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Biomedical subjects

I Singh

Publications and source records attributed to I Singh.

At least 181 records · Page 10Linked to original sources
PubMed1994

The protein coded by the X-adrenoleukodystrophy gene is a peroxisomal integral membrane protein.

The gene for adrenoleukodystrophy (X-ALD), a peroxisomal disease characterized by excessive accumulation of very long-chain (VLC) fatty acids (> C22:0), has recently been identified by positional cloning, and it is predicted to encode a protein (ALD-P) of 745 amino acids [(1993) Nature 361, 726]. Using Western blot analysis of subcellular organelles purified by isopycnic density gradient centrifugation from X-ALD and control fibroblasts, we show that the monoclonal antibodies directed against ALD-P cross-react with a 75 kDa protein in intact peroxisomes and that ALD-P is an integral component of the peroxisomal membrane. Moreover, no signal for ALD-P was detected in peroxisomes from X-ALD patients with deletion of the ALD gene.

Adrenoleukodystrophy↗
PubMed1994

Demonstration of glutathione peroxidase in rat liver peroxisomes and its intraorganellar distribution.

Earlier, we reported that rat liver peroxisomes contain Cu-Zn superoxide dismutase (J. Biol. Chem. 267, 6870), thereby suggesting a new antioxidant role for this organelle in free radical metabolism. In this study, we report for the first time that mammalian peroxisomes also contain glutathione peroxidase. Using highly purified rat liver peroxisomes isolated by Nycodenz gradient, we found that peroxisomes contain glutathione peroxidase which shows enzymatic activity with different substrates such as hydrogen peroxide, cumene hydroperoxide, and t-butyl hydroperoxide. This activity could be inhibited in vitro by mercaptosuccinate. Western blot analysis revealed that peroxisomes from control and ciprofibrate-treated livers show immunoreactive bands with antibodies raised against glutathione peroxidase. The intraperoxisomal distribution of glutathione peroxidase was investigated by using peroxisomal membrane and matrix proteins. The results revealed that glutathione peroxidase is a matrix enzyme. The presence of glutathione peroxidase in peroxisomes provides an alternate enzyme system responsible for the degradation of organic peroxides and the degradation of H2O2 under conditions in which catalase is inactivated (e.g., ischemia-reperfusion and endotoxemia). These findings suggest that glutathione peroxidase in peroxisomes may play a novel role in the cellular antioxidant responses to various oxidative stress conditions.

Animals↗
PubMed1994

Interphalangeal joint arthrodesis with oblique placement of an AO lag screw.

A damaged interphalangeal (IP) joint may be treated by fusion. Arthrodesis should leave the joint at the most functional angle and give sound bony union in the shortest possible time, maintaining maximum proximal and distal joint motion. The lateral oblique placement of a single AO lag screw, proximal to distal, achieves these aims. This method gives sufficient proximal bone for screw purchase and better control of the desired angle of fusion. This technique has led to fusion in 22 of 23 joints (96%), taking an average of 8.2 weeks.

Adult↗
PubMed1994

Mechanisms of virus uncoating.

In a virus particle, the genome is highly condensed and protected by proteins and membrane bilayers. Before it can be replicated in a new host cell, uncoating must take place. Recent studies on enveloped and nonenveloped animal viruses indicate that uncoating occurs through complex, multistep processes triggered by virus-host-cell interactions.

Animals↗
PubMed1994

Advance prediction of early death in patients starting maintenance dialysis.

Accurate information on short-term prognosis is needed to help patients, their doctors, and society to make appropriate decisions concerning starting dialysis. We sought to develop a clinically applicable prognostic scoring system to aid in the prediction of death within 6 months of starting maintenance dialysis. Factors potentially predictive of early death were examined retrospectively in an inception cohort of all 325 patients starting dialysis for irreversible renal failure between 1980 and 1991 at a single tertiary care center. The overall mortality rate was 22% at 6 months. Age, cardiac failure, ischemic heart disease, dysrhythmia requiring therapy, severe peripheral vascular disease, advanced neoplasia, ventilator dependency, coma, systemic sepsis, and hepatic failure were independent, significant, prognostic indicators for early death. Multivariate models were used to suggest weights for these variables in a simplified scoring system. Patients with scores < or = 4 (N = 201) had a 6-month mortality rate of 4%, whereas those with a score higher than 9 (N = 21) had a 6-month mortality rate of 100%. Thus, when age and multiple comorbid illnesses were taken into account, it was possible to identify with 100% accuracy 29% of the patients who died within 6 months of starting maintenance dialysis therapy, accounting for 6.5% of the cohort studied. A larger prospective study is warranted to validate this scoring system.

Aged↗
PubMed1994

Antioxidant enzymes in ciprofibrate-induced oxidative stress.

To understand the mechanism of peroxisome proliferator-induced oxidative stress in non-mutagenic carcinogenesis, the effect of ciprofibrate, a peroxisome proliferator, on the activities and protein amounts of various antioxidant enzymes in different subcellular compartments was examined. Ciprofibrate treatment for short-term (3 weeks) as well as long-term (12 weeks) duration increased the total cellular catalase activity, whereas superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities were decreased significantly. Withdrawal of ciprofibrate from the diet did not normalize these activities. The observed decreases in total cellular SOD and GPX activities following ciprofibrate treatment were due to significant decreases in cytosolic CuZn SOD and GPX, whereas mitochondrial levels of Mn SOD and GPX were relatively unchanged. The peroxisomal CuZn SOD and GPX activities were increased significantly after both short- and long-term treatment, whereas catalase activity was reduced. Western blot analysis of cytoplasm for GPX and CuZn SOD showed a significant decrease in GPX and CuZn SOD proteins. Mitochondrial GPX protein was found to be slightly decreased, whereas Mn SOD protein levels did not show any significant change. The excessive production of H2O2 by oxidases and O2- by the cytochrome P450 enzyme system, along with the observed loss of antioxidant protection by loss of activities of catalase in peroxisomes and GPX and CuZn SOD in cytoplasm, may be the critical factors in peroxisomal proliferator-induced oxidative stress and initiation and promotion of carcinogenesis by this class of non-mutagenic agents. Both enzyme activities, as well as protein amounts of GPX and CuZn SOD, were higher in peroxisomes but lower in cytoplasm in ciprofibrate-treated liver as compared to control liver. The Mn SOD protein was decreased in peroxisomes, whereas mitochondrial Mn SOD was relatively unaffected in ciprofibrate-treated liver as compared to control. These observations suggest that the regulation of expression of peroxisomal CuZn SOD and Mn SOD is different from their counterparts in other cellular compartments.

Animals↗
PubMed1994

SPECT in adult mosaic Down's syndrome with early dementia.

A 52-year-old patient with mosaic Down's syndrome exhibiting clinical features of early dementia who underwent high resolution SPECT neuroimaging is reported. While a CT scan of the brain showed no abnormality, cranial SPECT confirmed the presence of marked cortical blood flow deficits.

Alzheimer Disease↗
PubMed1994

Elderly people with learning disabilities in hospital: a psychiatric study.

In a study of 124 hospital residents with a learning disability aged 60 years and over, DSM-III-R diagnostic criteria were used to determine the prevalence of dementia (12.9%), mood disorder (8.9%) and schizophrenia (6.5%). The figure for dementia confirms the prevalence given in previous studies, but the figures for mood disorder and schizophrenia are higher. It was found that mood disorder was commoner in the age group 60-69 years (P > 0.01) and dementia was commoner in the age group 70-79 years (P > 0.01). There were no significant differences in the prevalence of schizophrenia with age.

Aged↗
PubMed1994

Opioids and suckling in relation to inhibition of oestradiol-induced LH secretion in postpartum ewes.

The effects of time postpartum and suckling status on the oestradiol-induced LH surge in ewes and some of the possible mechanisms involved were investigated. Lambs were removed from nonsuckled ewes at parturition (day 0) and the ewes hand-milked 12 and 48 h later to prevent discomfort. Nonsuckled ewes on day 1, 7, 14 or 28, and suckled ewes on day 7 or 28 postpartum were injected i.m. with 50 micrograms oestradiol benzoate (hour 0). A further eight suckled ewes were given oestradiol on day 1 (as above), and four were also given naloxone (1 mg kg-1 h-1) from 10 until 14 h after administration of oestradiol benzoate. There was no LH surge in response to oestradiol on day 1. In nonsuckled ewes the onset of the LH surge was significantly (P < 0.05) delayed when oestradiol was administered on day 7 (17.4 +/- 1.5 h), compared with when it was injected on days 14 and 28 postpartum (14.4 +/- 1.7 and 14.0 +/- 1.4 h). The LH surge was also delayed (P < 0.05) when oestradiol was administered on day 7 (18.0 +/- 2.8 h) in suckled ewes. There was no difference in the duration or amplitude of the LH surge with time postpartum in nonsuckled ewes. Suckling significantly (P < 0.05) reduced the amplitude of the LH surge on both day 7 (21.0 +/- 2.4 versus 26.4 +/- 2.3 ng ml-1) and day 28 (23.6 +/- 3.2 versus 28.8 +/- 2.9 ng ml-1), but had no effect on the onset or duration of the surge.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Cholera epidemic in Goa.

Two hundred and fifty stool samples were studied during an outbreak of cholera in Goa during the months of July to September, 1988. 80 strains of Vibrio were isolated with an isolation rate of 32%. 72.5% of those affected were adults. All strains of Vibrio cholerae isolated belonged to Eltor biotype, Fifty three (66.25%) of them being Ogawa serotype while 21 (26.25%) were Inaba. NAG Vibrios accounted for 6 (7.5%) strains. Antimicrobial sensitivity pattern showed high degree of sensitivity to chloramphenicol, gentamicin and naladixic acid.

Adolescent↗
PubMed1994

The carpal tunnel syndrome: clinical evaluation and results of surgical decompression.

We reviewed 357 patients with carpal tunnel syndrome who had surgical decompression of the carpal tunnel between January 1989 and April 1991. The male to female ratio was 1:6. In 40 patients, there was bilateral involvement. Only 38.5% of the patients complained of numbness or sensory disturbance in the median nerve distribution of the hand. Tinel and Phalen sign tests were positive in about two-thirds of the patients. Electromyographic studies were performed in 329 patients. The commonest surgical procedure was a simple release of the flexor retinaculum at the wrist. Nearly all the patients reported improved symptoms.

Adult↗
PubMed1993

Intraorganellar localization of CoASH-independent phytanic acid oxidation in human liver peroxisomes.

In human tissues phytanic acid is alpha-oxidized to pristanic acid in peroxisomes. Studies of the intraorganellar site of alpha-oxidation of [1-14C]phytanic acid to pristanic acid in peroxisomes isolated from human liver demonstrate that phytanoyl-CoA ligase is present in the peroxisomal membrane and that the enzyme system for alpha-oxidation of phytanic acid to pristanic acid is in the peroxisomal matrix. In contrast to the beta-oxidation system for fatty acids, the substrate for alpha-oxidation is free phytanic acid. The studies described in this manuscript report a novel fatty acid oxidation system where the substrate for the enzyme system is free fatty acid; however, phytanoyl-CoA ligase regulates the alpha-oxidation of phytanic acid at the organellar (peroxisomal) level.

Coenzyme A↗
PubMed1993

Alterations of peroxisomal function in ischemia-reperfusion injury of rat kidney.

We have previously demonstrated that ischemic injury results in the loss of peroxisomal functions (e.g., inhibition of catalase activity and fatty-acid beta-oxidation activity). To understand the molecular mechanism leading to the loss of peroxisomal beta-oxidation in ischemic tissue, we examined the levels of individual enzyme activities and proteins of the peroxisomal beta-oxidation system and overall fatty-acid oxidation in peroxisomes isolated from kidney exposed to ischemia-reperfusion injury. The peroxisomal beta-oxidation decreased with an increase in time of ischemic injury (53% and 43% of the control in kidneys exposed to 60 and 90 min ischemia, respectively). In vivo inactivation of catalase with aminotriazole and exposure of isolated peroxisomes to H2O2 resulted in inhibition of peroxisomal beta-oxidation system suggesting that this enzyme system is labile to excessive H2O2 produced during ischemic injury. The enzyme activities of lignoceroyl-CoA ligase, acyl-CoA oxidase, bifunctional enzymes and acyl-CoA thiolase (individual peroxisomal beta-oxidation enzymes) after 90 min of ischemia were 87, 80, 87 and 85% of the control, respectively. This decrease in enzyme activities was more pronounced following reperfusion (28, 11, 23 and 35% of the control, respectively). Immunoblot analysis of these enzymes indicated that the major loss of these enzyme activities during ischemia was due to their inactivation, whereas during reperfusion, proteolysis also contributed toward the observed loss of these activities. In summary, these results demonstrated that loss of peroxisomal beta-oxidation in ischemia-reperfusion injury was due to inactivation and proteolysis of beta-oxidation enzymes. Acyl-CoA oxidase was more sensitive to ischemia-reperfusion injury compared to other enzymes, and the overall loss of peroxisomal beta-oxidation may be a reflection of the loss of acyl-CoA oxidase activity, a rate-limiting enzyme.

Acyl-CoA Oxidase↗
PubMed1993

Purification of peroxisomes and subcellular distribution of enzyme activities for activation and oxidation of very-long-chain fatty acids in rat brain.

Brain contains high amounts of very-long-chain (VLC) fatty acids (> C22). Since mitochondria from liver and skin fibroblasts lack lignoceroyl-CoA ligase, in liver and skin fibroblasts fatty acids are exclusively oxidized in peroxisomes. Findings by Poulos and associates [9] suggested that contrary to liver and cultured skin fibroblasts brain mitochondria contain lignoceroyl-CoA ligase and can oxidize lignoceric acid. The present study was undertaken to develop a procedure for the isolation of subcellular organelles of higher purity from brain and to get a better understanding of the subcellular localization of the oxidation of VLC fatty acids in brain. The enzyme activities for activation and oxidation of palmitic and lignoceric acids were determined in peroxisomes, mitochondria, microsomes and a myelin fraction from rat brain and peroxisomes, mitochondria and microsomes purified from rat liver. Like in liver, brain lignoceroyl-CoA ligase activity in microsomes and peroxisomes was approx. 9 times higher than in mitochondria. In addition to palmitoyl-CoA ligase the antibodies against palmitoyl-CoA ligase inhibited the residual mitochondrial lignoceroyl-CoA ligase activity, meaning that lignoceroyl-CoA ligase activity in mitochondria was derived from palmitoyl-CoA ligase. Accordingly, in peroxisomes lignoceric acid was oxidized at 7 times higher rate than in mitochondria. Mitochondria were able to oxidize lignoceric acid efficiently when supplemented with lignoceroyl-CoA ligase activity from microsomes or myelin. These results show that in brain lignoceric acid is oxidized in peroxisomes and that lignoceroyl-CoA ligase activity is localized in peroxisomes and microsomes, but not in mitochondria. Peroxisomes and microsomes contain both lignoceroyl-CoA and palmitoyl-CoA ligases. Similar to peroxisomes and microsomes, the antibodies against palmitoyl-CoA ligase inhibited only the palmitoyl-CoA ligase activity in myelin but not the lignoceroyl-CoA ligase activity. These results suggest that in addition to palmitoyl-CoA ligase, myelin also contains lignoceroyl-CoA ligase.

Adrenoleukodystrophy↗
PubMed1993

Peroxisomal participation in the cellular response to the oxidative stress of endotoxin.

Exposure to a sublethal dose of endotoxin offers protection against subsequent oxidative stresses. The cellular mechanisms involved in generating this effect are not well understood. We evaluated the effect of endotoxin on antioxidant enzymes in liver peroxisomes. Peroxisomes have recently been shown to contain superoxide dismutase (SOD) and glutathione peroxidase (GPX) in addition to catalase. Peroxisomes were isolated from liver homogenates by differential and density gradient centrifugations. Endotoxin treatment increased the specific activity of SOD and GPX in peroxisomes to 208% and 175% of control activity, respectively. These findings correlated with increases in peroxisomal SOD and GPX proteins observed by immunoblot. Although the quantity of catalase protein was increased when assessed by immunoblot analysis, the specific activity of catalase was decreased to 68% of control activity. Activation of catalase with ethanol only restored catalase activity to control levels suggesting that catalase had undergone irreversible inactivation. The observed increase in GPX activity may represent a compensatory mechanism triggered by accumulating H2O2. The data presented here suggest for the first time that mammalian peroxisomal antioxidant enzymes are altered during the oxidative injury of endotoxin treatment.

Animals↗