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M Jacob

Publications and source records attributed to M Jacob.

At least 73 records · Page 4Linked to original sources
PubMed1997

Bovine retinal pigment epithelium contains novel types of phospholipase A2.

We have recently demonstrated the presence of phospholipase A2 (PLA2) activity in cells from bovine retinal pigment epithelium (RPE) [Jacob et al. (1996) J. Biol. Chem. 271, 19209-19218]. We report here our results on the characterization of this RPE-PLA2 activity. We show that RPE probably contains two types of PLA2 enzyme, as indicated by the results obtained with different PLA2-active fractions eluted from cation-exchange columns and treated with Ca2+/EGTA, dithiothreitol, p-bromophenacyl bromide or heat. These results, in addition to those from PLA2 assays using different substrates, also suggest that RPE-PLA2 enzymes are different from the well-known secretory, cytoplasmic and Ca2+-independent forms. Sequential extraction of RPE with (1) isotonic, (2) hypertonic and (3) detergent-containing PBS argues for the presence of weakly membrane-associated enzymes. Control experiments using 'back and forth' TLC allowed us to discriminate between PLA2 and phospholipase C/diacylglycerol lipase activity and confirmed that, in our assay conditions, the release of fatty acids was indeed due to PLA2 enzymes. These results, together with those obtained by treating RPE homogenates with H2SO4, guanosine 5'-[gamma-thio]triphosphate, ATP and different protease inhibitors, permitted us to make the first characterization of these RPE-PLA2 enzymes. We conclude that RPE contains novel types of PLA2 that are different from the secretory, cytoplasmic and Ca2+-independent forms.

Animals↗
PubMed1997

Diffusion control in an elementary protein folding reaction.

The cold-shock protein CspB (from Bacillus subtilis), a very small protein of 67 residues, folds extremely fast in a reversible N &lrharr; U two-state reaction. Both unfolding and refolding are strongly decelerated when the viscosity of the solvent is increased by adding ethylene glycol or sucrose. The folding of CspB thus seems to follow Kramers' model for reactions in which the reactants must diffuse together. It indicates that the compaction of the protein chain occurs in the rate-limiting step of folding. Chain diffusion to a productively collapsed form and the crossing of a high energy barrier are thus tightly coupled in this folding reaction, and the measured reaction rate depends on both the diffusion of the protein chain in the solvent and the magnitude of the activation energy. We suggest that in protein folding an energetic barrier is essential to separate the native from the unfolded conformations of a protein. This barrier protects the ordered structure of a native protein against continuous unfolding by diffusive chain motions and leads to apparent two-state behavior.

Bacillus subtilis↗
PubMed1997

A case-control analysis of risk factors in HIV transmission in South India.

A case-control study was done among patients attending our clinic for sexually transmitted diseases in South India to assess risk factors for human immunodeficiency virus (HIV) infection. Of 5,876 patients tested, 105 (1.79%) were HIV antibody positive (87 men, 18 women) by enzyme-linked immunosorbent assay and Western blot. They were compared with an equal number of age- and sex-matched patients without HIV antibody. Risk factors significant in the crude odds ratio analysis were occupation (truck drivers and truck cleaners), age at first exposure, and sexual contact with commercial sex workers. In the logistic regression analysis, only a history of past genital ulcer was a significant risk factor. Other important findings of this study were that (a) the spread of HIV to women is mostly from their infected husbands and (b) regular condom use was reported by less than 8% of patients and controls. Obviously, the current methods of education of the population are far from adequate.

Adult↗
PubMed1997

Pain in multiple leiomyomas alleviated by nifedipine.

We have confirmed the usefulness of nifedipine in the treatment of pain present in lesions of multiple skin leiomyomata. Our patient, a 28-year-old woman, had hundreds of skin lesions, proven histologically to be leiomyomata. Nifedipine (10 mg) three or four times daily was remarkably effective in diminishing pain that was more marked in the winter season.

Adult↗
PubMed1997

Linear IgA bullous dermatosis in south India.

BACKGROUND: A study of five cases of linear IgA dermatosis (LABD) in a referral hospital in South India is presented. METHODS: A dermatologic examination, skin biopsy, and direct immunofluorescence were carried out on all patients. Patients were then followed up. RESULTS: All five cases showed linear IgA deposits at the dermo-epidermal junction. One case in addition showed IgG and C3 deposits. All cases responded to treatment with dapsone. The treatment duration varied from 14 to 16 months and the fifth patient is still on treatment after 37 months. CONCLUSIONS: Linear IgA bullous dermatosis is a self-limiting bullous disorder. To the best of our knowledge this is the first report of LABD from India.

Adolescent↗
PubMed1997

2-[123I]-iodolisuride SPET visualizes dopaminergic loss in de-novo parkinsonian patients: is it a marker of striatal pre-synaptic degeneration?

The aim of this study was to assess the correlation between the functional integrity and density of striatal dopaminergic receptors and clinical data in 15 de-novo patients with idiopathic Parkinson's disease by single photon emission tomography (SPET) using 2-[123I]-iodolisuride (ILIS), a tracer based on the D2-dopamine receptor agonist lisuride. Deficient striatal uptake of ILIS correlated with the severity of the disorder, scored by the Unified Parkinson's Disease Rating Scale (UPDRS) (n = 15; ratio of ILIS uptake: basal ganglia/cerebellum [B/C] & UPDRS I-III, Spearman R = -0.562, P = 0.013), Beck's Depression Inventory (BDI) (n = 12; B/C & BDI, Spearman R = -0.825, P = 0.0009) and the ZUNG Depression Scale (ZDS) (n = 11; B/C & ZDS, Spearman R = -0.7425, P = 0.008). Experimental data indicate that lisuride shows a higher affinity for pre-synaptic dopaminergic autoreceptors than for post-synaptic D2-dopamine receptors under conditions of low applied ILIS concentrations as in this study. From the results of this study and these experimental data, we speculate that ILIS-SPET can visualize pre-synaptic striatal dopaminergic degeneration in Parkinson's disease.

Aged↗
PubMed1997

Intestinal tolerability of nitroxybutyl-flurbiprofen in rats.

BACKGROUND: Nitric oxide derivatives of non-steroidal anti-inflammatory drugs (NSAIDs) are thought to be much less ulcerogenic than their parent compounds. AIM: To compare the effect and potency of flurbiprofen and nitroxybutyl-flurbiprofen to uncouple mitochondrial oxidative phosphorylation (an early pathogenic event in NSAID enteropathy), increase intestinal permeability (transitional stage), and cause macroscopic small intestinal damage. METHODS: In vitro uncoupling potency was assessed using isolated coupled rat liver mitochondria and in vivo by electron microscopy of rat small intestinal mucosa (two hours after the drugs). A dose-response study with flurbiprofen (single doses of 5, 10, 20, and 40 mg/kg) and equimolar doses of nitroxybutyl-flurbiprofen was performed; assessing their effect on intestinal permeability (at 18-20 hours), with 51Cr EDTA, and the number of pointed (< 5 mm) and longitudinal (> 5 mm) small intestinal ulcers at 24 hours. RESULTS: Flurbiprofen, but not nitroxybutyl-flurbiprofen, stimulated coupled respiration in vitro. Both drugs, however, uncoupled in vivo; in the case of nitroxybutyl-flurbiprofen possibly because hydrolysis of its ester bond released free flurbiprofen. Intestinal permeability was uniformly and equally increased with both drugs compared with controls. The number of small intestinal ulcers, pointed and longitudinal, was significantly reduced with nitroxybutyl-flurbiprofen apart from the number of longitudinal ulcers with the highest dose. CONCLUSIONS: These studies show that nitroxybutyl-flurbiprofen is associated with significantly less macroscopic damage in the small intestine than flurbiprofen but was associated with mitochondrial damage in vivo and caused similar increases in permeability of the small intestine, suggesting that its beneficial effect is on the later pathogenic stages of the damage.

Animals↗
PubMed1997

Mitochondrial damage: a possible mechanism of the "topical" phase of NSAID induced injury to the rat intestine.

BACKGROUND: The "topical" effect of non-steroidal anti-inflammatory drugs (NSAIDs) seems to be an important cause of NSAID induced gastrointestinal damage. AIM: To examine the possible mechanism of the "topical" phase of damage in the small intestine. METHODS: Electron microscopy and subcellular organelle marker enzyme studies were done in rat small intestine after oral administration of indomethacin (doses varied between 5 and 30 mg/kg). The effect of conventional and non-acidic NSAIDs on rat liver mitochondrial respiration was measured in vitro in a Clarke-type oxygen electrode. RESULTS: The subcellular organelle marker enzymes showed mitochondrial and brush border involvement within an hour of indomethacin administration. Electron microscopy showed dose dependent mitochondrial changes following indomethacin administration consistent with uncoupling of oxidative phosphorylation (or inhibition of electron transport) which were indistinguishable from those seen with the uncoupler dinitrophenol. Parenteral indomethacin caused similar changes, but not in rats with ligated bile ducts. A range of NSAIDs, but not paracetamol or non-acidic NSAIDs which have a favourable gastrointestinal tolerability profile, uncoupled oxidative phosphorylation in vitro at micromolar concentrations and inhibited respiration at higher concentrations. In vivo studies with nabumetone and aspirin further suggested that uncoupling or inhibition of electron transport underlies the "topical" phase of NSAID induced damage. CONCLUSION: Collectively, these studies suggest that NSAID induced changes in mitochondrial energy production may be an important component of the "topical" phase of damage induction.

Acetaminophen↗
PubMed1997

Motivational and behavioral correlates of life satisfaction in an elderly sample.

This study examined the relationship between self-reported life satisfaction of elderly persons and their motivation for competence as assessed on self-ratings and indirect measures of needs for achievement and affiliation. Behavioral data relating to frequency of engaging in mastery-type activities, social interactions and exercise were also gathered. This sample described themselves as content with their lives and healthy relative to normative levels. As predicted, there was a marked discrepancy between self-report and implicit measures of motivation, with self-reported motives being significantly correlated with satisfaction (i.e., r = .33 for Achievement and r = .30 for Affiliation) and implicit motives not significantly correlated with satisfaction. Needs for achievement and affiliation on the whole did not significantly correlate with actual life circumstances. The results suggest that competence motivation may play a small part in the contentment which older individuals feel in their lives.

Achievement↗
PubMed1997

Leucocytopenia after rifampicin and ofloxacin therapy in leprosy.

New antimycobacterial agents and combined treatment regimens are being introduced for the treatment of leprosy. Ofloxacin is one such broad spectrum antimicrobial agent. In this study rifampicin plus ofloxacin were administered daily for 4 weeks (daily supervised dose). Two patients (and possibly a third patient who refused all investigations) out of 125 patients developed leucocytopenia during the third week of therapy. It was associated with fever, malaise, nausea and loss of appetite. They recovered after cessation of drug treatment. Patients receiving ofloxacin should be monitored for constitutional symptoms suggestive of this complication even though the risk of such complication may be minimal.

Adolescent↗
PubMed1997

Nutrition knowledge among adolescent high school female athletes.

The purpose of this study is to evaluate the effectiveness of an original sports nutrition education program in changing the nutrition behavior of the female high school varsity football teams of the Baseline League of Southern California. A total of 72 subjects from eight teams were randomly divided into two groups, control and experimental. Only the experimental group received nutrition education. Dietary habits of the athletes were studied through a pre- and post- 24-hour recall. A comparison of pretest scores of both groups showed no significant difference in level of nutrition knowledge. The posttest scores obtained after nutrition education showed a significant difference in nutrition knowledge for the experimental group. However, there was no significant improvement in dietary intake and food choices due to the limited duration of the study.

Adolescent↗
PubMed1997

Epidemiological features of acquired immunodeficiency syndrome in southern India.

AIDS was diagnosed in 187 men and 24 women (M:F = 8:1) from April 1987 till December 1994 at the Christian Medical College Hospital, Vellore. The doubling time of the occurrence of AIDS cases was 14 months; during 1987-90 there were an average of 5.7 cases per year; in 1991-93 there were 28 per year; in 1994 there were 104 cases. The mean age of patients was 33 yr for men and 31 for women. Among men, the primary mode of infection was heterosexual contact with female commercial sex workers. Among women, the most common source of infection was their husbands. There were 4 bisexuals and one homosexual subject who might have acquired infection by having sex with other men. There were 135 subjects from urban and 76 from rural communities. Most subjects belonged to the lower socio-economic classes. These data show that HIV infection had been very widespread in this region, both urban and rural.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Screening blood spots for inborn errors of metabolism by electrospray tandem mass spectrometry with a microplate batch process and a computer algorithm for automated flagging of abnormal profiles.

Metabolic profiling of amino acids and acylcarnitines from blood spots by automated electrospray tandem mass spectrometry (ESI-MS/MS) is a powerful diagnostic tool for inborn errors of metabolism. New approaches to sample preparation and data interpretation have helped establish the methodology as a robust, high-throughput neonatal screening method. We introduce an efficient 96-well-microplate batch process for blood-spot sample preparation, with which we can obtain high-quality profiles from 500-1000 samples per day per instrument. A computer-assisted metabolic profiling algorithm automatically flags abnormal profiles. We selected diagnostic parameters for the algorithm by comparing profiles from patients with known metabolic disorders and those from normal newborns. Reference range and cutoff values for the diagnostic parameters were established by measuring either metabolite concentrations or peak ratios of certain metabolite pairs. Rigorous testing of the algorithm demonstrates its outstanding clinical sensitivity in flagging abnormal profiles and its high cumulative specificity.

Algorithms↗
PubMed1997

Hypomelanosis of Ito with unusual associations.

Hypomelanosis of Ito (HOI) is a neurocutaneous disorder which clinically is a well-characterised disease, in which chromosomal instability may be a component. Various neurological and other non-cutaneous malformations have been reported in association with the characteristic swirling pattern of hypopigmentation. We report two cases of this rare condition, one with hitherto unreported associations.

Abnormalities, Multiple↗
PubMed1996

Presence of a light-independent phospholipase A2 in bovine retina but not in rod outer segments.

Rod outer segments (ROS) are responsible for the visual transduction process. Rhodopsin, which constitutes 85-90% of ROS proteins, absorbs light photons, changes its conformation, and then binds to a heterotrimeric G-protein called transducin. As a consequence, transducin dissociates into Talpha and Tbetagamma subunits. The presence in ROS of a phospholipase A2 (PLA2) stimulated by light and guanosine 5'-O-(3-thio)triphosphate was first demonstrated in 1987 (Jelsema, C. L.(1987) J. Biol. Chem. 262, 163-168). This led that author to conclude that ROS PLA2 could be involved in the phototransduction process, and raised the possibility of receptor-mediated activation of PLA2 via G-proteins in cell types other than rods. However, the biochemical characteristics and the role of this PLA2 have not been fully elucidated. We have tried to reproduce some of the results previously reported in order to further characterize this enzyme. We have found that, in our hands, there is neither light-dependent nor GTP-dependent PLA2 activity in intact purified ROS. We also failed to detect PLA1 activity in those ROS preparations. Nevertheless, we detected significant amounts of PLA2 activity in two subretinal fractions adjacent to ROS: RPE (enriched with retinal pigment epithelial cells) and P200 (presumably containing neuronal cells, Müller cells, and rod inner segments). The enzyme present both in RPE and P200 is light- and GTP-independent, Ca2+- and Mg2+-independent, and seems to be optimally active in the alkaline pH range. Our results suggest that there is, if any, vanishingly little PLA2 or PLA1 activity in intact purified ROS and that the activity levels previously reported in the literature could have been due to a contamination by either RPE or P200. This is supported by our observation that some contaminated ROS preparations were "PLA2 active."

Animals↗
PubMed1996

Skin lesions in HIV-positive and HIV-negative patients in south India.

BACKGROUND: Various dermatologic conditions have been reported to occur with increased frequency in human immunodeficiency virus (HIV)-positive individuals, but there are only a few studies comparing the prevalences of skin diseases in HIV-positive patients with those in matched HIV-negative controls. METHODS: Skin lesions in 129 HIV-positive patients and 258 HIV-negative controls were studied prospectively over an 18-month period from October 1991 to March 1993. RESULTS: Oral candida, tinea cruris, and ichthyosis were significantly more common in HIV-positive patients compared to controls. Several other dermatologic conditions were found only in the HIV-positive group. CONCLUSIONS: The pattern of skin lesions in Indian patients with HIV infection may be different from that in the West.

Adult↗