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Biomedical subjects

S Hirsch

Publications and source records attributed to S Hirsch.

At least 55 records · Page 3Linked to original sources
PubMed1996

NMDA receptor mRNA correlation with antemortem cognitive impairment in schizophrenia.

We investigated the expression of the N-methyl-D-aspartate (NMDA) receptor, an important glutamate receptor, in brains from a population of well characterized schizophrenic patients who prospectively consented to tissue donation. Levels of NR-1 mRNA in tissue homogenates of superior temporal cortex were reduced by 30% in cognitively impaired schizophrenic patients compared with controls (p < 0.04), while levels in patients without cognitive impairment showed no such reduction. The NR-1 mRNA deficit was significantly correlated with general cognitive function as rated with the Global Deterioration scale (p < 0.001), the Mini-Mental State examination (p < 0.01) and the premorbid IQ determined using the National Adult Reading Test (NART, p < 0.01). NR-1 mRNA concentration was not correlated with age, sex, pH or postmortem delay in the control and schizophrenia group when analysed separately or combined. There was, therefore, a significant correlation between NR-1 mRNA loss and cognitive deterioration in patients with schizophrenia.

Adult↗
PubMed1996

Interleukin 1 and tumor necrosis factor in obese alcoholics compared with normal-weight patients.

We performed a liver biopsy and measured plasma concentrations of interleukin 1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF-alpha), and spontaneous and lipopolysaccharide-stimulated in vitro monocyte production of IL-1 beta and TNF-alpha in 19 obese and 17 age-matched, normal-weight alcoholics admitted for treatment of their alcoholism. Nine healthy normal-weight alcoholics had cirrhosis in their liver biopsy (Fisher's exact test: P=0.031). A histologic score (derived from the sum of fat, necrosis, fibrosis, and inflammation in the biopsy) correlated with body mass index and the percentage body fat, calculated by using the sum of four skinfold-thickness measures. Plasma concentrations and spontaneous in vitro monocyte production of IL-1 beta and TNF-alpha were below detection limits. No significant differences were observed between normal-weight and obese alcoholics with or without cirrhosis and normal control subjects in lipopolysaccharide-stimulated monocyte production of IL-1 beta (6.5 +/- 0.8, 10.1 +/- 2.7, 7.9 +/- 1.6, and 5.28 +/- 4.24 micrograms/L, respectively) or TNF-alpha (2.8 +/- 0.4, 3.7 +/- 1.0, 3.0 +/- 0.44, and 1.97 +/- 1.01 micrograms/L, respectively). However, a positive correlation was found between IL-1 beta production and body mass index (r=0.333, P=0.047), percentage body fat (r=0.412, p=0.013), abdominal circumference (r=0.416, P=0.012), and total histologic score (r=0.331, P=0.049). A multiple-regression model accepted abdominal circumference as the only independent predictor of IL-1 beta production. TNF-alpha did not correlate with any of the above-mentioned indexes. We conclude that obese alcoholics have a higher frequency of histologic liver damage and that IL- 1 beta production by stimulated monocytes is related to abdominal fat accumulation.

Adult↗
PubMed1996

Fatty acid composition of liver total lipids in alcoholic patients with and without liver damage.

Alcohol ingestion may promote lipid peroxidation, and the presence of polyunsaturated fatty acids in liver lipids may be essential for the generation of liver damage through this mechanism. The aim of this study is to examine fatty acid composition of liver lipids in chronic alcoholics with and without histological liver damage. A percutaneous liver biopsy was performed to 28 patients hospitalized for treatment of their alcoholism. Liver total lipids were extracted from a portion of the tissue sample and fatty acid composition was measured by gas chromatography. Another piece of the sample was sent for histological study. Six patients had histological cirrhosis or alcoholic hepatitis in their biopsies, the rest of the patients had minimal changes. Patients with liver damage had higher levels of oleic acid and total monoenoic fatty acids, a higher 18:1/18:0 ratio, lower levels of polyunsaturated fatty acids, a lower 20:4/18:2 ratio, and a lower peroxidability index in liver total lipids, than patients without liver damage. Alcoholic patients with asymptomatic liver damage have less unsaturated fatty acids in liver total lipids than their counterparts with normal livers.

Adult↗
PubMed1996

Psychological symptoms, somatic symptoms, and psychiatric disorder in chronic fatigue and chronic fatigue syndrome: a prospective study in the primary care setting.

OBJECTIVE: This study assessed relationships among psychological symptoms, past and current psychiatric disorder, functional impairment, somatic symptoms, chronic fatigue, and chronic fatigue syndrome. METHOD: A prospective cohort study was followed by a nested case-control study. The subjects, aged 18-45 years, had been in primary care for either clinical viral infections or a range of other problems. Questionnaire measures of fatigue and psychological symptoms were completed by 1,985 subjects 6 months later; 214 subjects with chronic fatigue were then compared with 214 matched subjects without fatigue. Assessments were made with questionnaires, interviews, and medical records of fatigue, somatic symptoms, psychiatric disorder, and functional impairment. RESULTS: Subjects with chronic fatigue were at greater risk than those without chronic fatigue for current psychiatric disorder assessed by standardized interview (60% versus 19%) or by questionnaire (71% versus 31%). Chronic fatigue subjects were more likely to have received psychotropic medication or experienced psychiatric disorder in the past. There was a trend for previous psychiatric disorder to be associated with comorbid rather than noncomorbid chronic fatigue. Most subjects with chronic fatigue syndrome also had current psychiatric disorder when assessed by interview (75%) or questionnaire (78%). Both the prevalence and incidence of chronic fatigue syndrome were associated with measures of previous psychiatric disorder. The number of symptoms suggested as characteristics of chronic fatigue syndrome was closely related to the total number of somatic symptoms and to measures of psychiatric disorder. Only postexertion malaise, muscle weakness, and myalgia were significantly more likely to be observed in chronic fatigue syndrome than in chronic fatigue. CONCLUSIONS: Most subjects with chronic fatigue or chronic fatigue syndrome in primary care also meet criteria for a current psychiatric disorder. Both chronic fatigue and chronic fatigue syndrome are associated with previous psychiatric disorder, partly explained by high rates of current psychiatric disorder. The symptoms thought to represent a specific process in chronic fatigue syndrome may be related to the joint experience of somatic and psychological distress.

Adolescent↗
PubMed1996

A one year prospective study of the effect of life events and medication in the aetiology of schizophrenic relapse.

BACKGROUND: We set out to determine whether and to what degree life events independent of illness increase the risk of relapse in schizophrenia following withdrawal from medication in the previous 6 months, either by triggering a relapse in the following 4 weeks or by acting cumulatively over time. METHOD: Seventy-one patients fulfilling DSM-III-R criteria for schizophrenia with chronic illness were followed for 48 weeks and assessed on the LEDS scale. Half were treated with regular neuroleptic medication and half had been recently withdrawn from medication. A subgroup was randomised double-blind to treatment or placebo. RESULTS: A proportional hazards regression model showed that life events made a significant cumulative contribution over time (P < 0.05) to the risks of relapse and that ceasing medication made an independent contribution. The risk of relapse increased in proportion to the number of life events but no interaction between medication status and events could be detected, i.e. life events were not more closely associated with relapse on medication than off medication. For those of the sample exposed to the mean rate of life events during the study period, it was estimated that 23% of the relapse risk could be attributed to life events, and for those with twice the mean rate of events, 41%. In contrast, patients who continued on regular medication had 80% less risk of relapse than those who had been withdrawn from medication either by choice or under double-blind controlled conditions. CONCLUSIONS: A contribution of life events to the risk of relapse in schizophrenia was confirmed by this study but the hypothesis that life events trigger relapse was not supported, nor was the hypothesis that life events are more relevant to relapse in patients on maintenance medication than in patients off medication.

Adult↗
PubMed1996

[Methods to estimate body composition in the elderly: a critical analysis].

The objective of this study was to compare the values obtained for total body fat obtained with deuterium dilution, anthropometry and bioimpedance in 41 institutionalized elderly individuals (65-90 years old). The values obtained with each technique were compared using the graphic analysis proposed by Bland and Altman, that plots the difference between measurements with both methods against their average. In men (n = 20) and women (n = 21), the best degree of agreement was obtained between the values measured by deuterium dilution and those calculated from skinfolds (mean difference = 1.4% and 6.9%, respectively). The limits of agreement (+/-2SD), for skinfolds reached a maximum of 14.8% in men, and 16.8% in women. These values tend to underestimate fat in the obese and overestimate it in thinner subjects. For bioimpedance and deuterium dilution, the inter-method difference is significantly greater: 9.3% in men and 14.7% in women. This lack of agreement is attributed to the fact that the bioimpedance equipment utilizes equations validated for younger adults. In conclusion, estimation of body composition using skinfoids has the smallest difference compared to deuterium dilution, even though individual measurements are not clinically acceptable. Caution is recommended when using measurements of body composition in the elderly, due to large errors in the determinations.

Aged↗
PubMed1996

Mitogenic activation of the transferrin receptor gene promoter is modulated by inhibitors of tyrosine kinases and tyrosine phosphatases.

Transferrin receptor gene expression is coupled to cell proliferation of normal cells and is elevated in nearly all types of tumor cells. A mitogen-responsive region of the transferrin receptor gene promoter has been localized between -78 and -34 relative to the major transcriptional start. The promoter can be activated in quiescent fibroblasts by treatment with either vanadate or phenylarsine oxide, both of which are inhibitors of tyrosine phosphatases and lead to elevated levels of intracellular tyrosine-phosphorylated proteins. Vanadate can act synergistically with other mitogens and, when added together with serum, leads to superactivation of the promoter. Genistein, an inhibitor of certain tyrosine kinases, actually enhances promoter activity in cells treated with either vanadate or phenylarsine oxide. On the other hand, geldanamycin, which also reduces the level of tyrosine-phosphorylated proteins and promoters the morphological reversion of many transformed cell types, is a potent inhibitor of transferrin receptor promoter activation by mitogens. The differential effects of these two tyrosine kinase inhibitors is most likely caused by the specificity of the enzymes that they target. These results indicate that a tyrosine phosphorylation event plays a critical role in the signaling events that lead to activation of the transferrin receptor gene promoter in mitogen-stimulated cells. This is of interest because activation of this promoter is a delayed response that occurs several hours after mitogen addition.

3T3 Cells↗
PubMed1995

Fibroblasts at the transection site of the injured goldfish optic nerve and their potential role during retinal axonal regeneration.

The region at and around the site of optic nerve transection (ONS) in goldfish, topologically the equivalent of the glial scar in mammals, is reported to remain free of astrocytes over weeks, but its cellular constituents are unknown. To learn what type of cell occupies the site of injury and thus provides support for the rapidly regenerating retinal growth cones, immunostaining experiments at the light microscopic level and electron microscopic examinations were undertaken. Between 2 and 30 days after ONS, an area up to 150 micrograms wide at the transection site exhibits intense anti-fibronectin immunoreactivity. This site contained cells and processes with ultrastructural characteristics of fibroblasts and abundant collagen fibrils. Moreover, on fibroblast cultures derived from regenerating optic nerves, retinal axons grew to considerable density in vitro. Since fibroblasts are constituents of the interfascicular spaces and outer nerve sheath of the normal goldfish optic nerve, the present data imply that fibroblasts of either source migrate into the lesion. Judging form fibronectin immunostaining they remain there during the passage of regenerating axons, and thus may provide physical and perhaps molecular support for axon growth. The fibroblasts are again restricted to interfascicular spaces after restoration of the astrocytic glia limitans around regenerated fascicles.

Animals↗
PubMed1995

Postinfectious fatigue: prospective cohort study in primary care.

The idea that chronic fatigue has an infectious origin has become popular, but the main evidence for such an association has come from retrospective case-control studies, which are subject to ascertainment bias. We report a prospective study of the outcome of clinically diagnosed infections in patients presenting to UK general practitioners. Questionnaires assessing fatigue and psychiatric morbidity were sent to all patients aged 18-45 years in the study practices. The prevalence of chronic fatigue and chronic fatigue syndrome was then ascertained among 1199 people aged 18-45 who presented to the general practitioners with symptomatic infections and in 1167 people who attended the surgeries for other reasons. 84% were followed up at 6 months. 9.9% of cases and 11.7% of controls reported chronic fatigue (odds ratio 1.0 [95% CI 0.6-1.1]). There were no differences in the proportions who met various criteria for chronic fatigue syndrome. No effect of infection was noted when we excluded subjects who reported fatigue or psychological morbidity at the baseline screening. The strongest independent predictors of postinfectious fatigue were fatigue assessed before presentation with clinical infection (3.0 [1.9-4.7]) and psychological distress before presentation (1.8 [1.2-2.9]) and at presentation with the acute infection (1.8 [1.1-2.8]). There was no effect of sex or social class. Our study shows no evidence that common infective episodes in primary care are related to the onset of chronic fatigue or chronic fatigue syndrome.

Adolescent↗
PubMed1995

Cholecystokinin messenger RNA deficit in frontal and temporal cerebral cortex in schizophrenia.

No consistent markers of pathology have been established yet in schizophrenia, although abnormalities in frontal and temporal structures are indicated from positron emission tomography (PET) studies. We have used in situ hybridization to investigate functional changes focusing on the quantitation of cholecystokinin (CCK) mRNA, whose product has been shown to be depleted in schizophrenia. CCK mRNA and G(o) alpha-subunit mRNA were measured in eight schizophrenic and eight control subjects matched for age and postmortem delay. The study revealed a marked decrease in CCK mRNA of 83% in frontal cortex (BA10) and 63% in superior temporal cortex (BA22) in schizophrenia with no change in G(o) alpha-subunit mRNA in either region. This study was extended to a further series of eight patients to determine the reproducibility of this effect and to quantitate laminar changes in CCK mRNA. Quantitation of CCK mRNA in inner cortical layers (layer V/VI) was carried out in frontal and temporal cortex in comparison with G(o) alpha-subunit mRNA, which is also concentrated in this region; this study showed a similar selective decrease in CCK mRNA in frontal and temporal cortex of 47% and 51%, respectively. A confirmatory decrease in CCK mRNA was also obtained by slot blot analysis of CCK mRNA in tissue extracts of frontal cortex by reference to levels of beta-tubulin mRNA, CCK mRNA:beta-tubulin mRNA was significantly decreased (67%) in schizophrenic tissue compared to control tissue. There was no significant correlation of CCK mRNA loss with neuroleptic treatment or duration of illness.

Adult↗
PubMed1995

Import of a new chloroplast inner envelope protein is greatly stimulated by potassium phosphate.

A cDNA clone encoding a major chloroplast inner envelope membrane protein of 96 kDa (IEP96) was isolated and characterized. The protein is synthesized as a larger-molecular-weight precursor (pIEP96) which contains a cleavable N-terminal transit sequence of 50 amino acids. The transit peptide exhibits typical stromal targeting information. It is cleaved in vitro by the stromal processing peptidase, though the mature protein is clearly localized in the inner envelope membrane. Translocation of pIEP96 into chloroplasts is greatly stimulated in the presence of 80 mM potassium phosphate which results in an import efficiency of about 90%. This effect is specific for potassium and phosphate, but cannot be ascribed to a membrane potential across the inner envelope membrane. Protein sequence analysis reveals five stretches of repeats of 26 amino acids in length. The N-terminal 300 amino acids are 45% identical (76% similarity) to the 35 kDa alpha-subunit of acetyl-CoA carboxyl-transferase from Escherichia coli. The C-terminal 500 amino acids share significant similarity (69%) with USOI, a component of the cytoskeleton in yeast.

Amino Acid Sequence↗
PubMed1995

Suprahepatic vein oxygen tension in alcoholics with severe and mild liver damage.

We measured suprahepatic vein and arterial partial oxygen pressure in 35 alcoholics with severe (N = 7) or mild (N = 28) histological liver damage and without evidence of clinical liver failure. The suprahepatic vein was punctured with a fine needle, using a percutaneous approach. Suprahepatic vein partial oxygen pressure was lower and arterial-suprahepatic gradient higher in alcoholics with severe liver damage compared to those with mild damage (35.1 +/- 1.7 vs 44.1 +/- 2.1 and 58.9 +/- 3.7 vs 45.9 +/- 2.4 mm Hg, respectively; P < 0.001). Suprahepatic puncture was well tolerated and devoid of complications. It is concluded that alcoholics with severe liver damage have lower oxygen tensions in the suprahepatic vein, a phenomenon that supports the hypoxic theory of alcoholic liver disease.

Adult↗
PubMed1995

Effects of abstinence on sex hormone profile in alcoholic patients without liver failure.

Excessive ethanol ingestion induces hypoandrogenism in male subjects. To confirm its presence and to study its relationship with the degree of liver damage and alcohol abstinence, plasma sex hormones were measured in alcoholic patients without liver failure, after two different abstinence periods. Patients were 30 male chronic alcoholics admitted to the Alcoholism Ward for treatment of their addiction. On admission, we measured: testosterone (T), estradiol (E), follicle stimulating hormone (FSH), luteinizing hormone (LH) and sex-hormone binding globulin (SHBG). A liver biopsy was also performed. These measurements were repeated at discharge and were also done in 15 normal volunteers. On admission (mean abstinence 1.9 +/- 1.7 days) total T was similar to controls, FSH was lower (p < 0.02) and high levels of SHBG were found (3.5 fold increase, as compared to controls). Histologically, 9 patients had normal liver; 14 had moderate alterations and 7 showed marked alterations. Hormonal values were not different in these 3 groups. At discharge, 11.1 +/- 4.7 days after admission, T, E and FSH did not show significant changes but LH decreased (8.2 +/- 5.2 mIU/ml vs 12.9 +/- 4.1, p < 0.001); SHBG also decreased (65.4 +/- 21.6 nmol/l vs 117.2 +/- 33.3, p < 0.001) to values that still were twice those of controls. It is concluded that alcoholic patients without clinical signs of liver failure have normal plasma testosterone levels, irrespective of their histologic liver alterations and high plasma SHBG levels that decreased significantly after a short abstinence. The concomitant LH decrease suggests that hypoandrogenism is likely in these patients. Fast changes in SHBG levels rise the possibility that this protein is candidate marker of alcoholism.

Adult↗
PubMed1995

Protein turnover in abstinent and non-abstinent patients with alcoholic cirrhosis.

OBJECTIVE: This study was designed to measure the effect of chronic alcohol intake on leucine turnover in outpatients with stable alcoholic liver cirrhosis. METHODS: Protein turnover rate was measured using L [1-14C] leucine in ten outpatients with proven alcoholic cirrhosis and in five healthy controls. After the performance of the turnover, the patients were divided in two groups depending on the evidence of alcohol ingestion in the previous month. RESULTS: Non-abstinent patients had a significantly higher leucine flux and non-oxidative disposal (73.8 +/- 25.4 and 65.9 +/- 21.6) than abstinent cirrhotic patients (48.9 +/- 9.5 and 43.7 +/- 9.0) and normal controls 37.3 +/- 8.9 and 31.1 +/- 7.6 mumol/m2/min (p < 0.01). Leucine oxidation and serum leucine levels were similar in the three groups. CONCLUSION: Alcohol intake in alcoholic cirrhotic patients has a catabolic effect that could be associated with the nutritional imbalances observed in alcoholic liver disease.

Adult↗
PubMed1995

Effects of long-term vitamin E supplementation in alcoholic cirrhotics.

OBJECTIVE: Alcohol ingestion promotes lipoperoxidation and alters cellular antioxidant mechanisms. Alpha-tocopherol levels decrease in alcoholics as severity of liver damage increases. The aim of this protocol was to study the effects of a long-term oral 500 mg vitamin E daily supplementation in decompensated ambulatory alcoholic cirrhotics. PATIENTS AND METHODS: 67 subjects were included in this double blind trial; 33 patients received vitamin E and 34 patients received placebo tablets of identical appearance during 1 year. Each month, the patients were seen by a nurse practitioner who was in charge of detecting alcohol ingestion and checking adherence to treatment. Every 3 months, the patients underwent a medical examination, and blood samples were taken for clinical laboratory analysis and serum vitamin E measurement. RESULTS: Alpha-tocopherol levels were significantly lower in patients with more severe liver disease. This difference was not significant when vitamin E levels were corrected by cholesterol. Oral supplementation significantly increased serum vitamin E levels in the experimental group. Alcohol ingestion and hospitalization rates were similar in both groups. Life table analysis did not show significant differences in mortality between the two groups. DISCUSSION: Vitamin E supplementation with adequate doses of an alpha-tocopheryl acetate formulation during 1 year did not influence hepatic laboratory parameters, mortality or hospitalization rates of decompensated alcoholic cirrhotics, although serum levels of the vitamin significantly increased.

Adult↗
PubMed1995

Comparison of Mycoplasma arthritidis strains by enzyme-linked immunosorbent assay, immunoblotting, and DNA restriction analysis.

Twenty Mycoplasma arthritidis strains or isolates were compared by a combination of enzyme-linked immunosorbent assay by an antiserum adsorption technique, Western immunoblotting, and restriction analysis of chromosomal DNA. Antigenic markers that defined strains related to strains 158p10p9, PG6, and H606 were identified. In addition, restriction analysis allowed all 20 strains to be divided into six groups. Results of restriction analysis corresponded generally with antigenic similarities, although the former did not allow grouping with as fine a precision as the latter. However, intrastrain antigenic variability, which is common among many Mycoplasma species, including M. arthritidis, introduced a complicating factor into our attempts at antigenic analysis. While serologic and antigenic analyses remain useful, we recommend that they be used with caution and in combination with other techniques for identifying and characterizing new isolates and newly acquired strains. Combinations of these techniques have proven to be useful in our laboratory for quality control and for uncovering interesting relationships among strains subjected to animal passage and their less virulent antecedents and among strains originally classified as the same but obtained from different sources and maintained, sometimes for decades, in different laboratories.

Animals↗