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Biomedical subjects

H Cohen

Publications and source records attributed to H Cohen.

At least 91 records · Page 5Linked to original sources
PubMed2000

The reaction mechanism of nitrosothiols with copper(I).

Copper and other transition metal ions and their complexes are catalysts for the decomposition of nitrosothiols. In this way they catalyze the biological functions of nitrosothiols. The kinetics and mechanism of the reaction of two nitrosothiols, S-nitrosothiolactic acid and S-nitrosoglutathione (GSNO), with copper(I) are reported. The kinetics of the reaction of Cu(MeCN)+(n) (n=0-3) with the nitrosothiols were studied. The results indicate that Cu+(aq) is the active species in the GSNO system, with k(Cu+(aq)+GSNO)=(9.4 +/- 2.0) x 10(7) dm3 mol(-1) s(-1). The results also indicate that the Cu(MeCN)+(n) (n=0-3) complexes react with S-nitrosothiolactic acid. Transient species are formed in these processes. The results suggest that these species contain copper(I) and thiol. The results shed light on the catalytic role of copper complexes in the decomposition of S-nitrosothiols.

Copper↗
PubMed2000

Pregnancy outcome is not affected by antiphospholipid antibody status in women referred for in vitro fertilization.

OBJECTIVE: To determine the prevalence of antiphospholipid (aPL) and anti-beta 2 glycoprotein I (anti-beta2-GPI) antibodies in women referred for IVF and to prospectively evaluate the effect of these antibodies on IVF outcome. DESIGN: Prospective observational study. SETTING: A university hospital and IVF unit. PATIENT(S): Three hundred eighty consecutive women referred for IVF. INTERVENTION(S): Blood samples taken before commencement of IVF cycles were tested for the presence of aPL (lupus anticoagulant [LA], anticardiolipin [aCL], and antiphosphatidyl serine antibodies [aPS]) and anti-beta2-GPI antibodies. MAIN OUTCOME MEASURE(S): Antibody prevalence, pregnancy rates, and live birth rates. RESULT(S): Of the total 380 women, 89 tested persistently positive for aPL (23.4%). None of 176 women tested for IgG aPS antibodies had a positive titer. Only 3.3% (11 of 329) tested positive for anti-beta2-GPI antibodies. Pregnancy rate, live birth rate, gestational age at delivery, and birth weight were not affected by aPL status. CONCLUSION(S): Although women referred for IVF have a high prevalence of aPL, these antibodies do not affect the outcome of treatment. Screening women undergoing IVF for aPL is not justified.

Adult↗
PubMed2000

Autonomic dysfunction in patients with fibromyalgia: application of power spectral analysis of heart rate variability.

OBJECTIVES: To assess the interaction between the sympathetic and parasympathetic systems in patients with fibromyalgia syndrome (FM), using power spectrum analysis (PSA) of heart rate variability (HRV). In addition, we explored the association between HRV, measures of tenderness, FM symptoms, physical function, psychological well being and quality of life. METHODS: We studied 22 women with FM and 22 age-matched healthy women. Twenty-minute electrocardiogram recordings were obtained in a supine position during complete rest. Spectral analysis of R-R intervals was done by the fast-Fourier transform algorithm. RESULTS: Heart rate was significantly higher in FM patients compared with controls (P < .006). FM patients had significantly lower HRV compared with controls (P= .001), and higher low-frequency (LF) and lower high-frequency (HF) components of PSA than controls (P < .001). Quality of life, physical function, anxiety, depression, and perceived stress were moderately to highly correlated with LF, HF (in normalized units), and LF/HF. No association was observed between HRV parameters and measures of tenderness and FM symptoms. CONCLUSIONS: The basal autonomic state of patients with FM is characterized by increased sympathetic and decreased parasympathetic tones. Autonomic dysregulation may have implications regarding the symptomatology, physical and psychological aspects of health status.

Algorithms↗
PubMed2000

Structural analysis of two HLA-DR-presented autoantigenic epitopes: crucial role of peripheral but not central peptide residues for T-cell receptor recognition.

Specific and major histocompatibility complex (MHC)-restricted T-cell recognition of antigenic peptides is based on interactions of the T-cell receptor (TCR) with the MHC alpha helices and solvent exposed peptide residues termed TCR contacts. In the case of MHC class II-presented peptides, the latter are located in the positions p2/3, p5 and p7/8 between MHC anchor residues. For numerous epitopes, peptide substitution studies have identified the central residue p5 as primary TCR contact characterized by very low permissiveness for peptide substitution, while the more peripheral positions generally represent auxiliary TCR contacts. In structural studies of TCR/peptide/MHC complexes, this has been shown to be due to intimate contact between the TCR complementarity determining region (CDR) three loops and the central peptide residue. We asked whether this model also applied to two HLA-DR presented epitopes derived from an antigen targeted in type 1 diabetes. Large panels of epitope variants with mainly conservative single substitutions were tested for human leukocyte antigen (HLA) class II binding affinity and T cell stimulation. Both epitopes bind with high affinity to the presenting HLA-DR molecules. However, in striking contrast to the standard distribution of TCR contacts, recognition of the central p5 residue displayed high permissiveness even for non-conservative substitutions, while the more peripheral p2 and p8 TCR contacts showed very low permissiveness for substitution. This suggests that intimate TCR interaction with the central peptide residue is not always required for specific antigen recognition and can be compensated by interactions with positions normally acting as auxiliary contacts.

Antigen Presentation↗
PubMed2000

Peptic ulcer and Helicobacter pylori.

Although there has been an explosion of data not only since the discovery of H. pylori in 1982, but also since the first comprehensive review of H. pylori in the Gastroenterology Clinics in 1993, much remains to be learned. In 1993, there were many skeptics doubting the importance of H. pylori in ulcer disease. Although this skepticism has dissipated, many ulcer patients infected with H. pylori still do not receive appropriate therapy. This situation possibly relates to the safety, efficacy, and simplicity of prescribing acid-suppressive therapy in contrast to the confusion regarding anti-H. pylori treatment regimens. Among the many continuing unanswered questions regarding the role of H. pylori and PUD are the still enigmatic nature of host, environmental, and H. pylori-related factors that determine outcome. Why do only some infected individuals (and why do more men than women) develop PUD, and what determines whether gastric ulcers or duodenal ulcers develop? What is the explanation for the seasonal variation in ulcer disease? Although PUD is an infectious disease, are other environmental factors critical for the manifestation of ulcers in association with infection? What factors govern the outcome of the combination of H. pylori infection and NSAID use? Has attention been too focused first on the pathophysiology of acid secretion and now on H. pylori? In curing H. pylori in association with PUD, are clinicians going to displace disease northward, substituting erosions, inflammation, and neoplasia (and associated symptoms) in the esophagus and gastroesophageal junction for an ulcer crater (and its associated symptoms) in the duodenum or stomach? The epidemiology of PUD is changing--in more recent reports of ulcer patients, H. pylori and NSAID use are less prevalent than in earlier reports. These questions and comments should not be misinterpreted as advocating a lack of aggressiveness in diagnosis and treatment of H. pylori in the setting of PUD, however. Nevertheless, the pendulum is swinging.

Anti-Ulcer Agents↗
PubMed2000

Plasma renin activity in the emergency department and its independent association with acute myocardial infarction.

Elevated plasma renin activity (PRA) is associated with increased risk of future myocardial infarction (MI) in ambulatory hypertensive patients. The present study evaluated the relationship of PRA to the diagnosis of acute MI in patients presenting to an emergency department with suspected acute MI. PRA was measured upon entry to the emergency department, before any acute treatment, as part of the standard evaluation of 349 consecutive patients who were hospitalized for suspected MI. Diagnosis of acute MI was confirmed in 73 patients, and ruled out in 276. They did not differ in age (65.9 +/- 2 v 66.1 +/- 1 years), systolic (143 +/- 4 v 140 +/- 2 mm Hg), or diastolic (81 +/- 2 v 81 +/- 1 mm Hg) pressures. Median PRA was 2.7-fold higher in acute MI (0.89 v 0.33 ng/L/s; P < .001). In a multivariate analysis controlling for other cardiac risk factors and prior drug therapy, PRA as a continuous variable was the predominant independent factor associated with acute MI (P < .0001), followed by white race (P = .002) and history of hypertension (P = .047). The height of the PRA level upon entry to the emergency department was directly and independently associated with the diagnosis of acute MI. These new findings extend earlier reports because they encompass acute MI patients, include both hypertensive and normotensive patients, and control for potentially confounding variables. Based on these observations, a randomized clinical trial is warranted to determine whether measurement of PRA in acute MI could refine the process by which treatments are applied.

Aged↗
PubMed2000

Administration of high-dose ketoconazole, an inhibitor of steroid synthesis, prevents posttraumatic anxiety in an animal model.

Acute psychological stress is the presumed immediate cause of post-traumatic stress disorder (PTSD), and may also contribute to other anxiety disorders. Abnormal activity of the hypothalamic-pituitary-adrenal (HPA) axis has been tentatively implicated in some of the features of these disorders. Ketoconazole (KTCZ), an imidazole derivative, is a potent inhibitor of gonadal and adrenal steroidogenesis. The aim of this study was to explore the effects of KTCZ blockade of adrenal steroidogenesis, and consequent elevation of adreno-corticotropic hormone (ACTH), on a model of chronic post-traumatic anxiety in rats. Amelioration of anxious behaviors after reduction of corticosterone would suggest that corticosterone (and by implication cortisol in humans) is an important mediator of anxious symptoms: exacerbation of such behaviors would suggest that corticosterone elevations are only secondary, and possibly implicate corticotropin releasing hormone (CRH) and/or ACTH in the pathogenesis of anxious symptoms. We exposed rats for 10 min to cat scent, a prima facie valid model for acute psychological stress, with and without high dose KTCZ for 14 days. Treatment with KTCZ abolished the chronic behavioral effects of acute exposure to a cat scent. Lower levels of anxious behavior in KTCZ-treated and exposed rats were accompanied by lower plasma corticosterone, ACTH and prolactin (PRL) levels compared to untreated exposed rats. Results in this model implicate corticosterone, but not ACTH, in the pathogenesis of chronic anxiety following acute psychological stress.

Animals↗
PubMed2000

Cognitive decline in patients with Cushing's syndrome.

Chronic exposure to elevated glucocorticoid levels in Cushing's syndrome (CS), is associated with deficits in cognitive function and in emotion. The hippocampus plays a crucial role in the behavioral manifestations of the syndrome as it is richest in glucocorticoid receptors and is thus particularly vulnerable to glucocorticoid excess. The wide distribution of glucocorticoid receptors throughout the cerebral cortex, however, suggests that several cognitive functions can also be affected by the dysregulation of glucocorticoids. In this study, we investigated how an excess of glucocorticoid hormones affects cognitive processes. Nineteen patients with chronic hypercortisolemia due to CS were compared to healthy controls matched for age, sex, education, and occupation in tests of processing of visual and spatial information, memory, reasoning and concept formation, language and verbal functions, and attention. Multivariate and univariate analyses revealed overall differences in tests of treatment of visual and spatial information, reasoning and concept formation as well as in verbal and language performance, with poorer performance from CS patients. Differences were also observed in nonverbal aspects of memory and in attention tasks. The results suggest that chronic exposure to elevated levels of cortisol is associated with deficits in several areas of cognition, particularly those involving processing of selective attention and visual components. This study also shows that hormones play an important role in the modulation of cognitive function and that their influence on cerebral structure and function merits closer scrutiny.

Adult↗
PubMed2000

Pancreatic and duodenal homeobox gene 1 induces expression of insulin genes in liver and ameliorates streptozotocin-induced hyperglycemia.

Insulin gene expression is restricted to islet beta cells of the mammalian pancreas through specific control mechanisms mediated in part by specific transcription factors. The protein encoded by the pancreatic and duodenal homeobox gene 1 (PDX-1) is central in regulating pancreatic development and islet cell function. PDX-1 regulates insulin gene expression and is involved in islet cell-specific expression of various genes. Involvement of PDX-1 in islet-cell differentiation and function has been demonstrated mainly by 'loss-of-function' studies. We used a 'gain-of-function' approach to test whether PDX-1 could endow a non-islet tissue with pancreatic beta-cell characteristics in vivo. Recombinant-adenovirus-mediated gene transfer of PDX-1 to the livers of BALB/C and C57BL/6 mice activated expression of the endogenous, otherwise silent, genes for mouse insulin 1 and 2 and prohormone convertase 1/3 (PC 1/3). Expression of PDX-1 resulted in a substantial increase in hepatic immunoreactive insulin content and an increase of 300% in plasma immunoreactive insulin levels, compared with that in mice treated with control adenovirus. Hepatic immunoreactive insulin induced by PDX-1 was processed to mature mouse insulin 1 and 2 and was biologically active; it ameliorated hyperglycemia in diabetic mice treated with streptozotocin. These data indicate the capacity of PDX-1 to reprogram extrapancreatic tissue towards a beta-cell phenotype, may provide a valuable approach for generating 'self' surrogate beta cells, suitable for replacing impaired islet-cell function in diabetics.

Adenoviridae↗
PubMed2000

Sustained delivery and expression of DNA encapsulated in polymeric nanoparticles.

Sustained release polymeric gene delivery systems offer increased resistance to nuclease degradation, increased amounts of plasmid DNA (pDNA) uptake, and the possibility of control in dosing and sustained duration of pDNA administration. Furthermore, such a system lacks the inherent problems associated with viral vectors. Biodegradable and biocompatible poly(DL-lactide-co-glycolide) polymer was used to enacapsulate pDNA (alkaline phosphatase, AP, a reporter gene) in submicron size particles. Gene expression mediated by the nanoparticles (NP) was evaluated in vitro and in vivo in comparison to cationic-liposome delivery. Nano size range (600 nm) pDNA-loaded in poly(DL-lactide-co-glycolide) polymer particles with high encapsulation efficiency (70%) were formulated, exhibiting sustained release of pDNA of over a month. The entrapped plasmid maintained its structural and functional integrity. In vitro transfection by pDNA-NP resulted in significantly higher expression levels in comparison to naked pDNA. Furthermore, AP levels increased when the transfection time was extended, indicating sustained activity of pDNA. However, gene expression was significantly lower in comparison with standard liposomal transfection. Seven days after i.m. injections in rats, naked pDNA and pDNA-NP were found to be significantly more potent (1-2 orders of magnitude) than liposomal pDNA. Plasmid DNA-NP treatment exhibited increased AP expression after 7 and 28 days indicating sustained activity of the NP.

3T3 Cells↗
PubMed2000

Storage pool defect in pooled buffy coat platelet concentrates within the shelf-life period.

Platelet concentrate (PC) transfusions are useful for maintaining haemostasis in a variety of clinical situations. The function of transfused platelets is of critical importance, and changes on storage of buffy coat-prepared PC may influence their haemostatic potential. Total platelet adenine nucleotide content and platelet aggregation responses were studied, serially, in pooled buffy coat-derived PCs (n = 7), stored under UK recommended blood bank conditions, over the stipulated shelf-life of 5 days. Mean platelet volume (MPV), platelet counts and platelet distribution width (PDW) were also quantified. Total platelet ADP content decreased from 4.45+/-0.78 to 3.71+/-0.69 nmol/108 platelets (P<0.01, day 1 versus day 5, mean +/- SEM) over the shelf-life period. This was associated with reduced aggregatory responses: responses (expressed as percentage of maximum height) to 5 and 10 microM ADP decreased from 10.8+/-2.8% to 1.0+/-1.0% (P<0.005, 5 microM, day 1 versus day 5) and from 18.0+/-5.4% to 4.7+/-2.2% (P<0.02, 10 microM, day 1 versus day 5) while the decreased responsiveness was more pronounced for 4 microg/ml of collagen: 49.0+/-13.3% to 7.2+/-7.1% (P<0.01, day 1 versus day 4) and 49.9 +/-13.3% to 2.1+/-1.9% (P<0.001, day 1 versus day 5). These data indicate an acquired storage pool defect that is maximal by day 4 or 5 and accompanied by decreased platelet function, characterized by significant decreases in platelet aggregation responses. Addition of freeze-thawed plasma (autologous day 1) to PCs on days 2, 3, 4 and 5 did not alter the responses to ADP and collagen.

Adenosine Diphosphate↗
PubMed2000

Serum potassium and cardiovascular mortality.

BACKGROUND: The impact of serum potassium on mortality is inadequately defined. OBJECTIVE: To determine the association of serum potassium with mortality. METHODS: We analyzed NHANES I Epidemiological Follow-up Study data from 1974-1992. Of 2,992 subjects with baseline serum potassium, 156 were excluded because their vital status was not known. A total of 2,836 subjects with serum potassium within 2.7-5.4 mmol/L were studied. All-cause and cardiovascular mortality were assessed controlling for sociodemographic status, smoking, medical history, and clinical characteristics. RESULTS: At baseline, mean age was 46.6 years, and mean serum potassium was 4.07 mmol/L. Subjects were stratified into three groups by mean +/-1 standard deviation of serum potassium: low, 2.7-3.7 mmol/L (N = 477); middle, 3.8-4.4 mmol/L (N = 1,982); and high, 4.5-5.4 mmol/L (N = 377). The cardiovascular mortality rate per 1,000 person-years adjusted for age, gender, and race for the high serum potassium group (8.1) was significantly higher than the middle (5.3) and low (6.5) serum potassium groups. Further analysis, controlling for age, gender, race, smoking status, cholesterol, and history of diabetes, renal disease, and cardiovascular disease, revealed that the increased cardiovascular mortality among subjects with moderately increased serum potassium was most prominent in those reporting use of diuretics (hazard ratio, 2.65; 95% confidence interval [95% CI], 1.20 to 5.85) and those with abnormal renal function (hazard ratio, 1.89; 95% CI, 1.05 to 3.41). CONCLUSION: In this general population sample with mostly normal serum potassium, higher serum potassium was independently associated with increased cardiovascular mortality.

Cardiovascular Diseases↗
PubMed2000

Double-blind, randomized, controlled trial of atosiban and ritodrine in the treatment of preterm labor: a multicenter effectiveness and safety study.

OBJECTIVE: This study was undertaken to compare the efficacy and safety of intravenous administration of atosiban versus ritodrine for the treatment of preterm labor. STUDY DESIGN: Women with preterm labor and intact membranes diagnosed at 23 to 33 gestational weeks (n = 247) were randomly assigned to treatment arms and received atosiban (6.75 mg intravenous bolus, 300 microg/min for 3 hours, then 100 microg/min intravenously) or ritodrine (0.10-0.35 mg/min intravenously) for as long as 18 hours. Tocolytic effectiveness was assessed in terms of the numbers of women who had not been delivered after 48 hours and after 7 days. Safety was assessed in terms of maternal side effects and neonatal morbidity. Secondary outcomes included mean gestational age at delivery and mean birth weight. An intent-to-treat analysis was performed with the Cochran-Mantel-Haenszel test. RESULTS: The proportion of women who had not been delivered at 48 hours was 84.9% (n = 107) in the atosiban group and 86.8% (n = 105) in the ritodrine group. At 7 days 92 women had still not been delivered in both the atosiban (73.0%) and ritodrine (76.0%) groups. Neither of these differences was statistically significant. The incidence of maternal cardiovascular side effects was substantially lower in the atosiban group (4.0% vs 84.3%, P <.001). In addition, intravenous therapy was terminated more frequently as a result of maternal adverse events in the ritodrine group (29.8%) than in the atosiban group (0.8%). The overall occurrences of fetal adverse events in the two treatment groups were comparable. Neonatal morbidity was similar between the treatment groups after adjustment for unbalanced enrollment of women with multiple pregnancies and for gestational ages within treatment groups. CONCLUSION: Atosiban was comparable in clinical effectiveness to conventional ritodrine therapy but was better tolerated than ritodrine, with no evidence of significant maternal or fetal adverse events. Neonatal morbidity, which was similar between the two treatment arms, was apparently related to the gestational age of the infant rather than to the exposure to either tocolytic agent.

Adult↗
PubMed2000

Neuromotor development and language processing in developmental dyspraxia: a follow-up case study.

A longitudinal study of a child (MV) with developmental verbal dyspraxia was conducted to determine to what extent language development and motor performance in this clinical diagnosis followed a similar course of maturation. Patient MV was observed for two years from the age of 5 years and 6 months. Initially, this young patient exhibited unintelligible and atypical speech production (multiword utterances without consonants), delay in balance and coordination, and impairments in rhythmic tasks; but she was otherwise developing normally with no intellectual impairment or behavioral disorder. MRI scans showed moderately enlarged ventricles, a thin, incompletely myelinated corpus callosum and intact basal ganglia. Two years later, MV's performance was nearly normal only in comprehension aspects of language. In contrast, production aspects of language and speech and neuromotor development showed very little improvement after two years. These observations first suggest that development of receptive and expressive domains within language may be asynchronous, and that the progression of motor control of language appears to follow a parallel course to neuromotor development.

Apraxias↗