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Biomedical subjects

M Srinivasan

Publications and source records attributed to M Srinivasan.

At least 73 records · Page 4Linked to original sources
PubMed2000

HLA and Mooren's ulceration.

BACKGROUND: Mooren's ulcer is a progressive intractable destructive peripheral ulceration of the cornea, probably of autoimmune aetiology. The disease is rare in the northern hemisphere but is more common in southern and central Africa and the Indian subcontinent. Although rare, its predominance in certain racial groups and their second generation migrants worldwide indicates a genetic as well as a geographic predisposition. The highly polymorphic human leucocyte antigens (HLA) confer genetic susceptibility to several autoimmune disorders. Therefore, a possible link between Mooren's ulcer and HLA type was investigated. METHODS: Patients (n=22) with non-infective destructive peripheral corneal inflammatory disease were recruited worldwide. Differential diagnosis confirmed Mooren's ulceration in 12 cases. HLA typing (HLA-A, B, C, DRB, DQB) was performed by serology and PCR using sequence specific primers. The patients came from varied ethnic backgrounds and their HLA typing results were compared with published data from ethnically matched control populations. RESULTS: Of the 12 patients with Mooren's ulcer, 10 (83%) were HLA-DR17(3) positive (including all nine patients of Asian, Indonesian, and black African origin), and 10 (83%) were HLA-DQ2 positive. The frequency of HLA-DR17(3) and DQ2 was higher in the Mooren's ulcer group compared to published data from ethnically matched control populations, where the expected antigen frequencies range between 5% and 40%. CONCLUSION: These results suggest a possible association between HLA-DR17(3) and/or DQ2 and susceptibility to Mooren's ulcer.

Adolescent↗
PubMed2000

Malignant infantile osteopetrosis presenting with neonatal hypocalcaemia.

Presentation characteristics were reviewed in 14 children from 12 families with malignant infantile osteopetrosis seen at two large referral centres for bone marrow transplantation. Children from six of these families presented initially with symptoms of hypocalcaemia. These comprised early or late neonatal convulsions in six cases (corrected serum calcium < 1.5 mmol/l), and vomiting and irritability (serum calcium 1.68 mmol/l) in another. One other related child had severe and persistent jittering episodes almost certainly attributable to hypocalcaemia. In seven of eight cases, these symptoms developed during the first 14 days of life. Although occasionally reported previously, malignant infantile osteopetrosis remains essentially unrecognised as a cause of neonatal hypocalcaemia, often resulting in diagnostic confusion and delay. This is important in the context of curative haemopoietic stem cell transplantation where preservation of sight may depend on early intervention.

Biomarkers↗
PubMed2000

Adaptive changes in insulin secretion by islets from neonatal rats raised on a high-carbohydrate formula.

Artificial rearing of neonatal rats on a high-carbohydrate (HC) milk formula resulted in the immediate onset of hyperinsulinemia. This study examines, in islets of 12-day-old HC rats, adaptive changes that support the hyperinsulinemic state. Increases in plasma glucagon-like peptide-1 (GLP-1) levels and islet GLP-1 receptor mRNA supported increased insulin secretion by HC islets. Isolated HC islets, but not mother-fed (MF) islets, secreted moderate amounts of insulin in a glucose- and Ca(2+)-independent manner. Under stringent Ca(2+)-free conditions and in the presence of glucose, GLP-1 plus acetylcholine augmented insulin release to a larger extent in HC islets. Levels of adenylyl cyclase type VI mRNA and activities of protein kinase A, protein kinase C, and calcium calmodulin kinase II were increased in HC islets. A tenfold increase in norepinephrine concentration was required to inhibit insulin secretion in HC islets compared with MF islets, indicating reduced sensitivity to adrenergic signals. This study shows that significant alterations at proximal and distal sites of the insulin secretory pathway in HC islets may support the hyperinsulinemic state of these rats.

Adaptation, Physiological↗
PubMed2000

Preventing psychological trauma in soldiers: the role of operational stress training and psychological debriefing.

Armed conflict is associated with significant long-term psychiatric morbidity. Interventions to reduce the incidence of psychiatric disorder following psychological trauma may be classified into three categories. Primary prevention includes the selection, preparation and training of individuals likely to be exposed to potentially traumatizing events. Secondary prevention comprises a variety of brief psychological techniques immediately or shortly after traumatizing life events, the best known of which is Psychological Debriefing. Tertiary interventions comprise the treatment of established PTSD and others. Psychiatric morbidity was studied in 106 British soldiers returning from UN peace-keeping duties in the former Republic of Yugoslavia. All 106 soldiers received an Operational Stress Training Package prior to their deployment and a randomly selected group also received a post-operational PD. Very low rates of PTSD and other psychopathology were found overall and the Operational Stress Training Package may have contributed to this. Elevated CAGE scores suggestive of significant alcohol misuse were observed in both groups and chemical avoidance behaviours arising from this may have masked psychopathology. CAGE scores diminished significantly in the debriefed group by the end of the follow-up period suggesting that PD may have been of benefit despite the apparent absence of PTSD. This study also demonstrates that a high incidence of psychiatric morbidity is not an inevitable consequence of military conflict.

Adolescent↗
PubMed2000

Sodium bicarbonate--an alternative to hyaluronidase in ocular anaesthesia for cataract surgery.

PURPOSE: To evaluate and compare the safety, efficacy and cost-effectiveness of 7.5% sodium bicarbonate buffered lidocaine (pH 7.2) with hyaluronidase mixed lidocaine (pH 4.6) for local anaesthesia in cataract surgery. METHODS: This prospective study comprised two parts. Part I: We evaluated the ocular and systematic anaesthetic safety and efficacy of 7.5% sodium bicarbonate buffered lidocaine on 112 consecutive patients undergoing cataract extraction with intraocular lens (IOL) implantation. At 12-week postoperative follow up final visual acuity and detailed fundus examination was done. Part II: It was conducted as a double blind, randomized comparative clinical trial involving 120 patients undergoing cataract surgery under retrobulbar anaesthesia. Patients were randomly assigned to one of the two groups: 60 eyes received 2 ml of 2% lidocaine with 1:200,000 epinephrine and 1 ml of 7.5% sodium bicarbonate, (0.299 mmol/ml); the remaining 60 eyes received 2 ml of 2% lidocaine with 1:200,000 epinephrine and 450 units of hyaluronidase (15 U/ml). In the event of incomplete akinesia, retrobulbar blocks were supplemented at 10 minutes. Onset and duration of anaesthesia and akinesia were assessed and compared in both groups. RESULTS: The pH-adjusted lidocaine group did not show any demonstrable variation in blood pressure (BP) or other systemic reaction. No anaesthesia-related adverse ocular effects were observed either during or after surgery. Thirty-one eyes (51.6%) achieved complete anaesthesia and akinesia within 5 minutes compared to 13 eyes (21.6%) in the hyaluronidase group. However, the overall mean onset time of anaesthesia and akinesia, repeat block rate and the duration of the anaesthesia were comparable in both the groups--p: 0.14). Twelve weeks postoperatively 88.39% of patients showed a best corrected visual acuity of 6/18 or better (73.21%-6/12 or better). CONCLUSION: In this study, sodium bicarbonate buffered 2% lidocaine was found to be a safe and effective local anaesthetic, with reduced time of onset, and improved quality of both anaesthesia and akinesia. Sodium bicarbonate (7.5%) may be used as an alternative to hyaluronidase in ocular anaesthesia. It is readily available and is cost effective.

Adult↗
PubMed2000

Metabolic programming by nutrition during early development.

Incidence of obesity and diabetes is increasing at an alarming rate not only among the populations of the affluent nations but also amongst the populations of the developing nations. Understanding the mechanisms that cause the onset of these pathological conditions is a requisite to effectively tackling this problem. In this context the role of early nutritional experiences as a causative factor is being extensively investigated. This article briefly reviews the field of metabolic programming vis-a-vis an altered nutritional milieu during perinatal period and consequent adaptive metabolic patterning and metabolic imprinting in adult and/or consequent offspring.

Adaptation, Physiological↗
PubMed1999

Mooren ulcer in South India: serology and clinical risk factors.

PURPOSE: To investigate the rate of undiagnosed rheumatologic diseases and hepatitis C infection among patients with the clinical diagnosis of Mooren ulcer seen at Aravind Eye Hospital, Madurai, South India. METHODS: Twenty-one patients with the clinical diagnosis of Mooren ulcer and 44 control patients underwent a complete ophthalmic history and examination, as well as serologic testing for antinuclear antibodies, rheumatoid factor, antineutrophil cytoplasmic antibodies, herpes simplex virus 1 antibodies, and hepatitis C virus antibodies. RESULTS: There were no statistically significant differences in the rates of seropositivity for antinuclear antibodies, rheumatoid factor, antineutrophil cytoplasmic antibodies, herpes simplex virus 1 antibodies, and hepatitis C virus antibodies between patients with Mooren ulcer and control patients. Two patients with Mooren ulcer and four control patients were found to have a rheumatoid factor titer of greater than 1:20. One of the control patients, but none of the patients with Mooren ulcer, was found to have serologic evidence of hepatitis C infection. A history of corneal trauma, surgery, or infection was reported by 68% of patients with Mooren ulcer, compared with 20% of control patients (P < .001). Among patients with Mooren ulcer, bilateral disease occurred in 37% of patients, visual acuity was reduced to light perception in 15% of eyes, and perforation occurred in 19% of eyes. CONCLUSIONS: Nineteen (90%) of 21 patients with the clinical diagnosis of Mooren ulcer were found to have no evidence of an underlying rheumatologic disease by history, examination, or serologic testing, and none was seropositive for hepatitis C. However, patients with Mooren ulcer were more likely than control patients to report a history of corneal trauma, surgery, or infection.

Adolescent↗
PubMed1999

Computer simulation of the interaction of non-steroidal anti-inflammatory drugs: indoprofen and NS398 with cyclooxygenase.

We have applied computer simulation technique to study interaction of two anti-inflammatory drugs (NSAIDs) indoprofen and NS398 with cyclooxygenase (COX-1 and COX-2) enzymes. We have also investigated conformational flexibility of the two drugs by systematic search and simulated annealing molecular dynamics (SAMD) methods. Both the drugs were docked in the cyclooxygenase channel using in house docking program IMF1. The complexes were energy minimised by molecular mechanics (MM) method. These were heated for 30 picoseconds (ps), equilibrated for 110 ps at 300K and subjected to 'production simulation' for 110 ps by molecular dynamics (MD) method using Sanderís module of AMBER 5.0 package and united atom force field mostly from PARM96.DAT. Integration was carried out with time step of 0.001 ps, distance dependent di-electric constant with scaling factor 2.0 for 1-4 interaction and cut-off distance for non-bonded pair-list equal to 8A. The non-bonded pair-list was upgraded after every 20 cycles. The coordinate output from MD trajectories is analysed using analysis package of AMBER 5.0, MOLMOL, P-CURVES 3.0 and in house packages: ANALMD, ANALP1. We have observed perturbative changes in COX-1 and COX-2 structures due to indoprofen and NS398. In case of indoprofen specific changes between COX-1 and COX-2 were noted in helix D, H6, S6 and helix H8 in the cyclooxygenase cavity. In case of NS398 these were in helix B in membrane binding domain, helix H6, S8 and S10 in cyclooxygenase cavity and helices H14-H16 in small lobe close to haem binding region. Implications of these results in enzyme selectivity by NSAIDs is discussed here.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

A dietary intervention (high carbohydrate) during the neonatal period causes islet dysfunction in rats.

Artificial rearing of 4-day-old rat pups on a high-carbohydrate (HC) milk formula results in the immediate onset of hyperinsulinemia. To evaluate these early changes, studies on pancreatic function were carried out on 12-day-old HC rats and compared with age-matched mother-fed (MF) pups. The plasma insulin and glucagon contents were increased sixfold and twofold, respectively, in HC rats compared with MF rats. There was a distinct leftward shift in the glucose-stimulated insulin secretory pattern for HC islets. HC islets secreted insulin in the absence of any added glucose and in the presence of Ca(2+) channel inhibitors. The activities of glucokinase, hexokinase, glyceraldehyde-3-phosphate dehydrogenase, and pyruvate dehydrogenase complex were significantly increased in HC islets compared with MF islets. The protein contents of GLUT-2 and hexokinase were significantly increased in HC islets. These findings indicate that a nutritional intervention in the form of a HC formula only during the suckling period has a profound influence on pancreatic function, causing the onset of hyperinsulinemia.

Age Factors↗
PubMed1999

Use of Traditional Eye Medicines by corneal ulcer patients presenting to a hospital in South India.

PURPOSE: To investigate the nature and frequency of use of Traditional Eye Medicine (TEM) for corneal ulcer in patients from predominantly rural background. METHODS: We documented the the use of TEM by corneal ulcer patients presenting to a tertiary eye-care centre in South India during two months of 1996. RESULTS: Of 283 patients enrolled in the study, 135 (47.7%) of the patients used TEM. There was no difference with regard to age and sex distribution of patients using TEM and those who did. Patients with history of trauma were more likely to use TEM. Common forms of TEM used were human breast milk 61(45.2%), leafy matter 40(29.6%), castor oil 16 (11.9%), and hen's blood 8 (5.9%). CONCLUSION: Though the awareness of intraocular lens implantation for cataract surgery is very high in this segment of the population, it is still tragic that an awareness of primary eye care following trauma has not been created. Health education is mandatory to prevent this avoidable cause of blindness.

Adolescent↗
PubMed1998

Phosphorylation at the nuclear localization signal of Ca2+/calmodulin-dependent protein kinase II blocks its nuclear targeting.

Translocation of protein kinases with broad substrate specificities between different subcellular compartments by activation of signaling pathways is an established mechanism to direct the activity of these enzymes toward particular substrates. Recently, we identified two isoforms of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II), which are targeted to the nucleus by an alternatively spliced nuclear localization signal (NLS). Here we report that cotransfection with constitutively active mutants of CaM kinase I or CaM kinase IV specifically blocks nuclear targeting of CaM kinase II as a result of phosphorylation of a Ser immediately adjacent to the NLS of CaM kinase II. Both CaM kinase I and CaM kinase IV are able to phosphorylate this Ser residue in vitro, and mutagenesis studies suggest that this phosphorylation is both necessary and sufficient to block nuclear targeting. Furthermore, we provide experimental evidence that introduction of a negatively charged residue at this phosphorylation site reduces binding of the kinase to an NLS receptor in vitro, thus providing a mechanism that may explain the blockade of nuclear targeting that we have observed in situ.

Amino Acid Sequence↗
PubMed1998

Mooren's ulcer.

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Animals↗
PubMed1998

Follow-up study of British military hostages and their families held in Kuwait during the Gulf War.

On 2 August 1990 Iraq invaded Kuwait and held hostage all its inhabitants. Amongst those forced to stay were 71 British servicemen and their families who were held hostage for up to four and a half months. This study investigated the mental health status of this group of individuals at 6 and 18 months after the final hostage was released. Participants completed the Impact of Event Scale and the 28-item version of the General Health Questionnaire at both 6 and 18 months. In addition they completed a questionnaire regarding background factors, the dimensions of the trauma and the effects of their hostage experience. The Impact of Event Scale scores changed little over time whereas the General Health Questionnaire scores reduced significantly (p = .001) over the 12-month period suggesting that despite ongoing intrusive and avoidance phenomena levels of psychological distress did reduce. Those variables most strongly associated with a poor psychological outcome were witnessing physical violence and perceived deterioration in physical and mental health. Poor outcome at 6 months was strongly correlated with poor outcome at 18 months.

Adult↗
PubMed1997

The Tim54p-Tim22p complex mediates insertion of proteins into the mitochondrial inner membrane.

We have identified a new protein, Tim54p, located in the yeast mitochondrial inner membrane. Tim54p is an essential import component, required for the insertion of at least two polytopic proteins into the inner membrane, but not for the translocation of precursors into the matrix. Several observations suggest that Tim54p and Tim22p are part of a protein complex in the inner membrane distinct from the previously characterized Tim23p-Tim17p complex. First, multiple copies of the TIM22 gene, but not TIM23 or TIM17, suppress the growth defect of a tim54-1 temperature-sensitive mutant. Second, Tim22p can be coprecipitated with Tim54p from detergent-solubilized mitochondria, but Tim54p and Tim22p do not interact with either Tim23p or Tim17p. Finally, the tim54-1 mutation destabilizes the Tim22 protein, but not Tim23p or Tim17p. Our results support the idea that the mitochondrial inner membrane carries two independent import complexes: one required for the translocation of proteins across the inner membrane (Tim23p-Tim17p), and the other required for the insertion of proteins into the inner membrane (Tim54p-Tim22p).

Biological Transport↗
PubMed1997

Role of serine/threonine protein phosphatases in insulin regulation of Na+/K+-ATPase activity in cultured rat skeletal muscle cells.

In this study, we examined the potential role of serine/threonine protein phosphatase-1 (PP-1) and PP-2A in the mechanism of Na+/K+-ATPase activation by insulin in the rat skeletal muscle cell line L6. Incubation of L6 cells with insulin caused a time- and dose-dependent stimulation of ouabain-sensitive plasma membrane Na+/K+-ATPase activity. Pretreatment with okadaic acid (OA; 0.1-1 microM) or calyculin A (1 microM) blocked insulin's effect on Na+/K+-ATPase activation. Low concentrations of OA that specifically inhibit PP-2A were ineffective. Immunoprecipitation of the enzyme from 32P-labeled cells with an antibody directed against the alpha-1 subunit of the enzyme revealed a 60% decrease in 110-kDa protein phosphorylation in insulin-treated cells. The presence of calyculin A blocked insulin-mediated dephosphorylation of Na+/K+-ATPase, whereas low concentrations of OA were ineffective. To further confirm the role of PP-1, we used L6 cell lines that overexpress the glycogen/SR-associated regulatory subunit of PP-1, PP-1G. Overexpression of PP-1G resulted in a 3-fold increase in insulin-stimulated PP-1 catalytic activity. This was accompanied by a 30% increase in basal Na+/K+-ATPase activity and a >2-fold increase in insulin's effect on pump activity. Inhibition of phosphatidylinositol-3 kinase with wortmannin blocked insulin-stimulated PP-1 activation as well as the dephosphorylation and activation of Na+/K+-ATPase. We conclude that insulin regulates the activity of Na+/K+-ATPase by promoting dephosphorylation of the alpha subunit via an insulin-stimulated PP-1 and that phosphatidylinositol-3 kinase-generated signals may mediate insulin activation of PP-1 and Na+/K+-ATPase.

Androstadienes↗
PubMed1997

Cataract progression in India.

AIMS: The study was undertaken to test the feasibility of using the LOCS III cataract grading scale in the field and to determine the rate of cataract progression over a 1 year period of time. METHODS: For 150 subjects between the ages of 33 and 55 who attended the refraction clinic at Aravind Eye Hospital in Madurai, India, lens abnormalities were graded at the slit lamp using the LOCS III scale. One year later, 99 of the subjects were re-evaluated by the same methodology to assess the amount of lens change. RESULTS: Interrater reliability was high. A change of 0.5 or more in lens colour, cortical, nuclear, or posterior subcapsular cataract was observed in at least one eye of 54% of the subjects. CONCLUSION: The LOCS III grading scale is a feasible method for measuring lens changes in the field with the slit lamp. Cataract progression in India is rapid enough to permit intervention studies to be performed with relatively small numbers of subjects over a short period of time (that is, 600 subjects for 2 years).

Adult↗