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3896902
Sixteen families were contacted two to seven years after the death of their spina-bifida baby following transfer to a specialist unit and the parents' subsequent decision against active treatment. There was little evidence of serious long-term problems of adjustment on any of the measures assessing marital relationships, parental physical and mental health, and decisions about later pregnancies. Parents welcomed the unit's policy of encouraging frequent contact with their baby, and thought that it had facilitated the grieving process.
3896908
Antibody to hepatitis A virus (anti-HAV) and IgM class antibody to HAV (IgM anti-HAV) in sera from 73 patients with hepatitis A and from 550 normal subjects were measured by enzyme immunoassay (EIA) and the results were compared with those of radioimmunoassay (RIA). Since RIA has the disadvantage of requiring radioisotopes and special equipment, the clinical applicability of EIA and possible methodological problems were evaluated. The EIA for anti-HAV showed an excellent correlation with RIA, indicating its usefulness for the demonstration of the immune status in these subjects. Positive results of anti-HAV were obtained in the early stage after the onset of hepatitis A. However, pretreatment for inactivation of samples was required. False-positive reactions were found in sera to which sodium azide was added as preservative. In the measurement of IgM anti-HAV, a fundamental study revealed quite satisfactory results, correlation with the results of RIA was excellent. In patients with hepatitis A, the titers reached a peak in the second to third week, followed by a gradual decline. Changes to a negative reaction were never encountered within three months. We concluded that the EIA is an useful tool in the diagnosis of hepatitis A and can replace RIA.
3896909
Pericholecystic abscess is a serious complication of cholecystitis. Though preoperative diagnosis is easy by gray-scale ultrasonography, there has been no case reported in which the communication between pericholecystic abscess and the gallbladder was demonstrated ultrasonically. We experienced a case in which the communication route between a pericholecystic abscess and the gallbladder was successfully demonstrated by a real-time electric linear scanner. Furthermore, the abscess was successfully treated by percutaneous drainage following ultrasonically guided puncture. This success demonstrates that ultrasonography by a real-time scanner can be effective for diagnosis and treatment of acute cholecystitis and pericholecystic abscess.
3896910
This paper describes an ultrasound method of assessing gastric emptying time based on measurements of the gastric antrum, which is visible in almost all subjects before and after meals. A total of 54 subjects were examined including 18 normal subjects and 36 subjects with idiopathic functional dyspepsia. The emptying time was determined in all subjects by measuring the changes in the cross-sectional area of the gastric antrum. In a subgroup of 34 subjects the volume of the whole antropyloric region was also considered. Measurements were taken by the same observer after fasting and at regular 30-min intervals after a standard 800-cal meal. Final emptying time (calculated in relation to the start of the meal) was considered to be the time at which the antral area or volume returned to basal value. Final emptying time (mean +/- SD) was 248 +/- 39 min in normal subjects and 359 +/- 64 min in patients with functional dyspepsia (p less than 0.001). A significantly higher degree of dilatation of the gastric antrum was found in dyspeptic patients than in control subjects. Barium x-ray of the stomach in 19 subjects always confirmed the ultrasound finding on the presence or absence of contents within the stomach. We conclude that this kind of ultrasound study of the antropyloric region allows accurate determination of total gastric emptying time.
3896911
A patient presented with large intrahepatic tumoral masses 36 yr after the initial detection of multiple liver metastases during a gastrectomy. The operation had been performed to remove four ulcerated polypoid gastric lesions. Reexamination of the previous liver and gastric biopsy specimens revealed a gastric leiomyoblastoma with metastases to the liver. The smooth muscle origin of this tumor was confirmed by positive staining for desmin intermediate filaments. This very long survival is extremely unusual in cases of metastatic gastric leiomyoblastoma.
3896912
Most of the gastrointestinal tract and the biliary tract have a cyclic motor activity. The electric counterpart of this motor activity is called cyclic myoelectric activity. A typical motor cycle in the LES, stomach, and small intestine is composed of a quiescent state, followed by progressively increasing amplitude and frequency of contractions culminating in a state of maximal contractile activity. The colonic motor cycle has only the quiescent and the contractile states. In the small intestine, these motor complexes migrate in an aborad direction, and in the colon in both orad and aborad directions. The mechanisms of initiation and migration of these complexes are best understood in the small intestine. Both the initiation and migration of these complexes seem to be controlled by enteric neural mechanisms. The functions of the enteric mechanisms may be modulated by the central nervous system and by circulating endogenous substances. The mechanisms of initiation of these complexes are not completely understood in the rest of the gastrointestinal tract and in the biliary tract. The physiologic function of these motor complexes that occur only after several hours of fast in the upper gastrointestinal tract of nonruminants may be to clean the digestive tract of residual food, secretions, and cellular debris. This function is aided by a coordinated secretion of enzymes, acid, and bicarbonate. In ruminants, phase III activity is associated with the distal propulsion of ingested food. The function of colonic motor complexes that are not coordinated with the cyclic motor activities of the rest of the gastrointestinal tract may be only to move contents back and forth for optimal absorption.
3896915
The results of preliminary investigations into specific immunohistochemical detection of the estrogen receptor in breast cancer tissue by means of monoclonal antibodies are presented. Thirty-one tumor tissue samples stored in a tumor tissue bank for between 10 and 35 months were immunohistochemically studied. The comparison between the immunohistochemical result and the result of the biochemical estrogen receptor assay show a large measure of agreement (90%). The comparison of the results with regard to response to endocrine therapy in cases of metastatization shows that immunohistochemical detection furnishes at least as much information as the dextran-coated charcoal method.
3896914
In order to define normal endoscopic ultrasonographic anatomy with particular emphasis on the pancreas, we studied 25 patients using a prototype ultrasound fiberoptic endoscope (model GF-UM1) and endoscopic ultrasound observation unit (model EU-M1) developed by the Olympus Corporation. We obtained a number of good quality scans of various retroperitoneal structures, and in several cases pancreatic texture and even the pancreatic duct could be appreciated. Differentiation of mucosal from intramural diseases of the hollow gut and from diseases of the retroperitoneal organs can be made by means of endoscopic ultrasonography.
3896922
An abnormality in the primary structure of dog haemoglobin was observed 1-20 days after their whole body irradiation with 190 keV X-rays (4.0 Gy). It consisted in a substitution of tryptophane residue in position 15 of the beta-chain for serine. The percentage of abnormal beta-chains in different time intervals after irradiation was determined. The structural changes have functional impact: an increasing haemoglobin affinity to oxygen. This could be explained on the basis of changes in the tertiary structure of haemoglobin, which may result from the substitution Trp 15----Ser15 in the beta-chain which may influence the haeme ability to bind oxygen.
3896923
A collection of 77 unique missense mutations distributed across the gene encoding staphylococcal nuclease (nuc) has been assembled. These mutations were induced by random gap misrepair mutagenesis of the cloned gene and were identified in E. coli transformants expressing reduced levels of nuclease activity. Four nuc- mutations which alter amino acid residues at positions outside of the active site region of the enzyme were submitted to a second round of mutagenesis, and characterization of several independent NUC+ isolates lead to the identification of three second-site suppressor mutations within the protein-coding sequence of the nuc gene. On separation from the mutation originally suppressed and recombination with a number of other nuc- mutations, all three suppressors displayed the property of "global" suppression, i.e., phenotypic suppression of the nuclease-minus character of multiple different alleles. A simple and generally applicable strategy was used to obtain efficient homologous recombination between plasmids for purposes of mapping nuc- mutations, mapping second-site suppressors and constructing double mutant combinations from pairs of single mutations.
3896924
Saccharomyces cerevisiae diploids homozygous for the rad52-1 mutation have previously been shown to lose chromosomes mitotically. Spontaneous events and events following low levels of X-ray or methyl methanesulfonate treatment result in monosomic diploids, whereas higher levels of treatment result in near haploidization. This rad52-1-dependent chromosome loss has been used to develop a new mapping method which can be used to assign a previously unmapped gene to a chromosome. Chromosome loss mapping can be done in either of two ways: if a diploid, homozygous for rad52-1 but heterozygous for a variety of other recessive markers, is constructed with an unmapped recessive mutation in coupling with known chromosomal markers, chromosome loss will result in the coordinate expression of the mutation and other recessive markers on the same chromosome; if, however, the diploid is constructed with the unmapped mutation in repulsion to chromosomal markers, then even haploidization will never result in the coordinate expression of the unmapped mutation and other markers on the same homologous chromosome pair--This mapping method and subsequent tetrad analyses have been used to locate hom6 on chromosome X, ade4 on chromosome XIII and cdc31 on chromosome XV and to demonstrate that met5, previously assigned to chromosome V, actually maps to chromosome X; the met- marker on chromosome V has been shown to be met6. GAL80 and SUP5, previously assigned to an unmapped fragment, have now been mapped to the right arm of chromosome XIII.
3896925
Using the chromosome loss-mapping method of Schild and Mortimer, I have mapped several new temperature-sensitive mutations that define five CDC genes. Modified procedures were used to facilitate mapping temperature-sensitive mutations in general, and these modifications are discussed. The mutations were assigned to specific chromosomes by chromosome loss procedures, and linkage relationships were determined subsequently by standard tetrad analysis. Four of the mutations define new loci. The fifth mutation, cdc63-1, is shown to be allelic to previously known mutations in the PRT1 gene.
3896927
Phenotypic reversion of ethanolamine-requiring Saccharomyces cerevisiae cho1 mutants is predominantly due to recessive mutations at genes unlinked to the chromosome V cho1 locus. The recessive suppressors do not correct the primary cho1 defect in phosphatidylserine synthesis but circumvent it with a novel endogenous supply of ethanolamine. One suppressor (eam1) was previously mapped to chromosome X, and 135 suppressor isolates were identified as eam1 alleles by complementation analysis. Additional meiotic recombination studies have identified a second genetic locus, eam2, that falls in the eam1 complementation group but maps close to the centromere of chromosome IV. Although the normal EAM1 and EAM2 alleles are fully dominant over recessive mutant alleles, their dominance fails in diploids heterozygous for defects in both genes simultaneously. The unusual complementation pattern could be explained by interaction of the gene products in formation of the same enzyme.
3896926
The pms1 mutants, isolated on the basis of sharply elevated meiotic prototroph frequencies for two closely linked his4 alleles, display pleiotropic phenotypes in meiotic and mitotic cells. Two isolates carrying recessive mutations in PMS1 were characterized. They identify a function required to maintain low postmeiotic segregation (PMS) frequencies at many heterozygous sites. In addition, they are mitotic mutators. In mutant diploids, spore viability is reduced, and among survivors, gene conversion and postmeiotic segregation frequencies are increased, but reciprocal exchange frequencies are not affected. The conversion event pattern is also dramatically changed in multiply marked regions in pms1 homozygotes. The PMS1 locus maps near MET4 on chromosome XIV. The PMS1 gene may identify an excision-resynthesis long patch mismatch correction function or a function that facilitates correction tract elongation. The PMS1 gene product may also play an important role in spontaneous mitotic mutation avoidance and correction of mismatches in heteroduplex DNA formed during spontaneous and UV-induced mitotic recombination. Based on meiotic recombination models emphasizing mismatch correction in heteroduplex DNA intermediates, this interpretation is favored, but alternative interpretations involving longer recombination intermediates in the mutants are also considered.
3896930
The spontaneous rate of occurrence of two characters of malignant transformation was studied in mouse embryo fibroblasts C3H10T1/2, clone 8. This cell line, though "immortal" in vitro, is characterized by a normal phenotype in respect to many other properties. The spontaneous rate of occurrence of anchorage-independence (aga+) and dense foci on cell monolayer varied in different experiments from 0.65 X 10(-6) to 1.2 X 10(-6) and from 1.2 X 10(-6) to 3.6 X 10(-6) per cell per generation, respectively. The fluctuation test has shown that both characters occur as random spontaneous events. The altered colony morphology proved to be stable in all 28 foci of independent origin tested. In most cases, the morphological transformants were anchorage-independent. It is suggested that the occurrence of the characters studied is due to mutation in a gene with pleiotropic effect.
3896928
We have examined spontaneous, interchromosomal mitotic recombination events between his4 alleles in both Rad+ and rad52 strains of Saccharomyces cerevisiae. In Rad+ strains, 74% of the His+ prototrophs resulted from gene conversion events without exchange of flanking markers. In diploids homozygous for the rad52-1 mutation, the frequency of His+ prototroph formation was less than 5% of the wild-type value, and more than 80% of the gene conversion events were accompanied by an exchange of flanking markers. Most of the rad52 intragenic recombination events arose by gene conversion accompanied by an exchange of flanking markers and not by a simple reciprocal exchange between the his4A and his4C alleles. There were also profound effects on the kinds of recombinant products that were recovered. The most striking effect was that RAD52-independent mitotic recombination frequently results in the loss of one of the two chromosomes participating in the gene conversion event.
3896929
Deletions in the argD, crp, cysG genes (73-74 min of the Escherichia coli genetic map) were obtained by heat induction of the phage lambda c1857 b221 rex::Tn5 integrated previously into the cysG gene by homologous recombination in the cysG::Tn5 mutant. Properties of the deletions obtained suggest the gene order: argD-crp-cysG.
3896931
Biological nitrogen fixation is catalyzed by nitrogenase, an enzyme complex exclusive to prokaryotes. We used the yeast Saccharomyces cerevisiae to study the synthesis, and subsequently the assembly, of nitrogenase components in a eukaryote. Here, the Klebsiella pneumoniae nifH gene, encoding the subunit of the Fe protein (Kp2) component of nitrogenase, was expressed in S. cerevisiae from the yeast ADHI promoter. The nifH gene product, detected in yeast by immunoblot analysis with anti-Kp2 antibodies, exhibited the same electrophoretic mobility in SDS-polyacrylamide gels as that of the Kp2 subunit synthesized in K. pneumoniae. Estimates of Kp2 antigen and assays of beta-galactosidase activity specified by nifH'-'lacZ fusions showed that the level of nifH product was similar in anaerobically and aerobically grown yeast, but varied with different transforming plasmids and in various haploid and diploid yeast strains. A cistron located downstream to nifH in a transcript resembling the polycistronic mRNA of the nifHDKY operon in K. pneumoniae is not translated in yeast.
3896932
The construction of cloning vectors based on the replicon of plasmid ColD-CA23 is reported. These vectors, like ColD itself, autoamplify when cultures of host bacteria enter the stationary phase of growth, thereby resulting in a substantial increase in the expression of cloned genes as a consequence of the increase in gene dosage. The principal advantage of these vectors is that, unlike the situation pertaining to other expression vectors, the increase in expression of genes cloned in ColD vectors does not require any experimental intervention (i.e., occurs naturally), and takes place at high cell densities. The vectors show high stability in Escherichia coli strains and are compatible with ColE1-type cloning vectors.
3896933
Erwinia chrysanthemi are phytopathogenic enterobacteria causing soft-rot disease due to pectolytic enzymes degrading plant cell walls. We constructed a genomic library from Sau3A-digested E. chrysanthemi B374 DNA cloned in the BamHI site of the broad-host-range cosmid pMMB33 grown in Escherichia coli. Out of 1500 kanamycin-resistant (KmR) transductants of E. coli, nine pectolytic-enzyme-positive clones were identified. One of these contained the pEW325 cosmid with a 35-kb insert of Erwinia DNA. Cell extracts of E. coli harboring the cosmid pEW325 were fractionated on a polyacrylamide electrofocusing gel; bands with pectolytic activity were found to co-focus with pectolytic enzymes of E. chrysanthemi B374 strain. Cosmid pEW325 encodes three pectolytic enzymes PL10, PL20 and PL130 with isoelectric points of about 9.3, 9.2 and 4.6, respectively. These enzymes are lyases that cleave polygalacturonate by transelimination, and give rise to unsaturated products. A 15-kb HindIII fragment coding for polygalacturonate lyases was subcloned in pBR322, and a physical map of the resulting plasmid pPL01 was constructed. Starting from the pPL01, various endonuclease-generated fragments were subcloned into pBR322. Genes encoding pectate lyases were localized within an 8-kb fragment (pPL04) and then in a 2.7-kb fragment (pPL03). Polygalacturonate lyases are expressed at various levels; they accumulated in the periplasmic space of E. coli host, whereas E. chrysanthemi secreted these enzymes into the culture medium.
3896935
We describe the construction and properties of pEMBLY plasmids. They belong to a new family of yeast shuttle vectors which are derived from plasmid vector pEMBL9 and offer the following improvement: relatively small size; large number of cloning sites; screening for insert-containing plasmids on indicator plates; different combinations of genes which complement auxotrophic deficiencies and sequences that support DNA replication in Saccharomyces cerevisiae; and ability to isolate the plasmid DNA in single-stranded (ss) form. The yeast S. cerevisiae can be efficiently transformed by these plasmids in both the ss and double-stranded (ds) forms. Finally, the presence of the phage f1 intergenic region allows one to obtain the cloned sequences in the ss form upon infection with the wild-type ss phage [Dotto et al., Virology 114 (1981) 463-473].
3896934
The deletion events that have plagued attempts to maintain molecular clones with long palindromic DNA sequences in Escherichia coli have been shown to be less frequent in recBCsbcB hosts [Collins et al., Gene 19 (1982) 139-146]. This study sought to determine if such hosts would permit the stable propagation of plasmid clones carrying the deletion-generating, 206 nucleotide (nt) long, imperfect palindrome derived from the 5' terminus of the genome of minute virus of mice (MVM), an autonomous parvovirus [Astell et al., Nucleic Acids Res. 11 (1983) 999-1018]. To this end these hybrid plasmids were used to transform several different mutant recBCsbcB hosts, followed by the isolation and restriction mapping of plasmid DNA from selected transformants. Characterization of plasmid DNA isolated from a recBCsbcBrecF host indicated deletion-resistant propagation of the intact species. Sequence analysis of unamplified and chloramphenicol (Cm)-amplified plasmid DNA obtained from these clones confirmed the integrity of the palindromic region of the viral DNA insert.
3896936
A hybrid cosmid coding for pectate lyase (PL) activity was identified from an Erwinia carotovora genomic library by an immunological screening method. A 7-kb DNA fragment was identified which codes for three proteins identical in size to proteins with PL activity purified from E. carotovora culture supernatants. The three proteins had apparent Mrs of 41, 44 and 44 X 10(3) as estimated by SDS-PAGE. None of the PLs were exported from Escherichia coli strain HB101 but all were found in the periplasmic space. Plant tissue was macerated by the PLs made in E. coli.
3896937
A synthetic gene coding for an analogue of somatomedin-C/insulin-like growth factor I (Sm-C/IGF-I) was synthesized by solid support phosphoramidite chemistry and subsequently cloned and expressed in Escherichia coli as a fusion protein. The gene, designed with a threonine codon substituted for a methionine codon at position 59 was expressed fused to an eight-amino acid leader peptide under the direction of the E. coli tryptophan promoter. The fusion protein, termed L0-[Thr59]-Sm-C/IGF-I was purified extensively (greater than 97%) and found to be 60% as active as native Sm-C/IGF-I in a radioimmunoassay and 50% as potent as native Sm-C/IGF-I in a radioreceptor assay. Like native Sm-C/IGF-I it was also mitogenic for Balb/c 3T3 cells. After removal of the eight amino acid leader peptide by cyanogen bromide treatment, the resulting threonine analogue, termed [Thr59]-Sm-C/IGF-I was 80% as potent as native Sm-C/IGF-I in both the RIA and the radioreceptor assays. It was also mitogenic in Balb/c 3T3 cells. These two analogues, therefore, display biological activities similar to human-derived Sm-C/IGF-I.
3896938
All newly diagnosed patients should be evaluated for ureteral obstruction and impaired renal function. Partial ureteral obstruction frequently responds to androgen suppression therapy. Most patients eventually have significant pain, usually due to bone destruction from metastases. Pharmaceutical palliation is usually required. Drug intervention should be on a regular schedule--avoid prn dosage of pain medications.
3896949
The distribution of fibronectin in the chorioretinal interface of the monkey eye was studied by indirect immunofluorescent and immunoelectron microscopic techniques. Immunofluorescent staining revealed fibronectin in Bruch's membrane and the choriocapillaris. Immunoelectron microscopic techniques revealed fibronectin associated with basement membranes, collagen fibers and elastic fibers in Bruch's membrane; the stromal side of the basement membrane of the choriocapillaris also showed staining. This study thus demonstrates that fibronectin is an integral component of Bruch's membrane in the monkey eye.
3896961
The pathology of the alimentary tracts of nine patients dying of Salmonella typhimurium infection is reviewed. Two patients had previous gastric operations, supporting previous reports that such patients are more susceptible to food poisoning. Four had no parietal (oxyntic) cells in the gastric mucosa, suggesting hypo- or anacidity. Only one had acute gastritis. None had acute enteritis, but in half of the patients, subtle histological changes suggested an 'enteropathy'. Acute diffuse colitis with abundant crypt abscesses, without stromal abscesses in the lamina propria, was the most constant finding and reparative features started very early, and occurred in later deaths. Under ideal circumstances this crypt abscess is readily distinguished from that of idiopathic ulcerative colitis, but can be confused with the crypt abscess of acute bacillary (sonne) dysentery. While the florid colonic changes may have settled in the late deaths, active inflammation is commonly present in the appendix mucosa on histology. The pathology of the alimentary tract in S typhimurium infection differs from that of S typhi and S paratyphi infections. There is little evidence of gastroenteritis, although subtle changes occur in the stomach and small intestine. The features are those of acute diffuse colitis with histological appendicitis, distinguishable from idiopathic ulcerative colitis.
3896962
A model has been developed for ordering diagnostic tests in jaundiced patients. The system proceeds in two steps: (i) diagnostic hypotheses are calculated for each patient from the results of physical examination and routine biological investigations; (ii) given these hypotheses, the most efficient test (out of 22) for reaching the final diagnosis is selected using four criteria: diagnostic value, risk, financial cost, and time in obtaining the result. This model was tested in 62 patients. In 43 of them (69%), the selected test was sufficient for reaching a diagnostic accuracy of 100%. In this group of patients, a mean of 3.7 (range 1-6) tests per patient was ordered by physicians. In the 19 remaining patients, the selected test was not sufficient for the final diagnosis, thus requiring a multiple choice process. It is suggested that such a system could help physicians to improve the care of patients by more efficient ordering of diagnostic tests.
3896964
Forty patients with biopsy proven chronic active hepatitis were studied, 22 received (+)-cyanidanol-3 in a dose of 3 g daily and 18 placebo. Side effects related to cyanidanol were fever (four patients), haemolysis (one patient) and urticaria (one patient). All side effects subsided on discontinuation of the medication. Cyanidanol had an effect no better than placebo on symptoms, laboratory tests, and histological findings on liver biopsy.
3896974
From 1970 to 1982, remission rates from large series of patients with a median age of approximately 50 years continue to exceed 50% and in series of younger patients may be as high as 75%. These improved results have been due to the combination of cytosar and an anthracycline in RI programs. The current major question is whether or not "consolidation" therapy has improved long-term disease-free survival. Our current results, covering the decade 1970-1980 and using more and more intensive RC programs, do not demonstrate an increase in the percentage of long-term survivors. The results from 1980 to 1982 are encouraging, but must be tempered by the fact that late relapses of adult ANLL are becoming more frequent and 2-year follow-up is much too short an evaluation period. In addition, the prolonged survival in program D may be due to the more intensive RI program and not at all related to the RC. At the present time, our experience lends no support to the theory that more intensive RC programs meaningfully prolong long-term survival.
3896977
A total of 232 previously untreated adults with acute nonlymphoblastic leukaemia were consecutively entered into four successive studies. In the first, complete remission rates and survival were inferior to a group treated on the same regimen in London, suggesting population differences, possibly on the basis of late referral and poor nutritional status. In the second study the addition of the epipodophyllotoxin VP16-213 to conventional doses of doxorubicin and cytosine arabinoside improved complete remission rate and median duration of survival. In the third study this induction programme was unchanged and short duration of intensification was compared with an extended period, but no statistically significant difference was demonstrated. In the fourth study, which is currently active, the role of the epipodophyllotoxin VP16-213 (Cape Town Regimen/CTR III) was compared with the same two agents in combination with thioguanine (DAT), but to date no difference in remission rate or survival is evident. Four conclusions are supported by data from these studies. First, the addition of VP16-213 to doxorubicin and cytosine arabinoside improves complete remission rate, prolongs median duration of complete remission and survival, with shortening of the time taken to achieve this status in our population. Second, evidence to date shows no advantage for the DAT programme containing thioguanine over CTR III in which this latter agent is replaced by the epipodophyllotoxin VP16-213. Third, there is no statistically significant difference in survival once patients have achieved complete remission following randomisation to receive 6 months in comparison with 15 months of intensification therapy. Finally, of the previously described prognostic factors, only response to initial chemotherapy has proved significant.(ABSTRACT TRUNCATED AT 250 WORDS)
3896982
Non-steroidal anti-inflammatory drugs are theoretically contra-indicated in the haemophilias but might be useful for those patients with chronic arthritic pain, as long-term strong analgesics are also undesirable. We carried out studies of platelet function and coagulation in 8 normal controls and 7 haemophiliacs while they were taking sequentially benoxaprofen and salsalate. No significant alterations in platelet function, bleeding time or coagulation occurred with either drug. In a subsequent double-blind controlled clinical trial using ibuprofen and placebo 8 of 9 patients had a significant reduction in pain score whilst using ibuprofen without significant change in the frequency of bleeds or the amount of concentrate used. Laboratory measures of coagulation also failed to reveal any adverse effect of the active drug. Non-steroidal anti-inflammatory drugs may be beneficial and may be used with caution in haemophilia.
3896983
Vitamin K-dependent carboxylase is found in the liver, where it is involved in the synthesis of four blood coagulation factors and protein C. The hepatic enzyme has partly been purified and several mechanisms have been postulated for the vitamin K-dependent carboxylation reaction. Recently the enzyme has also been detected in other tissues including the lung, kidney, spleen, testis, bone and arterial vessel wall. The proteins produced by these non-hepatic carboxylases are now being characterized, but in most cases their function is still unknown. This paper is meant to review our present knowledge in this field.
3896986
Recent advances in medical technology are confounding traditional definitions of life and death and even of who is a person. This article considers the implications of these developments for social workers and presents a technique for helping clients make decisions in the face of ethical dilemmas created by new medical technologies.
3896987
The effects of dl-erythro-4-benzyl-alpha-(4-hydroxyphenyl)-beta-methyl-l-piperidine-eth anol tartrate (ifenprodil tartrate) on rabbit platelet aggregation in vitro and ex vivo were studied. Ifenprodil tartrate inhibited platelet aggregation in vitro induced by ADP, collagen and epinephrine. It also inhibited 5-hydroxytryptamine (5-HT) uptake into platelets and 5-HT release from platelets. Since these inhibitory effects of ifenprodil tartrate on the functions of rabbit platelets were similar to the effects of imipramine, the effects of ifenprodil tartrate may be due to the stabilizing action of ifenprodil tartrate on the platelet membrane. The platelet aggregation by ADP was significantly inhibited in rabbits after oral administration of ifenprodil tartrate, the maximal plasma level of ifenprodil being reached at 20 ng/ml ex vivo, while the maximal level was only 1/40 of the minimal concentration of ifenprodil tartrate necessary to inhibit platelet aggregation in vitro. These results indicate that factors other than ifenprodil tartrate acting directly on the platelets (e.g., PGI2 which is an endogenous inhibitor of platelet aggregation) are involved in inducing the inhibitory effects of ifenprodil tartrate on platelet aggregation ex vivo. The effects of ifenprodil tartrate on both PGI2 release from the aorta and the inhibitory effects of PGI2 on platelet aggregation in vitro were investigated: PGI2 was found to intensify the inhibitory effects of ifenprodil tartrate on platelet aggregation in vitro, but there was little effect, if any, on PGI2 release. Therefore, it is considered that the ex vivo effects of ifenprodil tartrate might be due to its interaction with endogenous PGI2 in the blood.
3896989
Twenty chemicals, including 16 aromatic amines, were studied in the Salmonella/mammalian-microsome mutagenicity test using the bacterial strains TA100 and TA98 to compare the activation potential of liver preparations from several mammalian species. The hepatic post-mitochondrial supernatants (S-9 fractions) of rat, mouse, hamster, dog, monkey and man were used for metabolic activation. Striking quantitative and even qualitative differences were apparent in the capacity of the different preparations to activate the compounds to mutagens. All compounds that gave positive results in the Ames test when activated with a liver preparation from Aroclor-pretreated rats were also identified as mutagens when tested in the presence of S-9 from one or more other species. Four substituted anilines, however, were converted to mutagenic metabolites only in the presence of a post-mitochondrial fraction of hamster liver. Three human carcinogens, 2-aminoanthracene, benzidine and cyclophosphamide were detected as mutagens under various experimental conditions, including metabolic activation by human or monkey liver S-9. There were no qualitative differences in the mutagenic responses obtained in assays with human and monkey liver S-9.
3897007
In a literary synopsis we inform about eating addiction or binges already known in antiquity and differentiated as bulimos (fames bovina) respectively as kynorexia (fames canina), partially in a still true description. The syndrome, occurring increasingly since one decade, consists of periodically pathological and excessive devouring of food, mostly consecutive restrictive diet and/or vomiting, use of laxatives, depressivity, experience of shame and guilt s.o. At a prevalency of 5% of the (psychiatric) patients mainly women (95%) are concerned, showing a postpubertary begin of disease. In spite of certain connexions to the anorexia nervosa we have to define the bulimia as its counterpart. The different etiological conceptions suppose an epilepsy-like disorder, an attachment to the (endogenic) depression or the presumption of neuro-endocrine events. Largely it is applied to intra- and interpsychical neurotic conflictuality, though actually behavioristical aspects seem to be preferred. The therapeutic intentions comprise anticonvulsives and antidepressives in view of medicamentous treatment; the psychical treatment comprises psychoanalysis, outpatient and inpatient clinical psychotherapy and all actually usual methods up to self-help groups.
3897009
The effect of ionic zinc on the binding of 125I-insulin to a variety of tissues with well-characterized insulin receptors has been assessed. In the isolated rat adipocyte, zinc (250 to 1000 microM) showed dose-dependent stimulation of insulin specific binding, with little change in non-specific binding. This effect was rapid and sustained during a 60 min incubation and was due to a Zn-mediated increase in the number of available binding sites. No changes in binding affinity were apparent. A similar but smaller stimulation of insulin binding was observed at lower Zn concentrations (25-50 microM) in rat liver membranes. In this tissue, higher doses of Zn caused a marked rise in non-specific binding and resulted in the loss of any apparent specific binding of insulin. Similar effects were seen in IM-9 lymphocytes and human placental membranes, although in this latter case the Zn effect on non-specific binding was less marked. These data indicate that ionic zinc exerts a tissue-specific stimulation of insulin binding to its receptors. An intriguing corollary, that requires further study, is that this effect may be related to the known association of insulin with Zn, and thus to an enhancement of insulin action in vivo, at least on the adipocyte.
3897010
Diabetic oral glucose tolerance test together with hyperinsulinemia in a patient with decompensated acute intermittent porphyria is contrasted to normal findings in compensated acute intermittent porphyria (AIP). Results point to the essential role of insulin for the depression of porphyrin precursor overproduction as a mediator of the "glucose effect".
3897013
34 adolescents referred for excessive height prediction (HP) (11 boys with HP greater than 196 cm, 23 girls with HP greater than 180 cm) were treated for 9-15 months with bromocriptine (5-7.5 mg/day). Minor and transient side effects were observed in 20% of the subjects at the beginning of the treatment. Treatment had to be stopped in 1 boy complaining of asthenia and headache. Puberty developed normally, 19 girls experienced menarche during treatment and 1 continued regular menses. Bromocriptine treatment induced: (1) a significant decrease (p less than 0.001) in growth velocity from (mean +/- SEM) 8.6 +/- 0.4 to 5.3 +/- 1.5 cm/year in boys and from 7.1 +/- 0.2 to 4.6 +/- 0.6 cm/year in girls; (2) a twofold mean increase in skeletal maturation rate. Adult HP was reduced significantly from 202 +/- 1.4 to 195.4 +/- 1.2 cm in boys, and from 184 +/- 0.7 to 179.8 +/- 0.7 in girls. These results confirm our previous report suggesting that bromocriptine is a valuable alternative to sex steroid treatment in order to limit the final height in excessively tall adolescents.
3897014
The spontaneous release of growth hormone (GH) during nocturnal sleep was studied at age 5-19 years in 44 male and 15 female patients with severe growth retardation (-2.1 to -6.5 SD) among whom 43 were prepubertal and 16 pubertal. Comparison with the results of classical stimulation tests with ornithine, arginine and/or insulin showed good agreement in cases of classical hypopituitarism (n = 14) as in patients who seemed to be endocrinologically normal (n = 27). In 18 patients (31%) there was a discrepancy between sleep release and responses of GH to stimulation test: treatment with hGH was available in only 4 of these children and enhanced sharply their growth rate. It is suggested that a large span of intermediary situations exists between normal GH secretion and complete GH deficiency, deserving a controlled therapeutic trial with hGH.
3897015
This study compares the peak serum growth hormone (GH) concentration during slow wave sleep with the serum GH responses to insulin-induced hypoglycaemia and intravenous arginine infusion in 23 children referred because of short stature (20) or precocious puberty (3). Peak serum GH concentration during sleep correlated significantly with peak GH response to insulin hypoglycaemia (r = 0.64, p less than 0.01) and arginine infusion (r = 0.57, p less than 0.01). 3 children had subnormal (less than 15 mU/l) peak serum GH concentrations during sleep but normal responses to either insulin-induced hypoglycaemia or intravenous arginine infusion. 1 child had a normal peak serum GH response to sleep but subnormal responses to insulin and arginine. Sleep studies of GH secretion may be indicated when the GH responses to pharmacological stimuli are inconsistent with the observed growth pattern.
3897016
The induction of puberty by the administration of subcutaneous 15-micrograms pulses of gonadotrophin-releasing hormone (GnRH) every 90 min during day and night is described in two patients. Too rapid an induction of puberty occurred in one patient while initial progress in the other ceased after the development of pituitary desensitisation. We have attributed these results to the use of GnRH pulses in too high amplitude, and we suggest a more appropriate dose regimen.
3897024
Genetic polymorphism of human factor I (C3b inactivator) has been described using polyacrylamide gel isoelectric focusing electrophoresis of neuraminidase-treated EDTA plasma samples followed by electrophoretic blotting technique. In 435 individuals three different common patterns were observed, and these were controlled by two common alleles at a single locus. The results of typing family material confirmed autosomal codominant Mendelian inheritance. Two common alleles were designated FI*B and FI*A, and gene frequencies were estimated to be 0.8931 and 0.1069 for FI*B and FI*A, respectively. The distribution of phenotypes fitted the Hardy-Weinberg equilibrium. Linkage studies failed to show close linkage between factor I and the major histocompatibility complex.
3897025
C2 typing is performed by immunofixation with anti-C2 antiserum instead of by a hemolytic overlay. This method gives sharp band definition, is less cumbersome than the hemolytic overlay, gel files are easily made, and it also enables one to describe putative new nonhemolytic variants. C2 allele frequencies were studied in a sample of the normal Spanish population and were found to be similar to other Caucasoids. HLA-Bw62,-Cw3, and -DR4 were significantly associated with C2 B. Concordantly, the only C2*B extended HLA haplotype found in family material was Bw62-Cw3-Bw6-(DR4)-Bf*S-C2*B-C4A*3 B*2-(GLO*1). C4A*4 B*2 and C4A*4 B*4 are not found within the same haplotype together with C2*B and Bw62 or Bw22 respectively, nor do other C2*B haplotypes occur with common HLA-B alleles. These results may favour the hypothesis that the Bw62-C2*B haplotype is produced by one mutation arising in the Bw62-C2*C haplotype and that subsequent crossovers can explain other C2*B haplotypes (including Bw22-C2*B).
3897017
The rapid, single injection, multiple indicator dilution technique has been, with suitable modeling of hepatic venous outflow curves, the standard approach for quantitative kinetic assessment of tracer cell entry and intracellular sequestration in the steady state, both in the in situ and the isolated perfused liver. Analysis of the underlying system yields, for a substance sequestered within liver cells, identical theoretical expressions for expected cumulative tracer fractional recovery and the steady-state fractional outflow recovery of the bulk substance whose behavior is being traced. Luxon and Forker (Am. J. Physiol. 1982; 243:G76-G89) pointed out that experimental cumulative tracer fractional recovery must match the value predicted by use of fitted model parameters in the theoretical recovery expression, and that this agreement must be regarded as the hallmark of successful fitting and modeling. Their attempts to demonstrate this agreement, by use of previously published data, were unsuccessful; this led them to question whether previous model analyses were valid. To reexamine the question we, therefore, analyzed three sets of data, on bilirubin, free fatty acid and galactose uptake, including those they had previously analyzed. We found excellent agreement between experimentally determined cumulative tracer recovery and theoretically predicted recovery. The theoretical recovery expression, now validated experimentally, provides a direct way of using fitted parameters for the rapid calculation of outflow recovery, which should prove generally useful in this area of kinetics. Demonstration of the expected agreement, moreover, restores confidence in the self-consistency of procedures used in the past to analyze multiple indicator dilution data.
3897033
The different patterns of pneumonia are classified and show the various manifestations of the disease, indicating the necessary specific diagnostic procedures. Only by description and recognition of the possible pathogenic agents, an adequate therapy can be initiated as described in the last chapter.
3897034
The in vitro analysis of B-cell function has become more important recently. For this purpose, polyclonal B-cell activators (PBAs) and adequate test systems are now available. We compared the protein A plaque assay which is applied to determine the number of immunoglobulin(Ig)-secreting cells and the ELISA (enzyme linked immunosorbent assay) which is employed for the measurement of the amounts of secreted Ig. The number of Ig-secreting cells and the amounts of Ig in the culture supernatants after stimulation of mononuclear cells with PBAs correlated significantly, i.e. a B-cell activation can be detected by both test systems. The variation coefficients of the protein A plaque assay were higher than those of the ELISA. Furthermore, the protein A plaque assay is a very time-consuming method; therefore, an ELISA should be applied for the routine diagnostic of immunodeficiencies. Nevertheless, the protein A plaque assay remains important for the research of immunopathological diseases and for the determination of in vivo activated B-cells (spontaneous plaques) which can increasingly be observed in immunological disorders like AIDS (acquired immunodeficiency syndrome) or systemic lupus erythematosus.
3897036
The terminal C5b-9 complement complex was investigated in 15 aortic, 2 femoral fibrous plaques and 5 fatty streaks aortic intimae using indirect immunofluorescence and immunoperoxidase. All the fibrous plaques presented C5b-9 deposit-like threads in the fibrous cap and masses in the amorphous areas of the plaque. The deposits were frequently associated with other immune-related proteins such as: IgG, IgA, IgM, Clq, C3c and C4 which were simultaneously investigated. Fatty streaks intimae presented no C5b-9 and complement component deposits. Whereas the demonstration of the complement components could merely reflect a non-specific trapping, the presence of assembled C5b-9 in the damaged tissue is more indicative of the involvement of complement activation in the progression of atherosclerotic lesions.
3897037
Using a solid-phase immunoassay (ELISA), serum binding to dsDNA, cardiolipin, beta 2-microglobulin (beta 2m) and Keyhole limpet haemocyanin (KLH) has been investigated in patients with systemic lupus erythematosus (SLE). Serum binding to DNA, cardiolipin and beta 2m was significantly increased in SLE sera, compared with normal sera; in addition, serum binding to KLH was also significantly increased. There were, however, no significant correlations between serum binding indices to DNA, beta 2m, cardiolipin or KLH; furthermore, in inhibition experiments no clear cross-reactions of lupus sera for these four ligands were detected. These data indicate that SLE sera bind to DNA, as well as to other apparently diverse ligands. Increased serum binding to these ligands may be attributable to a particular characteristic of the immunoglobulin molecules--or groups of immunoglobulin molecules - produced in these patients.
3897043
To assess factors in overweight persons that account for a tendency toward hypertension, 33 very obese women, 26 to 77 years of age, were studied. Blood pressures in these 33 women varied from low normal to mildly hypertensive. None of them had taken medication for high blood pressure, and none had diabetes mellitus. The effect of independent variables--age, body mass index (weight/height2), fasting serum glucose levels, fasting serum insulin levels, and 24-hour urinary sodium excretion--on systolic and diastolic blood pressure was assessed. There was no correlation between sodium excretion and blood pressure. Age did not correlate with diastolic blood pressure but did correlate with systolic blood pressure when body mass index, serum glucose level, and insulin level were controlled. Diastolic blood pressure correlated with body mass index and serum glucose level, but only the latter remained significant when all independent variables were considered together. Both systolic and diastolic blood pressure were found to be significantly related to fasting serum insulin level (r = 0.47, p = 0.005 and r = 0.68, p less than 0.001) even when age, weight, and serum glucose level were controlled (r = 0.41, p = 0.025 and r = 0.62, p less than 0.001 respectively). The relation between serum insulin and blood pressure was more pronounced in those women with a family history of hypertension. These data indicate that insulin may play a major role in the regulation of blood pressure in obesity and that the previously accepted relation of weight to blood pressure may depend on blood levels of insulin.
3897044
A direct pressor effect of alcohol is proposed as the basis for the association between regular alcohol consumption and an increase in blood pressure found in population studies. To examine this further, a randomized controlled crossover trial of the effects of varying alcohol intake on blood pressure in 46 healthy male drinkers was conducted. From an average of 336 ml of ethanol per week, alcohol consumption was reduced by 80% for 6 weeks by drinking a low alcohol content beer alone. This reduction was associated with a significant reduction in systolic and diastolic blood pressure (p less than 0.001 and p less than 0.05 respectively). The mean difference in supine systolic blood pressure during the last 2 weeks of normal or low alcohol intake was 3.8 mm Hg, which correlated significantly with change in alcohol consumption (r = 0.53, p less than 0.001). Reduction of alcohol intake also caused a significant decrease in weight (p less than 0.001). After adjustment for weight change, an independent effect of alcohol on systolic but not diastolic blood pressure was still evident, with a 3.1 mm Hg fall predicted for a decrease in consumption from 350 ml of ethanol equivalent per week to 70 ml per week (p less than 0.01). Systolic blood pressure rose again when normal drinking habits were resumed. These results provide clear evidence for a direct and reversible pressor effect of regular moderate alcohol consumption in normotensive men and suggest that alcohol may play a major role in the genesis of early stages of blood pressure elevation.
3897051
In a randomized trial 49 patients with fracture of the neck of the femur and an age of less than 70 years or a high level of physical activity were allocated to treatment with a sliding screw plate or a sliding nail plate fixation. The patients were followed for 2-5 years. At follow-up the union rate was found to be 86.2 per cent of the fractures in the screw plate group and 73.7 per cent in the nail plate group (P less than 0.3). Necrosis of the femoral head was encountered in respectively 10 and 21 per cent. Hip replacement was necessary in respectively 23.3 and 31.6 per cent. The nail slid out of the femoral head, resulting in recurrence of the fracture's displacement in three fractures with a sliding nail plate, and in none with a sliding screw plate (P = 0.053). Secondary loss of the femoral neck's angle was more frequently seen in the sliding nail plate group (P less than 0.01). In conclusion, the sliding screw plate gives better fixation of fractures of the neck of the femur and was followed by a lower frequency of reoperation than after an unthreaded device.
3897052
Soluble Plasmodium falciparum exoantigens in crude culture supernatant fluids induced protective immunity against experimental falciparum malaria in Bolivian Saimiri sciureus monkeys. Susceptible squirrel monkeys were vaccinated with an aluminum hydroxide-fortified fraction purified from culture supernatants of P. falciparum Indochina I and Geneve/SGE-1 by cation-exchange (sulfopropyl-trisacryl) chromatography. Animals immunized with sulfopropyl-purified and corresponding control immunogens were challenged with whole blood containing monkey-adapted virulent organisms of the Indochina I strain. Hematological, serological, and parasitological profiles, including the appearance of crisis forms, served as potential indicators of protection. This immunogen conferred significant clinical protection of squirrel monkeys against needle challenge with the homologous Indochina I strain and a moderate degree of heterologous strain immunity.
3897045
To gain insight into the factors involved in the maintenance of sodium balance in patients with chronic renal failure, we studied 10 patients with a creatinine clearance of 11.5 +/- 4.0 ml/min after equilibrium on 20 and 120 mEq of sodium per day. The measurements included blood pressure, plasma volume, blood volume, extracellular fluid volume, plasma renin activity, plasma aldosterone, and plasma norepinephrine. For comparison, eight normal volunteers were studied after equilibration on 20, 200, and 1128 mEq of sodium per day. The latter intake was chosen to match the high sodium intake per residual renal function in the patients. In the patients, equilibrium after raised sodium intake was accompanied by a marked increase in blood pressure and blood volume, a moderate fall in plasma renin activity and levels of aldosterone and norepinephrine, and only little expansion of the interstitial space. The 24-hour creatinine clearance rose by 21.2 +/- 7.2%. Fractional sodium excretion (X 100%) was 5.3 +/- 0.8% during the 120 mEq sodium diet. In the normal volunteers, increasing the sodium intake from 20 to 1128 mEq/day evoked no consistent change in blood pressure but caused a comparable rise in blood volume, considerable suppression of plasma renin activity, aldosterone, and norepinephrine, and a much larger increase in interstitial volume. Their creatinine clearance had risen by 22.4 +/- 6.5%, and their fractional sodium excretion during the 1128 mEq sodium intake was 3.9 +/- 0.2%.(ABSTRACT TRUNCATED AT 250 WORDS)
3897053
The inoculation of a temperature-sensitive mutant of Salmonella typhimurium induced a long-lasting infection in susceptible (C57BL/6) and resistant (A/J) mice. During week 1 of infection, the number of bacteria in the spleens was similar in both mouse strains. Then, the decrease of bacteria was more rapid in the resistant strain. Splenomegaly and granulomatous hepatitis were more severe in the susceptible strain. The immune response induced by this infection was studied. In both mouse strains delayed-type hypersensitivity to Salmonella antigens was present, and resistance to reinfection with a virulent strain of S. typhimurium or with Listeria monocytogenes appeared with the same kinetics. Thus, it does not seem that the gene(s) controlling natural resistance to S. typhimurium act(s) on acquired immunity.
3897054
Four hundred fifty Escherichia coli strains of 45 O serogroups and subgroups and 112 serotypes were studied to determine their patterns of adherence to HeLa cells. Adherence was exhibited by strains of 17 O serogroups and subgroups, but within these groups more than one adherence pattern was frequently observed. However, within each serotype, the adherence pattern was highly consistent. Localized adherence (LA) was observed much more frequently in serotypes that we considered to be enteropathogenic E. coli serotypes (93%) than in other serotypes (14%), whereas diffuse adherence (DA) occurred predominantly among nonenteropathogenic E. coli strains. Determination of biochemical characteristics showed that within O serogroups, nonmotile strains tended to have the same behavior as motile strains with the LA adherence pattern, suggesting that they were derived from these motile strains. LA and non-LA strains of the same serotype differed biochemically. LA appears to be a property of most E. coli commonly considered to be enteropathogenic and should assist attempts to determine which E. coli are enteropathogenic and to elucidate their pathogenic mechanisms.
3897055
L-Cysteine potentiates 100-fold the hydrogen peroxide-induced killing of a growing culture of Escherichia coli K-12 (Berglin et al., J. Bacteriol. 152:81-88). In the present study it is shown that hydrogen sulfide is formed from L-cysteine and that sodium sulfide could substitute for L-cysteine in the potentiation of hydrogen peroxide-induced killing of E. coli K-12. Addition of an amino acid, L-leucine, L-valine, or L-alanine, to an L-cysteine-containing medium with a growing culture of E. coli K-12 inhibited hydrogen sulfide formation and the potentiation of hydrogen peroxide-induced killing. These amino acids did not inhibit hydrogen sulfide formation from L-cysteine by a cell extract, and they did not inhibit the potentiation by sulfide of hydrogen peroxide-induced killing. This indicated that the amino acids protected the culture from L-cysteine-potentiated, hydrogen peroxide-induced killing by inhibiting the transport of L-cysteine into the cell. The potentiation by sodium sulfide of hydrogen peroxide-induced killing was abolished by the metal ion chelator 2,2'-bipyridyl. This indicated that metal ions, in addition to sulfide, were involved in the killing. Toxic effects of hydrogen peroxide are often presumed to be mediated by hydroxyl radicals formed in iron-catalyzed reactions. It was demonstrated that iron sulfide was more efficient than ferrous iron in catalyzing the formation of hydroxyl radicals from hydrogen peroxide. It was suggested that hydrogen sulfide formed in polymicrobial infections may play an important role in the host defense by potentiating the antimicrobial effect of hydrogen peroxide produced by phagocytic cells.
3897058
The relationship between extracellular proteinase and the virulence for mice in Candida albicans was studied by using a set of three isolates. The set included a proteinase-producing parent (C9), a proteinase-deficient mutant derived from C9 by nitrous acid treatment (C9M1), and a spontaneous revertant (C9M1M) obtained by mouse passage of C9M1. The morphological markers and the carbon assimilation pattern were identical in these isolates. Isolate C9 produced a high level of proteinase in vitro and caused fatal infection (100%) within 21 days. The mutant produced no detectable enzymes in vitro, and all mice survived until day 22. Only 30% of the mice infected with C9M1 died between day 23 and 30. The isolates recovered from the dead mice were found to be proteinase sufficient, indicating that the mice died after the organism in tissue had reverted. The C9M1M isolate produced proteinase in vitro at 44% the level of C9 and induced fatal infection in 90% of the mice within 30 days. The number of CFU recovered from the kidneys correlated with the level of proteinase produced in vitro and, in turn, the rate of fatal infection produced by the isolates. These results support a previous observation indicating that proteinase activity is one of the virulence factors associated with C. albicans.
3897056
Serum-opsonized group A streptococcal cell walls, consisting of peptidoglycan-polysaccharide polymers (PG-APS), induced monolayers of human neutrophils, monocytes, and eosinophils to aggregate. When erythrocytes were present in the incubation medium, they also were associated with the leukocyte aggregates. By immunofluorescence staining, PG-APS was localized at the site of cell-to-cell contact. By scanning electron microscopy the cells appeared to adhere to one another by surface contact; filopodia often acted as connectors, particularly in leukocyte-erythrocyte interaction. Cellular binding of PG-APS and aggregation were dependent upon C3 fixation. No aggregation was observed when heat-inactivated serum was used as an opsonin. In contrast to peptidoglycan, an activator of the alternative complement pathway, the group-specific polysaccharide moiety of PG-APS induced no cellular aggregation. Rosette formation was observed in suspensions when neutrophils were incubated with erythrocytes coated with C3b-opsonized PG-APS. Cell monolayers bound serum-opsonized PG-APS, but aggregation was observed only when serum was present in the incubation medium. Similar results were obtained with C5-deficient serum. No aggregation was observed with heat-inactivated serum or bovine serum albumin. A heat-labile serum component(s) appears to be required to elicit leukocyte aggregation. It is suggested that C3 fixed to PG-APS acts as a bridge to link cells together in clusters as a result of common recognition of C3 by leukocyte and erythrocyte complement receptors.
3897057
Hepatic dysfunction is a poorly understood and highly lethal component of multiple-system organ failure. Both in vivo and in vitro studies of "liver" function have generally neglected hepatocyte-Kupffer cell interactions. In the following experiments, isolated hepatocytes were cocultivated with unstimulated peritoneal cells, predominately macrophages, which served as a readily available Kupffer cell analog. Coculture of hepatocytes with peritoneal cells resulted in little or no change in [3H]leucine incorporation into hepatocyte protein. When gentamicin-killed Escherichia coli cells (GKEC) were added to coculture, there was a marked decrease in hepatocyte [3H]leucine incorporation. In contrast, GKEC added to hepatocytes alone had no effect. Kinetic data revealed an 8-h delay before any significant decrease in leucine incorporation into hepatocyte protein after the addition of GKEC to the coculture. The maximal decrease in hepatocyte [3H]leucine incorporation occurred 24 h after GKEC were added. The decrease observed 24 h after GKEC were added disappeared almost completely after 48 h of coculture. Similar alterations in cocultured hepatocyte protein synthesis were observed after the addition of phorbol myristate acetate, lipopolysaccharide, or muramyl dipeptide, a component of bacterial peptidoglycan. Hepatocyte viability by trypan blue exclusion was unchanged, and gross morphology by light or electron microscopy was unaffected. We propose that during sepsis, macrophages (Kupffer cells) respond to circulating microbial products and mediate alterations in hepatocyte function. These experiments underscore the important role of Kupffer cell function in attempts to understand hepatic malfunction in multiple-system organ failure.
3897061
Antibiotic-treated and untreated Syrian hamsters were inoculated intragastrically with Candida albicans to determine whether C. albicans could opportunistically colonize the gastrointestinal tract and disseminate to visceral organs. Antibiotic treatment decreased the total population levels of the indigenous bacterial flora and predisposed hamsters to gastrointestinal overgrowth and subsequent systemic dissemination by C. albicans in 86% of the animals. Both control hamsters not given antibiotics and antibiotic-treated animals reconventionalized with an indigenous microflora showed significantly lower gut populations of C. albicans, and C. albicans organisms were cultured from the visceral organs of 0 and 10% of the animals, respectively. Conversely, non-antibiotic-treated hamsters inoculated repeatedly with C. albicans had high numbers of C. albicans in the gut, and viable C. albicans was recovered from the visceral organs of 53% of the animals. Examination of the mucosal surfaces from test and control animals indicated further that animals which contained a complex indigenous microflora had significantly lower numbers of C. albicans associated with their gut walls than did antibiotic-treated animals. The ability of C. albicans to associate with intestinal mucosal surfaces also was tested by an in vitro adhesion assay. The results indicate that the indigenous microflora reduced the mucosal association of C. albicans by forming a dense layer of bacteria in the mucus gel, out-competing yeast cells for adhesion sites, and producing inhibitor substances (possibly volatile fatty acids, secondary bile acids, or both) that reduced C. albicans adhesion. It is suggested, therefore, that the indigenous intestinal microflora suppresses C. albicans colonization and dissemination from the gut by inhibiting Candida-mucosal association and reducing C. albicans population levels in the gut.
3897060
The bactericidal and opsonizing effects of normal human serum on six strains of Salmonella typhimurium LT-2 having different lipopolysaccharide (LPS) composition were demonstrated through five indices. Complement activity in the presence of antibody was important for the opsonization of all six strains and for the bactericidal effect on rough mutants. Complement activity, either in the presence or absence of antibody, was involved in the ingestion strains of SL 901 (SR) and SL 1032 (Rd1) by human neutrophils. Strain SH 5014 (Rb2) was avidly ingested by neutrophils and totally dependent on complement activity in the presence of antibody. The ingestion of strain SH 2201 (S) was also mediated exclusively by complement activity in the presence of antibody but not as efficiently as were rough mutants. Antibody, as demonstrated by quantitative fluorescence, enhanced the complement activity on the ingestion of the S, SR, and Rb2 strains by neutrophils. The intracellular killing of six strains was enhanced significantly by complement activity in the presence of antibody. The overall survival in the presence of serum and neutrophils decreased as the LPS became shorter. Complement activity in the presence of antibody enhanced extracellular killing only for strains SL 901 (SR) and his 515 (Ra). It was shown that there was no difference between SR and Ra strains in all five indices, suggesting that the one additional O-antigen side chain does not make the SR strain more resistant than the Ra strain. Although resistance by S. typhimurium to host defense mechanisms increases as the LPS chain length increases, the specific LPS structure appears to be of greater importance, especially with respect to opsonization.
3897063
Mutants of the bacterial fish pathogen Aeromonas salmonicida selected for inability to digest casein concomitantly lost hemolytic activity against horse erythrocytes under certain conditions. Mixtures of wild-type with mutant culture supernatants indicated that mutants produce an inactive precursor of a hemolysin which was activated by autogenous caseinase and, with less efficiency, by other serine proteases. Selective inhibition or repression of caseinase production in the wild-type strain also resulted in the production of an inactive precursor of a hemolysin. The precursor of hemolysin was also activated by a serum factor which appeared to exert its maximum effect at the bacterial surface or after entry into the bacterial cell. These results could affect the interpretation of studies evaluating the role of individual extracellular products in the pathogenesis of A. salmonicida infections.
3897062
Self-transferable plasmid pIP1100 confers to Escherichia coli an unusually high level of resistance (1 to 2 mg/ml) to erythromycin by production of an erythromycin esterase. The effect of pIP1100 on the destiny of E. coli strains in the intestines of gnotobiotic mice was studied. In germfree mice, pIP1100 was efficiently transferred to a plasmid-free E. coli recipient. Intestinal counts of the donor, the recipient, and the transconjugants were greater than 8.5 log CFU/g of feces. When erythromycin was added to the diet of the mice, counts of the plasmid-bearing strains were only slightly lowered and partial inactivation of erythromycin was observed in the feces. Transfer of pIP1100 also occurred in human-flora-associated mice. In this model all the E. coli strains were subject to microbial antagonisms caused by the anaerobic components of the flora. However, strains harboring pIP1100 were strongly inhibited (less than 2.5 log CFU/g of feces), whereas their plasmid-free counterparts persisted at much higher population levels (greater than 5.2 log CFU/g of feces). The ecological disadvantage conferred by pIP1100 to E. coli when a complex human flora was concomitantly present in the intestine of the mice persisted during erythromycin administration. These results provide an explanation for the low incidence of isolation of highly erythromycin-resistant E. coli strains despite the extensive use of the antibiotic.
3897059
The differences between blastospores and germ tubes of Candida albicans, as previously shown by immunofluorescence, were further studied by comparing digests of cell walls of both growth forms. Organisms were surface labeled with 125I, and cell walls were digested enzymatically. When Zymolase digests were treated with polyclonal, polyspecific antiserum to C. albicans 441B, which stains only germ tubes in immunofluorescence assays, components of molecular weights 200,000 and 155,000 were immunoprecipitated from digests of germ tubes of strain B311, but nothing was recovered from blastospores. Whereas the 200,000-molecular-weight component was found in the three strains tested, the 155,000-molecular-weight component was found only in strain B311. When Zymolase digests were treated with unadsorbed antiserum, which stains both blastospores and germ tubes in immunofluorescence assays, an additional component was precipitated from digests of both growth forms with a molecular weight greater than the 200,000-molecular-weight marker. All three antigens were mannoproteins, as was shown by their abilities to bind concanavalin A and to be labeled by 125I. Also, all antigens were located on the cell surface, as was shown by the following criteria: adsorption of antisera with live organisms removed antibody to these components, and antibody eluted from surfaces of whole organisms precipitated all components. Components common to both growth forms, as well as germ tube-specific components, were detected in trypsin and chymotrypsin digests, but their molecular weights differed from those of Zymolase digests. Thus, germ tube-specific surface determinants as well as determinants common to both growth forms were detected on enzymatically released cell wall components.
3897064
A ureolytic strain of Proteus mirabilis, isolated from a patient with infectious kidney stones, produced struvite (MgNH4PO4 X 6 H2O) and apatite [Ca10(PO4)6CO3] crystals in vitro when grown in artificial urine. Surface-attached crystals were encased in a slime-like layer. Scanning electron microscopy revealed that surfaces submerged in the artificial urine were colonized by P. mirabilis. Bacteria-associated crystals appeared soon after colonization and eventually became coated with an amorphous substance. Energy-dispersive X-ray analysis of these crystals revealed the presence of Mg, Ca, and P which are major components of struvite and apatite. Transmission electron microscopy of surface scrapings revealed that the glycocalyx of P. mirabilis contained a large number of crystals. Based on these observations and previous work, a theory for infectious renal calculogenesis is proposed. The kidney is initially colonized by invading ureolytic pathogens. These pathogens secrete copious amounts of glycocalyx which facilitates adhesion of the organisms to the kidney, provides protection for these bacteria, and serves to bind struvite and apatite crystals that result from bacterial urease activity. Growth of these calcified microcolonies into mature stones is characterized by continued bacterial growth, incorporation of urinary mucoproteins into the matrix along with bacterial glycocalyx, and a continued deposition of struvite and apatite crystals due to the high pH. The mature stone, in effect, represents an enlarged "fossilized" bacterial microcolony.
3897066
The quantity of streptococcal cell wall localized in the joints of rats of strains which are either susceptible (Sprague-Dawley, LEW/N, M520/N) or resistant (Buffalo, WKY/N, F344/N) to cell wall-induced chronic erosive arthritis was measured after intraperitoneal injection of group A streptococcal cell wall fragments. Susceptibility or resistance was not associated with a difference in the amount of cell wall localized in limbs or other tissues. It is concluded that although localization of cell wall in joint tissue is essential for development of arthritis, the relative resistance of certain rat strains reflects genetic regulation of inflammatory response rather than a quantitative difference in localization of cell wall in joints.
3897065
Three putative Treponema pallidum ligands (P1, P2, and P3) that bind host fibronectin were characterized by peptide mapping. Papain digestion of each protein yielded a comigrating peptide of approximately 12,000 molecular weight. An antibody to this protein fragment inhibited T. pallidum host cytadherence, indicating that this peptide may be the functional domain of these treponemal adhesins.
3897067
Lymph node cells from mice infected with live Mycobacterium bovis BCG were fused with BW5147 cells after short-term culturing in vitro. Both mycobacterium- and self-reactive T-cell hybridomas were identified. Some T-cell hybridoma clones displayed dual reactivity to self and to self plus mycobacterial antigen but did so to a different degree, indicating that infection with mycobacteria stimulates autoreactive immune responses.
3897068
Beta-interferon was administered by intravenous infusion to 16 patients affected with fulminant hepatitis B virus infection in third or fourth-grade coma. Ten patients presented a superinfection or a co-infection due to the delta (delta)-agent. None had detectable interferon (IFN) activity before therapy was begun. Besides fever, no significant side-effects were observed during treatment. Both the IFN-treated group as well as the "historical" control group, made up of 70 cases of fulminant virus hepatitis, not treated with IFN and observed during a previous ten year-period, received supportive therapy; survival rates were similar in both groups. Furthermore, the presence or absence of the delta-agent did not appear to affect survival rates significantly.
3897071
The treatments of mild hypertension with atenolol and prazosin in occupationally active men and women were compared in a double blind cross-over with placebo. The hypotensive effect of the beta-adreno-receptor blocking drug, atenolol, were striking and in accordance with current knowledge, using one daily dose of 100 mg. In contrast, the hypotensive effect of taking 2 mg prazosin twice a day was modest, averaging about 3% when compared with placebo, somewhat less but still detectable during the performance of muscular exercises. Atenolol medication significantly reduced heart rate and blood pressure responses to muscular exercises, covering a range of work loads experienced during ordinary working days. No increased feeling of muscular fatigue or other discomfort during muscular work compared to that on prazosin and placebo medication could be detected. It was therefore concluded that atenolol medication was a useful treatment of mild hypertension and did not reduce the normal working ability and exercise tolerance. Prazosin medication did not significantly change working ability and exercise tolerance.
3897073
Mice (C57BL/6, n = 5) were given a single intravenous injection of soluble bovine serum albumin (BSA)-rabbit anti-BSA immune-complexes (IC) prepared at five-fold antigen excess. The mice were sacrificed 15 and 30 min, and 1, 2, 4 and 12 h after injection. Granular immunofluorescence for BSA and rabbit IgG, in a pattern consistent with IC aggregation, was observed in the alveolar walls and in the cytoplasm of alveolar cells. Moderate immunofluorescence was observed 15 min after IC injection and maximal immunofluorescence was observed at 30-60 min which decreased rapidly 2 h after IC administration. Only a trace amount of immunofluorescence was observed at 4 h and none was seen at 12 h. Light microscopic immunoperoxidase staining showed localization of IC in the interstitium of the alveolar septa and in type I alveolar cells and alveolar macrophages. By immunoelectronmicroscopy, the uptake of IC in the cytoplasm of type I alveolar cells and alveolar macrophages was confirmed.
3897075
Previous studies have demonstrated that the renal prostaglandin system participates in the recovery from ischemic events, in diuresis and in natriuresis. This study was undertaken to probe renal prostaglandin E2 synthesis during the first and second weeks after renal transplantation. Urinary prostaglandin E2 excretion was greatly elevated immediately after transplantation, compared to the second week, and differences in urine PGE2 concentration were also significant. This suggests that enhanced prostaglandin synthesis accompanies the resumption of renal function after transplantation.
3897070
Epidemiological studies have mapped the occurrence of hepatitis B among health personnel with the use of specific serologic markers and thereby made rational preventive precautions possible. Follow-up studies have demonstrated the effect of this prevention, and the newly developed hepatitis B vaccine has further improved the possibilities for effective prophylaxis against occupational hepatitis B. On the other hand, there is the chemically induced occupational liver damage. Only a few of the thousands of industrially used chemicals have been sufficiently investigated for hepatotoxicity and the list of suspected and confirmed hepatotoxic agents is still growing. The worrisome example of vinylchloride-induced serious liver disease among PVC-workers, revealed after 42 years of industrial use by alert clinicians, calls for intensified activities in the field of occupational hepatotoxicity. However, the clinical, biochemical, and morphological features of liver disease are often vague and unspecific. A non-invasive, convenient quantitative liver function test is needed. Circumstantial evidence and a few epidemiological studies suggest that part of the so-called cryptogenic liver diseases, such as liver cirrhosis, may be caused by occupational exposure to chemicals. This should be further studies. Animal experiments have shown that one chemical agent may potentiate the hepatotoxic effect of another chemical agent. This should be the subject of investigations in the work environment, where exposure to various chemicals is the rule rather than the exception. Alcohol consumption may also interfere with the hepatotoxicity of occupationally used chemicals.
3897077
Ceftazidime was used in 19 patients at high risk owing to severe impairment of natural defense systems. The therapeutic efficacy and adverse reactions produced by cephalosporin, as evaluated on the basis of the results of clinical investigations and laboratory tests, were regarded as positive.
3897069
Antiserum against Escherichia coli J5, a "rough" mutant of E. coli 0111, has been reported to confer broad-spectrum protection against serologically unrelated gram-negative bacteria. In order to re-evaluate these findings, we examined the influence of rabbit antiserum against E. coli J5 on the phagocytosis of heterologous gram-negative bacteria by rabbit granulocytes in vitro and its ability to protect mice against gram-negative bacterial infection. In vitro, J5 antiserum enhanced the phagocytosis of E. coli 0111, E. coli 06 and Serratia marcescens 06/014:H2 when compared to normal rabbit serum. However, J5 antiserum did not enhance the phagocytosis of Klebsiella pneumoniae type 2 and Pseudomonas aeruginosa serotype 9. In vivo, the protective effect of J5 antiserum against lethal gram-negative infection was not superior to that of normal (pre-immune) serum with the exception of E. coli 0111 septicemia. In contrast, type-specific antiserum against each of the smooth gram-negative bacteria markedly enhanced phagocytosis in vitro and exerted significant protection in vivo. Thus, in this study antiserum against E. coli J5 proved to be of limited value for opsonization of gram-negative bacteria and protection against gram-negative bacterial infection.
3897078
Despite alcohol being the earliest and most widely known of mood-altering substances, there have always been attempts to restrict and control its use. National prohibition of alcohol represents the most ambitious attempt to provide a legal framework for such restrictions. The present paper, following a comparative-historical approach, looks at the course of alcohol prohibition policies in two countries with differing ethnic backgrounds, religious orientations, and stages of economic development: the United States and India. Tracing the historical forces which shaped the prohibition policies in both the countries and their apparent lack of success, the paper identifies some common elements. Among the more important, though with situational variations, are the high degree of moralistic and patriotic fervor associated with prohibition efforts, the projection of guilts and fears of the proponents onto alcohol use, and aspects of culture conflict and opposing group interests. Dysfunctions introduced into the control system by socioeconomic changes resulted in prohibition being either abandoned or altered substantially in both countries.
3897079
During the years 1957 to 1963, we introduced the concept of the onset of anaerobic metabolism to measure cardiopulmonary and peripheral aerobic performance capacity. On the basis of bicycle and crank ergometer work with load increments of 3 min duration, we described a point at which the pulmonary ventilation (VE) increases at a greater rate than O2 uptake (VO2). Because the changes of the arterial blood lactate (Laa) and VE coincide we defined this point as the "point of the optimal ventilatory efficiency," identical with the "O2 endurance performance limit," later called "anaerobic threshold" by Wasserman et al.
3897080
The effect of low calorie diet on blood pressure, catecholamines, plasma renin activity (PRA) and aldosterone was examined in 22 obese subjects (19 hypertensives and 3 borderline hypertensives). A significant decrease in blood pressure (P less than 0.05) was observed in all patients after 10 days on the diet. Twenty subjects showed a significant decrease in norepinephrine (NE) levels (P less than 0.05) and two patients showed an extreme increase in NE level. On reexamination six months later these two patients presented with high NE levels and predict blood pressure levels despite having lost 15 and 18 kg respectively. The study group showed a significant decrease in mean PRA (P less than 0.05). A correlation was observed between changes in NE levels and PRA (r = 0.42, P less than 0.05) and between changes in PRA and aldosterone (r = 0.54, P less than 0.05). The reduction in blood pressure associated with caloric restriction in these obese patients may be a result of reduced sympathetic nervous system activity.
3897082
A double-blind controlled study was performed in unselected obese outpatients to assess the effects of ephedrine on weight loss. Patients were treated for 3 months with placebo (group I), 25 mg t.i.d. or 50 mg t.i.d. of ephedrine hydrochloride orally administered (groups II and III, respectively). Dietary treatment consisted of 1000 kcal/day for females and 1200 kcal/day for males. The three groups were matched for age, sex, body mass index and pre-treatment spontaneous caloric intake. Weight loss was similar in all groups. Patients in group III (ephedrine 150 mg/day) showed significantly more side effects than the placebo group. These results do not seem to favour the hypothesis that ephedrine, a thermogenic agent, may be effective in the therapy of unselected simple obesity. On the other hand, it cannot be excluded that the drug may be useful in obese patients in whom defective thermogenesis may be clearly demonstrated.
3897081
The role of the gut hormone GIP (gastric inhibitory polypeptide; glucose-dependent insulinotropic polypeptide) in the development of hyperinsulinemia of pre-obese (fa/fa) Zucker rats was investigated. Plasma GIP levels were compared in lean and fa/fa pups from 21 to 35 days of age. The onset of both basal and glucose-stimulated hyperinsulinemia was studied. Possible causal roles for glucose, GIP and acetylcholine in hyperinsulinemia were investigated in the isolated perfused pancreas preparation. Immunocytochemical studies of pancreatic islets were also carried out. Glucose-stimulated hyperinsulinemia was present in fa/fa rats at 21 days of age but fasting hyperinsulinemia did not become apparent until 35 days of age. At no time did plasma GIP levels differ between lean and fa/fa rats. Immunocytochemical analysis of the pancreas revealed enlarged islets in fa/fa rats from 7 days of age onward. In the in vitro perfused pancreas of 21 day old fa/fa pups the insulin response was not different from that of lean controls in the presence of glucose (300 mg/dl) plus GIP or acetylcholine. An increased pancreatic insulin response to glucose (300 mg/dl or 80 mg/dl) plus GIP in fa/fa compared to lean animals was observed at 35 days of age. These data suggest that defects in the beta-cell response to GIP become apparent at 35 days of age in fa/fa rats resulting in a loss of the glucose threshold for the insulinotropic action of GIP and onset of fasting hyperinsulinemia in vivo. Causal factors for glucose-stimulated hyperinsulinemia at 21 days of age appear to be complex and not easily replicated in in vitro experiments.
3897085
A systematic approach to structure-activity studies is described. Its application to the vasopressin field made possible the preparation of vasopressin analogs with very high and very specific antidiuretic activity, analogs with increased pressor specificity, and analogs with high agonistic-antagonistic properties.
3897087
A 22-month-old child with familial infantile nephrotic syndrome due to diffuse mesangial sclerosis is presented. The case history of this patient is exceptional because of evidence of an immunologic pathogenesis of the renal disease, documented by characteristic immunofluorescent and electron-microscopy findings.
3897090
Urinary retention in children is rarely caused by an extrinsic compression of an extragonadal pelvic mass. The sonographic appearance of these masses are divided into 3 categories: 1) solid, 2) fluid-filled, and 3) mixed. Familiarity with the sonographic spectrum of these lesions can limit the differential diagnosis, will suggest specific follow-up procedures needed for an accurate diagnosis and will eliminate the need for unnecessary invasive workups.
3897092
Platinum drugs have chemical as well as biochemical and biological effects on cells, all of which may interact with radiation effects. They inhibit recovery from sublethal and potentially lethal radiation damage. They produce a pattern of chromosome aberrations analogous to that from alkylating agents. Cellular sensitivity to platinum is increased when glutathione levels are reduced, just as is radiosensitivity. There is a pattern of drug sensitivity throughout the phases of the cell cycle which is different from that for radiosensitivity. The ideal platinum drug-radiation interaction would achieve radiosensitization of hypoxic tumour cells with the use of a dose of drug which is completely non-toxic to normal tissues. Electron-affinic agents are employed with this aim, but the commoner platinum drugs are only weakly electron-affinic. They do have a quasi-alkylating action however, and this DNA targeting may account for the radiosensitizing effect which occurs with both pre- and post-radiation treatments. Because toxic drug dosage is usually required for this, the evidence of the biological responses to the drug and to the radiation, as well as to the combination, requires critical analysis before any claim of true enhancement, rather than simple additivity, can be accepted. The amount of enhancement will vary with both the platinum drug dose and the time interval between drug administration and radiation. Clinical schedules may produce an increase in tumour response and/or morbidity, depending upon such dose and time relationships.
3897088
Three adolescents with clinical nephrotic-nephritic picture were noted to have diffuse proliferative and exudative glomerulonephritis. Although focal membranous changes were noted in two of the initial biopsies, evolution into classical membranous glomerulopathy was seen in subsequent biopsies. This study suggests a relationship between these two different patterns of immune complex-associated glomerular injury, and confirms extrapolations made from experimental models of chronic serum sickness.
3897093
Time-lapse microscopy revealed that the proportion of non-dividing cells after irradiation was the same under both conditions of PLD repair and non-PLD repair, suggesting that PLD is repaired in an error-free and -prone manner, respectively, or that PLD repair operates only on that mode of cell death which involves post-irradiation mitosis.
3897094
Drug-radiation interactions in haemopoietic tissue were assessed as the lethality of mice within 7-28 days after whole-body irradiation. The investigated drugs were adriamycin (ADM), bleomycin (BLM), cyclophosphamide (CTX), 5-fluorouracil (5-FU), methotrexate (MTX), mitomycin C (MM-C) and cis-diamminedichloroplatinum II (cis-DDP). The drugs were administered as single doses 15 min before graded doses of whole-body irradiation or at different intervals from 7 days before to 7 days after fixed radiation doses. ADM, CTX, 5-FU, MM-C and cis-DDP enhanced the radiation response when administered 15 min before irradiation. The dose effect factor (DEF) was 9.11 for 5-FU and in the range 1.25-1.59 for the other drugs. MTX administration 15 min before irradiation had no effect (DEF 1.00). However, MTX increased lethality if given 1-3 days after irradiation (DEF 1.21-1.76) and protected against lethality if given 1-3 days before irradiation (DEF 0.83). A similar time dependence was observed for ADM, CTX, 5-FU, MM-C and cis-DDP. Protection against lethality was not observed but in all these cases the lethality was significantly lower at administration 1-3 days before than 1-3 days after irradiation. A proper investigation of the effect of BLM was not possible as the combination of this drug and whole-body irradiation caused a high rate of gastrointestinal deaths.
3897091
A 19-year-old girl having a sporadic form of idiopathic multicentric osteolysis with nephropathy is described. She was first diagnosed as having sporadic carpotarsal osteolysis at the age of 6. Her proteinuria was first detected at 15 years of age and renal biopsy specimens obtained at the same age were compatible with those of focal segmental glomerulosclerosis with interstitial fibrosis and tubular atrophy. Immunofluorescence microscopy revealed negative deposits of Ig G, Ig A and C3 but a trace amount of mesangial Ig M in unsclerosed segments of the glomeruli. Electronmicroscopy showed no specific changes. Renal vascular changes such as proliferation of vascular intima and medial hypertrophy were not demonstrated in the present case. It is our conclusion that focal segmental glomerulosclerosis is part of the spectrum of nephropathy in the sporadic form of idiopathic multicentric osteolysis.
3897089
Between 1974-1979, 64 renal cadaveric transplants were performed in 54 pediatric recipients at our institution. Forty eight of these 64 transplants experienced at least one episode of acute rejection. These patients were divided in two equal groups including 24 transplants in 21 recipients, one group treated with chemical immunosuppression alone, the other group treated by chemical immunosuppression and radiotherapy. Kidney survival at 2 years was 54.1% (13/24) in the control group treated by chemical immunosuppression alone. In the group treated by radiotherapy and immunosuppression, kidney survival after 2 years gave a success rate of 45.8% (11/24). Thus, it would appear that addition of radiotherapy to standard immunosuppressive treatment exerted no beneficial long term effect in acutely rejected renal transplants. In view of the disappointing results obtained with radiotherapy, it is felt that this mode of treatment should be restricted to use in particular circumstances as a temporary means of immunosuppression where systemic immunosuppression is hazardous.
3897115
This study shows that alloantigen presentation via the anterior chamber (AC) of the eye coupled with a single high dose cyclophosphamide (CP) (100 mg/kg) treatment effectively suppresses the skin graft rejection reaction of the recipient. Lewis (Le) rats bearing allogeneic Brown Norway (BN) skin implants in the AC of the eye demonstrate a modest increase in the survival time of orthotopic BN skin grafts. A slight prolongation of the survival of orthotopic BN skin grafts was also demonstrated in nonimplant or syngeneic implant-bearing Le recipients which received a single injection of a large dose of CP. Augmentation of suppression was evident in rats which were treated with a single dose of 75 mg/kg CP but not 25 mg/kg. The augmentation of suppression was evident when CP treatment and skin grafting of the recipient occurred on either 0, 7, or 14 days postimplantation. Recipient splenectomy did not interfere with the augmentation of suppression.
3897116
In order to clarify the factors responsible for the cellular infiltrate characteristic of anterior uveitis, the authors have induced inflammation in rabbits by the intravitreal injection of 100 ng of Escherichia coli or Salmonella endotoxin (ET). A 2% concentration of aqueous humor 18 to 24 hr after ET consistently induced monocyte migration as measured in modified Boyden chambers. Activity was significantly greater in these samples than in aqueous after saline injection or 3 hr after endotoxin injection (prior to cellular infiltrate). Using either sephadex G-75 molecular sieve chromatography or a cibacron blue column, the vast majority of migratory activity co-eluted with albumin. Serum albumin, however, at a comparable concentration did not induce migration. Activity was largely heat- and acid-stable and was maximal in the presence of a concentration gradient, indicating that it was chemotactic rather than chemokinetic. A second peak of activity eluted from the G-75 column just prior to a marker with molecular weight of 427 and was also present in eluates from normal aqueous humor. Chloroform:methanol extraction, radioimmunoassay, and high performance liquid chromatography indicated that a small portion of the chemotactic activity could be ascribed to lipid including leukotriene B4. In contrast to the prominence of complement (C5a) derived chemotactic activity resulting from intravenous ET, C5a was not a major contributor to aqueous chemotactic activity subsequent to local ET. These observations demonstrate that leukocyte migration factors in aqueous humor can be characterized and compared. This approach can be used to test the hypothesis that subsets of anterior uveal inflammation might be distinguished on the basis of associated chemotactic factors.
3897118
The changes of the biliary tree following distal bile duct obstruction and its release were confirmed by biliary scintigraphy and monitored by serial ultrasonography, computed tomography, and values of serum bilirubin and alkaline phosphatase in 14 mongrel dogs. The degree and rate of biliary dilatation were independent of cholecystectomy. The most rapid rate of extrahepatic dilatation occurred within the first 48 hours, while dilated intrahepatic ducts were first recognized three to six days after obstruction. Following release of the obstruction, the degree and rate of resolution of the biliary dilatation were independent of the duration of ligation (one vs. two weeks) and cholecystectomy. The dilatation resolved slowly. Dilated intrahepatic ducts were recognized for as long as eight to 13 days, while extrahepatic biliary dilatation was still present for 13 weeks, at which time the experiment was terminated. It is postulated that the extrahepatic biliary dilatation will approach a plateau approximately one month after total biliary obstruction. It appears that if the obstruction lasts more than one week, it results in irreversible damage to the elasticity of the extrahepatic ducts. Thus, after release of the obstruction, serial biliary imaging is indicated until a new baseline of the biliary tree diameter has been established.
3897119
Forty-eight patients with shoulder pain and 15 normal volunteers underwent rotator cuff imaging using high resolution real time ultrasound. The potential diagnostic value of sonography in detecting rotator cuff tears was evaluated by correlating ultrasound findings with surgical findings in 19 patients, 12 of whom also underwent preoperative arthrography. The preoperative ultrasound diagnosis was correct in 18 of the 19 patients undergoing surgery for possible rotator cuff tears. In the group of 12 surgical patients undergoing both preoperative arthrography and sonography, ultrasound correctly predicted the presence of a rotator cuff tear in 12 of 12 patients, while arthrography predicted cuff tears in only nine of 12. Good anatomic definition of the rotator cuff was obtained in both symptomatic and asymptomatic groups. The characteristic appearance of the normal and pathologic rotator cuff is described. Rotator cuff sonography promises to be a valuable new diagnostic tool for evaluating patients with suspected rotator cuff tears.
3897120
An ultrasound phantom was constructed simulating fetal femurs in amniotic fluid. Bones of 26, 36, 50, 58, and 70 mm, representative of gestational ages ranging from 17 to 36 weeks, were scanned with mechanical sector, phased sector, and linear array systems (ATL, Diasonics, Acuson, and GE). Measurements were made with the bone in both a horizontal and nearly vertical orientation at 5, 10, and 15 cm from the transducer. The ultrasound measurements were compared with the true bone length. With bones in a nearly vertical orientation (parallel to the ultrasound beam) the ultrasound measurements corresponded more closely to the true bone length regardless of the type of equipment or distance from the transducer. The wide aperture linear system was most accurate with no measurable difference from the actual bone length and a mechanical sector scanner had the largest error which was 6 mm. In the horizontal position (perpendicular to the beam) the smallest errors occurred when the bone was in the focal zone. This ranged from no error for the wide aperture linear array to 8 mm for the mechanical sector scanner. When the bone was not in the focal zone the error ranged from 8 to 26 mm for the mechanical sector scanner. Errors in ultrasound-measured femur lengths can be shown to result from the focal characteristics of the equipment as well as the orientation and distance of the bone from the transducer. These differences can produce errors in estimation of gestational age as large as ten weeks.
3897135
Between July 1982 and April 1984, 22 patients underwent cardiac transplantations at the Texas Heart Institute with a cumulative follow-up of 188 patient-months (mean of 8.6 months and a range of 0.5 to 21). The actuarial survival rate at 20 months was 72%. Strict selection criteria for potential recipients and donors, optimal perioperative management, which includes endomyocardial biopsy, and most important the introduction of cyclosporine are the major factors that led to these increasing survival rates. The high incidence of cyclosporine-related complications, especially hypertension and myocardial fibrosis, will require long-term evaluation to adequately assess the therapeutic effectiveness of this new immunosuppressive agent.
3897138
The most common reason to perform cardiac transplantation is dilated cardiomyopathy. Alterations in cardiac output secondary to decreased contractility and increased preload and afterload will, over time, lead to progressive deterioration of the patient with this type of end-stage cardiac disease. Heart transplantation is now an accepted therapy for these patients. This article focused on the patient in the period awaiting cardiac transplantation. Five pertinent nursing diagnoses were identified and discussed. A case study approach was utilized to highlight patient problems and nursing interventions.
3897143
A highly specific enzyme-linked immunosorbent assay (ELISA) was developed for the rapid identification and quantification of hemoglobin C in hemolysates. The procedure involves coating the surface of microtiter wells with Hb C and then addition of monospecific rabbit antibodies that recognize the unique beta 6 GLU----LYS substitution in Hb C. Next, an antibody to rabbit gamma-globulin conjugated with alkaline phosphatase is added, followed by substrate; a yellow color is formed due to the enzymatic hydrolysis of the substrate, which can be measured spectrophotometrically. For quantification purposes, a hemolysate containing Hb C is introduced just prior to the addition of the Hb C antibody. This results in blocking the attachment of the anti-Hb C to the Hb C coated to the plastic surface. Upon addition of anti-rabbit gamma-globulin conjugate and substrate, there is a consequent reduction or elimination of color formation. Since the degree of diminution of color formation is dose-dependent, standard curves can be developed for quantification of Hb C in unknowns. Of the total hemoglobin, the amounts of Hb C in heterozygotes averaged 27.3 +/- 5.7% by ELISA and 25.1 +/- 3.9% by radioimmunoassay (RIA). In SC individuals the corresponding values were 30.2 +/- 10.1% by ELISA and 24.7 +/- 10.9% by RIA. In homozygotes, Hb C values averaged 83.2 +/- 4.2% by ELISA and 85.0 +/- 6.6% by RIA. Subjects with Hb C beta(+)-thalassemia had 66.5 +/- 3.7% Hb C as measured by ELISA and 63.5 +/- 9.1% as determined by RIA. The ELISA procedure offers distinct advantages for Hb C identification and quantification over other techniques in parameters such as specificity, sensitivity, and rapidity.
3897145
A sensitive immunohistochemical technique was used to demonstrate zinc metallothionein in rat and human liver and ileum. In the liver, immunoreactivity was observed within the hepatocyte nucleus and cytoplasm, in sinusoids, canaliculi and blood vessels. In the ileum, immunoreactivity was present in the enterocyte nucleus and cytoplasm, and in the lamina propria. The effects of fasting alone and fasting with zinc injection were studied. In the liver, maximum staining was observed after 6 h fasting in the sinusoids, canaliculi and hepatocyte cytoplasm, and this pattern was not present in zinc injected animals. In the ileum, the greatest staining in the enterocyte cytoplasm and basal region was in control animals and after 6 and 12 h fasting. A similar pattern was observed in zinc-injected animals. Decreased staining was seen after 18 h fasting in both liver and ileum. In human ileum, the patients with colitis had less metallothionein immunoreactivity and those on steroid therapy had more immunoreactivity than the controls. We suggest a physiological transport and short term storage function for zinc metallothionein in rat and man.