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S L Cohen

Publications and source records attributed to S L Cohen.

At least 37 records · Page 2Linked to original sources
PubMed1996

Structural similarity between TAFs and the heterotetrameric core of the histone octamer.

A complex of two TFIID TATA box-binding protein-associated factors (TA FIIs) is described at 2.0A resolution. The amino-terminal portions of dTAFII42 and dTAFII62 from Drosophila adopt the canonical histone fold, consisting of two short alpha-helices flanking a long central alpha-helix. Like histones H3 and H4, dTAFII42 and dTAFII62 form an intimate heterodimer by extensive hydrophobic contacts between the paired molecules. In solution and in the crystalline state, the dTAFII42/dTAFII62 complex exists as a heterotetramer, resembling the (H3/H4)2 heterotetrameric core of the histone octamer, suggesting that TFIID contains a histone octamer-like substructure.

Amino Acid Sequence↗
PubMed1996

Influence of matrix solution conditions on the MALDI-MS analysis of peptides and proteins.

Sample-matrix preparation procedures are shown to greatly influence the quality of the matrix-assisted laser desorption/ionization (MALDI) mass spectra of peptides and proteins. In particular, dramatic mass discrimination effects are observed when the matrix 4-hydroxy-alpha-cyanocinnamic acid is used for analyzing complex mixtures of peptides and proteins. The discrimination effects are found to be strongly dependent on the sample-matrix solution composition, pH, and the rates at which the sample-matrix cocrystals are grown. These findings demonstrate the need to exercise great care in performing and interpreting the MALDI analysis of biological samples. The results also indicate that there is a reverse-phase chromatographic-like dimension in the sample-matrix preparation procedures that can be exploited to optimize the analysis. The present work describes the conditions under which the majority of components of a complex mixture of peptides and proteins can be successfully measured.

Amino Acid Sequence↗
PubMed1995

Weight-reducing effects of the plasma protein encoded by the obese gene.

The gene product of the ob locus is important in the regulation of body weight. The ob product was shown to be present as a 16-kilodalton protein in mouse and human plasma but was undetectable in plasma from C57BL/6J ob/ob mice. Plasma levels of this protein were increased in diabetic (db) mice, a mutant thought to be resistant to the effects of ob. Daily intraperitoneal injections of either mouse or human recombinant OB protein reduced the body weight of ob/ob mice by 30 percent after 2 weeks of treatment with no apparent toxicity but had no effect on db/db mice. The protein reduced food intake and increased energy expenditure in ob/ob mice. Injections of wild-type mice twice daily with the mouse protein resulted in a sustained 12 percent weight loss, decreased food intake, and a reduction of body fat from 12.2 to 0.7 percent. These data suggest that the OB protein serves an endocrine function to regulate body fat stores.

Adipose Tissue↗
PubMed1995

Probing the solution structure of the DNA-binding protein Max by a combination of proteolysis and mass spectrometry.

A simple biochemical method that combines enzymatic proteolysis and matrix-assisted laser desorption ionization mass spectrometry was developed to probe the solution structure of DNA-binding proteins. The method is based on inferring structural information from determinations of protection against enzymatic proteolysis, as governed by solvent accessibility and protein flexibility. This approach was applied to the study of the transcription factor Max--a member of the basic/helix-loop-helix/zipper family of DNA-binding proteins. In the absence of DNA and at low ionic strengths, Max is rapidly digested by each of six endoproteases selected for the study, results consistent with an open and flexible structure of the protein. At physiological salt levels, the rates of digestion are moderately slowed; this and the patterns of cleavage are consistent with homodimerization of the protein through a predominantly hydrophobic interface. In the presence of Max-specific DNA, the protein becomes dramatically protected against proteolysis, exhibiting up to a 100-fold reduction in cleavage rates. Over a 2-day period, both complete and partial proteolysis of the Max-DNA complex is observed. The partial proteolytic fragmentation patterns reflect a very high degree of protection in the N-terminal and helix-loop-helix regions of the protein, correlating with those expected of a stable dimer bound to DNA at its basic N-terminals. Less protection is seen at the C-terminal where a slow, sequential proteolytic cleavage occurs, correlating to the presence of a leucine zipper. The results also indicate a high affinity of Max for its target DNA that remains high even when the leucine zipper is proteolytically removed. In addition to the study of the helix-loop-helix protein Max, the present method appears well suited for a range of other structural biological applications.

Amino Acid Sequence↗
PubMed1995

Kidney and urinary tract disease in ancient Babylonia, with translations of the cuneiform sources.

The large corpus of Babylonian medical texts is much less known to medical history than the contemporary medical papyri from Egypt, but offer a rich new source of information regarding ancient diagnosis and treatment of disease. The Babylonian physicians systematically noted systems related to kidney and urinary tract diseases. Pharmacological prescriptions tended to consist of plant and mineral substances administered either orally in drinks, or were inserted directly into the urethra through a tube.

History, Ancient↗
PubMed1995

Varicella gangrenosa with toxic shock-like syndrome due to group A streptococcus infection in an adult: case report.

Varicella gangrenosa is a rare and serious complication of chickenpox that has been described in children only. We describe a case of an adult with varicella gangrenosa that presented as necrotizing fasciitis of a limb. This infection is caused by group A streptococcal superinfection of the skin lesions due to chickenpox. It can be misdiagnosed, with fatal consequences. Because of prompt recognition and aggressive surgical and medical treatment, the patient survived without loss of the affected limb.

Adult↗
PubMed1994

Heparin clearance during continuous veno-venous haemofiltration.

OBJECTIVE: To determine whether premature clotting of haemofiltration circuits could be related to heparin removal across the filter membrane into the ultrafiltrate. DESIGN: Randomised study using either unfractionated (n = 8) or low molecular weight (n = 7) heparin for anticoagulation of the haemofiltration circuit at 1000 and 600 U/h respectively. Samples were drawn at 1 and 2 h from arterial and venous limbs of the haemofilter circuit for measurement of plasma heparin (as anti-Factor Xa activity), antithrombin III and haematocrit. Ultrafiltrate samples were collected at the same time for measurement of anti-Xa activity. SETTING: Intensive care unit. PATIENTS: Patients in acute renal failure requiring haemofiltration. RESULTS: Both unfractionated and low molecular weight heparin plasma levels were within the range required for therapeutic anticoagulation in all but one patient at 2 h. Ultrafiltrate anti-Xa levels were insignificant. Antithrombin III levels in these critically ill patients were subnormal in 11 of the 15 studies. CONCLUSIONS: Despite their small sizes, neither unfractionated nor low molecular weight heparins cross the haemofilter membrane into the ultrafiltrate in any measurable quantity. Both heparins were present in plasma at a level suitable for therapeutic anticoagulation. Subnormal levels of antithrombin III may be an important factor in determining filter longevity.

Acute Kidney Injury↗
PubMed1994

The cost of intensive care: a comparison on one unit between 1988 and 1991.

OBJECTIVE: To assess the changes in cost of intensive care in one unit after a 3 year period and to evaluate the relative costs of an integrated high dependency unit. DESIGN: Combined retrospective and prospective audit of all expenditure incurred in an intensive care/high dependency unit over two periods: April 1988-February 1989 and January-July 1991. SETTING: Combined 13-bedded intensive care/high dependency unit of a central London teaching hospital. RESULTS: The overall cost rose by 50%. Hidden costs such as infrastructure maintenance, capital assets, pathology and radiology services accounted for nearly a quarter of total expenditure. Pharmacy and supplies each accounted for some 10% of total expenditure whereas staff costs exceeded 50%. The cost of the intensive care section rose by 14% of 1149 pounds per patient day as increased bed occupancy offset increases in nurse: patient ratios and expenditure on consumables. However, the cost of the high dependency unit section rose by 87% to 437.83 pounds. This was due to a lower bed occupancy (through increased patient turnover), improved staffing ratios, and increased utilisation of equipment and supplies. CONCLUSIONS: Intensive care is an increasingly expensive speciality, the costs for which are rising over and above the rate of general inflation. Staff costs are by far the largest single item of expenditure. Large reductions in spending on drugs and consumables are unlikely to provide considerable savings on the total budget. Hidden costs account for a high proportion of the budget and should be taken into account when evaluating cost. The significantly lower cost of high dependency care should encourage studies into its cost-effectiveness.

Health Services Research↗
PubMed1994

Cardiac prognosis of patients with carotid stenosis and no history of coronary artery disease. Veterans Affairs Cooperative Study Group 167.

BACKGROUND AND PURPOSE: Patients with carotid stenosis have a high frequency of asymptomatic coronary artery disease (CAD). The purpose of this study of patients with asymptomatic carotid stenosis was to test the hypothesis that patients without a history of CAD have the same cardiac prognosis as patients with a history of CAD. METHODS: Men enrolled in the Department of Veterans Affairs study on the efficacy of carotid endarterectomy for asymptomatic carotid stenosis underwent a baseline cardiac evaluation (history, physical examination, and electrocardiogram) to document previous angina or myocardial infarction. Patients were randomized to medical therapy alone or medical therapy and carotid endarterectomy. Medical therapy consisted of aspirin 650 mg twice daily and treatment of risk factors. All episodes of angina, myocardial infarction, or sudden death during follow-up (average of 47.9 months) were recorded. RESULTS: Of 444 men enrolled in the study, 200 (45%) had a history of CAD. During the study 86 (43%) of 200 patients with CAD and 81 (33%) of 244 patients without a history of CAD had cardiac ischemic events (P = .03). In patients without a history of CAD, the first cardiac event was myocardial infarction or sudden death in 45 patients (56%). Factors that were independently associated with cardiac events in patients without a history of CAD were diabetes (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.15 to 3.97), intracranial occlusive disease (OR, 2.13; 95% CI, 1.13 to 4.02), and peripheral vascular disease (OR, 2.04; 95% CI, 1.14 to 3.66). Forty-two percent of patients with two of these factors and 69% of patients with all three factors had cardiac events. CONCLUSIONS: Men with carotid stenosis and no history of CAD have a lower rate of cardiac events than men with carotid stenosis who have a history of CAD. However, a subgroup of patients with carotid stenosis and no history of CAD who have coexistent intracranial occlusive disease, diabetes, or peripheral vascular disease have a risk of cardiac events similar to that of patients with a history of CAD.

Aged↗
PubMed1994

Effects of reinforcement history on responding under progressive-ratio schedules of reinforcement.

The effects of experimental history on responding under a progressive-ratio schedule of reinforcement were examined. Sixteen pigeons were divided into four equal groups. Groups 1 to 3 were trained to peck a key for food under a fixed-ratio, variable-ratio, or differential-reinforcement-of-low-rate schedule of reinforcement. After training, these pigeons were shifted to a progressive-ratio schedule, later were shifted back to their original schedule (with decreased rates of reinforcement), and finally were returned to the progressive-ratio schedule. Pigeons in Group 4 (control) were maintained on the progressive-ratio schedule for the entire experiment. To test for potential "latent history" effects, pigeons responding under the progressive-ratio schedule were injected with d-amphetamine and given behavioral-momentum tests of prefeeding and extinction. Experimental histories affected responding in the immediate transition to the progressive-ratio schedule; response rates of pigeons with variable-ratio and fixed-ratio histories were higher than rates of pigeons with differential-reinforcement-of-low-rate and progressive-ratio-only histories. Pigeons with differential-reinforcement-of-low-rate histories, and to a lesser degree pigeons with variable-ratio and fixed-ratio histories, also had shorter postreinforcement pauses than pigeons with only a progressive-ratio history. No consistent long-term effects of prior contingencies on responding under the progressive-ratio schedule were evident. d-Amphetamine and resistance-to-change tests failed to reveal consistent latent history effects. The data suggest that history effects are sometimes transitory and not susceptible to latent influences.

Animals↗
PubMed1993

Heat-induced conformational changes in proteins studied by electrospray ionization mass spectrometry.

A simple and effective device for investigating heat-induced denaturation of proteins by electrospray ionization mass spectrometry is described. Results are presented for the denaturation as a function of temperature and solution pH of bovine ubiquitin and bovine cytochrome c. These results are in concert with and extend the earlier results of LeBlanc et al. (Org. Mass Spectrom. 1991, 26, 831). The cooperative effects of pH and temperature on the denaturation of ubiquitin and cytochrome c were investigated. Electrospray ionization mass spectrometry is also shown to be a useful probe of the reversibility of heat-induced denaturation of proteins. Finally, it is demonstrated that heat-induced denaturation can be used to improve the mass spectrometric response of proteins that do not normally yield useful spectra when the solubilized protein is electrosprayed at ambient temperatures.

Animals↗
PubMed1993

Tests of behavior momentum in simple and multiple schedules with rats and pigeons.

Four experiments examined the relationship between rate of reinforcement and resistance to change in rats' and pigeons' responses under simple and multiple schedules of reinforcement. In Experiment 1, 28 rats responded under either simple fixed-ratio, variable-ratio, fixed-interval, or variable-interval schedules; in Experiment 2, 3 pigeons responded under simple fixed-ratio schedules. Under each schedule, rate of reinforcement varied across four successive conditions. In Experiment 3, 14 rats responded under either a multiple fixed-ratio schedule or a multiple fixed-interval schedule, each with two components that differed in rate of reinforcement. In Experiment 4, 7 pigeons responded under either a multiple fixed-ratio or a multiple fixed-interval schedule, each with three components that also differed in rate of reinforcement. Under each condition of each experiment, resistance to change was studied by measuring schedule-controlled performance under conditions with prefeeding, response-independent food during the schedule or during timeouts that separated components of the multiple schedules, and by measuring behavior under extinction. There were no consistent differences between rats and pigeons. There was no direct relationship between rates of reinforcement and resistance to change when rates of reinforcement varied across successive conditions in the simple schedules. By comparison, in the multiple schedules there was a direct relationship between rates of reinforcement and resistance to change during most tests of resistance to change. The major exception was delivering response-independent food during the schedule; this disrupted responding, but there was no direct relationship between rates of reinforcement and resistance to change in simple- or multiple-schedule contexts. The data suggest that rate of reinforcement determines resistance to change in multiple schedules, but that this relationship does not hold under simple schedules.

Animals↗
PubMed1992

Urinary excretion of beta 2-glycoprotein-1 (apolipoprotein H) and other markers of tubular malfunction in "non-tubular" renal disease.

AIM: To determine whether urinary beta 2-glycoprotein-1 assays can provide improved discrimination between chronic renal diseases which are primarily of tubular or glomerular origin. METHODS: Urinary beta 2-glycoprotein-1, retinol-binding protein, alpha 1-microglobulin, beta 2-microglobulin, N-acetyl-beta-D-glucosa-minidase and albumin were measured in 51 patients with primary glomerular disease, 23 with obstructive nephropathy, and 15 with polycystic kidney disease, and expressed per mmol of creatinine. Plasma beta 2-glycoprotein-1 was assayed in 52 patients and plasma creatinine in all 89. The findings were compared between the diagnostic groups and with previously published data relating to primary tubular disorders. RESULTS: All 31 patients with plasma creatinine greater than 200 mumol/l excreted increased amounts of beta 2-glycoprotein-1, retinol-binding protein, and alpha 1-microglobulin, and 29 had increased N-acetyl-beta-D-glucosaminidase; the quantities were generally similar to those found in comparable patients with primary tubular pathology. Among 58 with plasma creatinine concentrations under 200 mumol/l, increases in beta 2-glycoprotein-1, retinol-binding protein, and alpha 1-microglobulin excretion were less common and much smaller, especially in those with obstructive nephropathy and polycystic disease. The ratios of the excretion of albumin to the other proteins provided the clearest discrimination between the patients with glomerular or tubular malfunction, but an area of overlap was present which embraced those with obstructive nephropathy and polycystic disease. CONCLUSIONS: Increased excretion of beta 2-glycoprotein-1 due to a raised plasma concentration or diminution of tubular reabsorption, or both, is common in all the forms of renal disease investigated, and both plasma creatinine and urinary albumin must be taken into account when interpreting results. Ratios of urinary albumin: beta 2-glycoprotein-1 greater than 1000 are highly suggestive of primary glomerular disease and those less than 40 of primary tubular disease. Used in this way, beta 2-glycoprotein-1 assays provide superior discrimination between glomerular and tubular malfunction when compared with retinol binding protein but the best discrimination is provided by albumin: alpha 1-microglobulin ratios.

Acetylglucosaminidase↗
PubMed1991

Septal lesions lower responding under fixed-ratio schedules of reinforcement.

Albino Sprague-Dawley rats with complete septal lesions and rats with control operations were studied under fixed-ratio (FR) schedules of reinforcement. Both groups were trained for 10 sessions each under FR 10, 20, 40, 60, 80, and 100. In contrast to findings from progressive FR studies and some simple FR studies, septal lesions resulted in lower overall and local response rates along with longer postreinforcement pauses. These effects were especially evident during the FR 100 schedule of reinforcement. A comparison of reinforcement rate as a function of FR size within the context of behavioral economics (i.e., a demand function) indicated that septal lesions did not alter the reward value of food. These findings suggest that responding on FR schedules of reinforcement can be altered by the various procedures used to train rats to reach the terminal value of a reinforcement schedule.

Analysis of Variance↗