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Biomedical subjects

S Cohen

Publications and source records attributed to S Cohen.

At least 289 records · Page 16Linked to original sources
PubMed1995

Insight into blood-pressure control in SHR via the response to acute hemorrhage: a spectral analysis approach.

In this study we investigated, by means of the spectral analysis approach, the possible alterations in the activity of the pressor-control mechanisms in relation to the development of essential hypertension. Since the maintenance of controlled arterial blood pressure (ABP) levels is achieved by a continuously fluctuating control system, instantaneous ABP varies continuously in direct correlation with the activation of various control branches. The power spectrum of ABP fluctuations thus provides a quantitative measure of the activity of the various controlling mechanisms. Two strains of rats, Spontaneously Hypertensive Rats (SHR) and Wistar-Kyoto normotensive rats (WKY), were subjected to acute hemorrhage, a procedure known to trigger a strong response, of both the neural (autonomic nervous system) and the hormonal (renin-angiotensin and vasopressin) systems. ABP was continuously recorded from the caudal artery in conscious, 1-month-old SHR and WKY. Three groups of rats were studied. Group 1, acute 2-ml hemorrhage; Groups 2, injection of prazosin (2.5 mg/kg) or Group 3, captopril (4 mg/kg), each followed by bleeding as in the group 1. Spectral analysis of ABP fluctuations was performed on time traces of 20 min duration. The low-frequency part of the power spectrum was analyzed. Three frequency bands were investigated: 0.004-0.04 Hz, 0.04-0.07 Hz and 0.07-0.1 Hz. In SHR, although the baseline mean ABP levels were similar to those of WKY, ABP fluctuations were significantly dampened in SHR in each of the three frequency ranges. Hemorrhage induced, in both strains, a similar fall in mean ABP accompanied by an increase in the slow ABP fluctuations. However, in SHR, the response was significantly greater that that of WKY. The steepest response was observed in the slowest, 0.004-0.04 Hz frequency band, 8.7 +/- 1.7 vs. 1.5 +/- 0.4 times the baseline levels. However, this intense increase in power after hemorrhage brought the two strains to similar levels. The difference in the response to bleeding was eliminated, in the three frequency ranges, by alpha 1 blockade. Captopril reduced the response to bleeding in SHR, to the level observed in WKY in all three frequency bands. Spectral analysis of the spontaneous oscillations in ABP unmasks abnormalities which conventional blood pressure measurements cannot detect in 1-month-old, still normotensive SHR. It thus, provides a tool to study the dynamics of the abnormalities which precede the development of hypertension. Bleeding amplifies the malfunction observed in SHR under baseline conditions, since the mean ABP levels were similar in both strains before and after bleeding, SHR seem to retain the ability to respond to a fall in blood volume by requiring a greater recruitment of the control mechanisms than WKY.

Acute Disease↗
PubMed1995

Phosphorylation and activation of the DNA binding activity of purified Stat1 by the Janus protein-tyrosine kinases and the epidermal growth factor receptor.

The activation of Janus protein-tyrosine kinases (Jaks) and the subsequent phosphorylation and activation of latent signal transducers and activators of transcription (Stats) are common elements in signal transduction through the cytokine receptor superfamily. To assess the role and specificity of Jaks in Stat activation, we have utilized baculovirus expression systems to produce Stat1 and the Jaks. Co-expression of Stat1 with Tyk2, Jak1, or Jak2 resulted in the specific tyrosine phosphorylation of Stat1 at Tyr701, the residue phosphorylated in mammalian cells stimulated with interferon gamma. Alternatively, Stat1, purified to apparent homogeneity from insect cell extracts, was phosphorylated at Tyr701 in Jak immune complex kinase reactions. Phosphorylation of purified Stat1 was necessary and sufficient for the acquisition of DNA binding activity. The specificity in both systems was indicated by the inability of a Jak2 catalytically inactive mutant (Jak2-Glu882) or the Tec protein-tyrosine kinase to phosphorylate Stat1. However, immune complex-purified epidermal growth factor receptor was capable of phosphorylating purified Stat1 at Tyr701 and activating its DNA binding activity in in vitro reactions.

Amino Acid Sequence↗
PubMed1995

Time to relax research use of patents.

The conditions under which research is exempt from European patent law are ambiguous, and current judicial interpretation is too restrictive. A liberal approach would be a welcome boost to small research-based companies.

Europe↗
PubMed1995

The rationale for continuous maintenance treatment of reflux esophagitis.

Reflux esophagitis is a chronic process associated with frequent episodes of relapse in many patients. In addition, the disease may be progressive in at least some patients. Erosion of the esophageal mucosa precedes the development of some of the complications of the condition. There is accumulating evidence that continuous treatment of patients with erosive esophagitis effectively maintains symptomatic remission and absence of esophageal erosions. Whether such treatment will prevent the development of complications has not yet been demonstrated. We investigated a number of questions concerning the natural history and complications of erosive esophagitis and the need for maintenance treatment for patients with severe manifestations of disease as well as the impact of continuous maintenance treatment on the natural history of reflux esophagitis and its complications.

Chronic Disease↗
PubMed1995

Zinc-directed inhibitors for zinc proteinases.

Zinc proteinases have been recognized as a distinct class of proteolytic enzymes in which at least one ion of zinc is involved directly in catalysis. This family includes a growing number of biologically important enzymes which are attractive targets for rational drug design. In this paper we examine the special features of the zinc binding environment of these enzymes in order to gain information which could be useful in the preparation of 'zinc-directed' selective inhibitors. Carboxypeptidase A (CPA) is presented as a model for one class of zinc proteinases, and the active-site zinc and its interactions are examined with the primary focus on geometrical considerations. The three-dimensional structure of the native and apoenzyme are discussed, together with the high-resolution structure of several enzyme-inhibitor complexes. This paper will first present a structural analysis of CPA derivatives and then discuss a series of zinc model compounds which have been prepared and characterized in order to examine the ligand and geometrical preferences of the zinc in an unstrained system. X-ray crystallography (macromolecular and small molecule) is the main experimental method used for the structural analyses, while complementary computational methods have been used for the examination of electrostatic potentials. The results from the various experimental efforts are assembled in order to draw general conclusions on the potential use of the zinc ion as the primary target for inhibitor binding. The results of these studies suggest that the zinc ion is important for both the binding and the catalytic activation of the substrate as well as for stabilization of the tetrahedral reaction intermediate.

Journal Article↗
PubMed1995

Epidermal growth factor induces the tyrosine phosphorylation and nuclear translocation of Stat 5 in mouse liver.

Intraperitoneal injection of epidermal growth factor into mice results in the appearance of multiple tyrosine-phosphorylated proteins in liver nuclei within minutes after administration. We have previously identified three of these proteins as Stat 1 alpha, Stat 1 beta (p91, p84), and Stat 3 (p89). In the present report we demonstrate that Stat 5 (p92), the recently described prolactin inducible transcription factor detected in mammary glands, is the major tyrosine-phosphorylated protein translocated to the nucleus in mouse liver in response to epidermal growth factor. Furthermore, gel-shift analysis and affinity purification revealed that Stat 5, Stat 1 alpha, and Stat 1 beta specifically bind to the prolactin inducible element upstream of the beta-casein promoter.

Animals↗
PubMed1995

Modulation of topoisomerase activities by tumor necrosis factor.

A number of chemotherapeutic agents which inhibit the DNA topoisomerases markedly potentiate cell death mediated by tumor necrosis factor, suggesting a role for these enzymes in the TNF cytotoxic mechanism. To investigate this possibility, topoisomerase I and II activities were assayed following TNF addition to murine L929 cells. Topoisomerase I and II activities increased within 15 min of TNF addition and returned to baseline levels within 1 and 2 hr, respectively. The increases in both topoisomerase activities were blocked by H-7 (but not H-8) and similar increases were seen following PMA addition. However, concentrations of H-7 which blocked the increased topoisomerase activities had no effect on TNF cytotoxicity nor on the enhancement of TNF cytotoxicity by topoisomerase inhibitors. Thus, in these cells topoisomerase activities are directly modified by TNF during the initial phases of a cytotoxic response. However, neither TNF cytotoxicity nor the enhancement of TNF cytotoxicity by topoisomerase inhibitors appears to require the TNF-mediated increases in topoisomerase activities.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1995

Displaying electrocorticographic findings on gyral anatomy.

Human electrocorticographic findings recorded from subdural arrays of electrodes were topographically mapped directly onto magnetic resonance images of gyral anatomy. With this technique gyri involved in generating somatosensory evoked potentials and epileptic phenomena are easily identified. Regions of the cortex which exhibit local spectral changes associated with cognitive tasks can also be visualized. These composite images of structure and function can provide insight regarding the functional organization of human cortex in relation to gyral anatomy and localized pathologic rhythms.

Brain Mapping↗
PubMed1995

Beta 2-adrenergic receptor density and cardiovascular response to mental stress.

In this study we evaluated effects of an acute experimental stressor on beta 2-adrenoceptor density and examined the relationships of baseline receptor density to cardiovascular reactions induced by stress. In addition, we investigated whether any observed alterations in receptor density were associated with concomitant redistribution of circulating lymphocyte populations. Receptor density and lymphocyte subsets were determined before and immediately following performance of a frustrating laboratory task in 22 male volunteers. Blood pressure, heart rate (HR), and plasma catecholamine concentrations were also assessed at baseline and during task performance. Parallel measurements were obtained among 11 unstressed control subjects. Receptor density increased significantly between baseline and posttask measurements, but equally so in experimental and control subjects. Numbers of T suppressor/cytotoxic and natural killer cells increased selectively among subjects assigned to the experimental (stress) condition. However, there was no association between lymphocyte subset distribution and receptor density. Interindividual variability in pretask receptor density correlated significantly with heart rate and systolic blood pressure (SBP) reactivity during the initial 3 min of mental stress, but not over the entire task period. In addition, baseline receptor density correlated with SBP (but not HR) reactivity after covariance adjustment for the concomitant change in plasma catecholamine concentrations.

Adolescent↗
PubMed1995

[Caloric and nitrogen intake during pre- and post-operative periods. method and duration].

Preoperative nutritional support is analysed from 7 prospective studies. Clinical benefits from nutrient intake and duration are not demonstrable. In one study, preoperative long-chain triglycerides infusions are associated with more postoperative complications. Postoperative nutrition is analysed from 20 articles. No one considers the clinical benefit with regard to quantitative and qualitative intakes.

Amino Acids↗
PubMed1995

In vitro evaluation of polymerized liposomes as an oral drug delivery system.

The physical characteristics of polymerized liposomes for potential use as an oral drug delivery system were examined in vitro. The trap efficiency in monomeric liposomes composed of 1,2-di (2,4-octadecadienoyl) phosphatidylcholine was increased from 3% for original multilamellar vesicles to 35% for freeze-thaw treated liposomes. Polymerized liposomes with azobis (isobutyronitrile) and azobis (2-amidinopropane) hydrochloride as radical initiators showed complete stability against solubilization by Triton X-100, a detergent chosen to mimic bile salts. Release rates of 14C-BSA and 14C-sucrose in media simulating the gastro-intestinal fluids was 50% less than from regular liposomes composed of hydrogenated egg phosphatidylcholine mixed with cholesterol (molar ratio 1:1), which can be regarded as one of the most stable types of regular liposomes. It was estimated that, when administered orally, polymerized liposomes can reach the intestine while maintaining their vesicle structure and keeping at least 75% of their original content.

Administration, Oral↗
PubMed1995

State and trait negative affect as predictors of objective and subjective symptoms of respiratory viral infections.

State and trait negative affect (NA) were measured in healthy people immediately before an illness was induced through exposure to a respiratory virus. State NA, disease-specific health complaints (e.g., runny nose, congestion, and sneezing), and an associated objective marker of disease severity (mucus secretion weights) were assessed daily during the illness. Baseline trait and state NA were both associated with increased numbers of subsequent complaints. Although greater numbers of complaints among people high in state NA were explicable in terms of greater disease severity, the association of trait NA and symptoms was independent of objective disease. The trait NA complaint association was also independent of state NA and hence not attributable to trait-elicited state affect. Greater trait NA was associated with biases in complaining during but not before illness. This suggested failure to discriminate between symptoms rather than increased sensitivity or hypochondriacal response.

Adolescent↗
PubMed1995

Concordance in the face of a stressful event: when do members of a dyad agree that one person supported the other?

Students reported behaviors they expected from a primary support persons in response to an upcoming exam. After the exam, students and support persons independently reported behaviors the supporter provided. There was only moderate agreement within dyads about the occurrence of supportive behaviors (kappa = .39). Dyad intimacy, fulfilled expectancies, student and supporter social competence, and commal orientation all were associated with greater concordance. There was also greater agreement on behaviors rated by judges as helpful than harmful and in dyads that included a woman than in man-man dyads. Greater dyad intimacy and more fulfilled expectancies accounted for why there was greater concordance in dyads that included a women, and more fulfilled expectancies accounted for why there was greater concordance on positive than negative behaviors.

Adolescent↗
PubMed1995

Pathways linking affective disturbances and physical disorders.

Comorbidity of psychological and physical disorders is substantial. This article presents a broad theoretical framework for identifying factors that contribute to and maintain comorbid conditions. The authors propose heuristic models of how co-occurrences of psychological and physical disorders are developed and maintained. The models specify biological, behavioral, cognitive, and social pathways that may account for comorbidity. Although the authors' discussion of psychological disorders is limited to the role of affective disturbances (subclinical negative moods as well as mood and affective disorders), the pathways they identify are thought to contribute to co-occurrences of other psychological disorders and physical disease as well. The authors emphasize that pathways linking comorbid states are bi-directional and that operative pathways differ depending on the specific affective response, illness behavior, disease, or disease stage.

Combined Modality Therapy↗
PubMed1995

The koro (genital retraction) syndrome and its association with infertility: a case report.

The koro syndrome is a psychiatric disorder characterized by acute anxiety and a deep-seated fear of shrinkage of the penis and its ultimate retraction into the abdomen, which will cause death. Concurrence of the koro (genital retraction) syndrome with a pathological condition of the urogenital system has rarely been described. We report a case of koro associated with infertility. Within 3 weeks of treatment with haloperidol the classic symptoms of koro disappeared. To our knowledge this case represents the sixth report of the koro syndrome associated with urogenital pathology and the first report of its association with infertility.

Adult↗