/- 134 mV). Four different time-related indices were analyzed: t/2recovery = 6.0 +/- 5.5 sec; trecovery (time to reach the initial value) = 16.7 +/- 11.5 sec; tmax (peak of overshoot) = 48.2 +/- 20.6 sec and t/2 overshoot (time to reach 50% of the tmax on the downslope) = 97.4 +/- 31.8 sec. The simultaneously monitored skin temperature changes lagged significantly behind the LDF changes probably due to the large heat capacitance of the tissue. It is expected that the described results obtained from 20 normal subjects will serve as a basis for future clinical studies involving skin perfusion disorders.
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3894886
|
The nucleotide sequence of the gene rpsD for the ribosomal protein S4 of three thermosensitive mutants of Escherichia coli K12 was determined. It was found that two of them contained regional multiplications of a nucleotide sequence within the gene rpsD. In one case, it is a duplication of a 31 nucleotide stretch and in another it is a triplication of a 41 nucleotide stretch. The thermosensitive phenotype of the two mutants is unstable and reverts at the frequency of approximately 10(-4). The revertants regain the wild-type nucleotide sequence. We postulate that the two mutant genes that contain regional multiplications possibly take an intra-strands secondary structure, which is cleaved to regenerate the wild-type sequence, probably during DNA replication.
|
3894888
|
Variation in the cell respiration rate of pigmented and nonpigmented strains of Serratia marcescens was exhibited. The respiration rate of a pigmented strain decreased earlier than that of nonpigmented strains in the late exponential or early stationary phase. However when prodigiosin synthesis was not induced by exchange of carbon sources in the medium, the decrease in the respiration rate of the pigmented strain was the same as that of nonpigmented strains. Measurement of the oxygen consumption rate in the sonicated cell membrane by adding NADH solution showed that the rate in the pigmented strain was lower than that in nonpigmented strains. Furthermore, the cell membrane of prodigiosin-induced organisms was more sensitive to respiration inhibitors than that of pigment-noninduced organisms of the pigmented strain. These results showed that the respiration activity was decreased by prodigiosin synthesis in S. marcescens.
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3894889
|
A rapid micro-test method for mumps virus neutralization was developed. In this method, a 96-well tissue culture plate was used for preparation of cell monolayers and the PAP staining technique was used for visualization of mumps virus infected cells. Clusters of infected cells were observed as a focus and the numbers of foci could be counted by the naked eye 2 days after the infection. A linear relationship between virus dilutions and focus numbers was observed. When neutralizing antibodies in sera from cases of natural mumps infection were assayed, a good correlation was observed between those obtained by the focus reduction method applying the micromethod and those obtained by the ordinary plaque method. Our results indicate that this micromethod is useful in mumps virus neutralization tests and it has many advantages over other methods previously reported.
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3894890
|
Methylcellulose-elicited peritoneal macrophages from BALB/c mice were cultivated in vitro and inoculated with dengue virus (DV). At intervals thereafter portions of the culture fluids were taken and titrated for viral infectivity. Extracts from Ascaris suum and Parascaris equorum, either crude or Sephadex G-100 fractionated, were examined for effects on the multiplication of DV. The macrophage cultures treated with the above substances produced larger amounts of DV compared with untreated control cultures. The enhancing effect of the substances depended on doses added and duration of treatment and was suppressed by co-treatment with carrageenan, a specific macrophage-inhibiting agent, but was not related to the viability of cultured cells. In fluorescent antibody (FA) as well as infectious center assay experiments, it was shown that the DV-infected cells were found more frequently in treated cultures than in untreated control cultures. In the treated cultures phagocytosis by cultured cells was also of a higher magnitude than that in untreated cultures. In cocultures of macrophages and splenocytes from the same line of mice, no additive effect of splenocytes was noted. The limulus amebocyte lysate clotting enzyme reaction (Limulus test) indicated that involvement of bacterial lipopolysaccharides in the enhancement phenomena was negligible. The data so far obtained suggest that the enhancing effect was due to direct action of the parasitic extracts on macrophages. Four Sephadex G-100 fractions from the crude extracts showed similar activities; however, the effects of fractions I and III appeared to be comparatively strong. Significance of the findings in relation to the pathogenesis of DV infection was discussed.
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3894896
|
The enthusiasm for performing coronary artery bypass graft (CABG) surgery in Australia is increasing. The results of a number of careful trials which have compared surgical with medical treatment have now appeared. While there is agreement on both the increased survival provided by CABG surgery in those with left main coronary artery stenosis and the relief of symptoms in patients in whom medical therapy has failed to control severe angina, there is debate about the value of surgery in other types of disease. With improvements in medical therapy, the most recent trials have failed to show a significant overall survival benefit from surgery, although it is generally considered that surgery can relieve angina and that, in at least some groups of persons with stenosis of all three main coronary vessels (triple-vessel disease), surgery may prolong life. Alternative methods of prolonging survival among people with ischaemic heart disease include the reduction of risk factors (such as hypertension, raised blood cholesterol levels and cigarette smoking), as well as treating patients with beta-blocking agents after a myocardial infarction. We suggest it is likely that a combination of these approaches could be more effective in terms of lives saved than is CABG and may be less expensive. The current expansion of CABG surgery in Australia should be viewed in this light.
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3894918
|
Patients with cerebral ischemia comprise an extremely heterogeneous group that makes analysis of treatment extremely difficult. Given the wide range of findings in the literature, one may select specific reports to justify a predetermined viewpoint. The study of Easton and Sherman has elicited a disproportionate amount of attention. Of the thousands of reported patients in the literature, this study of 228 patients with high postoperative morbidity and mortality has regrettably been cited often as the potential representative of surgical outcome in community hospitals. Undoubtedly, surgical skill varies and may affect results. Not all studies, however, support the contention that such procedures can only be performed adequately by surgeons who frequently do such operations. Most importantly, this study should redraw our attention to the fact that the success of the individual surgeon must be evaluated for any given procedure. With proper selection of patients, both carotid endarterectomy and EC-IC bypass procedures have proved to be safe and effective. In general, technical advances have heralded surgical results that appear to be superior to medical management, or no treatment, in a wide range of patients with cerebrovascular disease. Surgical results can only be evaluated when a procedure is fully developed technically and a large number of cases are accumulated. For carotid endarterectomy, and more recently EC-IC bypass, the necessary information is becoming available. However, the classification of patients to which these procedures should be applied has lagged behind. Given the variability in patients with cerebrovascular disease, this is somewhat understandable. Properly controlled studies would necessarily be unrealistically large. However, the technology and subsequent data that should be developed throughout the next decade will provide us with important information about brain ischemia and metabolism. This new technology should allow us to more completely define the exact nature of ischemic events in the individual patient. This will lead to better classification of patients and, ultimately, will improve patient selection for any methods of treatment, either medical or surgical.
|
3894919
|
Craniofacial surgery is a relatively new subspecialty that offers correction for many complex congenital, traumatic, and tumor-related deformities of the head and face. An experienced and extensive craniofacial team is imperative to the long-term success of a craniofacial surgery program. A greater awareness of the syndromes and deformities involved, and of the corrections possible, leads to earlier diagnosis, appropriate early care (sometimes life-sustaining), and the establishment of proper long-term treatment plans.
|
3894920
|
As I have indicated in the foregoing discussion, there are several syndromes that with various degrees of proof seem to be caused by unilateral vascular compression of a cranial nerve at the brain stem. Jannetta has summarized this concept as follows: "As we age, our arteries elongate and our brains 'sag'. As a consequence of these processes, redundant arterial loops and bridging or intrinsic hindbrain veins may cause cross-compression of cranial nerve root entry zones in the cerebellopontine angle. This pulsatile compression can be seen to produce hyperactive dysfunction of the cranial nerve. Symptoms of trigeminal or glossopharyngeal neuralgia (somatic sensory), hemifacial spasm (somatic motor), tinnitus and vertigo (special sensory), and some cases of 'essential' hypertension are caused by these vessels compressing cranial nerves V, IX-X, VII, VIII, and left X and medulla oblongata. Using microsurgical techniques, the symptoms may be relieved by vascular decompression. . .".
|
3894921
|
The myelopathy that may accompany cervical spondylosis is examined with reference to pathogenesis, clinical features, investigations, and treatment. The importance of canal size, disk degeneration, osseous changes, the cervical motion segments, and vasculature are presented. Frequent clinical patterns, radiologic and electrophysiologic investigations, and surgical treatments are discussed. An eclectic approach appears to be best.
|
3894922
|
Thoracic disc herniation is uncommon. An incidence of 0.25 to 0.75 per cent of protruded disks are in the thoracic region. A peak incidence is noted in the fourth decade with 75 per cent of the protruded disks occurring below T8. Pain is the most common initial symptom, present in 57 per cent of the cases, followed by sensory disturbances and motor involvement. By the time of diagnosis, 90 per cent of the patients have signs of spinal-cord compression. Although myelography has been considered the test of choice, 8 per cent false negative results and a correct preoperative diagnosis of 56 per cent has been reported. Now, with CT scanning with and without metrizamide, more accurate diagnoses can be achieved, even with cases in which myelography is negative. There has been a considerable improvement in the surgical treatment of herniated thoracic disks with over an 80 per cent rate of success for surgical approaches other than the posterior approach (decompressive laminectomy). An early and accurate diagnosis, coupled with improvement in the surgical approach, offers a much better prognosis for patients with thoracic disk herniation.
|
3894923
|
Chemonucleolysis with chymopapain is accepted by many surgeons as a reasonable alternative to lumbar diskectomy for the treatment of lumbar disk disease. Approximately 70 to 75 per cent of carefully selected patients are successfully treated following this therapy, but extreme care must be exercised for precise needle placement and prompt and vigorous management of major allergic reactions. Methods to avoid major complications and their management, should they occur, are discussed.
|
3894924
|
It should be obvious from the magnitude of the problem, its persistence in our society, and the failures of our treatment methods to date, though much improved over our past efforts, that much remains to be learned and understood about low back pain and sciatica. The causes, the treatments, and the methods of prevention all need to be researched further. The intellectually honest, inquiring clinician has an opportunity to make a meaningful contribution in this area.
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3894925
|
Intraoperative real-time ultrasound imaging in the neurosurgical operating room is most useful in localizing, characterizing, and guiding the instrumentation of lesions of the brain and spinal cord. In the future, more and more operative procedures will be done using intraoperative ultrasound guidance. The ultrasound scanner, as developed for neurosurgery, will become another instrument in the neurosurgeon's armamentarium.
|
3894928
|
The role of pancreatic hormones on hepatic regeneration after partial hepatectomy was studied in dogs with a new portal blood flow diversion which did not use vein graft. Right lobe of the liver received blood from the pancreas, stomach, duodenum and spleen, whereas the left lobe received blood from the intestine. Venous anastomoses were patent in 70% of survival animals for 12 weeks. Right lobe of the liver, from which 10% of the whole liver weight was removed, revealed rapid accumulation of glycogen and weight in the early stage of regeneration but failed to show sufficient removal of indocyanine green (ICG). On the other hand, left lobe, from which 40% of the liver was removed, revealed a slow and steady regenerative process and maintained efficient ICG removal throughout the study. The results revealed that endogenous pancreatic hormones could be a transient stimulating factor in the early stage of hepatic regeneration but do not require supplementation.
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3894929
|
A 51-year old obese man had been followed up for diabetes mellitus and hypertension. Hepatomegaly was noted on routine examination without any complaints in 1981. Through further investigation of the liver, a large hyperechoic mass lesion was shown between right kidney and the liver on ultrasonogram. On admission, diabetes was controlled by diet alone and blood pressure was 160/90 mmHg. without medication. There were no abnormal findings in laboratory data including hormone assays. The mass showed fat density on CT scan and hypovascularity on angiogram. The mass was diagnosed as benign non-functioning right adrenal tumor, most likely myelolipoma. By operation, the tumor was removed through long subcostal incision. The tumor was well defined and encapsulated, 14 X 8 X 8cm. in size and 480g. in weight. Microscopically the tumor was typical myelolipoma with a mixture of hematopoietic and adipose tissue. Postoperative course was uneventful and the patient discharged on 17-th postoperative day. Myelolipoma of the adrenal gland is a rare non-functioning benign tumor consisting of fat cell and bone marrow element. Only 30 resected cases of adrenal myelolipoma have been reported in the world including 7 cases in our country.
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3894930
|
Because cytotoxicity by an alkylating agent such as N-methyl-N'-nitrosoguanidine is markedly increased in adenine methylase-deficient dam-3 Escherichia coli, it was of interest to assess whether mismatch repair was similarly important in the repair of DNA damage induced by cis-diamminedichloroplatinum(II) (CDDP). The results demonstrate that after exposure to 5-40 microM CDDP, dam-3 E. coli are 2-15-fold more sensitive to the cytotoxic effects of this agent. Further, dam-3 mutL451 E. coli deficient in mismatch repair was as resistant as wild type. trans-Diamminedichloroplatinum(II) treatment did not cause marked increments in cytotoxicity in dam-3 E. coli compared to wild type. The rate of excision of platinum was significantly reduced in dam-3 E. coli compared to wild type, demonstrating that differences in the repair of CDDP-induced DNA damage underlie enhanced cytotoxicity by this agent. Lastly, mutagenesis by CDDP was abrogated in umuDC- E. coli, showing that this gene product mediates mutagenesis by this agent.
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3894931
|
Whilst separation techniques relying on gravitational forces have become relatively sophisticated in their application to biology the same is not true for magnetic separation procedures. The use of the latter has been limited to the few cells which contain paramagnetic iron. However with the development of several different types of magnetic particles and selective delivery system (e.g. monoclonal antibodies) the use of magnetic separation techniques is growing rapidly. This review describes the different types of particles currently available, the magnetic separation technique applied to the different magnetic compounds and illustrates major uses to which magnetic separation procedures are currently applied in the area of biology and medicine.
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3894934
|
We have used a set of deletion mutations in the ARS1 element of Saccharomyces cerevisiae to measure their effect on chromosome stability. This work establishes the previously proposed existence of three domains in ARS1. Domain C, which we have previously inferred, but not proved, to be a part of ARS1, is now established. In addition, we show that increasingly large deletions of the domain have increasingly large effects, which was not realized before. Furthermore, we have provided the first positive evidence for the central importance of a 14-base-pair core sequence containing the ARS consensus element by showing that it has the ability to act as a replicator on a plasmid containing no other ARS1 flanking sequence. The method of analyzing plasmid stability used in our study employs a novel and sensitive flow cytometry assay for beta-galactosidase. We discuss ways in which flow cytometry, based on this assay, could be generalized beyond its particular application in this work to studying other aspects of the cell biology of yeast and higher cells. The actual flow cytometry method will be described in detail elsewhere.
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3894932
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The glutathione reductase from E. coli was rapidly inactivated following aerobic incubation of the pure and cell-free extract enzymes with NADPH, NADH and other reductants. The inactivation of the pure enzyme depended on the time and temperature of incubation (t 1/2 = 2 min at 37 degrees C), and was proportional to the [NADPH]/[enzyme] ratio, reaching 50% in the presence of 0.3 microM NADPH and 45 microM NADH respectively, at a subunit concentration of 20 nM. Higher pyridine nucleotide concentrations were required to inactivate the enzyme from cell-free extracts. Two apparent pKa, corresponding to pH 5.8 and 7.3, were determined for the redox inactivation. The enzyme remained inactive even after eliminating the excess NADPH by gel chromatography. E. coli glutathione reductase was protected by oxidized and reduced glutathione against redox inactivation with both pure and cell-free extract enzymes. Ferricyanide and dithiothreitol protected only the pure enzyme, while NADP+ exclusively protected the cell-free extract enzyme. The inactive glutathione reductase was reactivated by treatment with oxidized and reduced glutathione, ferricyanide, and dithiothreitol in a time-and temperature-dependent process. The oxidized form of glutathione was more efficient and specific than the reduced form in the protection and reactivation of the pure enzyme. The molecular weight of the redox-inactivated E. coli glutathione reductase was similar to that of the dimeric native enzyme, ruling out aggregation as a possible cause of inactivation. A tentative model is discussed for the redox inactivation, involving the formation of an 'erroneous' disulfide bridge at the glutathione-binding site.
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3894933
|
Three clones for the human tumor antigen p53 were isolated from a cDNA library prepared from A431 cells. One of these clones, pR4-2, contains the entire coding region for human p53. This clone directs the synthesis of a polypeptide with the correct molecular weight and immunological epitopes of an authentic p53 molecule in an in vitro transcription-translation reaction. Although the pR4-2 clone contains the coding region for p53, it is not a full-length copy of the human p53 mRNA. Northern analysis showed that the p53 mRNA is approximately 2,500 nucleotides long, whereas the pR4-2 insert is only 1,760 base pairs in length. Analysis of the DNA sequence of this clone suggests that the human p53 polypeptide has 393 amino acids. We compared the predicted amino acid sequence of the pR4-2 clone with similar clones for the mouse p53 and found long regions of amino acid homology between these two molecules.
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3894935
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Extragenic suppressors of +1 frameshift mutations in proline codons map in genes encoding two major proline tRNA isoacceptors. We have shown previously that one isoacceptor encoded by the SUF2 gene (chromosome 3) contains no intervening sequence. SUF2 suppressor mutations result from the base insertion of a G within a 3'-GGA-5' anticodon, allowing the tRNA to read a 4-base code word. In this communication we describe suppressor mutations in genes encoding a second proline tRNA isoacceptor (wild-type anticodon 3'-GGU-5') that result in a novel mechanism for translation of a 4-base genetic code word. The genes that encode this isoacceptor include SUF7 (chromosome 13), SUF8 (chromosome 8), trn1 (chromosome 1), and at least two additional unmapped genes, all of which contain an intervening sequence. We show that suppressor mutations in the SUF7 and SUF8 genes result in G-to-U base substitutions at position 39 that disrupted the normal G . C base pairing in the last base pair of the anticodon stem adjacent to the anticodon loop. These anticodon stem mutations might alter the size of the anticodon loop and permit the use of a 3'-GGGU-5' sequence within the loop to read 4-base proline codons. Uncertainty regarding the exact structure of the mature suppressor tRNAs results from the possibility that anticodon stem mutations might affect sites of intervening sequence removal. The possible role of the intervening sequence in the generation of mature suppressor tRNA is discussed. Besides an analysis of suppressor tRNA genes, we have extended previous observations of the apparent relationship between tRNA genes and repetitive delta sequences found as solo elements or in association with the transposable element TY1. Hybridization studies and a computer analysis of the DNA sequence surrounding the SUF7 gene revealed two incomplete, inverted delta sequences that form a stem and loop structure located 165 base pairs from the 5' end of the tRNA gene. In addition, sequences beginning 164 base pairs from the 5' end of the trn1 gene also exhibit partial homology to delta. These observations provide further evidence for a nonrandom association between tRNA genes and delta sequences.
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3894936
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Cultured mouse peritoneal cells from unstimulated mice developed plaque-forming activity against isologous bromelain-treated erythrocytes. Several IgM monoclonal autoantibodies obtained by fusion of peritoneal cells from NZB or CBA origin with BALB/c myeloma cells were purified by affinity chromatography on trimethyl ammonium (TMA) column on the basis of their cross-reactivity with TMA, phosphorylcholine (PC) or choline haptens. Binding affinity for PC hapten was of the order of 10(3) M-1. Idiotypic studies with a polyclonal rabbit anti-idiotypic reagent revealed strong cross-reactions with all hybridoma autoantibodies thus far tested. In addition, the rabbit anti-idiotypic serum detected idiotypes or cross-reactive idiotypes in the sera of NZB and CBA as well as BALB/c mice. N-terminal amino acid sequence analyses of three hybridoma autoantibodies from NZB mice and one from CBA mice were carried out. The sequences of the first 32 residues of the four heavy chains showed that three were identical while one had one amino acid interchange; they belong to the VHIII-subgroup. The light chains were identical in the first 35 residues with the exception of a substitution at position 3 in two light chains and are members of the VK-9-subgroup. These results entirely support the idiotypic data. These monoclonal autoantibodies from NZB and CBA mice although isolated and eluted from PC-related haptens do not have any apparent structural nor idiotypic relationship to PC-specific antibodies. Idiotypic and V-region N-terminal sequence data suggest that these autoantibodies constitute a highly restricted family of molecules likely to be encoded by unique germ-line genes which may be expressed as such or as somatic variants in different mouse strains.
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3894937
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Human plasma kininogens were purified by immunoadsorption on Sepharose columns using two different approaches, either removing protein impurities with the respective immunospecific polymers or applying an anti-kininogen-specific immunoadsorbent column. An anti-kininogen serum developed and investigated in this laboratory in earlier studies was used. This antiserum recognizes the native conformational determinants in the kininogen heavy chain, the common denominator in plasma kininogens, and reacts with three heterogeneous molecular forms of high mol. wt kininogen (mol. wts 103,000, 92,000 and 90,000) as well as with low mol. wt kininogen. Heterogeneity of kininogens was shown by SDS gel electrophoresis and immunoelectrophoresis. With the antibody-specific polymers the yield was 80-100% compared to 75% or lower when several consecutive immunoadsorption steps were applied to remove impurities. Both methods serve the purpose of preparing immunologically pure kininogens suitable for immunization.
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3894947
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The assay of mutagenic activity of toxic drugs is difficult to perform and analyze, because one needs to know the kinetics of both effects in order to draw reliable conclusions. This is the case with niflumic acid (NA), which reduced the viability of S. typhimurium TA1535 100 times in the Ames test, but the background microcolonies show no difference from controls and the number of revertants was not altered by the drug. A test which measures the kinetics of growth of viable bacteria and mutants in liquid medium has been developed and applied to NA. No mutagenic activity was detected and elimination of the toxicity from the medium is suggested.
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3894950
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The effects of ethylene dibromide (EDB) exposure to male rats on several neurotransmitter enzymes have been examined in various brain regions of the F1 progeny, from 7 to 90 days of age. The choline acetyltransferase activity was significantly increased at 21 days old, in most brain regions studied in the F1 progeny of the EDB-treated males, but not at 7, 14 or 90 days old. The acetylcholinesterase activity was altered in different brain regions of the F1 progeny of the EDB-exposed males at both 14 and 21 days old but not at 7 or 90 days old. Glutamic acid decarboxylase activity was increased in corpus striatum but decreased in frontal cortex only at 21 days of age. These neurochemical changes in the developing brain of F1 progeny of EDB-treated males at low doses may be associated with behavioral abnormalities observed early in their development.
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3894949
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Strain TA102 of S. typhimurium is a new histidine-requiring mutant, particularly suited to the detection of oxidative mutagens acting at A.T base pairs. 10 oxidizing chemicals, previously tested in strain TA102, were used to evaluate the mutagenic sensitivity of the L-arabinose forward mutation assay of S. typhimurium with respect to those types of mutagens. The mutagenicity of each compound was determined by liquid test, measuring both the frequency of mutants among the survivors and the absolute number of mutants growing in selective plates with traces of D-glucose. Strain BA13 with a wild-type lipopolysaccharide barrier was used as compared to the deep rough derivative strain BA9. The chemicals studied were: bleomycin, t-butyl hydroperoxide, chromium trioxide, cumene hydroperoxide, formaldehyde, glyoxal, glutaraldehyde, hydrogen peroxide, paraquat, and phenylhydrazine. Additionally, ultrasonic oscillation was used as a presumable non-mutagenic lethal control treatment. The L-arabinose forward mutation assay detected the mutagenic activity of all the chemicals under study with a high degree of sensitivity, including paraquat which is unable to revert strain TA102. Positive responses were obtained at doses equivalent to or 10 times lower than the doses detected by strain TA102. The results support the idea that the L-arabinose forward mutation assay could replace the set of specific tester strains used by the histidine reverse mutation assay in general screening for genetic toxins.
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3894952
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A straightforward positive selection for genetic duplication is possible in strains of Salmonella typhimurium that carry the aroC321 allele. Strains with a single copy of this allele require phenylalanine, tyrosine and tryptophan for growth. Such strains give rise to tryptophan prototrophs, which still require phenylalanine and tyrosine, through the formation of a duplication that includes about 30% of the chromosome. We have constructed strains that permit the simultaneous study of duplications and mutations and have used these strains to explore the effects of DNA repair processes on the induction of duplications by ultraviolet light (UV). UV causes dose-dependent increases in the frequency of duplications in bacteria. The exposure required to induce duplications is much less in a delta uvrB strain than in repair-proficient strains, suggesting that duplications result from DNA lesions that are subject to excision repair. The photoreversibility of UV-induced preduplication lesions implicates pyrimidine dimers in the induction of duplications. Unlike its effect on the induction of mutations, the error-prone repair process associated with plasmid pKM101 does not enhance the induction of duplications. The prevention of duplication-formation by a recA mutation suggests that the formation of duplications involves recombinational events. Taken together, the data indicate that the same DNA lesions can be mutagenic and recombinagenic in bacteria, but that the two effects involve different pathways of processing DNA damage.
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3894951
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The kinetics of near ultraviolet light-mediated phototransformation of 2-aminofluorene (2-AF) was studied using high performance liquid chromatography (HPLC) and the Ames/Salmonella mutagenicity bioassay. Employing tester strains TA98, TA1538, and the nitroreductase-deficient TA98NR without the addition of exogenous metabolic enzymes, we were able to detect and discriminate between the UVA exposure-dependent formation of two stable photoproducts, 2-nitrosofluorene (2-NOF) and 2-nitrofluorene (2-NO2F). Mutagenicity of irradiated 2-AF solutions (using dimethyl sulfoxide as a solvent) in the various tester strains indicates the rapid formation of the photo-labile 2-NOF, after which 2-NO2F accounts for the preponderance of mutagenic activity. Continued UVA irradiation (greater than 72 h at 6.8 J/m2/s) of 2-AF results in the formation of greater than 30 photoproducts resolvable on HPLC, several of which, in addition to 2-NOF and 2-NO2F, are mutagenic on Salmonella but are chemically undefined to date. Prolonged irradiation ultimately destroys the photo-induced mutagenicity of 2-AF. However, UVA-induced 2-AF photoproducts are stable for several weeks when stored in sealed vials in the dark. Light potentiated oxidation of aromatic amines constitutes an alternative mechanism for the transformation of aromatic amines into proximate mutagens/carcinogens.
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3894953
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Spontaneous reversion of the base-pair substitution trpE8 marker in the LT2 sub-line of Salmonella typhimurium is significantly increased in the presence of the ultraviolet light-protecting and mutation-enhancing plasmid pKM101. The numbers of Trp+ revertants arising on plates of defined medium supplemented with trace amounts of nutrient broth have been found to depend upon the nature of the carbon source provided to support growth of both the background lawn and any revertants which may arise. For example, the yield of Trp+ revertants can be some 5-8 times greater when glycerol is the carbon source as compared to when glucose is the carbon source. S. typhimurium strain TA100, which carries the base-pair substitution hisG46 marker and pKM101, shows a similar response, although the difference is much smaller. Time-course experiments using both carbon sources indicate that the final trpE8----Trp+ mutation yield is depressed by glucose rather than enhanced by a "mutagenic' effect of glycerol. These results are consistent with the idea that a glucose-repressible function responsible for generating mutations can be switched on by growth on glycerol as sole carbon source. Evidence is also presented that many more mutational events occur in response to a mild temperature stress (42 degrees) in populations growing on glycerol as carbon source than occur in populations growing on glucose.
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3894954
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A mutant of Escherichia coli K12 was isolated which shows enhanced resistance towards near-ultraviolet (NUV) light plus 8-methoxypsoralen (MPS) compared with its wild-type parent strain. The PUVA (NUV + MPS)-resistant strain remains as sensitive for far-ultraviolet (FUV) light as its parent strain. A recA- derivative of this mutant strain was as sensitive to PUVA as its reca- parental strain. A polyacrylamide gel electrophoresis study of total cell lysates from the mutant bacteria showed that a protein of approximately 55 kd was synthesised in higher concentrations compared with its synthesis in the wild-type parent strain. Furthermore, synthesis of this protein was reduced in the recA- derivative of the mutant strain suggesting that the recA gene product might be acting as a regulator of the synthesis of the 55-kd protein. It is suggested that in E. coli damage to DNA by PUVA can be repaired by a specific RecA LexA-inducible repair system and the repair efficiency is enhanced if the 55-kd protein is present in concentrations higher than that synthesised by the wild-type parent E. coli.
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3894955
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We have studied the effects of different repair capacities on reversion of two Escherichia coli strains (lacZ19124 and lacZ19136) by 9-aminoacridine (9AA) and the acridine half-mustard ICR191. Introduction of a uvrB mutation into these strains led to enhanced ICR191-induced reversion of lacZ19136 and reduced ICR191-induced reversion of lacZ19124. 9AA-induced reversion of lacZ19124 was essentially unchanged while reversion of lacZ19136 was reduced. Plasmid pKM101 reduced reversion of the two markers by each of the mutagens, except in the case of ICR191-induced reversion of the lacZ19124 marker where mutagenesis was slightly enhanced. Mutations in the recA and lexA genes had minimal effects on ICR191- and on 9AA-induced reversion of the lacZ markers; although 9AA-induced reversion of the lacZ19124 marker was somewhat reduced, most of the other results indicated that mutation yields were if anything higher in the recA or lexA backgrounds. Mutagenesis by 9AA and ICR191 would therefore appear to occur independently of the inducible error-prone repair process commonly referred to as SOS repair.
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3894957
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The identification of N-nitrosothiazolidine (NTHZ) in smoked meat products prompted us to evaluate this compound for mutagenicity by the Salmonella assay. NTHZ was prepared in 99 + % purity by the nitrosation of the cysteamine-formaldehyde reaction mixture without isolation and purification of the resulting amine, and from thiazolidine, directly. Mutagenic activity was observed with TA100 without metabolic activation in the former, but not the latter preparation. An examination of the precursors, reaction intermediates, and HPLC separation of the NTHZ from the mutagenic product demonstrated that the genotoxic activity resulted from a synthesis-produced trace contaminant.
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3894959
|
Contrary to findings published up to now, allyl chloride, a well known directly acting mutagen for Salmonella typhimurium, is efficiently activated by rat-liver homogenate (S9 mix) under non-standard mutagenicity testing conditions. Its indirect, S9-mediated mutagenic activity is greatly enhanced when longer than standard preincubation times are applied. The indirect mutagenicity of allyl chloride, thus revealed, greatly exceeds its direct mutagenic activity. Obviously, standard mutagenicity testing conditions cannot be regarded as reliable tools for the evaluation of the full genotoxic potential of allyl chloride and, possibly, of other related compounds.
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3894960
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Several polycyclic aromatic compounds (PAC) including nitrated and oxygenated derivatives of polycyclic aromatic hydrocarbons (PAH) were tested for mutagenic activity in the Salmonella/microsome assay. Among the compounds tested the isomer mix of nitro-1-hydroxypyrenes showed the highest direct mutagenic response in both the Salmonella strain TA98 and TA100 (1251 revertants/micrograms and 463 revertants/micrograms, respectively). The direct-acting mutagenicity of the nitro-1-hydroxypyrene isomer mix was dependent upon reduction of the nitro function as evidenced by the decrease in activity observed with the nitroreductase-deficient and arylhydroxylamine esterifying-deficient tester strains. The oxygenated derivatives of PAH containing aldehyde or keto groups showed weak or no mutagenic responses. In most cases addition of S9 was essential for any mutagenic activity and the strain TA100 was more sensitive than the strain TA98. Within this group, 7H-dibenzo[c,g]fluoren-7-one showed the highest mutagenic effect; 7 and 22 revertants/micrograms using the strains TA98 and TA100, respectively.
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3894958
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Mutagenic activity was observed in sediments of the Suimon River bed with and without S9 mix. The direct-acting mutagens in the sediment were investigated. The sediment was extracted with methanol and fractionated on a Silica gel column. The benzene fraction from the Silica gel column exhibited mutagenic activity without S9 mix in strain TA98, while it failed to show mutagenic activity in nitroreductase-deficient strain TA98NR. This observation led to the suspicion that nitro compounds were the direct-acting mutagens of these samples. The benzene fraction was treated by heptafluorobutyric anhydride (HFBA) and investigated with gas chromatography equipped with an electron capture detector (GC-ECD). 2-Nitrofluorene, 4,4'-dinitrobiphenyl, 2,7-dinitrofluorene and 1-nitropyrene were detected and measured quantitatively. The mutagenic activity of a mixture of these compounds was compared with that of the original fraction and the direct-acting mutagenicity of Suimon River sediment can be explained by these nitroarenes, especially 1-nitropyrene.
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3894963
|
Acute graft versus host disease remains a major cause of morbidity and mortality in allogeneic bone marrow transplantation. To date, no clinically useful test has been reported that will predict the occurrence of graft versus host disease in genotypic HLA-identical donor-recipient pairs. We have developed a skin-explant model using donor lymphocytes that have been sensitized against recipient lymphocytes in vitro and cocultured with the recipient's skin. Histologic changes compatible with acute graft versus host disease are found in the positive explants. To date 32 patients have been tested in a prospective manner. Among the 18 recipient-donor pairs that were positive, 16 patients were found to have histologic Grade 2 or higher graft versus host disease of the skin on biopsy. Among the 14 negative pairs, only 3 patients had histologic Grade 2 or higher graft versus host disease of the skin on biopsy. Thus, the model has a sensitivity of 84 per cent and a specificity of 85 per cent, and is a significant predictor of the histologic occurrence of graft versus host disease (P less than 0.0005 by chi-square test). The test may be useful in the selection of donors for bone marrow transplantation and in the planning of prophylaxis against graft versus host disease.
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3894956
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Exposures of Salmonella typhimurium strain TA100 with and without S9 metabolic activation to low ppm levels of pure peroxyacetyl nitrate (PAN) in the gas phase were conducted. Measurements of the gas-phase PAN exposure concentration and the concentration of its decomposition products in surrogate test media led to a measured mutagenic activity of 34 +/- 5 revertants/mumole. The data indicate that PAN is a relatively weak direct-acting mutagen with TA100.
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3894969
|
In a prospective study to evaluate the prevalence and predictive potential of circulating islet-cell antibodies, we have screened 1723 "normal" first-degree relatives (parents, siblings, and offspring) of patients with insulin-dependent diabetes mellitus. The prevalence of islet-cell antibodies on initial screening was 0.9 per cent (16 of 1723). Over a maximal follow-up period of two years, insulin-dependent diabetes mellitus developed in 2 of 16 relatives with islet-cell antibodies and in 1 of 1707 without antibodies. In addition, 6 of 12 nondiabetic relatives with islet-cell antibodies had abnormally low insulin responses--below the third percentile in 6 and below the first percentile in 4--on their initial intravenous glucose challenge. Thus, prospective islet-cell antibody screening of high-risk first-degree relatives, in combination with intravenous glucose-tolerance testing, is capable of identifying immunologically abnormal persons with profoundly diminished beta-cell function, who are presumably at increased risk of insulin-dependent diabetes mellitus.
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3894961
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The excretion of mutagens in the urine of cigarette smokers was studied as a model for absorption and elimination of complex carcinogenic and mutagenic mixtures in humans. Urine was collected from an occasional smoker who smoked 1 cigarette (17 mg tar/cigarette) and from a heavy smoker (smokes approximately 20 cigarettes/day) who quit for 2 days and then resumed smoking. Urine samples were collected for 6 days, including a 2-day pre-smoking period for the occasional smoker and pre-abstention period for the heavy smoker, respectively. Mutagen excretion patterns were determined by extracting the mutagens in each urine sample with XAD-2 resin and testing the extract in a microsuspension modification of the Salmonella/microsome liquid-incubation assay using bacterial strain TA98 with metabolic activation. Peak mutagenic activity of the urine collected from the two smokers appeared 4-5 h after the beginning of smoking. Activity decreased to pre-smoking "baseline' levels in approximately 12 h for the occasional smoker, and the activity for the heavy smoker approached the occasional smoker's 'baseline' in approximately 18 h after the cessation of smoking. The mutagen excretion patterns of the occasional smoker after smoking a single cigarette suggests that, the mutagens, as detected by the Salmonella assay, are absorbed rapidly (3-5 h) and are eliminated from the body following first order kinetics. The excretion rate constant for the occasional smoker was approximately 0.1 h-1 and the half-life (T1/2) was approximately 7 h.
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3894971
|
We examined the effects of caffeine and meals on blood pressure and heart rate in 12 patients with autonomic failure. The influence of caffeine on plasma norepinephrine, epinephrine, and renin activity was also studied. Caffeine 250 mg, raised blood pressure by 12/6 mm Hg, from 129 +/- 25/78 +/- 12 (mean +/- S.D.) to a maximum of 141 +/- 30/84 +/- 16 mm Hg at 45 minutes (P less than 0.01), but did not change heart rate, levels of norepinephrine, or epinephrine, or plasma renin activity. Blood pressure fell by 28/18 mm Hg after a standardized meal, from 133 +/- 32/80 +/- 15 to a minimum of 105 +/- 21/62 +/- 12 mm Hg at 60 minutes (P less than 0.01). After pretreatment with 250 mg of caffeine, the standardized meal induced a fall of only 11/10 mm Hg, from 140 +/- 33/79 +/- 7 to 129 +/- 31/69 +/- 13 mm Hg at 60 minutes (P less than 0.05 vs. values after the control per day for seven days) in five patients, postprandial blood pressures remained higher after caffeine than after placebo (P less than 0.05). We conclude that caffeine is a pressor agent and attenuates postprandial hypotension in autonomic failure, and that this effect is not primarily due to elevations in sympathoadrenal activity or activation of the renin-angiotensin system. Caffeine may be useful in the treatment of orthostatic hypotension due to autonomic failure, especially in the postprandial state.
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3894977
|
The substantial repertoire of laser radiation--its coherence, range of intensity and frequency, controlability of focal area and of beam length--has been comprehensively explored in the contexts of micro- and macro-diagnostics of cells, biochemical kinetics, therapy and surgery.
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3894979
|
Leprosy, a chronic infectious disease afflicting between 10 and 15 million people, is caused by the obligate intracellular parasite Mycobacterium leprae. Although M. leprae was the first identified bacterial pathogen of man, basic biochemical, immunological, diagnostic and therapeutic investigations have been severely limited because it remains one of the few human pathogens that have not been cultured in vitro. An M. leprae recombinant DNA expression library was constructed to provide a source of genes encoding proteins relevant for such studies. Monoclonal antibodies directed against M. leprae specific antigens have been used to isolate the genes encoding the five most immunogenic protein antigens of the leprosy bacillus. We report here that M. leprae specific epitopes recognized by all of 13 monoclonal antibodies tested were produced by recombinant phage in Escherichia coli.
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