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[Demonstration of tumor inhibiting properties of a strongly immunostimulating low-molecular weight substance. Comparative studies with ifosfamide on the immuno-labile DS carcinosarcoma. Stimulation of the autoimmune activity for approx. 20 days by BA 1, a N-(2-cyanoethylene)-urea. Novel prophylactic possibilities]. | A report is given on the recent discovery of outstanding immunological properties in BA 1 [N-(2-cyanoethylene)-urea] having a (low) molecular mass M = 111.104. Experiments in 214 DS carcinosarcoma bearing Wistar rats have shown that BA 1, at a dosage of only about 12 percent LD50 (150 mg kg) and negligible lethality (1.7 percent), results in a recovery rate of 40 percent without hyperglycemia and, in one test, of 80 percent with hyperglycemia. Under otherwise unchanged conditions the reference substance ifosfamide (IF) -- a further development of cyclophosphamide -- applied without hyperglycemia in its most efficient dosage of 47 percent LD50 (150 mg kg) brought about a recovery rate of 25 percent at a lethality of 18 percent. (Contrary to BA 1, 250-min hyperglycemia caused no further improvement of the recovery rate.) However this comparison is characterized by the fact that both substances exhibit two quite different (complementary) mechanisms of action. Leucocyte counts made after application of the said cancerostatics and dosages have shown a pronounced stimulation with BA 1 and with ifosfamide, the known suppression in the post-therapeutic interval usually found with standard cancerostatics. In combination with the cited plaque test for BA 1, blood pictures then allow conclusions on the immunity status. Since IF can be taken as one of the most efficient cancerostatics--there is no other chemotherapeutic known up to now that has a more significant effect on the DS carcinosarcoma in rats -- these findings are of special importance. Finally, the total amount of leucocytes and lymphocytes as well as their time behaviour was determined from the blood picture of tumour-free rats after i.v. application of BA 1. The thus obtained numerical values clearly show that further research work on the prophylactic use of this substance seems to be necessary and very promising. | 22 |
The effect of o-salicylate upon pentose phosphate pathway activity in normal and G6PD-deficient red cells. | The effect of the major metabolite of aspirin, namely salicylic acid, upon the pentose phosphate pathway (PPP) of normal and G6PD-deficient red cells has been studied. Salicylic acid was shown to inhibit this pathway in proportion to the amount present. At any concentration of this substance there was greater inhibition of the PPP in G6PD-deficient than in normal red cells. | 35 |
Purification and properties of Escherichia coli dihydrofolate reductase. | Dihydrofolate reductase has been purified 40-fold to apparent homogeneity from a trimethoprim-resistant strain of Escherichia coli (RT 500) using a procedure that includes methotrexate affinity column chromatography. Determinations of the molecular weight of the enzyme based on its amino acid composition, sedimentation velocity, and sodium dodecyl sulfate gel electrophoresis gave values of 17680, 17470 and 18300, respectively. An aggregated form of the enzyme with a low specific activity can be separated from the monomer by gel filtration; treatment of the aggregate with mercaptoethanol or dithiothreitol results in an increase in enzymic activity and a regeneration of the monomer. Also, multiple molecular forms of the monomer have been detected by polyacrylamide gel electrophoresis. The unresolved enzyme exhibits two pH optima (pH 4.5 and pH 7.0) with dihydrofolate as a substrate. Highest activities are observed in buffers containing large organic cations. In 100 mM imidazolium chloride (pH 7), the specific activity is 47 mumol of dihydrofolate reduced per min per mg at 30 degrees. Folic acid also serves as a substrate with a single pH optimum of pH 4.5. At this pH the Km for folate is 16 muM, and the Vmax is 1/1000 of the rate observed with dihydrofolate as the substrate. Monovalent cations (Na+, K+, Rb+, and Cs+) inhibit dihydrofolate reductase; at a given ionic strength the degree of inhibition is a function of the ionic radius of the cation. Divalent cations are more potent inhibitors; the I50 of BaCl2 is 250 muM, as compared to 125 mM for KCl. Anions neither inhibit nor activate the enzyme. | 46 |
Bile acids. XLVII. 12alpha-Hydroxylation of precursors of allo bile acids by rabbit liver microsomes. | Rabbit liver microsomal preparations fortified with 0.1 mM NADPH effectively promote hydroxylation of [3beta-3H]- or [24-14C]allochenodeoxycholic acid or [5alpha,6alpha-3H2]5alpha-cholestane-3alpha,7alpha-diol to their respective 12alpha-hydroxyl derivatives in yields of about 25 or 65% in 60 min. Minor amounts of other products are formed from the diol. The requirements for activity of rabbit liver microsomal 12alpha-hydroxylase resemble those of rat liver microsomes. Of a number of enzyme inhibitors studied only p-chloromercuribenzoate demonstrated a marked ability to inhibit the reaction with either tritiated substrate. There was no difference in the quantity of product produced from the tritiated acid or the 14C-labeled acid. No clear sex difference was found in activity of the enzyme, nor was an appreciable difference noted in activity of the enzyme between mature and immature animals. | 65 |
Myosin from arterial smooth muscle: isolation following actin depolymerization. | The contractile proteins from arterial smooth muscle are highly soluble, and can be extracted at I = 0.05. However, they can be precipitated by a prolonged dialysis at pH 6 to give an actomyosin with a high, although variable, actin:myosin ratio. The sedimentation behavior of this actomyosin at high ionic strength was examined as a function of pH, protein concentration and composition by preparative ultracentrifugation. Comparisons with synthetic skeletal muscle actomyosins of similar composition demonstrated significant differences in the behaviors of these two systems. It was found that much smooth muscle actomyosin is not dissociated by normally relaxing conditions, and that it sediments at a slower rate than F-actin. The solubility of the supernatant protein (a myosin-enriched actomyosin) in 0.2 M K Cl (pH 7) depended on the pH during centrifugation. A lower solubility was associated only with a higher actin concentration in the supernatant, suggesting a dependence on actin repolymerization. Pure myosin was selectively precipitated from the supernatant by polyethylene glycol-6000, but only when the protein was soluble at low ionic strength. The solubility of purified myosin was similar to that of myosin from striated muscles. A relationship between the presence of depolymerized actin and the high solubility of smooth muscle contractile proteins is suggested. | 85 |
Polymer concentration dependence of the helix to random coil transition of a charged polypeptide in aqueous salt solution. | The helix to coil transition of poly(L-glutamic acid) was investigated in 0.05 and 0.005 M aqueous potassium chloride solutions by use of potentiometric titration and circular dichroism measurement. Polymer concentration dependence of the transition was observed in the range from 0.006 to 0.04 monomol/e in 0.005 M KG1 solution. The polymer concentration dependence can be interpreted by current theories of the transition of charged polypeptides and of titration curves of linear weak polyelectrolytes taking the effect of polymer concentration into consideration. | 96 |
Inhibitory postsynaptic actions of taurine, GABA and other amino acids on motoneurons of the isolated frog spinal cord. | The actions of glycine, GABA, alpha-alanine, beta-alanine and taurine were studied by intracellular recordings from lumbar motoneurons of the isolated spinal cord of the frog. All amino acids tested produced a reduction in the amplitude of postsynaptic potentials, a blockade of the antidromic action potential and an increase of membrane conductance. Furthermore, membrane polarizations occurred, which were always in the same direction as the IPSP. All these effects indicate a postsynaptic inhibitory action of these amino acids. When the relative strength of different amino acids was compared, taurine had the strongest inhibitory potency, followed by beta-alanine, alpha-alanine, GABA and glycine. Topically applied strychnine and picrotoxin induced different changes of post-synaptic potentials, indicating that distinct inhibitory systems might be influenced by these two convulsants. Interactions with amino acids showed that picrotoxin seletively diminished the postsymaptic actions of GABA, while strychnine reduced the effects of taurine, glycine, alpha- and beta-alanine. But differences in the susceptibility of these amino acid actions to strychnine could be detected: the action of taurine was more sensitively blocked by strychnine compared with glycine, alpha- and beta-alanine. With regard to these results the importance of taurine and GABA as transmitters of postsynaptic inhibition on motoneurons in the spinal cord of the frog is discussed. | 128 |
Effects of zinc-smelter emissions on forest soil microflora. | Within 2 km of a zinc (Zn) smelter in Palmerton, Pennsylvania, near the Lehigh Water Gap, up to 13.5% Zn by weight has been measured in the O2 horizon of the soil, and up to 8% Zn in the A1 horizon. The total numbers of bacteria, actinomycetes, and fungi (measured by dilution plate counts) were greatly reduced in the most severely Zn-contaminated soils compared with control soils. The reduction of microbial populations may be a partial cause of the decreased rate of litter decomposition at Lehigh Gap. Growth of most bacteria from control sites was reduced by 100 to 200 muM Zn, most actinomycetes by 100 muM Zn, and most fungi by 100 to 1000 muM Zn in thin-Pablum extract agar (TPab). All the tested actinomycetes and non-spore-forming bacteria isolated from Zn-contaminated Lehigh Gap soils were Zn-tolerant, growing normally in media containing 600-2000 muM Zn. Most fungi, regardless of source, were capable of at least 50% of normal growth at 700 muM Zn. Zinc-tolerant bacteria, actinomycetes, and fungi were readily isolated from low-Zn soils, suggesting that selection for Zn tolerance may proceed rapidly. Acidophilic Mortierella species have been selectively eliminated near the smelter, apparently because of elevated soil pH. Peryronellaea glomerata (Corda) Goidanich and Coniothyrium spp. were found only in the high-Zn soils. | 142 |
Effects of decreasing arterial blood pressure on cerebral blood flow in the baboon. Influence of the sympathetic nervous system. | The influence of the sympathetic nervous system on the cerebral circulatory response to graded reductions in mean arterial blood pressure was studied in anesthetized baboons. Cerebral blood flow was measured by the 133Xe clearance method, and arterial blood pressure was decreased by controlled hemorrhage. In normal baboons, the constancy of cerebral blood flow was maintained until mean arterial blood pressure was approximately 65% of the base-line value; thereafter, cerebral blood flow decreased when arterial blood pressure was reduced. Superior cervical sympathectomy of 2-3 weeks duration did not affect the normal response. In contrast, both acute surgical sympathectomy (cervical trunk division) and alpha-receptor blockade (1.5 mg/kg of phenoxybenzamine) enhanced the maintenance of cerebral blood flow in the face of hemorrhagic hypotension in that cerebral blood flow did not decrease until mean arterial blood pressure was approximately 35% of the base-line value. The results indicate that the sympathetic nervous system is not involved in the maintenance of cerebral blood flow in the face of a fall in arterial blood pressure. Indeed, the implication is that the sympathicoadrenal discharge accompanying hemorrhagic hypotension is detrimental to, rather than responsible for, cerebral autoregulation. | 153 |
Serum lactate dehydrogenase activity ratios with different substrates. | 1. The lactate dehydrogenase activity of 89 sera from patients suffering myocardial infarction and of 55 sera from patients with hepatocellular damage was assayed under optimal conditions using pyruvate, alpha-oxobutyrate, hydroxypyruvate and glyoxylate as substrates. Activity was also measured with lactate as substrate at different pH values. 2. The ratios of activities under these different assay conditions were calculated for both series of patients. Correct differentiations for single ratios ranged from virtually nil for hydroxypyruvate/alpha-oxobutyrate to is greater than 93 per cent for glyoxylate/hydroxypyruvate and glyoxylate/alpha-oxobutyrate. This was little improved by the use of multiple ratios involving up to seven separate assays. 3. The activity ratio of hydroxypyruvate to pyruvate which is consistently greater than unity was found to be inverted in a case of morphine poisoning. | 159 |
Arterial catecholamines in hypoxic exercise in man. | 1. We measured the minute ventilation and arterial blood catecholamine concentrations in four normal men standing and at two levels of moderate treadmill exercise breathing 14% oxygen or air. 2. Minute ventilation was significantly higher during hypoxic exercise than during normoxic exercise at an oxygen uptake of 1500 ml/min. 3. Arterial plasma noradrenaline during hypoxic exercise at an oxygen uptake of 1500 ml/min was significantly greater than at rest. 4. Arterial plasma noradrenaline during normoxic exercise at an oxygen uptake of 1500 ml/min was not elevated above the resting concentration. 5. The results are compatible with the suggestion that increased concentrations of arterial plasma noradrenaline contribute to the hypoxic potentiation of the respiratory response to moderate exercise. | 171 |
An evaluation of factors affecting the in vitro bioassay for erythropoietin. | Two main aspects of the in vitro mouse foetal liver cell assay for Erythroid Stimulating Factor (ESF) in human sera have been investigated. The haem extraction process has been shown to give specific and quantitative recovery of 59Fe labelled haem from haemoglobin thus confirming that the material assayed in human sera is stimulating the synthesis of this protein. The extraction procedure can be simplified considerably by prior mixing of the reagents without significantly influencing the results. Several serum constituents (citrate, testosterone, B12, folic acid and iron) have been investigated over a range of concentrations for possible effects on the cultures. Generally only small effects on haem synthesis were observed. It is concluded that variations in the levels of these factors in sera from treated patients will not produce any significant alterations in the estimated ESF concentrations. | 250 |
[Synthesis of N-substituted isoindolines]. | Some derivatives of isoindoline were prepared in order to test their cardiovascular activity. Pharmacological tests showed that some of the compounds had moderate alpha-blocking and coronarodilatory activity whereas others had some local anesthetic activity. | 251 |
Gluconic acid production by Penicillium puberulum. | Twenty-five Penicillium species isolated from Egyptian soil were examined for their ability to produce gluconic acid in surface culture. Of the eight species capable of producing gluconic acid, Penicillium puberulum gave the maximum yield (91% gluconic acid from glucose after 7 days of fermentation with 3% CaCO3). Peptone was the best nitrogen source for acid fermentation and glucose was superior to sucrose. Addition of low concentrations of KH2PO4 and MgSO4 - 7 H2O stimulated acid production. An initial pH of 6.1 was most favourable for acid accumulation and addition of CaCO3 was necessary for maximum acid production. | 288 |
Phenomenon of hot-cold hemolysis: chelator-induced lysis of sphingomyelinase-treated erythrocytes. | Staphylococcus aureus produces a phospholipase C specific for sphingomyelin (beta-hemolysin). Erythrocytes with approximately 50% sphingomyelin in their membranes, e.g., from sheep, have been shown to have up to 60% of this phospholipid hydrolyzed by this enzyme at 37 C in isotonic buffered saline without hemolysis. Cooling of sphingomyelinase C-treated erythrocytes to 4 C causes complete lysis of the cells, a phenomenon known as hot-cold hemolysis. The addition of ethylenediaminetetraacetate (EDTA) to sheep erythrocytes preincubated with sphingomyelinase C was found to induce rapid hemolysis at 37 C. The treated cells became susceptible to chelator-induced hemolysis and to hot-cold hemolysis simultaneously, and the degree of lysis of both mechanisms increased equally with prolonged preincubation with sphingomyelinase C. Erythrocytes of species not readily susceptible to hot-cold hemolysis were equally insusceptible to chelator-induced lysis. Chelators of the EDTA series were the most effective, whereas chelators more specific for Ca2+, Zn2+, Fe2+, Cu2+, and Mg2+ were without effect. The rate of chelator-induced lysis was dependent on the preincubation period with beta-hemolysin and on the concentration of chelator added. The optimal concentration of EDTA was found to equal the amount of exogenously added Mg2+, a cation necessary for sphingomyelinase C activity. Hypotonicity increased the rate of chelator-induced hemolysis, whereas increasing the osmotic pressure to twice isotonic completely inhibited chelator-induced lysis. The data suggest that exogenously added and/or membrane-bound divalent cations are important for the stability of sphingomyelin-depleted membranes. The phenomenon of hot-cold hemolysis may be a consequence of the temperature dependence of divalent ion stabilization. | 333 |
Degradation of myxovirus virion RNA by periodate. | Extensively degraded RNA was isolated from virions of influenza virus which had been oxidized with sodium m-periodate. Similarly, although to a lesser extent, RNA isolated from periodate-treated ribonucleoprotein of influenza virus was also degraded. In contrast, influenza virus RNA, if first freed from other virion components, was not degraded by periodate oxidation. | 344 |
Phospholipase D activity of gram-negative bacteria. | A phospholipase hydrolyzing cardiolipin to phosphatidic acid and phosphatidyl glycerol was characterized in gram-negative bacteria but was absent in preparations of gram-positive bacteria, Saccharomyces cerevisiae, and rat liver mitochondria. In cell-free extracts of Escherichia coli, Salmonella typhimurium, Proteus vulgaris, and Pseudomonase aeruginosa, this cardiolipin-hydrolyzing enzyme had similar pH and Mg2+ requirements and displayed a specificity which excluded phosphatidyl glycerol and phosphatidyl ethanolamine as substrates. | 360 |
Expression of the hut operons of Salmonella typhimurium in Klebsiella aerogenes and in Escherichia coli. | The normal hut (histidine utilization) operons, as well as those with mutations affecting the regulation of their expression, of Salmonella typhimurium were introduced on an F' episome into cells of S. typhimurium and Klebsiella aerogenes whose chromosomal hut genes had been deleted and into cells of Escherichia coli, whose chromosome does not carry hut genes. The episomal hut operons respond in a manner very similar to induction and catabolite repression in all three organisms. The small differences found reflect both different abilities to take up inducers from the medium and different degrees of catabolite repression exerted by glucose. | 362 |
Transport of molybdate by Clostridium pasteurianum. | The transport of 99MoO42- into dinitrogen-fixing cells of Clostridium pasteurianum was investigated. Transport of molybdate in this organism is energy dependent; sucrose is required in the minimal media, and the system is inhibited by the glycolysis inhibitors, NaF, iodoacetic acid, and arsenate. The cells accumulate molybdate against a concentration gradient, and the uptake shows a marked dependence on temperature (optimum 37 C) and pH (optimum 6.0). The rate of molybdate uptake with increasing molybdate concentrations shows saturation kinetics with an apparent Km and Vmax of 4.8 X 10(-5) M and 55 nmol/g of dry cells per min, respectively. Inhibition studies with the anions SO42-, S2O32-, WO42-, and VO32- show that SO42- and WO42- competitively inhibit MoO42- uptake (apparent Ki [SO42-] is 3.0 X 10(-5) M; apparent Ki [WO42-] is 2.4 X 10(-5), whereas S2O32- and VO32- have no inhibitory effect. Exchange experiments with MoO42- show that only a small percentage of the 99MoO42- taken up by the cells is exchangeable. Exchange experiments with WO42- and SO42- indicate that once inside the cells WO42- and SO42- cannot substitute for MoO42-. | 364 |
D-Lactate dehydrogenase of Peptostreptococcus elsdenii. | D-Lactate dehydrogenase has been purified to near homogeneity from Peptostreptococcus elsdenii. As isolated, the enzyme contains flavine adenine dinucleotide and a tightly bound metal cofactor. Inactivation by ortho-phenanthroline occurs in two steps and is partially blocked by D-lactate. Reactivation by divalent metal ions occurs, with divalent zinc being the most effective. When ferricyanide is used as the electron acceptor, D-lactate has an apparent K0.5 of 3.3 M0.46; its binding is negatively cooperative with a Hill coefficient of 0.46. Replacement of ferricyanide by the other components of the electron transport system yields hyperbolic kinetics with an apparent Km for D-lactate of 26 mM. The apparent Km for ferricyanide is 2.2 X 10(-4) M. Phosphate and pyrophosphate compounds stimulate the D-lactate:ferricyanide activity. These properties suggest that interaction of this enzyme with other electron transport proteins in the chain may enhance D-lactate binding and, hence, the rate of electron transport. | 368 |
Studies on trypsin inhibitor in barley. I. Purification and some properties. | To clarify the properties and functions of a trypsin inhibitor from Japanese barley in comparison with the inhibitor from Pirkka barley, an inhibitor was isolated from the barley Hordeum distichum L var. emend Lamark by extraction with 1% NaCl, ammonium sulfate fractionation and repeated chromatography on DEAE-cellulose and CM-cellulose. The final purified preparation of the inhibitor was found to be homogeneous by both chromatographic and electrophoretic analysis. The inhibitor was thermostable and was stable over the broad pH range from 2 to 11. No inhibition was observed by heavy metal ions and many reagents at 10(-2) M, except that p-chloromercuribenzoate caused a 69% loss of activity. The inhibitor was subjected to isoelectric focusing at pH 7.51 and its molecular weight was calculated to be 14,200+/-900 by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The apparent dissociation constant for the complex between the inhibitor and trypsin[EC 3.4.21.4] was 1.64 X 10(-7)M with casein as a substrate. One microgram of purified inhibitor inhibited 1.5 mug of pure trypsin in the hydrolysis of alpha-N-benzoyl-DL-arginine-p-nitroanilide. By chemical modification of arginyl residues in the inhibitor with 1,2-cyclohexanedione, the inhibitor was shown to be an arginine inhibitor. The inhibitor contained relatively many basic amino acids and few half cystines as compared with Pirkka barley trypsin inhibitor. | 380 |
Structural studies of two ovalbumin glycopeptides in relation to the endo-beta-N-acetylglucosaminidase specificity. | Heterogeneities of the two ovalbumin glycopeptides, (Man)5(GlcNAc)2Asn and (Man)6(GlcNAc)2Asn, were revealed by borate paper electrophoresis of oligosaccharide alcohols obtained from the glycopeptides by endo-beta-N-acetylglucosaminidase H digestion and NaB3H4 reduction. The structures of the major components of the oligosaccharides were determined by the combination of methylation analysis, acetolysis, and alpha-mannosidase digestion. Based on the results, the whole structures of the major components of (Man)5(GlcNAc)2Asn and (Man)6(GlcNAc)2Asn were elucidated as Manalpha1 leads to 6[Manalpha1 leads to 3]-Manalpha1 leads to 6[Manalpha1 leads to 3[Manbeta1 leads to 4GlcNAcbeta1 leads to 4GlcNAc leads to Asn and Manalpha1 leads to 6[Manalpha1 leads to 3]Manalpha1 leads to 6[Manalpha1 leads to 2Manalpha1 leads to 3]Manbeta1 leads to 4GlcNAcbeta1 leads to GlcNAc leads to Asn, respectively. Since endo-beta-N-acetylglucosamini dase D hydrolyzes (Man)5(GlcNAc)2Asn but not (Man)6(GlcNAc)2Asn, the presence of the unsubstituted alpha-mannosyl residue linked at the C-3 position of the terminal mannose of Manbeta1 leads to 4GlcNAcbeta1 leads to 4 GlcNAcAsn core must be essential for the action of the enzyme. | 389 |
Trypsin-sensitive photosynthetic activities in chloroplast membranes from Chlamydomonas reinhardi, y-1. | Location of electron transport chain components in chloroplast membranes of chlamydomonas reinhardi, y-1 was investigated by use of proteolytic digestion with soluble or insolubilized trypsin. Digestion of intact membrane vesicles with soluble trypsin inactivates the water-splitting system, the 3-(3,4-dichlorophenyl)-1,1-dimethylurea inhibition site of Photosystem II, the electron transport between the two photosystems as well as the ferredoxin NADP reductase. Reduction of NADP with artificial electron donors for Photosystem I could be restored, however, by addition of purified reductase to trypsin-digested membranes. Electron transfer activities of Photosystems I and II reaction centers were resistant to trypsin digestion either from outside or from within the thylakoids when active trypsin was trapped inside the membrane vesicles by sonication and digestion carried out in the presence of trypsin inhibitor added from outside. In the latter case, the water-splitting system was also found to be resistant to digestion. Polyacrylamide-bound insolubilized trypsin inactivated only the ferredoxin NADP reductase. Photosynthetically active membranes obtained at different stages of development showed a basically similar behavior toward trypsin. | 400 |
Methods to improve detection of pneumococci in respiratory secretions. | Simple methods to enhance the detection of pneumococci in respiratory secretions are needed. Sheep blood agar containing 5 mug of gentamicin per ml was more often positive (89%) than either standard sheep blood agar (54%) or mouse inoculation (65%) in recovering pneumococci from 62 adult and pediatric patients. In adults, the direct quellung test on sputum smear was a rapid, sensitive method for predicting subsequent pneumococcal isolation by culture (19 of 20 patients, 95%). The quellung test and gentamicin plate show improved sensitivity over current techniques for pneumococcal detection and can be recommended for general use. | 421 |
On the interactions between pancreatic lipase and colipase and the substrate, and the importance of bile salts. | The interactions between pancreatic lipase and colipase and the substrate and the effect of bile salts on these interactions have been investigated by the use of kinetic experiments and studies on the semiquantitative phase distribution of lipase and colipase activities. The results suggest that lipase binds to hydrophobic interfaces with partial irreversible inactivation. Bile salts in the range of micellar concentrations and above a pH of about 6.5 displace lipase from this binding, resulting in a reversible in activation. At pH values below about 6.5, lipase binds strongly to the substrate even in the presence of bile salt, and a low activity peak is seen around pH 5.5. This is the result of the binding of lipase to the "supersubstrate" and the activity of the catalytic site. In the presence of bile salt, colipase promotes the binding of lipase to the "supersubstrate" but not to other hydrophobic interfaces, and catalytic activity is reestablished. Kinetic data indicate that the binding between colipase and lipase in the presence of substrate is strong and occurs in an approximately stoichiometric relationship. | 446 |
An electrophysiological analysis of chemoreception in the sea anemone Tealia felina. | 1. Electrophysiological techniques have been employed to examine the nature of the response observed in the ectodermal slow-conduction system (SSI) when dissolved food substances contact the column of Tealia felina. The response seems to consist entirely of sensory activity which may continue for periods of many minutes, provided that the stimulatory chemicals remain contacting the column. 2. The interval between each evoked pulse gradually increases as the sensory response progresses. This does not result from fatigue in the conduction system but involves a genuine process of sensory adaptation. This may occur over a period of several minutes, which is much longer than comparable adaptation in higher animals. 3. Physiological evidence suggests that the chemoreceptors involved are dispersed throughout the column ectoderm and are absent from the pedal disc, oral disc, tentacles and pharynx. 4. The basic role of the SSI in coordinating behavioural activity in sea anemones is reviewed. It is concluded that it functions primarily as a single, diffuse-conducting unit responsible for transmitting frequency-coded sensory information from ectodermal chemoreceptors to ectodermal (and perhaps endodermal) effectors. | 449 |
Binding of bile acids to cholestyramine at gastric pH conditions. | The binding of bile salts to cholestyramine was studied under varying conditions of pH and added electrolyte. The taurine-conjugated bile salts were strongly absorbed by the anion-exchange resin at low pH and in the presence of chloride anions. Glycocholic acid binding was very weak at low pH but increased strongly with increasing pH. The presence of chloride ions strongly decreased the amount of glycocholate bound by the anion-exchange resin. | 486 |
The formation of synapses in amphibian striated muscle during development. | 1. A study has been made of the formation of synapses in developing reinnervated and cross-reinnervated amphibian twitch muscles which receive either a focal (iliofibularis) or a distributed (sartorius) innervation from 'en plaque' nerve terminals using histological, ultrastructural and electrophysiological techniques. 2. During the development of the tadpole through metamorphosis to the adult frog, the sartorius myofibres increased in length at about twice the rate of the iliofibularis myofibres, due to a fast rate of growth at their insertions on to the pelvic tendon. 3. The short iliofibularis and sartorius myofibres of young tadpoles (800 mum long) possessed only a single synapse and the iliofibularis myofibres did not receive any further innervation during development. However the sartorius myofibres received further transient innervation on the new muscle laid down during development at the fast growing pelvic insertion, until the distance between the original synapse formed on the myofibres and the synapse at the pelvic end of the muscle was about 12 mm. 4. During development synapses possessed either skewed, multimodal, or unimodal m.e.p.p. amplitude-frequency distributions; the intervals between m.e.p.p.s. were not distributed randomly according to a Poisson process, as m.e.p.p.s. of similar amplitudes tended to be separated by very short intervals; the unit-size e.p.p. had a similar amplitude-frequency distribution as the m.e.p.p.s. if these had a unimodal distribution. 5. Reinnervation or cross-reinnervation of the sartorius and the iliofibularis muscles in adults or at a late stage of development simply reconstituted the normal focal and distributed innervation patterns of the muscles, as found in the control muscles of the contralateral and unoperated legs. 6. These observations on synapse formation in amphibia are consistent with the hypothesis that during development the axon making the initial synaptic contact on the muscle cells induces a property over a length of muscle membrane adjacent to this site which makes it refractory to synapse formation; thus during reinnervation or cross-reinnervation of adult muscles this refractory property constrains synapse formation to these sites. | 494 |
The avian erythrocyte: a study of fixation for electron microscopy. | The quality of ultrastructural preservation of the avian erythrocyte achieved using various fixation techniques is evaluated. Different combinations of initial fixatives, buffers and post-fixation procedures were tested as well as variations in fixative osmolarity, pH and temperature. Of the commonly used initial fixatives (glutaraldehyde, acrolein and formaldehyde), 2% glutaraldehyde, alone in a slightly hypertonic buffer containing divalent ions, produced optimum erythrocyte preservation. The osmolarity was balanced using a non-electrolyte such as a sucrose. The addition of 12% hexylene glycol to the buffer solutions also improves erythrocyte preservation, as evidenced by the increased stability of the marginal microtubules, microfilaments and proteinaceous material. The use of Spurr low-viscosity epoxy resin enables the cells to be collected using low gravitational centrifugation. | 508 |
Lipoxygenase isozymes of peanut. | Lipoxygenase was isolated and partially purified from peanut seed by ammonium sulfate precipitation, gel filtration, and ion exchange column chromatography. Three isozymes of lipoxygenase were identified. Two had pH optima of 6.2, and the other an optimum of 8.3. Molecular weight of each isozyme was 7.3 x 10(4), as determined by gel filtration. The alkaline optimum isozyme was not inhibited by NaCN and was inhibited by CaCl2 except at very low concentrations. The acid optimum isozymes were inhibited by NaCN and were stimulated by CaCl2 concentrations up to ca. 0.7 mM. | 580 |
The regulation of striatal tyrosine hydroxylase. Effects of gamma hydroxybutric acid and healperidol. | Gamma-hydroxybutyric acid (GHBA) in doses that increased the striatal dopamine (DA) content of rat brain failed to increase the affinity of striatal tyrosine hydroxylase (TH) for its pterdine cofactor or to change the sensitivity of the enzyme to the inhibition by DA. Haloperidol (1 mg/kg) decreased the apparent Km of striatal TH for the pteridine cofactor. However, when GHBA was injected before haloperidol it prevented the decrease in the apparent Kn of TH, in a dose related manner. In vitro GHBA (10(-4) M) neither changed the stimulation of the striatal adenylyl cyclase by DA nor its inhibition by haloperidol. These results suggest that in striatal dopaminergic terminals the Kn of TH for the pteridine cofactor is regulated by an molecuular mechanism which requires that the impulse flow in the DA neurons is unimpaired. | 629 |
The influence of cortisol on the enzymes of fatty acid synthesis in developing mammalian lung and brain. | Administration of cortisol to fetal rabbits resulted in a 42% inhibition of pulmonary de novo fatty acid synthesis from acetyl coenzyme A (CoA) (P = less than 0.025). This was associated with inhibition of acetyl-CoA carboxylase (EC. 6.4.1.2.) activity (P = less than 0.01) and a tendency towards decreased activity of fatty acid synthetase. There was no effect on pulmonary microsomal fatty acid elongation activity. Light and electron microscopic examination of the apex of the right lung of control and cortisol-treated animals revealed changes consistent with accelerated lung maturation in the treated animals. The in vitro activities of acetyl-CoA carboxylase and fatty acid synthetase were similar in rabbit lung and thus acetyl-CoA carboxylase activity does not appear to be rate limiting for de novo fatty acid synthesis in lung. No significant change in the activity of enzymes associated with de novo fatty acid synthesis of microsomal fatty acid elongation was found in fetal brain after cortisol exposure. However, in a parallel study on fatty acid synthesis in fetal liver, cortisol administration resulted in a 30% increase in fatty acid synthetase activity (P less than 0.025). The finding of cortisol-induced inhibition of de novo fatty acid synthesis in fetal rabbit lung may be related to the known inhibitory effect of cortisol on lung growth in the fetus. | 648 |
Intranasal betamethasone valerate in seasonal rhinitis. | A double-blind study comparing betamethasone valerate and placebo aerosols was carried out in 40 patients with a history of seasonal allergic rhinitis and positive skin tests to grass pollens. Analysis of the symptoms recorded on a daily record card for a period of one month indicated that the mean monthly symptom-score was lower for all symptoms in the group on active therapy and that this reached statistical significance for the symptom of sneezing. Significantly more antihistamine tablets were used by the placebo group as compared with the active group (p less than 0-05). The patients' assessment of their treatment was in favour of betamethasone valerate (p less than 0-05). No clinically significant side-effects were associated with the treatment, which was well tolerated. | 665 |
Light-dependent absorption and selective scattering changes at 518 nm in chloroplast thylakoid membranes. | The light-induced absorbance change at 518 nm of isolated chloroplasts consists of a rapid phase, and a slow phase which is complete in about 20 sec. The slow component of the 518 nm absorbance change correlates with the light-induced change in 90 degrees light scattering at 518 nm. Both show a similar time course, similar pH dependence with a maximum at pH 6.0, and similar sensitivity to inhibitors and to treatment of the chloroplasts with a low concentration of glutaraldehyde. Their light minus dark difference spectra are similar with maxima at about 520 nm. It is concluded that they are manifestations of the same phenomenon, and the slow absorbance increase at 518 nm is due to enhanced scattering. It is proposed that the light-induced changes in scattering at 518 nm reflect alterations in selective dispersion, due to proton uptake and conformational changes in the chloroplast thylakoid membrane. | 669 |
Mechanism of action of penicillin: triggering of the pneumococcal autolytic enzyme by inhibitors of cell wall synthesis. | During penicillin treatment of an autolysin defective mutant pneumococcus we have observed three novel phenomena: (i) Growth of the mutant cultures is inhibited by the same concentrations of penicillin that induce lysis in the wild type. (ii) Mutant bacteria treated with the minimum growth inhibitory concentration of penicillin will lyse upon the addition of wild-type autolysin to the growth medium. Chloramphenicol and other inhibitors of protein synthesis protect the cells against lysis by exogenous enzyme. Sensitivity of the cells to exogenous autolysin requires treatment with penicillin or other inhibitors of cell wall synthesis (e.g., D-cycloserine or fosfonomycin) since exogenous autolysin alone has no effect on bacterial growth. (iii) Treatment with penicillin (or other inhibitors of cell wall synthesis) causes the escape into the medium of a choline-containing macromolecule that has properties suggesting that it contains pneumococcal lipoteichoic acid (Forssman antigen). Each one of these three phenomena (growth inhibition, sensitization to exogenous autolysin, and leakage of lipoteichoic acid) shows the same dose response as that of the penicillin-induced lysis of wild-type pneumococci. On the basis of these findings we propose a new hypothesis for the mechanism of penicillin-induced lysis of bacteria. It is suggested that inhibition of cell wall synthesis by any means triggers bacterial autolytic enzymes by destabilizing the endogenous complex of an autolysin inhibitor (lipoteichoic acid) and autolytic enzyme. Escape of lipoteichoic acid-like material to the growth medium is a consequence of this labilization. Chloramphenicol protects bacteria against penicillin-induced lysis by interfering with the activity of the autolytic enzyme, rather than by depleting the concentration of the enzyme at the cell surface. | 674 |
Evaluation of combined pharmacological and psychotherapeutic treatment in patients with functional abdominal disorders. | 78 patients suffering from various functional abdominal complaints have been trated in a 2 x 2 double-blind design: (a) psychotherapy with Ro 5-3350 (TH/Ro); (b) psychotherapy with placebo (TH/P); (c) Ro 5-3350 without psychotherapy (NIH/Ro); (d) placebo without psychotherapy (NTH/P). Results show that a considerable amount of improvement cannot be ascribed to the two critical factors or the interaction of both, but are due to unspecific influences in the course of treatment. Some of the results concerning the combination of TH and the psychotropic drug pose interesting questions for further research and bare implications for double-blind trials of psychotropic drugs. The results suggest that possibly properties of any psychotropic drug have to be related to a doctor-patient relationship within which the personal problems of the patient are dealt with. In order to evaluate such properties, special methodological precautions have to be taken. These will be briefly discussed. | 725 |
Alterations in norepinephrine pattern in the damaged myocardium in the rat. | In the albino rat, the evolvement of myocardial necrosis induced by a single injection of ISO was accompanied by a fall in total NE. Pretreatment with propranolol and pargyline protected against ISO-induced necrosis and myocardial hypertrophy, but did not influence the ISO-induced depletion of NE stores. The depletion of NE stores is not due to impairment in synthesis or increased intraneuronal metabolism of NE since, in ISO-treated rats, neither cardiac tyrosine hydroxylase activity nor MAO activity was altered. The decrease in endogenous NE is not due to a defect in the storage of NE. The ability of myocardium to take up and store NE returned to normal within 48 hours, whereas endogenous levels returned to normal within 5 days, even in the presence of demonstrable necrosis. Thus, there is lack of correlation between chemical and morphological changes, since catecholamine depletion occurred in the absence of morphologically demonstrable tissue injury, and the function of the adrenergic neuron returns to normal in the presence of demonstrable necrosis. | 742 |
[Biosynthesis of flavins and its regulation in the yeast Pichia guilliermondii]. | The nature of riboflavin precursors was studied in the yeast Pichia guilliermondii. By means of mutants with blocked GMP-synthetase the purine precursors of riboflavin were shown to belong to guanylic compounds. Accumulation of 2,4,5-triamino-6-oxypyrimidine, 2,5-diamino-6-oxy-4-ribitylaminopyrimidine, 2,6-dioxy-5-amino-4-ribitylaminopyrimidine (DOARAP) and 6,7-dimethyl-8-ribityllumasine occurs in the riboflavin-deficient mutants divided into five biochemical groups. This fact evidences for identity of riboflavin precursors in the yeast P. guilliermondii and Saccharomyces cerevisiae. Synthesis of DOARAP by the washed off cells of the mutants with the blocked lumasine synthetase is strongly inhibited by riboflavin; cycloheximide in the absence of riboflavin has no effect on this process. Consequently, flavinogenesis in P. guilliermondii is regulated according to the type of negative feedback by means of retroinhibition mechanism. A change in the content of flavins in the cells has no effect on synthesis of riboflavin synthetase; at the same time iron deficiency in the cells evokes derepression of this enzyme. Incubation of the cells rich in iron with o-phenantroline or alpha, alpha'-dipyridyl also causes derepression of riboflavin synthetase which is inhibited by cycloheximide. A deficiency of hem in the mutants which need epsilon-aminolevulinic acid does not affect the riboflavinsynthetase activity of the cells. Evidently, in P. guilliermondii a certain form of nonheminic iron might take part in regulating synthesis of riboflavin synthetase and other enzymes participating in riboflavin biosynthesis. Riboflavin overproduction is established to require formation of purines de novo. With the absence of flavinogenesis enzymes derepression a genetic disturbance in regulation of purinic nucleotides biosynthesis results in stimulation of flavinogenesis. The properties were studied for 680 time purified riboflavinkinase from cells of P. guilliermondii as well as for three phosphatases possessing the optimum of the activity at pH 3.5, 5.5 and 8.6, which ARE ABLE OF HYDROLYSING FMN. A change in the content of flavins and iron in the cells has no effect on the activity of riboflavinkinase in this species. Evidently, the mechanisms of riboflavin and flavin nucleotides biosynthesis regulation would be different in P. guilliermondii. | 834 |
[Catecholamines, cholinergic and serotoninergic complexes as criteria of prognosis in acute cranio-cerebral trauma]. | In experiments on 30 animals and in observations over the course of acute closed craniocerebral trauma in 24 patients is was found that the course and prognosis of a posttraumatic period were dependent on the functional activity of the sympathoadrenal system and cholin- and serotoninergic processes. Based on the data obtained, it is concluded that the character of neurohumoral interrelations can serve as the prognostic criterion in craniocerebral traumas, whereas the information about these processes--in selecting the appropriate therapy. | 839 |
[Sympathico-adrenal system activity in a primary immune response]. | Experiments were carried out on linear mice immunized with sheep erythrocytes; it was found that the primary immune respose developed against the background of significant changes in the state of the sympathico-adrenal system, whose activity was determined by the dynamics of catecholamines in the blood and in the tissues of a number of organs, including the thymus, the spleen and the lymph nodes. By comparing the value of specific and neurohumoral indices it was revealed that the neurohumoral shifts preceded the maximal development of the immune response. On the example of studying the catecholamine dynamics the opinion on a close association between the state of the regulatory mechanisms and the effector formations responsible for the formation of specific immunological reactions was confirmed. It is suggested that a full-value immunological response developed on condition of activation of the sympathico-adrenal system. | 877 |
Further characterization of the association of glyceraldehyde-3-phosphate dehydrogenase with reticulocyte membranes. | 1. The behaviour and properties of membrane-bound GAPDH of rabbit reticulocytes were investigated. 2. The bound GAPDH is more resistant to inactivation by KCl than the soluble enzyme (allotopy). 3. The bound enzyme is released by electrolytes. This effect does not only depend on the ionic strength but additionally on the kind of ions, pH-value and protein concentration. 4. A comparison of the releasing effect of NAD analogues shows the necessity of the 5'-AMP moiety in the structure of the effector. 5. The represented results demonstrate the specifity of the GAPDH-membrane binding in rabbit reticulocytes. | 880 |
[Effect of the vagus nerve on isolated rabbit atria in ganglionic blockade due to hexamethonium]. | By quantitative stimulation of the vagus nerves of isolated rabbit atria frequency-response relations were obtained for both the electrotropic effect (reduction of the area of the monophasic action potential) and the inotropic response. An addition of hexamethonium in a final concentration of 10(-5) g/ml resulted in a diminution of vagal effectivity in the range of lower and medium frequencies of stimulation, and was connected with a shift of the frequency-response characteristic to the right. At higher frequencies vagal effectivity was increased. In contrast to the inhibitory effect of hexamethonium the facilitating action is irreversible. By raising the concentration up to 4-10(-5) g/ml the vagal effects were reduced to a large extent, and the frequency dependence of the response was abolished at medium frequencies. In the range of 20 sec(-1) to 100 sec(-1) this dependence was re-established and may be considered as a part of a normal frequency-response relation extremely shifted to the right. The time courses of both types of effect are characterized by a steep rise and a decay of the response during the stimulation period. A mathematical handling of the frequency-response characteristics provides quantitative evidence for the extent of the hexamethonium blockade of vagal ganglion cells in the atria; furthermore it leads to the conception of these cells to act as a distributing system for a homogeneous innervation by a widespread divergency of postganglionic fibres. | 881 |
Comparative study of virological infections in asthmatic and nonasthmatic children. | The author shows complex analyses: clinical, laboratory, X-rays, bronchoscopical, bronchographical and measuring lung function tests as well as the serological examinations in blood serum of both groups of asthmatic and nonasthmatic children with virological infection. The calculation of statistically significant differences between the various diagnostical results of both groups has confirmed that in asthmatic children virological infection of the respiratory tract, pathological findings in X-ray and lung function tests, bronchiectasis and secondary bacteriological invasion occurs statistically significantly more often than in nonasthmatic children. | 884 |
[Tumour hyperacidulation through intravenous glucose infusion enhanced by amygdalin and beta-glucosidase application (author's transl)]. | Tumour peracidity in otherwise moderately hyperacidulated tumours or tumour regions of DS carcinosarcoma-bearing Wistar rats attained by glucose infusion was substantially increased by simultaneous infusion of amygdalin and intratumoral i.m. or i.v. application of beta-glucosidase. Here the pH value of healthy tissue, measured at the sceletal muscle, remained unchanged. By means of the said process, tumour hyperacidulation has been raised to a level of deltapH =0.97; attaining a pH difference between tumourous and normal tissue of up to deltapH = 1.6. In one case, the slope of pH reduction in the tumour increased to 870%. Moreover, combined administration of glucose, amygdalin and beta-glucosidase evoked a significant cancerostatic effect hypogenesis, tumour regression) being comparable with the action of an Ifosfamid dosage of 150 mg-kg-1. However, i.m. and i.v. application of beta-glucosidase under narcosis results in an overall process that still remains somewhat too toxic. Hence optimizing studies are intended with the particular aim to further improve the comparability of this process. | 979 |
Metachromatic leukodystrophy. Ultrastructural and enzymatic study of a case of variant O form. | A variant of metachromatic leukodystrophy (MLD), Austin disease, is characterized by a multiple isozyme deficiency of arylsulfatase. A 3 1/2-year-old girl with progressive mental and physical deterioration had decreased activities of arylsulfatases A and B in the leukocytes, shown by acylamide gel electrophoresis. Under the electron microscope, biopsy specimens of the brain and the peripheral nerve showed lamellar structures with socalled zebra bodies in the cytoplasmic processes of glial cells, granulo-membranous inclusions with fingerprint configurations in neurons, and myelinlike material in Schwann cells. Results from our study suggest an intricate nature of this dysmetabolic disorder, which shows ultrastructural changes usually seen in classic MLD, a deficiency of arylsulfatase A only, concomitant with those seen in mucopolysaccharidoses such as Hurler and Sanfilippo syndromes. | 985 |
Plastid development in primary leaves of Phaseolus vulgaris. Development of plastid adenosine triphosphatase activity during greening. | The etioplasts of dark-grown bean leaves showed ATPase (adenosine triphosphatase) activity which had a pH optimum of 8.5, was stimulated by dithiothreitol and unaffected by light-triggering. Bean chloroplasts showed a low activity of dark-induced ATPase with a pH optimum of 8.5 and a substantial amount of light-triggered activity with a pH optimum of 8.0. The light-triggered activity depended on dithiothreitol and Mg2+ and was promoted by phenazine methosulphate. Light-triggered ATPase activity was completely inhibited by 20mum-dicyclohexylcarbodi-imide. Etioplasts developed light-triggered ATPase activity in response to 30 min illumination of the etiolated leaves. During the 48 h of light-induced greening of dark-grown leaves there was a 70% increase of the chloroplast ATPase activity found after light-triggering and a 30% fall in the dark-induced activity, both expressed on a per leaf basis. As the larger part of these changes occurred during the first 30 min of illumination, it is concluded that most or all of the chloroplast ATPase was present in the etioplast, a conclusion identical with that of Lockshin et al. (1971) for maize. During 48 h of greening there was a tenfold increase in the amount of thylakoid membrane in the leaf together with an 83% fall in the ATPase activity per m2 of thylakoid membrane, measured after light-triggering. | 990 |
Determination of polyadenylate-rich ribonucleic acid in the nucleus and in the cytoplasm of plasmacytoma cells. | A number of parameters affecting the adsorption of rRNA and poly(A)-containing RNA to Millipore filters were investigated separately. Binding of both types of RNA to the filter was dependent on the concentration of RNA, pH and Mg2+ concentration of the reaction mixture. Both types of RNA bound to the filter optimally at slightly acid pH values. The binding of poly(A)-containing RNA to the filter exhibited a broad pH-dependence compared with that of rRNA. The ratio of poly(A)-rich RNA/rRNA retained by the filter was maximal between pH7 and 8. The presence of 1 mM-EDTA or a high concentration of NaCl (over 0.5M) decreased the affinity of RNA for the filter. The amount of poly(A)-containing RNA in the nucleus and in the cytoplasm of a plasmacytoma cell line (MPC-11) labelled with [32P]Pi was determined by the Millipore-filter technique under conditions that minimized contamination by rRNA. These data were compared with the estimations made by oligo(dT)-cellulose chromatography. The results obtained by these two methods were in good agreement for RNA labelled for short periods (up to 2h). In long labelling and pulse-chase experiments, however, contamination of the filter by rRNA of increasing specific radioactivity in the cytoplasm gave an erroneous value for poly(A)-containing RNA by the Millipore-filter technique. Determinations made on the nuclear fraction by these two methods did not show significant variation in short- and long-term labelling experiments. | 999 |
Properties of 5-aminolaevulinate synthetase and its relationship to microsomal mixed-function oxidation in the southern armyworm (Spodoptera eridania). | 1. Activity of 5-aminolaevulinate synthetase was measured in the midgut and other tissues of the last larval instar of the southern armyworm (Spodoptera eridania Cramer, formerly Prodenia eridania Cramer). 2. Optimum conditions for measuring the activity were established with respect to all variables involved and considerable differences from those reported for mammalian enzyme preparations were found. 3. Maximum activity (20 nmol/h per mg of protein) occurs 18-24 h after the fifth moult and thereafter decreases to trace amounts as the larvae age and approach pupation. 4. Synthetase activity was rapidly induced by oral administration (in the diet) of pentamethylbenzene, phenobarbital, diethyl 1,4-dihydro-2,4,6-trimethylpyridine-3, 5-dicarboxylate, and 2-allyl-2-isopropylacetamide. 5. Puromycin inhibited the induction of synthetase by pentamethylbenzene. 6. Induction of 5-aminolaevulinate synthetase correlated well with the induction of microsomal N-demethylation of p-chloro-N-methylaniline, except for phenobarbital, which induced the microsomal oxidase relatively more than the synthetase. | 1,004 |
The distribution and elimination of radioactivity in the rat after administration of 14C-4-acetamidophenyl-2-acetoxybenzoate (benorylate). | Following oral administration of 4-acetamido-phenyl-2-acetoxybenzoate (carboxyl-14C) (benorylate) to rats, no gross differences were detected 7.5 h after administration with respect to the distribution of 14C in various tissues, including the upper sections of the small intestine. A high concentration of 14C was found in the lower sections of the intestine 4 h after administration. The 14C in the intestine was present as unchanged benorylate, as detected by thin-layer chromatography, suggesting that benorylate absorption was slow. Intravenous injection of 14C-benorylate to rats showed that the drug had a relatively high elimination rate from the blood with a half-life of 1.9 h. In blood benorylate must be rapidly hydrolysed enzymatically since no 14C-metabolites, other than salicylic acid, could be detected. | 1,051 |
Lysosomal hydrolases of the epidermis. 3. Peptide hydrolases. | Four distinct peptide hydrolases (EC 3-4) have been characterized in guinea-pig epidermis; these are cathepsin B1, cathepsin C, cathepsin D and arylamidase. Their properties are consistent with those of lysosomal enzymes. Cathepsin E was not detected. | 1,081 |
[Kinetics and mechanism of action of horseradish peroxidase in the reaction of dioxyfumaric acid oxidation with atmospheric oxygen]. | Quantitative kinetic data are given on the oxidation reaction of dioxyfumaric acid (DFA) with atmospheric oxygen in the presence of horseradish peroxidase (HRP) depending on pH. Activation constants of oxidation with hydrogen peroxide and Mn ions are determined at pH 3.0. Autocatalytic character of FRA oxidation is shown to be due to the formation of H2O2 and other hydro peroxide-type compounds in the reaction, HRP convertions in the DFA--O2 system are studied using spectrophotometry. A mechanism of the initiation of free radicals in HRP--DFA--O2 system is proposed. | 1,108 |
[Activity of polynucleotide phosphorylase in ribosomal fraction of rat liver]. | A method of isolating polynucleotidephosphorylase (PNPase) containing polyribosome fraction from rat liver is described. PNPase is found to be bind to RNA in polyribosomes with weak electrostatic bonds which are easily broken down in a weak alkaline medium with ionic strength more than 0.1 beta-22P-labelled ADP, GDP, UDP and CDP are found among the products of endogenous RNA degradation in the fraction of total polyribosomes in the presence of 32P-orthophosphate. A considerable change in the base composition of PNP-degraded RNA is observed at different incubation times of total polyribosomes with 32P-orthophosphate: G+C//A+U ratio increased from 2.3 to 3.1, and purines/pyrimidines ratio-from 0.47 to 1.06 with the increase of the incubation time. Specific activity of PNP in ribosome fractions obtained under ultracentrifugation of total polyribosomes in succrose density gradient (0.3-1.0 M) increased in the direction from the fraction of heavy polysomes to trimers and dimers and then dropped at the region of monomers (80 S particles). The data obtained give no possibility to determine the type of PNP-bound RNA in polyribomes of rat liver. | 1,115 |
Fluroxene toxicity induced by phenobarbital. | Because of reports of fluroxene toxicity in man, the effect of phenobarbital treatment on the toxicity and metabolism of fluroxene was studied in 9 rhesus monkeys. Six monkeys that were exposed to a mean calculated alveolar fluroxene concentration of 5.8% for 4-hr periods up to a total of 16 hr showed no evidence of toxicity. Two animals were sacrificed after a single 4-hr exposure to obtain control measures of fluroxene metabolites in tissues. Four monkeys that had previously survived received exposures to fluroxene and 3 monkeys that had no exposure to fluroxene died during fluroxene anesthesia after treatment with phenobarbital (mean time, 3 hr). Toxicity was manifested by arterial hypotension, pulmonary edema, and arterial hypoxemia. Phenobarbital treatment enhanced production of fluroxene metabolites, including the highly toxic trifluoroethanol. Concentrations of trifluoroethanol in mixed-expired gas, blood, and urine, and of total nonvolatile fluorine in blood, urine, and tissues of animals treated with phenobarbital were 2 to 10 times as in control animals. The results suggest that the rhesus monkey is a valuable model for the study of fluroxene pharmacology and that inclusion of an enzyme-inducing challenge in the evaluation of potential toxicity of other anesthetics seems warranted. | 1,168 |
Plasma concentrations and the time-course of beta blockade due to propranolol. | The effectiveness of intravenously administered propranolol in antagonizing the chronotropic effect of isoproterenol and exercise has been investigated, and has been found at all times to be a predictable function of its plasma concentrations according to the classical drug-receptor theory for competitive antagonism. The data show further that the relationship between effectiveness and time depends on the way in which antagonism is measured. If the dose ratio to isoproterenol (DR) is measured, then (DR-1) declines with time in parallel with drug concentration. On the other hand, if propranolol's effects are measured as percentage reduction in a given response, then this declines linearly with time, even though plasma concentrations decline exponentially. This fact explains why confusion has in the past arisen concerning the relationship of the duration of beta blockade and pharmacokinetic half-life. | 1,169 |
Comparative biotransformation of triflubazam in rats, dogs, and monkeys. | The biotransformation of 14C-triflubazam (ORF 8063; 1-methyl-5-phenyl-7-trifluoromethyl-1H-1,5-benzodiazepin-2-4-[3H,5H]-dione) was investigated in rats, dogs, and monkeys. Urinary metabolites, representing 65, 74, and 87%, respectively, of the total urinary radioactivity excreted by these three species, were isolated by preparative layer chromatography and characterized by various spectral techniques including gas chromatography/mass spectrometry, solid probe mass spectrometry, polarimetry, and infrared and nuclear magnetic resonance spectrometry. No parent drug was found in the urine of any species. Four metabolites were isolated from the rat including the 4'-hydroxyphenyl, dihydrodiol, and 3'-methoxy-4'hydroxy derivatives. N-demethylated metabolites were not isolated from rat urine. Five metabolites were isolated from dog urine, including 4-hydroxyphenyl, dihydrodiol, and catechol derivatives of triflubazam. Unlike the case of the rat, a catechol-O-methyl ether was not detected in dog urine. Six metabolites were isolated from monkey urine. The only major difference in metabolism in the monkey was the existence of both the dihydrodiol and N-desmethyldihydrodiol metabolites. No catechol-0-methyl ether was detected in monkey urine. Biotransformation through a common arene oxide intermediate can be proposed for these three animal species. | 1,219 |
N-hydroxyamobarbital: the second major metabolite of amobarbital in man. | After oral administration of 14C-labeled amobarbital to healthy subjects, most of the radioactivity was recovered in urine and only 4-5% in feces over a period of 6 days. No unchanged amobarbital was excreted. Two major metabolites were found and isolated. One was 3'-hydroxyamobarbital, which has been previously identified by Maynert. The second could be identified as N-hydroxyamobarbital on the basis of its spectral and chemical properties. | 1,222 |
The trypsin and chymotrypsin inhibitors in chick peas (Cicer arietinum L.). Purification and properties of the inhibitors. | From a crude extract of chick peas (Cicer arietinum L.) inhibitors of trypsin and chymotrypsin were isolated by affinity chromatography on a column of trypsin-Sepharose 6B. The content of inhibitors was found to be 1.5 g/kg. They were further separated into six isoinhibitors by ion-exchange chromatography on DEAE-Sephadex A-25. Two of the isoinhibitors accounted for about 50% of the isolated inhibitors and were further purified to a homogeneous state. The isoinhibitors had a molecular weight of about 10000 as determined by molecular-sieve chromatography on Sephadex G-75. They were stable towards extremes of pH and temperatures up to 75 degrees C or towards digestion by pepsin. They were also stable in 6 M urea but not in 6 M guanidine-HCl. The intact inhibitors were destroyed when the peas were cooked at 100 degrees C or when they were toasted at 130 degrees C. The four major inhibitors had similar amino acid compositions and did not contain detectable amounts of free sulfhydryl groups, tryptophan or carbohydrate. Cysteine is the dominant amino acid residue in all of them and accounted for about 20% of their amino acid content. The isoelectric point of the isoinhibitors lies in the range of pH 4.9-8.6 and two of the major inhibitors had isoelectric points of pH 4.75 and pH 4.96. They inhibited chymotrypsin to the same extent but differed in their inhibitory activities towards trypsin, indicating that they are mixtures of native and trypsinmodified forms and that they probably have separate sites for the two enzymes. They did not inhibit other proteolytic enzymes belonging to two groups (i.e., serine or cysteine enzymes) or originating from different sources (i.e., animals, plants or bacteria). | 1,266 |
Incorporation of (1-14C)palmitoyl-CoA into phosphatidylcholine by plasma membranes of rat submaxillary glands in vitro. | 1. On incubation with the isolated rat submaxillary gland plasma membranes, [1-14C]palmitoyl-CoA was incorporated mainly into phosphatidylcholine and hydrolysed to [1-14C]palmitic acid and CoASH. 2. The addition of lysophosphatidylcholine enhanced the incorporation into phosphatidylcholine and lowered the hydrolysis of palmitoyl-CoA markedly. 3. In the presence of lysophosphatidylcholine, palmitoyl-CoA incorporation into phosphatidylcholine was maximum at 0.1 mM palmitoyl-CoA, 0.5 mM lysophosphatidylcholine and between pH 7.0 and 9.0. 4. The incorporation into phosphatidylcholine was stimulated by Na+, K+ and K-, inhibited by Ca2+ and Mg2+ and unaffected by sodium deoxycholate and ATP. 5. Epinephrine inhibited the incorporation of palmitoyl-CoA into phosphatidylcholine in the presence or absence of ATP, the inhibition being more in the presence of ATP than in its absence. Dibutyryl adenosine 3':5'-monophosphate mimicked the inhibitory effect of epinephrine. | 1,278 |
Analysis of skin grafts across the MSA-barrier in mice pretreated with sera from specifically or syngeeically grafted donors. | Prolonged survival of weakly incompatible skin allografts in mice (across the barrier presented by the MSA) can be induced by pretreating the recipients not only with a specific anti-MSA serum (obtained on day 5 after a single MSA-incompatible skin graft) but also be means of control serum obtained in a similar way from the recipients of fully compatible (syngeneic) skin grafts. Administration of serum from non-grafted mice had no effect on graft survival. The similar biological effect of both sera had a counterpart in their similar content and spectrum of glycosaminoglycans. Also in the skin grafts themselves, the course of both qualitative and quantitative changes of GAG in the early postgrafting period was in the allogeneic and syngeneic situation similar. The possible role of these substances in the serum and at the site of grafting and their effect on the outcome of the allograft response are discussed. | 1,295 |
Impaired Sertoli cell function in experimental cryptorchidism in the rat. | The production of testicular androgen-binding protein (ABP), as a measure of Sertoli cell function, was studied after unilateral or bilateral experimental cryptorchidism in adult rats. Two or 4 weeks after the testis had been translocated to the abdomen, no major changes were found in the concentration of ABP per mg protein, although there was a marked and progressive decrease in ABP content per testis. However, the rate of ABP production was greatly decreased, as measured by the accumulation of ABP during 16-h ligation of the efferent ducts or by the production of ABP by testis mince in an in vitro system. This indicates that the Sertoli cell function is severly impaired by the intra-abdominal position. | 1,296 |
The structures of the phytochrome chromophore in both photoreversible forms. | Spectral measurements of phytochrome are performed after unfolding of the peptide chain. By comparison with bile pigments of known structure, structure 1a, containing a hydrogenated ring A, is deduced for the PR chromophore. Its spectral properties indicate that the chromophore of the physiologically active PFR form has lost the double bond of the bridge joining rings A and B. | 1,334 |
Suppressor T cells and host resistance to tye 111 pneumococcus after treatment with antilymphocyte serum. | The antibody response to type III pneumococcal polysaccharide (SS-II) was significantly increased in mice treated with antilymphocyte serum (ALS). BALG/c mice given 0.25 ml of ALS on days -1, 0, and 1 relative to the days of immunization with 0.5 mug of SSS-II had a 20-fold increment (11,383 increased to 199,917) in the number of splenic plaque-forming cells enumerated on day 5 compared with untreated, immunized controls. This effect has been attributed to the elimination of subpopulation of thymus-derived lymphocytes (T cells) that has suppressor function. The present series of experiments relate the augmented antibody response to SSS-II in mice treated with ALS to increased host resistance after infection with Streptococcus pneumoniae, type III (Pn-II). The 50% lethal dose of Pn-III in niminnunized mice was 102 and the 100% lethal dose was 103 organisms. Mice immunized with 0.5 mug of SSS-III and challenged 5 days later with Pn-III were completely protected against a dose of up to 108 organisms. Mice treated with 0.25 ml of ALS on days -1, 0, and 1, immunized with SSS-III on day 0, and challenged with 2.5 X 10(9) Pn-III on day 5 had a mean survival time of greater than 100 h compared with 16 h for immunized non-serum-treated controls. Animals given a single injection of ALS before immunization showed no increase in resistance, whereas mice treated after immunization had significant prolongation of survival times. Untreated, immunized mice challenged with 5 X 10(9), 1 X 5 X 10(8) Pn-II survived 14 to 19 h, whereas ALS-treated animals had mean survival times of 48, 174, and 222 h, respectively. These findings suggest that immunoregulatory T cells may have a biologically significant effect in a narrow zone in which the normal host immune response is insufficient but still potentially capable of providing some additional degree of protection if suppressor cells are elimated. | 1,345 |
[Past and present aspects of diarrheal disease in childhood. Clinical study and treatment (author's transl)]. | The etiologic and pathophysiologic findings described in the first part of this paper have important consequences: The recognition of the specific etiology of diarrhea requires new laboratory methods: most of these, however, are technically easy to perform and do not require a large laboratory. A long-ranging consequence of this changed concept is a well-founded modification of therapy. The most important discovery was, that in a well balanced glucose electrolyte solution sodium and glucose enhance their absorption mutually and increase the absorption of water by solvent drag. Since in most acute diarrheas the mechanisms of absorption of glucose and electrolytes are retained this mechanism can be utilized for fast oral rehydration and reinstitution of normal intestinal homeostasis. Prompt institution of a diet consisting of the previously mentioned glucose-electrolyte solution usually prevents severe dehydration and the need for stationary treatment. The elimination of lactose and long chain fatty acids from the diet prevents continuation of the pathologic osmotic and chemical conditions in the intestine. Antibiotics are not indicated in acute diarrhea with the exception of diarrhea caused by enteroinvasive E. Coli or Shigella, in the case of Salmonella-gastroenteritis even contraindicated. Further research concentrates on the development of drugs for neutralisation of E. Coli enterotoxin and the prevention of diarrheas by development of effective vaccines. | 1,346 |
Interaction of adrenergic antagonists with prostaglandin E2 and tetrahydrocannabinol in the eye. | Both alpha- and beta-adrenergic antagonists have been utilized in an atempt to discern the site of action of prostaglandin (PG) and tetrahydrocannabinol (THC) in the eye. Both alpha- and beta-adrenergic antagonists (alpha-antagonists, phentolamine and phenoxybenzamine; beta-antagonists, propranolol and sotalol) cuased a dose-dependent reduction in intraocular pressure and blood pressure and increased total outflow facility. The results are consistent with the concept that both alpha- and beta-adrenergic receptors are present in the anterior uvea and that vasomotor tone is essential to the maintenance of normal intraocular pressure. No antagonist reduced the PG-induced elevation of intraocular pressure unless the blood pressure was severely lowered. All antagonists inhibit the normal PG-induced increase in total outflow facility, indicating that these agents protect the blood-aqueous barrier from breakdown without altering the vasodilatory response to PG. All antagonists reduced the fall in intraocular pressure produced by THC by approximately 50 per cent, except for sotalol which completely abolished the intraocular pressure fall. Only the alpha-adrenergic antagonists prevented the THC-induced increase in total outflow facility. The results indicate that true outflow facility may well be regulated exclusively by alpha-receptors. The data are consistent with the effect of THC being primarily a vasodilation of the efferent blood vessels of the anterior uvea. The partial inhibition by alpha-adrenergic antagonists may also suggest a lesser role of THC on the afferent vessels. | 1,356 |
Altered nutritional requirements associated with mutations affecting the structures of ribonucleic acid polymerase in Lactobacillus casei. | Rifampin-resistant mutants were isolated from Lactobacillus casei S1 and examined for possible simultaneous alteration in nutritional properties. Among the 36 mutants obtained either spontaneously or after mutagenesis with 2-aminopurine, 22 were found to be altered with respect to the specific growth requirements. The majority (20 of 22) of the latter mutants were shown to require L-glutamine in addition to the nutrients required by the parental strain for maximal growth, whereas the remaining mutants had apparently lost the requirement for L-aspartate. Further studies with one of the glutamine-requiring mutants revealed that the rifampin resistance of this strain is due to the resistance of ribonucleic acid polymerase itself and that a single mutation is responsible for both rifampin resistance and the glutamine requirement. These results strongly indicate that a structural alteration of the ribonucleic acid polymerase caused by the rifampin resistance mutation somehow affected glutamine metabolism, possibly through change in selective transcription of the genes involved. | 1,379 |
Derepression of certain aromatic amino acid biosynthetic enzymes of Escherichia coli K-12 by growth in Fe3+-deficient medium. | 3-Deoxy-arabino-heptulosonic acid 7-phosphate synthase, prephenate dehydratase, tryptophan synthase, and 2,3-dihydroxybenzoylserine synthase enzyme activities are derepressed in wild-type Escherichia coli K-12 cells grown on Fe3+-deficient medium. This derepression is reversed when FeSO4 is added to the growth medium. Addition of shikimic acid to the Fe3+-deficient growth medium caused repression of the first three enzyme activities but not of 2,3-dihydroxybenzoylserine synthase activity. Addition of 2,3-dihydroxybenzoic acid to the Fe3+-deficient growth medium has no effect on any of the above-mentioned enzyme activities. The Fe3+ deficiency-mediated derepression of 3-deoxyarabino-heptulosonic acid 7-phosphate synthase activity is due to an elevation of the tyrosine-sensitive isoenzyme; the phenylalanine-sensitive isoenzyme is not derepressed under these conditions. | 1,383 |
Effects of p-hydroxymercuribenzoate binding on the visible absorption spectrum of methemoglobin. | The binding of p-hydroxymercuribenzoate to human methemoglobin causes a perturbation of the visible heme abosrption spectrum which is expressed by an increase in absorbance in the high spin band regions, 480 to 510 nm and 590 to 640 nm, concomitant with a decrease in absorbance in the alpha- and beta-band absorption regions. The pH dependence of the p-hydroxymercuribenzoate-induced difference spectrum can be accounted for quantitatively by a 5% shift toward higher spin of the aquo form of methemoglobin, a 15% shift toward higher spin of the hydroxide form, and a shift in the apparent pKa for the water to hydroxide transition from 7.92 to 8.04 when mercurial is bound. The rate of these heme abosrbance changes is consistent with the rapid second order formation of the beta93 cysteine, mercury-mercaptide bond and does not represent a change due to the dissociation of methemoglobin tetramers into dimers, even though the latter, slow process does follow mercurial binding. The observation of an increase in spin produced by the binding of a reagent which also promotes dimer formation argues strongly against any direct correlation between an increase in spin and the appearance of deoxyhemoglobin-like conformations. | 1,392 |
High-resolution liquid chromatographic analysis of methylated purine and pyrimidine bases in transfer RNA. | Methylated and major purine and pyrimidine bases were separated and quantified by high-resolution liquid chromatography after hydrolyzing transfer ribonucleic acids (tRNAs). Separation was accomplished by eluting the hydrolyzed samples from an anion-exchange column with a concentration gradient of ammonium acetate at pH 9.2. Isolated sample of tRNA were hydrolyzed to the free bases with a trifluoroacetic acid-formic acid mixture of 200 degrees. Detection limits of 100-200 ng/ml were measured for the methylated bases; analytical data are reported for ten methylated bases plus the four major bases of calf liver and rat liver tRNA. | 1,412 |
Isolation of streptococcal nuclease B by batch adsorption. | A method has been developed for the preparation of streptococcal nuclease B by batch adsorpton to diethylaminoethyl-cellulose. The enzyme is homogeneous with respect to nuclease activity and is suitable for use as an antigen in measurement of anti-deoxyribonuclease B levels in sera. | 1,418 |
Kinetics of the antibody response to type III pneumococcal polysaccharide (SSS-III). I. Use of 125I-labeled SSS-III to study serum antibody levels, as well as the distribution and excretion of antigen after immunization. | A simple method was described for the preparation of 125I-labeled type III neumococcal polysaccharide (SSS-III) with a high specific radioactivity which retained the physical and immunologic properties of native SSS-III. SSS-III was used to study the serum and tissue levels of antigen, as well as its excretion, after i.p. injection. When an optimally immunogenic dose (0.5 mug) of antigen was given, greater than 90% of the injected antigen was excreted during the first 3 days after injection; however, after day 3, the SSS-III which remained in each mouse was firmly bound to various tissues, and less than 5 ng SSS-III was released into the circulation daily. SSS-III was also used in a Farr test to measure serum antibody levels; the kinetics for the appearance of PFC/spleen and serum antibody levels were measured at 24-hr intervals after immunization with 0.5 mug of antigen. Maximum PFC/spleen were observed on day 4 after immunization whereas the peak serum antibody level was seen on day 5. The decay of serum antibody level from its maximum value was much slower than that of the PFC/spleen. The data describing the distribution of SSS-III in vivo and the measurement of serum antibody levels indicated that treadmill neutralization was not a factor in determining the serum antibody levels after immunization with an optimally immunogenic dose of SSS-III. | 1,445 |
Inhibition of the antibacterial activity of gentamicin by urine. | Urinary levels of antibiotics determine the outcome of treatment of most urinary tract infections. The antibacterial effect of gentamicin against Escherichia coli and Pseudomonas aeruginosa in urine was studied. With use of urinary constituents in concentrations normally found in human urine, it was shown that urine has an inhibitory effect that is dependent upon the acidity and total osmolality of the urine, as well as upon the presence of individual solutes. Up to 40 times as much gentamicin may be needed to prevent the growth of E. coli or P. aeruginosa in concentrated, acidic human urine as is required in broth. This inhibitory effect may be particularly important when urinary concentrations of gentamicin are reduced either because of a reduction in dosage or because of decreased excretion due to renal insufficiency. | 1,450 |
Production and purification of the gamma haemolysin of Staphylococcus aureus 'Smith 5R'. | The gamma haemolysin of Staphylococcus aureus 'Smith 5R' was produced on Dolman-Wilson agar overlain with cellophane. Maximal yields of crude lysin with titres of 2000 to 4000 haemolytic units/ml were obtained within 24 h at 37 degrees C in 10% (v/v) CO2 in air, on medium adjusted to pH 7-0. The crude lysin was purified 2700-fold (with 75% recovery) by ultrafiltration, gel filtration and ammonium sulphate fractionation. The specific activity of the lysin was 10(5) haemolytic units/mg protein after the dialysed active precipitate was extracted with NaCl and reprecipitated with ammonium sulphate. Purified gamma lysin was homogeneous by disc electrophoresis and immunoelectrophoresis. | 1,465 |
Elementary osmotic pump. | The elementary osmotic pump is a new delivery system for drugs or other active agents; it delivers the agent by an osmotic process at a controlled rate. Control resides in the: (a) water permeation characteristics of a semipermeable membrane surrounding the formulated agent, and (b) osmotic properties of the formulation. In its simplest embodiment, the system is constructed by coating an osmotically activie solid agent with the rate-controlling, semipermeable membrane. This membrane contains an orifice of critical size through which solubilized agent is dispensed. The system can contain the agent in solid form at loading higher than 90% of the total volume, and the agent can be delivered at rates several orders of magnitude higher than can be achieved by solution diffusion through polymeric membranes. The delivery rate, the fraction of total content delivered at zero order, and the system's delivery portal size have been calculated for delivery of a single compound. Experimental work verified the theory. The release rate from the system was found to be independent of outside agitation when the system is not deformed by shaking action, the pH of the environment, and delivery portal size for sizes within a specified range. The delivery rate from this system in vitro and in the GI tract of dogs was found to be equal. | 1,510 |
Transfer of gases and metabolites in the equine placenta: a comparison with other species. | Mares and fetuses with indwelling catheters in the umbilical and uterine vessels have been used to monitor transplacental blood gas tensions, pH, O2 affinities and the concentration of various metabolites in fetal and maternal blood during late gestation. Measurements of umbilical and uterine blood flows and arterio-venous differences enabled the uptake of O2 and glucose by the fetus and the uterus to be estimated. The present findings are compared with those from other species in comparable conditions. | 1,529 |
Importance of the aromatic ring in adrenergic amines. 2. Synthesis and adrenergic activity of some nonaromatic six- and eight-membered ring analogs of beta-phenylethanolamine. | The synthesis of beta-phenylethanolamine analogs in which the phenyl ring is replaced by cyclohexyl, cyclohexen-4-yl, cyclooctyl, cyclooctenyl, cycloocta-1,3-dien-2-yl, cycloocta-1,5-dienyl, and cyclooctatetraenyl was accompanied by conversion of the corresponding aldehydes to the cyanohydrins followed by reduction with lithium aluminum hydride. A preparatively useful synthesis of 1-formylcyclooctatetraene is described utilizing the photocycloaddition of methyl propiolate to benzene followed by reduction to the alcohol and oxidation with MnO2. All compounds, as their hydrochloride salts, exhibited indirect adrenergic activity on the rat vas deferens. On the reserpinized rat vas deferens all compounds potentiated the effects of exogenous norepinephrine. The results are in agreement with the conclusion that the more saturated the ring moiety, the greater the affinity for the amine uptake site of the vas deferens and suggest that there is no important interaction between the drug and this uptake site that involves pi-complex formation. | 1,534 |
Sodium bicarbonate administration during cardiac arrest. Effect on arterial pH PCO2, and osmolality. | Arterial pH, Pco2, and osmolality were determined serially during cardiac resuscitation in patients and in dogs, with and without administration of sodium bicarbonate. These studies demonstrate that (1) in the absence of preexisting acidosis, severe acidosis can be prevented by adequate ventilation alone; (2) sodium bicarbonate administration results in a significant rise in arterial Pco2, which parallels the rise in pH despite adequate ventilation; (3) during prolonged cardiac and resuscitation, there is a rise in arterial osmolality that is accentuated by sodium bicarbonate. These studies suggest that sodium bicarbonate should not be used during resuscitation (1) in the absence of effective hyperventilation or where carbon dioxide removal is inadequate despite adequate ventilation, (2) in repeated doses, without confirmation of substantial acidosis, or (3) when cardiac arrest has been of brief duration and preexisting acidosis is unlikely. These studies also point to the need for a reappraisal of other buffers that do not elevate the arterial Pco2. | 1,554 |
[Presence of foreign body in hand and foot, diagnosed too late]. | On the basis of 7 years' material, the distribution of 73 foreign bodies - of non-metallic intensity - in the hand and the foot is discussed. The foreign bodies did not appear as new, fresh lesions, but they have been diagnosed after longer or shorter symptom-free state. In the case of fistulous process immediate removal has been performed, and in the case of closed cases - on the basis of the clinical picture - immediate removal - or removal after fixation for a few days was effective. In the author's opinion, fixation is - so long as acute symptoms are present - in all cases indispensable, - fixation is immediately followed by physicotherapy, in order to assure good functional results. | 1,592 |
[Infectious complications of primary osteosynthesis in aged patients]. | In respect of iatrogenic infections the elderly patients are to be considered as endangered. Modern traumatology increases this danger in consequence of the foreign materials placed in the wounds. The role of the antibiotic and chemotherapeutic prophylaxis is of utmost importance. Regrettably, the resistance of the pyogenics, especially of the strains in the hospitals is increasing, - in consequence, besides the maximal sterility the further improvement of the surgical technique and of the after-treatment are the most important tasks. In the case of infection aimed antibiotic and chemotherapeutic, resp., treatment may be successful. | 1,594 |
Mosquito-borne arboviruses in arctic america. | Mosquito-borne arboviruses are prevalent throughout subarctic regions of Canada and Alaska, principally in the boreal forest extending between latitudes 53 and 66 degrees N, but they have been identified in tundra regions as far north as 70 degrees N. All mosquito-borne agents have been bunyaviruses, comprising principally the snowshoe hare subtype of California encephalitis (CE) virus, but also Northway virus. Mosquito vectors comprise several Aedes species and Culiseta inornata, all of which have supported replication of CE virus following incubation at 13 degrees C or lower temperatures. Isolation of virus from wild-caught larvae points towards transovarial transfer. Principal vertebrate reservoirs of infection are mammals, especially snowshoe hares (Lepus americanus) and ground squirrels (Citellus undulatus). Where the boreal forest merges into prairie grassland around 53 degrees N, Culex tarsalis mosquitoes become prevalent, and an alphavirus, western equine encephalomyelitis, is detected more frequently than CE virus. | 1,602 |
[Stress incontinence in the woman (author's transl)]. | The morphology and function of the urethrovesical junction are described to give some understanding of the pathogenesis and therapy of female stress incontinence. Conservative procedures can only be helpful in stage-1 stress incontinence, whereas in stage 2 surgical treatment provides excellent results. | 1,609 |
Studies in vitro of lipogenesis in rat testicular tissue. | Testicular tissue was shown to contain the full complement of enzymes required for de novo synthesis of fatty acids. The enzymes capable of snythesizing palmitic acid from citrate, acetate, or acetyl CoA were found to be present in the soluble (cytoplasmic) fraction. These included fatty acid synthetase, acetyl CoA carboxylase, citrate-cleavage enzyme, malic enzyme, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase. Optimal conditions for assaying activities of fatty acid synthetase and acetyl CoA carboxylase in the soluble fraction from rat testes were established, and the activities of these two enzymes were determined to be 0.54 +/- 0.1 and 0.030 +/- 0.002 (nmoles of substrate incorporated into fatty acid per min per mg of soluble fraction protein), respectively. The activities of citrate-cleavage enzyme, malic enzyme, and the glucose-6-phosphate dehydrogenase/6-phosphogluconate dehydrogenase pair were also measured. The activities were 6.0 +/- 0.7, 34.9 +/- 4.2, and 29.9 +/- 9.3 nmoles/min/mg, respectively. | 1,621 |
[Development of Mycobacterium lacticolum and its synthesis of exopolysaccharide under conditions of varying acidity of the medium]. | Mycobacterium lacticolum 121 grows and synthesizes exopolysaccharide at the initial values of pH of the medium from 5.0 to 11.5. The accumulation of biomass is maximal (10 to 12 gram/litre) at pH 6.0 to 11.5; the rate of growth is highest at pH 8.0 to 11.5. The largest amount of exopolysaccharide (2.0 to 2.4 gram/litre) is produced in the medium at pH 8.0 to 11.0; the rate of its production is highest at pH 9.0 to 11.0. The growth of Mycobacterium lacticolum 121 and the biosynthesis of polysaccharide are optimal at pH 8.0 to 8.2. Changes in acidity of the medium have no effect on the qualitative composition, structure, and molecular weight of the polysaccharide. | 1,632 |
H+ transport and membrane-bound HCO - 3 ATPase in salivary duct epithelium. | An ATPase stimulated by HCO - ions and other oxybases and inhibited by SCN- has been found in main excretory duct of rat submaxillary gland, a tissue, capable of actively secreting HCO - 3 ions. No such ATPase was found in the rabbit duct, which normally does not secrete HCO - 3. The HCO - 3 ATPase was localized in the plasma membrane fraction of the homogenate, as evidenced by the marker 5'-nucleotidase. The activities of the HCO - 3 ATPase increased in metabolic alkalosis and decreased in metabolic acidosis in parallel to secretion of HCO - 3 and K+ ions by the duct epithelium. These findings provide further evidence that the membrane-bound HCO - 3 ATPase is involved in active H+/HCO - 3 transport. | 1,708 |
[Effect of cultivation conditions on the synthesis of citric and isocitric acids in Candida lipolytica on hexadecane medium]. | The influence of aeration, pH and iron concentration on the growth of yeast C. lipolytica 704 on the hexadecane medium and on the synthesis of citric and isocitric acids was investigated. The yeast synthesized citric acids actively during intensive aeration. The acid formation was strongly dependent on the medium acidity: pH 6.0 was most favourable for the synthesis of citric acids. The Fe concentration influenced significantly the ratio of the acids synthesized. At a low concentration of iron (0.005 mg Fe/l) equal amounts of citrate and isocitrate were formed; at an increased concentration isocitrate was in predominant formation. | 1,720 |
[Effect of the composition of the nutrient medium on the synthesis of acid-fast alpha-amylase by different strains of Aspergillus]. | The capacity of 86 strains of the Aspergillus fungus to synthesize acid stable alpha-amylase was examined. The strains of Asp. niger showing a high capacity of synthesizing the enzyme were isolated. Repeated cultivation of the selected cultures on the Minoda agar medium led to a 200% increase in the enzyme activity in the submerged culture. Addition of sodium nitrate to the Minoda medium during submerged cultivation allowed a 3-fold increase of the synthesis of acid stable alpha-amylase. | 1,736 |
Neuronal properties of hybrid neuroblastoma X sympathetic ganglion cells. | Clonal mouse neuroblastoma cells without tyrosine 3-monooxygenase [EC 1.14.16.2; tyrosine hydroxylase; L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating)] activity were fused with normal cells from embryonic mouse sympathetic ganglia. One of the 37 hybrid cell lines obtained possesses high tyrosine 3-monooxygenase activity and synthesizes dopamine. These cells also have excitable membranes and generate action potentials in response to electrical stimuli. Thus hybrid cells, generated by fusion of neuroblastoma cells with normal cells from the nervous system, can acquire neural properties not found with the parental neuroblastoma cells. | 1,745 |
Guanylate cyclase and cyclic-GMP phosphodiesterase activities in mammary glands of mice during pregnancy and lactation. | Guanylate cyclase and cyclic-GMP phosphodiesterase activities were measured in homogenates of mammary glands from virgin, pregnant, and lactating mice. Guanylate cyclase activities increased 35% in mammary tissues during pregnancy, and a further 40% increase was observed during lactation. Cyclic-GMP phosphodiesterase activity also increased during pregnancy but activities were not different in glands from lactating mice vs glands from pregnant mice. These results are discussed with regard to a possible role of cyclic-GMP in regulating lactational processes. | 1,796 |
The jumping mechanism of Xenopsylla cheopis. I. Exoskeletal structures and musculature. | The jumping apparatus of the flea, which includes highly modified direct and indirect flight muscles, is described: attention is drawn to the various specializations of the exoskeleton which stiffen the thorax and also provide the 'click' mechanism triggering take-off. A finger-like invagination of tall cells within the cavity of the developing pleural arch of the pharate adult secretes the resilin pad. This is illustrated with coloured photographs. It is suggested that winglessness of a Mecopteran-like ancestor pre-adapted fleas to a parasitic life-style, and that a jumping mode of progression was a primitive feature of the whole Order. Scattered throughout the Siphonaptera today are species which have secondarily lost the pleural arch and with it the power to execute large jumps. These are usually found among fleas parasitizing mammals inhabiting caves, subterranean burrows and runs, high aerial nests and snow or ice-bound habitats. Large pleural arches are associated with fleas infesting large mobile hosts. | 1,804 |
Drug-nucleic acid interaction: X-ray crystallographic determination of an ethidium-dinucleoside monophosphate crystalline complex, ethidium: 5-iodouridylyl(3'-5')adenosine. | The intercalative trypanosomal drug, ethidium bromide, forms a crystalline complex with the dinucleoside monophosphate, 5-iodiuridylyl(3'-5')adenosine (iodoUpA). These crystals are monoclinic, space group C2, with unit cell dimensions, a = 2.845 nm, b = 1.354 nm, c = 3.413 nm, beta = 98.6 degrees. The structure has been solved to atomic resolution by Patterson and Fourier methods, and refined by full matrix least squares to a residual of 0.29 on 2017 observed reflexions. The asymmetric unit contains two ethidium molecules, two iodoUpA molecules, twenty water molecules and four methanol molecules, a total of 156 atims excluding hydrogens. The two iodoUpA molecules are held together by adenine-uracil Watson-Crick base-pairing. Adjacent base-pairs within this paired iodoUpA structure and between neighbouring iodoUpA molecules in adjoining unit cells are separated by 0.68 nm. This separation results from intercalative binding by one ethidium molecule and stacking by the other symmetry is utilized in this model drub-nucleic acid interaction, the intercalative ethidium molecule being oriented such that its phenyl and ethyl groups lie in the narrow groove of the miniature nucleic acid double helix. Solution studies have indicated a marked sequence specificity for ethidium-dinucleotide interactions and a probable structural explanation for this has been provided by this study. | 1,810 |
Some metabolic approaches to improving myocardial performance during cardiac hypoxia. | Four possible metabolic approaches to improving cardiac function in the presence of myocardial hypoxia have been considered. 1. It appears that there is increasing evidence which suggests that free fatty acids are harmful to the ischemic heart. 2. Although it has been demonstrated that Krebs cycle intermediates can result in anaerobic energy formation by the mitochondria, and under certain extreme conditions can lead to improved performance of the heart, the potential for a physiologically important effect of this approach is probably limited. 3. The protection of the ischemic or hypoxic heart by alkalosis may be a feasible approach. The major beneficial effect appears to be exerted through more efficient conversion of energy that is already available to contractile performance rather than by increasing energy supply. 4. There appears to be some real potential for improving cardiac energy delivery via the glycolytic pathway. Calculations based on isolated rat heart studies indicate that, at 50% oxygenation, glycolytic ATP generation could totally correct for the deficit in mitochondrial ATP formation. Therefore, it is in the area of overcoming the inhibition of glycolytic ATP formation and tapping this potential metabolic pathway that energy delivery may be restored toward normal in the hypoxic and perhaps the borderline zone of underperfusion in the ischemic heart. The problem of the ischemic inhibition of glycolysis may partially be overcome by creating extracellular alkalosis, but this presumption will have to be tested. | 1,830 |
Human erythrocyte carbonic anhydrase B and C in chronic obstructive lung disease. | The levels of carbonic anhydrase B and C isozymes in human red cells were determined using a quantitative immunological technique in patients with chronic obstructive lung disease. A significant increase in the level of carbonic anhydrase B was observed in these patients, while the level of carbonic anhydrase C did not change substantially. Positive correlations were found between the level of carbonic anhydrase B and arterial CO2 tension and plasma HCO3 concentration. A negative correlation was observed between the levels of carbonic anhydrase B and blood pH. These findings suggest that the synthesis or degradation of carbonic anhydrase B isozyme is affected by arterial CO2 tension or plasma HC03 concentration. The clinical significance was also discussed in relation to these isozyme levels in red cell. | 1,869 |
[Hydrolysis of insoluble collagen of bull bones by Streptomyces griseus crystalline protease]. | Hydrolysis of collagen was studied in the bull bone tissues by the Str. griseus crystalline protease. The amount of collagen hydrolyzed by it composed 6.6% and 16% after 4-hour and 6-hour hydrolysis, respectively. When the enzyme:substrate ratio is 1:50 hydrolysis proceeds most intensively; with a decrease in the ratio up to 1:1000 the average amount of peptides increase from 2.6 up to 4 amino acidic residua, respectively. Under conditions of denaturated collagen hydrolysis the content of hydroxyproline in solution as compared with the native one increases; in this case the links with the presence of imino-acids are easier to split, the more resistant being those formed by hydroxyproline. Within the limit of 20-45 degrees C hydrolysis of protein intensifies with a temperature rise. Within the pH range of 5.0-11.0 the maximal amount of alpha- NH2-groups and hydroxyproline is observed at pH 8.5, the minimal--at PH 5.0. Hydroxyproline in the composition of peptides appears at the beginning of hydrolysis whereas the free one of enzymes of the longer effect 24 h after the beginning of the experiment composes 12.2% of its total content in the solved products. In the insoluble part of the substrate after 3-hour hydrolysis tyrosine composes less than 25% of its initial amount in protein whereas phenyl alanine--over 70%. After 6-hour hydrolysis the solved part of the system contains about 30% of alanine and 8.9 and 6% of glycine, proline and hydroxyproline, respectively. | 1,884 |
Bilateral testicular seminoma in intra-abdominal testes. | A seminoma of both intra-abdominal testes in a forty-five-year-old patient is reported. Discovery of the tumor was fortuitous during admission for upper lobe pneumonia. Of particular interest in this case is that seminoma was found in both undescended testes. Surgical extirpation of both degenerated testes along with prostatic utricle was performed. The patient refused radiotherapy. | 1,891 |
[Determination of GSH-DH activity (E.C.1.8.5.1) presence of the enzyme in different wheat varieties (author's transl)]. | 2,6-dichlorophenol-indophenol is more stable in 75% ethanol than in aqueous solution and ascorbic acid reacts considerably faster in this media than glutathione. The activity determination of glutathione: dehydroascorbic acid oxidoreductase was based on these observations by a photometric measurement of the ascorbic acid resulting from the catalysis. Extracts from various types of wheat were tested and relatively high enzyme activities were found. | 1,914 |
[Comparative study of Aujeszky's disease virus reproduction in a suspension of poultry embryonic cells and tissues (author's transl)]. | Reproduction of Aueski disease virus in suspension cultures of trysinized cells and mechanically minced tissue of chick, duck and quail embryos was compared. The optimal conditions for cultivation of vaccine and virulent strains of virus in these systems were determined. The advantages and prospects of using suspension cultures of minced avian embryo tissue for preparation of virus materials with high biological activity and in large volumes in comparison with trypsinized cell suspensions were demonstrated. | 1,907 |
Immunization against Q-fever of naturally infected dairy cows. | Dairy cows infected naturally with Coxiella burnetii as evidenced either by presence of phase II agglutinating antibodies in the blood or by shedding C. burnetii in the milk, were vaccinated subcutaneously with formalin-killed phase I C. burnetii organisms. Attempts to demonstrate C. burnetii in the milk of vaccinated dairy cows 47 days after vaccination were negative, while continuous shedding of C. burnetii in the milk of control non-vaccinated dairy cows was repeatedly demonstrated in the course of 123 days (period of investigation). No harmful systemic reaction following vaccination was observed. | 1,994 |
Biochemical and electrophoretic studies of erythrocyte pyridoxine kinase in white and black Americans. | The mean PNK activity in red blood cells from black subjects was only about 40% of that in whites. Among 51 whites examined, one was found to have enzyme deficiency. The estimated gene frequencies for PNKH (the common allele in whites which codes for higher enzyme activity) and PNKL (the common allele in blacks which codes for lower enzyme activity) were .35 and .65, respectively, for black donors, and .81 and .19, respectively, for white donors, The variant enzyme in persons with enzyme deficiency was associated with an increased rate of degradation in red cells during aging. No other biochemical or electrophoretic differences were detected. | 2,009 |
[Clinical and therapeutic problems posed by hangings. Apropos of 67 cases]. | Starting from a collection of 67 cases of hanging taken over by the Anesthesia Resuscitation Department belonging to Reims Hospital University Centre, the authors report their clinical observations and make an analytical confrontation of this type of accident according to various criteria such as: - the initial physical condition of the victims; - the evolution of the symptoms; - the various medical treatments used. The immediate consequences of miscarried hangings lead to a physio-pathological argument dealing mainly with the neurological and breathing manifestations. The elements of this argument enable the writers to back up certain therapeutic orientations among which hyperbaric oxygen therapy and early prescription of which seems to be wished for in the most severe forms of hanging. | 2,063 |
[Effect of the phosphorus concentration on novobiocin formation by the producer Act. spheroides]. | According to the literature data biosynthesis of novobiocin by Act. spheroides unlike other antibiotics does not practically depend on the phosphorus levels in the medium. In the present paper it is shown that production of novobiocin in natural media is sensitive to the concentration of mineral phosphorus in the medium. The optimal concentration of phosphorus for biosynthesis of novobiocin is almost within the same ranges as that for biosynthesis of streptomycin, tetracyclines and oleandomycin. | 2,094 |
[Characteristics of the oxidative metabolism in strains with varying levels of fucidin biosynthesis]. | Oxidative capacity of the fusidin-producing strains with various biosynthetic activity was studied comparatively. The studies showed that by their capacity to oxidize pyruvate and some metabolites of the tricarboxylic acid cycle (acetate, succinate, malate) the strains were arranged in the order reverse to their antibiotic activity. Such regularity was observed during the whole fermentation process and was most pronounced by the 3rd and 4th days (beginning of the idiophase). The rate of glucose oxidation was higher in more active strains. The same regularity was noted in the 2nd phase of the strain development associated with beginning of fusidin biosynthesis. In the 1st phase (the 1st and 2nd days) the strains almost did not differ by their capacity to oxidize glucose. By oxidation of phosphorylated ethers of carbohydrates (glucose-6-phosphate and fructoso-6-phosphate) the strains did not differ. Various fusidin-producing strains oxidized NAD-N and NADP-N approximately with the same rate. It is supposed that mutations leading to increased antibiotic production are associated with changes in acetate metabolism in the direction of more intensive biosynthesis of isoprenoid compounds, potential precursors of the fusidin molecule. | 2,097 |
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PubMed Abstracts Subset
This dataset contains a probabilistic sample of publicly available PubMed metadata sourced from the National Library of Medicine (NLM).
If you're looking for the precomputed embedding vectors (MedCPT) used in our work Efficient and Reproducible Biomedical Question Answering using Retrieval Augmented Generation, they are available in a separate dataset: slinusc/PubMedAbstractsSubsetEmbedded.
📄 Description
Each entry in the dataset includes:
title: Title of the publicationabstract: Abstract textPMID: PubMed identifier
The dataset is split into 24 .jsonl files, each containing approximately 100,000 entries, for a total of ~2.39 million samples.
🔍 How to Access
▶️ Option 1: Load using Hugging Face datasets (streaming)
from datasets import load_dataset
dataset = load_dataset("slinusc/PubMedAbstractsSubset", streaming=True)
for doc in dataset:
print(doc["title"], doc["abstract"])
break
Streaming is recommended for large-scale processing and avoids loading the entire dataset into memory.
💾 Option 2: Clone using Git and Git LFS
git lfs install
git clone https://huggingface.co/datasets/slinusc/PubMedAbstractsSubset
cd PubMedAbstractsSubset
After cloning, run
git lfs pullif needed to retrieve the full data files.
📦 Format
Each file is in .jsonl (JSON Lines) format, where each line is a valid JSON object:
{
"title": "...",
"abstract": "...",
"PMID": 36464820
}
📚 Source and Licensing
This dataset is derived from public domain PubMed metadata (titles and abstracts), redistributed in accordance with NLM data usage policies.
Used in:
Stuhlmann et al. (2025), Efficient and Reproducible Biomedical QA using RAG, arXiv:2505.07917
🏷️ Version
v1.0– Initial release (2.39M entries, 24 JSONL files)
📬 Contact
Maintained by @slinusc.
For questions or issues, please open a discussion or pull request on the Hugging Face dataset page.
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