Biomedical subjects
Publications and source records attributed to S Lerner.
Cardiac involvement in dermatomyositis has been well described; myocarditis and cardiac arrhythmias are the most frequent manifestations. An 8-year-old girl is presented, who developed pericardial tamponade in the course of the disease. It is the first time this association has been reported.
1. A group of 21 to 24-kDa proteins of pheochromocytoma (PC-12) cells was found in blot overlay assays to bind specifically [alpha-32P]GTP. Binding was inhibited by GTP analogues but not by ATP. Such small GTP-binding proteins were found in the cytosolic and in the particulate fraction of the cells, but they were unevenly distributed: about 75% of the small GTP-binding proteins were localized within the particulate fraction of the cells. Separation of these proteins by two-dimensional gel electrophoresis revealed the existence of seven distinct [alpha-32P]GTP-binding proteins. 2. Targeting of the small GTP-binding proteins to the particulate fraction of PC-12 cells requires modification by isoprenoids, since depleting the cells of the isoprenoid precursor mevalonic acid (MVA) by the use of lovastatin resulted in a 50% decrease in membrane-bound small GTP-binding proteins, with a proportionate increase in the cytosolic form. This blocking effect of lovastatin was reversed by exogenously added MVA. 3. In addition, metabolic labeling of PC-12 cells with [3H]MVA revealed incorporation of [3H]MVA metabolites into the cluster of 21 to 24-kDa proteins in a form typical of isoprenoids; the label was not removed from the proteins by hydroxylamine, and labeling was enhanced in cells incubated with lovastatin. The latter effect reflects a decrease in the isotopic dilution of the exogenously added [3H]MVA, as the addition of exogenous MVA reversed the effect of lovastatin on [3H]MVA-metabolite incorporation into the 21 to 24-kDa proteins. 4. Additional experiments demonstrated that isoprenylation is required not only for membrane association of small GTP-binding proteins, but also for their further modification by a methylation enzyme. This was evident in experiments in which the cells were metabolically labeled with [methyl-3H]methionine, a methylation precursor. The group of 21 to 24-kDa proteins was labeled with a methyl-3H group in a form typical of C-terminal-cysteinyl carboxylmethyl esters. Their methylation was blocked by the methylation inhibitors methylthioadenosine (MTA), 3-deazadenosine and homocysteine thiolactone as well as by lovastatin. MVA reversed the lovastatin block of methylation. 5. Two-dimensional gel analysis of the [3H]methylated proteins detected seven methylated small GTP-binding proteins that correspond to the isoprenylated proteins. Levels of the small GTP-binding proteins as well as isoprenylation and methylation were reduced by cycloheximide. 6. Distribution of the methylated proteins between particulate and cytosolic fractions was found to be similar to that of the small GTP-binding proteins (i.e., a 4:1 ratio).(ABSTRACT TRUNCATED AT 400 WORDS)
We investigated the effects of cholesterol, cholestyramine, and taurocholate feeding on steady state specific activities and mRNA levels of hepatic 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase and cholesterol 7 alpha-hydroxylase in the rat. Interruption of the enterohepatic circulation of bile acids (cholestyramine feeding) increased total HMG-CoA reductase activity 5-fold. Cholesterol and taurocholate administration suppressed total microsomal HMG-CoA reductase activities 87% and 65%, respectively. HMG-CoA reductase mRNA levels increased 3-fold with cholestyramine, did not decrease significantly with cholesterol feeding, but were markedly decreased after taurocholate treatment. Cholesterol 7 alpha-hydroxylase activity increased 4-fold with cholestyramine and 29% during cholesterol feeding, but decreased 64% with taurocholate. Cholesterol 7 alpha-hydroxylase mRNA levels rose 150% and 50% with cholestyramine and cholesterol feeding, respectively, but decreased 73% with taurocholate. The administration of cholesterol together with taurocholate prevented the decline in cholesterol 7 alpha-hydroxylase mRNA levels, but inhibition of enzyme activity persisted (-76%). Hepatic microsomal cholesterol concentrations increased 2-fold with cholesterol feeding but did not change with taurocholate or cholestyramine treatment. These results demonstrate that mRNA levels of HMG-CoA reductase are controlled by the hepatic taurocholate flux, whereas mRNA levels of cholesterol 7 alpha-hydroxylase are controlled by the cholesterol substrate supply. These end products, cholesterol and bile acids, exert post-transcriptional regulation on HMG-CoA reductase and cholesterol 7 alpha-hydroxylase, respectively.
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Cysts in the region of the prostate and seminal vesicles are interesting because of their differential diagnosis and embryological relevance. We present our experience with 5 cases that include a müllerian duct cyst, diverticulum of the spermatic tract, seminal vesicle cyst and 2 prostatic cysts. Transrectal ultrasonography had a significant role in the diagnostic evaluation of these cysts. Ultrasonographically guided transperineal needle aspiration added significant diagnostic information and might have a therapeutic value. After a review of the literature, we propose an algorithm for the evaluation and management of prostatic and seminal vesicle cysts.
Many believe that intragastric deactivation of lipase accounts for the frequent failure of orally ingested pancreatic enzymes to normalize fat absorption in patients with pancreatic insufficiency. To test this hypothesis, we measured fat absorption from a large test meal in six patients with pancreatic insufficiency after we had instilled Viokase directly into the postcibal duodenum in two doses, one to deliver lipase at about 10% of normal secretory rates and the other at four times this rate. Direct duodenal instillation of neither the low nor the high dose of Viokase, nor the low dose of Viokase plus sodium bicarbonate, normalized fat absorption from the test meal; none of these duodenal instillations significantly improved fat absorption over that after the test meal plus orally ingested Viokase. Despite these various treatments, the patients excreted an average of 25.5 g of dietary fat as opposed to 2.1 g excreted by six normal subjects after the same meal. We conclude that more than just intragastric destruction of lipase underlies the frequent failure of orally ingested pancreatin to normalize fat absorption in pancreatic insufficiency.
A committee of staff and patients conducted an informal evaluation of a therapeutic community on a 16-bed psychiatric unit. The committee reviewed the history, original intent, current purpose, and effectiveness of meetings held on the unit; when problems were identified, suggestions for change were formulated. The evaluation served to increase the efficiency of meetings and to counteract what the authors termed the "drift phenomenon," or the tendency of the original purpose or structure of a meeting to change over time. The process also fostered an atmosphere of mutual respect and an enhanced sense of purpose among the patients and staff who worked on the committee.
Decreased GFR and TmG and increased beta-2-microglobulin excretion were found in a worker with a nine-year exposure to cadmium. The patient's recent marked weight loss and other multiple symptoms could not be explained on these abnormalities or by results of other specialized studies. Increased urinary beta-2-microglobulin without proteinuria but with elevated blood and urine cadmium levels in this patient raises questions about which biological indicators will prove to be most helpful in effectively monitoring cadmium workers.
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Intrabronchial foreign bodies are occasionally encountered in adults but most available information in humans consists only of reports evaluating one or two cases. We surveyed our experience and found seven patients with intrabronchial foreign bodies who had been examined with the flexible fiberoptic bronchoscope, six of whom were managed successfully. Nine cases have been identified in the literature. Although there were no major complications in either our cases or those in the literature, several problems were identified which under other circumstances could have caused significant complications. We assessed all of these cases for situations which presented potential risk to the patient. These risks were grouped into the following problem categories: 1. selection of appropriate bronchoscope, 2. availability of appropriate instruments, 3. control of the foreign body, and 4. unexpected foreign bodies. Endoscopists planning to use the FFB in foreign body removal should be aware of the problems and hazards which may ensue if improperly managed, and should attempt to gain experience either in the animal laboratory or in models prior to approaching patients with foreign bodies with the flexible fiberoptic bronchoscope.
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Defined standards and a mechanism for evaluation of performance can help promote new and improve existing occupational health programs. Criteria must be based on sound principles, be comprehensive, discriminating and attainable. They should apply to small and large establishments with varying hazards. A successful program requires a multi-disciplinary effort involving physicians, nurses, industrial hygienists, health physicists, safety professionals, managers, technicians and labor. Assessment by on-site peer review is necessary. The criteria and process for their use must be accepted by the professions, labor and management. The Occupational Health/Safety Programs Accreditation Commission plans to use the document entitled Standards, Interpretations and Audit Criteria for Performance of Occupational Health Programs in its accreditation activities. The development and validation of this document and its use are described.
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