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Biomedical subjects

J C Wagner

Publications and source records attributed to J C Wagner.

At least 19 recordsLinked to original sources
PubMed1992

Purification and characterization of proteinase yscJ, a new yeast peptidase.

A newly recognized peptidase, designated proteinase yscJ, was purified from the yeast Saccharomyces cerevisiae. The enzyme is of non-vacuolar origin and cleaves the Tyr-Lys bond of the synthetic peptide substrate Cbz-Tyr-Lys-Arg-NH-Ph (Cbz, benzyloxycarbonyl; NH-Ph, 4-nitroanilide) and the Glu-Lys bond of the substrate Boc-Glu-Lys-Lys-NH-Mec (Boc, butoxycarbonyl; Mec, 4-methylcoumarinyl) with high efficiency. Optimum pH for cleavage of Cbz-Tyr-Lys-Arg-NH-Ph is in the range 7.0-7.5. The purified enzyme has a molecular mass of approximately 58 kDa, as judged by gel filtration on a Superose 12 FPLC column. Mercury compounds and EDTA were found to be potent inhibitors of proteinase yscJ activity.

Amino Acid Sequence↗
PubMed1991

Metabolic regulation of the trehalose content of vegetative yeast.

We have investigated the mechanism by which heat shock conditions lead to a reversible accumulation of trehalose in growing yeast. When cells of S. cerevisiae M1 growing exponentially at 30 degrees C were shifted to 45 degrees C for 20 min, or to 39 degrees C for 40 min, the concentration of trehalose increased by about 25-fold; an effect reversed upon lowering the temperature to 30 degrees C. This was compared to the more than 50-fold rise in trehalose levels obtained upon transition from the exponential to the stationary growth phase. Whereas the latter was paralleled by a 12-fold increase in the activity of trehalose-6-phosphate synthase, no significant change in the activities of trehalose-synthesizing and -degrading enzymes was measured under heat shock conditions. Accordingly, cycloheximide did not prevent the heat-induced accumulation of trehalose. However, the concentrations of the substrates for trehalose-6-phosphate synthase, i.e. glucose-6-phosphate and UDP-glucose, were found to rise during heat shock by about 5-10-fold. Since the elevated levels of both sugars are still well below the Km-values determined for trehalose-6-phosphate synthase in vitro, they are likely to contribute to the increase in trehalose under heat shock conditions. A similar increase in the steady-state levels was obtained for other intermediates of the glycolytic pathway between glucose and triosephosphate, including ATP. This suggests that temperature-dependent changes in the kinetic parameters of glycolytic enzymes vary in steady-state levels of intermediates of sugar metabolism, including an increase of those that are required for trehalose synthesis. Trehalose, glucose-6-phosphate, UDP-glucose, and ATP, were all found to increase during the 40 min heat treatment at 39 degrees C. Since this also occurs in a mutant lacking the heat shock-induced protein HSP104 (delta hsp104), this protein cannot be involved in the accumulation of trehalose under these heat shock conditions. However, mutant delta hsp104, in contrast to the parental wild-type, was sensitive towards a 20 min incubation at 50 degrees C. Since this mutant also accumulated normal levels of trehalose, we conclude that HSP104 function, and not towards a 20 min incubation at 50 degrees C. Since this mutant also accumulated normal levels of trehalose, we conclude that HSP104 function, and not the accumulation of trehalose, protects S. cerevisiae from the damage caused by a 50 degrees C treatment.

Glucose-6-Phosphate↗
PubMed1991

Background incidence of mesothelioma: animal and human evidence.

Evidence is presented showing that mesotheliomas can have causes other than exposure to asbestos dust, in both experimental animals and humans. In experimental animals, for example, results from two major experimental laboratories suggest that at least 10% may be taken for background incidence, whereas a third laboratory suggests that the experimental group must have a rate exceeding 30% "Background" also includes mesotheliomas found in association with nonfibrous and fibrous nonasbestiform agents. Mesotheliomas in humans can be broadly classified in a manner similar to those of experimental animals: (1) spontaneously occurring, (2) those with a latent period less than 10 years, (3) childhood mesotheliomas, (4) familial cases, (5) cases before the 20th century, (6) mineralogically negative mesotheliomas, and (7) mesotheliomas caused by nonasbestiform agents. The importance of the acceptance of these "background" cases lies in the fact that a basis is provided for the study of the incidence of disease associated with various types of asbestos.

Animals↗
PubMed1991

Carcinogenicity of the insulation wools: reassessment of the IARC evaluation.

In assessing the health evidence concerning man-made mineral fibers, the chemical composition, surface activity, durability, and size of fibers have to be taken into account. Special-purpose fine glass fibers need to be separated from the insulation wools (glass, rock, and slag wool). The epidemiological evidence is sufficient to conclude that there has been no mesothelioma risk to workers producing or using glass wool, rock wool, or slag wool. The epidemiological studies have been large and powerful, and they show no evidence of a cause-effect relationship between lung cancer and exposure to glass wool, rock wool, or slag wool fibers. There is some evidence of a small cancer hazard attached to the manufacturing process in slag wool plants 20 to 50 years ago, when asbestos was used in some products and other carcinogenic substances were present. However, this hazard is not associated with any index of exposure to slag wool itself. Animal inhalation studies of ordinary insulation wools also show that there is no evidence of hazard associated with exposure to these relatively coarse, soluble fibers. The evidence of carcinogenicity is limited to experiments with special-purpose fine durable glass fibers or experimental fibers, and only when these fibers are injected directly into the pleural or peritoneal cavity. Multiple chronic inhalation studies of these same special-purpose fine glass fibers have not produced evidence of carcinogenicity. It is suggested that the present IARC evaluation of the carcinogenic risk of insulation wools should be revised to Category 3: not classifiable as to carcinogenicity to humans.

Animals↗
PubMed1991

The discovery of the association between blue asbestos and mesotheliomas and the aftermath.

As this is the 30th anniversary of the publication of our paper "Diffuse pleural mesotheliomas and asbestos exposure in the north west Cape Province," and 1 December 1990 is the first anniversary of John Gilson's death, I think it is appropriate to subunit this paper. It covers the background of the discovery of the series of mesotheliomas in the north western region of the Cape Province, and the subsequent publication, which has become the most cited paper in industrial medicine. It was John Gilson who directed the next phase, which substantiated this discovery. He clarified the situation in his summary of the report to the director of the International Agency for Research in Cancer in 1972. This I have quoted in full and have had the temerity to update to 1990. I am sure that many will want to elaborate these views, and I hope that they will submit their opinions to this journal.

Asbestos↗
PubMed1991

Enhancement of athletic performance with drugs. An overview.

Drug use among athletes has become a recognised problem in sports. Athletes may use drugs for therapeutic indications, for recreational or social reasons, as ergogenic aids or to mask the presence of other drugs during drug testing. Stimulants were some of the first drugs used and studied as ergogenic aids. Amphetamines may increase time to exhaustion by masking the physiological response to fatigue. Caffeine may improve utilisation of fatty acids as a fuel source thereby sparing muscle glycogen. Cocaine and other sympathomimetic drugs have little or no effect on athletic performance. Anabolic steroids appear to have the potential to increase lean muscle mass and strength under certain conditions. Human growth hormone may also be used for an anabolic effect, but data on this effect are lacking. Erythropoietin may represent a pharmacological alternative to blood doping by increasing red blood cell mass. The use of narcotic analgesics is not necessarily ergogenic but can be harmful if used to allow participation of an athlete with a severe injury. According to the American College of Sports Medicine alcohol does not possess an ergogenic effect. However, it may be used to reduce anxiety or tremor prior to competition. Marijuana does not increase strength. Tobacco products may produce psychomotor effects or control appetite which may be beneficial to some athletes. Other drugs used by athletes include beta-blocking agents, diuretics, and a variety of nutritional supplements. In addition, diuretics and probenecid may be taken to mask drug contents in the urine. Whether the ergogenic effects are real or perceived, the potential for adverse effects exists for all of these drugs. Potential health complications represent a serious risk to an otherwise healthy population. Further research on the long term health risks in athletes taking ergogenic drugs is needed.

Adrenergic beta-Antagonists↗
PubMed1990

Antibiotic sensitivity and the prescribing information sheet: assisting the prescribing physician.

The concept conceived 5 years ago is now a reality. Physicians have information readily available for empiric prescribing from the home, office, or hospital. The other two hospitals in the city have implemented the systems. The reaction of physicians has been extremely favorable. In fact, two new publications for the outpatient/community and for the pediatric populations are now under way at the suggestion of physicians. Plans are in place to assess physician satisfaction and use of the information sheet within the coming year. Presently, too little time has passed to evaluate whether changes in prescribing have actually occurred. In fact, it may never be possible to identify how many instances of inadvisable prescribing are prevented with good initial information. However, for the relatively low cost involved, this has been an exciting new opportunity for education, as well as a method to promote cost-effective and appropriate antibiotic therapy.

Anti-Bacterial Agents↗
PubMed1990

Anabolic steroids--a review of the clinical toxicology and diagnostic screening.

Anabolic steroids have been used by athletes since the 1950s to increase size and strength in order to improve their performance. The abuse of these substances has since expanded to include junior high and high school male and female athletes and non-athletes. The anabolic and androgenic effects of these agents, when taken in the doses needed to produce increases in size and strength, result in significant serious adverse effects involving the skin, liver, cardiovascular, musculoskeletal, endocrine and reproductive systems. Some of these effects are irreversible. It is essential that clinical toxicologists, emergency room physicians and psychiatrists are familiar with the physical and psychological effects, as well as the changes in laboratory parameters, that typically occur from chronic use of anabolic steroids. The toxicities and representative clinical profiles of steroid users are presented, and the methods available for diagnostic screening using psychological testing and urine analysis are also reviewed.

Anabolic Agents↗
PubMed1989

Characterization of excessive collagen production during development of pulmonary fibrosis induced by chronic silica inhalation in rats.

The activation of collagen synthesis during development of silicotic fibrosis was studied in rats exposed, in dusting chambers, to respirable SiO2 for periods of 2, 4, 6 or 12 months. Control animals were exposed similarly to clean air or TiO2. Development of fibrosis was followed by histological examination, measurement of lung weight and determination of lung collagen content (as hydroxyproline). A steady increase in lung weight and collagen content together with changes in cellularity and metabolic activity of the lungs, as ascertained by chemical determination of DNA and RNA, were measured in the lungs of the SiO2-exposed animals. Hybridization of total lung RNA, extracted at each time point, with cDNA probes specific for type I and type III procollagen mRNA levels showed that the development of fibrosis was associated with increased levels, as compared to age matched controls, of pulmonary procollagen mRNAs. Interestingly, the highest levels of procollagen mRNAs were observed in young (pretreatment control) animals, suggesting that during pulmonary development collagen metabolism in lungs is even greater than during development of fibrosis. In rats exposed to SiO2 the increase in type III procollagen mRNA occurred earlier than the increase in type I procollagen mRNAs. These observations demonstrate both age-dependent and silicosis-related changes in pulmonary procollagen mRNA levels. The results suggest that development of silicosis is associated with an altered capacity of the lungs to regulate collagen accumulation.

Administration, Inhalation↗
PubMed1989

Pharmaceutical services at the Tenth Pan American Games.

The pharmaceutical services provided by volunteers, including more than 100 pharmacists, at the 1987 Pan American Games in Indianapolis, Indiana, are described. Pharmacists at a local hospital were given responsibility for doping control and operation of the medical clinic pharmacy at the games. Barracks at a U.S. Army facility within the games' boundaries were converted into the clinic; an area on the second floor was equipped as the pharmacy. The pharmacy secured the necessary licensure and obtained drug products and supplies. Volunteer pharmacists were recruited and instructed about responsibilities, procedures, and security. The formulary was based on the 1983 Pan American Games formulary, the 1988 Olympic Games formulary, and requests from the Pan American Sports Organization. In the 26 days that the pharmacy was open, 968 prescriptions were filled. The drugs most commonly prescribed were ibuprofen, terfenadine, acetaminophen, penicillin V potassium, clotrimazole cream, and naproxen. A doping control center located at each competition venue was staffed by a physician, pharmacists, nurses, medical technologists, and nonmedical personnel. After an event, selected athletes were escorted to a doping control center, where a medical history and urine sample were obtained. The urine was tested for pH and specific gravity, and the coded specimen bottles were sealed for transport to the laboratory. Each step was documented on special forms. A total of 981 athletes were tested; six athletes had positive test results. The 1987 Pan American Games provided a unique opportunity for pharmacists to assist in providing medical services at a large athletic event and to become involved in doping control.

Americas↗
PubMed1989

Non-occupational malignant mesotheliomas.

The mineral content of the lungs from 84 cases of malignant pleural mesothelioma was estimated by electron microscopy and energy-dispersive X-ray analysis. These cases were chosen because the history of asbestos exposure was absent, indirect or ill-defined. The occupational exposures were classified according to the method of Zielhuis, and the results indicated that this classification is unnecessarily complicated. The chrysotile counts in the lungs from these mesothelioma cases were similar to those in controls and in a previous series of mesotheliomas in which the majority had had direct exposure to asbestos. Amphibole counts were intermediate between those in controls and in the previous series of mesotheliomas with direct asbestos exposure. These findings confirm those of previous studies indicating that amphiboles are more important than chrysotile in the causation of malignant mesothelioma. The results confirm that some mesotheliomas develop in the absence of asbestos exposure.

Adult↗
PubMed1989

Mesothelioma in Cyprus.

For many years, the main source of asbestos in Cyprus was thought to be the chrysotile mine in the central mountains. When a woman, who had no connection with the mine, developed mesothelioma, it was surprising to discover tremolite asbestos bodies within her lung. However, further studies have shown that tremolite occurs as a contaminant within the chrysotile ore body. In this study we have shown that both chrysotile and tremolite can be found in domestic and environmental samples throughout the mountain region; in particular, numerous fine fibres of both materials are present in stucco. Preliminary radiological studies have shown pleural disease in the village population and 5 out of 13 known cases of mesothelioma have arisen in persons unconnected with the mine. This suggests an environmental contribution to asbestos-related disease on the island.

Air Pollutants↗
PubMed1989

Correlation between lung fibre content and disease in East London asbestos factory workers.

The lungs from 36 former workers at an East London asbestos factory dying of asbestos-related disease were compared with lung tissue from 56 matched control patients operated on in East London for carcinoma of the lung. The severity of asbestosis and the presence of pulmonary carcinoma or mesothelioma of the pleura or peritoneum were correlated with an asbestos exposure index and with the type and amount of mineral fibre of the lungs. Asbestosis was associated with far heavier fibre burdens than mesothelioma. Moderate or severe asbestosis was more common among those with carcinoma of the lung than in those with mesothelial tumours. Crocidolite and amosite asbestos were strongly associated with asbestosis, carcinoma of the lung and mesothelial tumours, whereas no such correlation was evident with chrysotile or mullite. It is suggested that greater emphasis should be placed on the biological differences between amphibole and serpentine asbestos fibre.

Aluminum Silicates↗
PubMed1989

Abuse of drugs used to enhance athletic performance.

The ergogenic potential of drugs used by athletes to enhance performance is reviewed, and areas of involvement for pharmacists interested in the problem of drug abuse in athletics are described. Athletes use drugs for therapeutic and recreational purposes, as supposed ergogenic aids, and to mask the presence of other drugs during testing. Because many athletes train for competition and not for health, they may view the risk-to-benefit ratio of ergogenic drugs as favorable and may begin using them at an early age. Alcohol is the drug most commonly used by student athletes. Although alcohol has no ergogenic benefit, it is viewed as a caloric source and an anxiolytic. Amphetamines do not prevent exhaustion but may mask fatigue, which can have dangerous consequences. Anabolic steroids appear to increase strength but frequently cause adverse reactions, primarily involving the hepatic and endocrine systems. Beta-blocking agents have been shown to reduce anxiety, hand tremor, and heart rate in precision sports like archery, but susceptible persons may experience serious adverse effects. Caffeine improves the efficiency of fuel use and reduces fatigue; its use has been banned by several athletic organizations. Neither cocaine nor marijuana causes any increase in strength. Secretion of human growth hormone may be stimulated by a variety of agents, but evidence that any subsequent increases in size and weight occur is lacking. Other substances tried by athletes include vitamins and minerals, naloxone, albuterol, and human recombinant erythropoietin. Opportunities in sports pharmacy exists in the areas of information retrieval and interpretation, drug testing, legislation to reclassify drugs, education, and research.(ABSTRACT TRUNCATED AT 250 WORDS)

Doping in Sports↗
PubMed1988

Correlation between fibre content of the lung and disease in east London asbestos factory workers.

The lungs from 36 past workers at an east London asbestos factory who had died from asbestos related disease were compared with lung tissue from 56 matched control patients being operated on in east London for carcinoma of the lung, correlating the severity of asbestosis and the presence of pulmonary carcinoma or mesothelioma of the pleura or peritoneum with an asbestos exposure index and type and amount of mineral fibre in the lungs. Asbestosis was associated with far heavier fibre burdens than mesothelioma. There was also a striking difference in the degree of asbestosis between the subjects with mesothelioma and those with carcinoma of the lung, the asbestosis being more severe in the latter. A further finding was that crocidolite and amosite were strongly associated with asbestosis, carcinoma of the lung complicating asbestosis, and mesothelioma, whereas no such correlation was evident with chrysotile or mullite. It is suggested that more emphasis should be placed on the biological differences between amphibole and serpentine asbestos fibre.

Asbestosis↗
PubMed1987

Hormone (pheromone) processing enzymes in yeast. The carboxy-terminal processing enzyme of the mating pheromone alpha-factor, carboxypeptidase ysc alpha, is absent in alpha-factor maturation-defective kex1 mutant cells.

Carboxy-terminal processing of the mating pheromone alpha-factor of the yeast Saccharomyces cerevisiae has been assumed to be due to the action of carboxypeptidase ysc alpha [(1985) EMBO J. 4, 173-177]. Here it is shown that a mutant (kex1) defective in alpha-factor maturation is defective in carboxypeptidase ysc alpha activity, indicating that the enzyme is indeed the processing catalyst. It is proposed that carboxypeptidase ysc alpha is the product of the KEX1 gene.

Carboxypeptidases↗
PubMed1987

Some characteristics of hormone (pheromone) processing enzymes in yeast.

The KEX2 gene-encoded, membrane-bound Ca2+-dependent thiol endoproteinase, proteinase yscF, responsible for processing of the precursor protein of the sex pheromone alpha-factor of the yeast Saccharomyces cerevisiae was solubilized from the membraneous fraction and partially purified. Gel filtration revealed an apparent Mr of the native protein of around 150,000. Ca2+ concentration for half-maximal activity was in the micromolar range and concentration of the substrate Cbz-Tyr-Lys-Arg-4-nitroanilide for half-maximal velocity was 0.05 mM. The enzyme able to cleave basic amino acids from the carboxy-terminus of peptides and probably involved in final maturation of the alpha-factor peptides generated by proteinase yscF is membrane-associated, active at neutral pH and responds strongly to the serine proteinase inhibitor phenyl-methylsulfonyl fluoride as well as to -SH group blocking agents.

Chromatography, Gel↗