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Biomedical subjects

M Srinivasan

Publications and source records attributed to M Srinivasan.

At least 91 records · Page 5Linked to original sources
PubMed1997

Epidemiology and aetiological diagnosis of corneal ulceration in Madurai, south India.

AIMS/BACKGROUND: To determine the epidemiological characteristics and risk factors predisposing to corneal ulceration in Madurai, south India, and to identify the specific pathogenic organisms responsible for infection. METHODS: All patients with suspected infectious central corneal ulceration presenting to the ocular microbiology and cornea service at Aravind Eye Hospital, Madurai, from 1 January to 31 March 1994 were evaluated. Sociodemographic data and information pertaining to risk factors were recorded, all patients were examined, and corneal cultures and scrapings were performed. RESULTS: In the 3 month period 434 patients with central corneal ulceration were evaluated. A history of previous corneal injury was present in 284 patients (65.4%). Cornea cultures were positive in 297 patients (68.4%). Of those individuals with positive cultures 140 (47.1%) had pure bacterial infections, 139 (46.8%) had pure fungal infections, 15 (5.1%) had mixed bacteria and fungi, and three (1.0%) grew pure cultures of Acanthamoeba. The most common bacterial pathogen isolated was Streptococcus pneumoniae, representing 44.3% of all positive bacterial cultures, followed by Pseudomonas spp (14.4%). The most common fungal pathogen isolated was Fusarium spp, representing 47.1% of all positive fungal cultures, followed by Aspergillus spp (16.1%). CONCLUSIONS: Central corneal ulceration is a common problem in south India and most often occurs after a superficial corneal injury with organic material. Bacterial and fungal infections occur in equal numbers with Streptococcus pneumoniae accounting for the majority of bacterial ulcers and Fusarium spp responsible for most of the fungal infections. These findings have important public health implications for the treatment and prevention of corneal ulceration in the developing world.

Adolescent↗
PubMed1997

Visually mediated odometry in honeybees

The ability of honeybees to gauge the distances of short flights was investigated under controlled laboratory conditions where a variety of potential odometric cues such as flight duration, energy consumption, image motion, airspeed, inertial navigation and landmarks were manipulated. Our findings indicate that honeybees can indeed measure short distances travelled and that they do so solely by analysis of image motion. Visual odometry seems to rely primarily on the motion that is sensed by the lateral regions of the visual field. Computation of distance flown is re-commenced whenever a prominent landmark is encountered en route. 'Re-setting' the odometer (or starting a new one) at each landmark facilitates accurate long-range navigation by preventing excessive accumulation of odometric errors. Distance appears to be learnt on the way to the food source and not on the way back.

Journal Article↗
PubMed1997

Honeybee vision: analysis of orientation and colour in the lateral, dorsal and ventral fields of view

The ability of honeybees (Apis mellifera) to learn and recognise peripherally presented patterns was investigated by training bees in a Y-maze which presented patterns on the side walls, the ceiling or the floor. We found that pattern orientation is learnt and recognised in the lateral and frontal visual field, but not in the dorsal or ventral fields. Colour information, in contrast, is used in the lateral and frontal as well as the ventral visual field, but not in the dorsal field. If pattern orientation is different on opposite sides of the visual field during training, both patterns are learned, but each on its own is sufficient for the bees to recognise the learnt stimulus. However, unilaterally learnt pattern information, be it orientation or colour, cannot be accessed when the test pattern is viewed on the other side. That is, interocular transfer of such information does not occur.

Journal Article↗
PubMed1997

Trial of chlorhexidine gluconate for fungal corneal ulcers.

AIMS: Suppurative corneal ulcers due to filamentous fungi are a serious and intractable problem in many tropical developing countries. In vitro studies and a small pilot study have shown that chlorhexidine gluconate is effective. The aim was to establish the optimum concentration which would be appropriate to use in a larger randomized clinical trial. METHODS: A masked randomized clinical trial of three concentrations of chlorhexidine compared with natamycin 5% was carried out in consecutive patients with established corneal ulcers shown by microscopy to contain fungal hyphae and later proven to be culture positive. Topical treatments were applied 1/2-hourly to 2-hourly for up to 5 days, with reduced frequency thereafter, and all patients were re-assessed at 21 days. RESULTS: Of 60 patients entered in the trial, 2 were lost to follow-up, and 12 were classified as 'severe' with little prospect of recovery. At 5 days the response was related to the concentration of chlorhexidine, with 0.2% giving the best results. Compared with the response to natamycin as the referent, the relative efficacy was 1.17 with chlorhexidine 0.05%, 1.43 with 0.1%, and 2.00 with 0.2%. The superiority of 0.2% chlorhexidine over natamycin was statistically significant (relative efficacy 2.20, p = 0.043) in patients not having had prior antifungal treatment. CONCLUSIONS: This preliminary study justifies further trials of chlorhexidine as a primary treatment for fungal corneal ulcers in circumstances where specific antifungal agents are not available.

Administration, Topical↗
PubMed1997

The initial complication rate of phacoemulsification in India.

PURPOSE: This study was designed to investigate the feasibility of teaching experienced surgeons to perform phacoemulsification in India, a cataract-endemic area. Complications occurring during surgery and the first postoperative day were documented and evaluated. METHODS: During a 1-month period, at the Aravind Eye Hospital in Madurai, India, the first 100 consecutive cataract operations performed by each of three experienced surgeons (a total of 300 cases), using phacoemulsification were prospectively evaluated. Multiple logistic regression was used to identify factors associated with intraoperative and postoperative complications. RESULTS: The mean age of patients was 57.4+/-9.3 years. The median best corrected preoperative visual acuity was 20/80. Mean surgical and phacoemulsification times were 15.8+/-3.7 minutes and 2.2+/-1.5 minutes, respectively. Complications occurred in 65 (21.7%) eyes. The most common was a rent in the posterior capsule, occurring in 40 (13.3%) eyes. There were significant variations in complication rate and in surgical time among the surgeons. The risk of experiencing a complication decreased as the number of phacoemulsifications performed increased. An increased risk of complications was associated with worse preoperative visual acuity and increasing patient age. CONCLUSIONS: With each successive case, the chances of experiencing a complication decreased 1%. Acceptable results were obtained within 1 month of performing the first phacoemulsification.

Adult↗
PubMed1996

Bacillus polymyxa stimulates increased Rhizobium etli populations and nodulation when co-resident in the rhizosphere of Phaseolus vulgaris.

Microbial competition for carbon sources is a primary determinant of rhizosphere ecology. We employed the PCR to examine the population fluctuations of a symbiotic nitrogen-fixing bacterium (Rhizobium etli) during the first 11 days following inoculation of Phaseolus vulgaris seedlings grown in the presence or absence of a common asymbiotic rhizosphere resident (Bacillus polymyxa). When B. polymyxa was applied as a co-inoculant, increases in both early rhizobial root populations and final root population densities were observed as compared to single inoculation with R. etli. Modifications to host plant growth (including increased lateral root formation and nodules number) were found concomitant with elevations in R. etli populations on plants co-inoculated with both bacterial genera. In contrast to the in planta results, population enhancements were not observed when R. etli and B. polymyxa were co-cultured in vitro using minimal media in the absence of the seedling. Addition of seed exudate to the growth media also failed to stimulate the population increases observed during co-release in planta. These results suggest that B. polymyxa acts indirectly (i.e., via the plant host) to increase R. etli populations. Our observed synergism among co-resident bacteria supports the hypothesis that microbial communities which colonize the spermosphere may play a significant role in plant development and rhizosphere ecology.

Bacillus↗
PubMed1996

Effect of tumor necrosis factor-alpha on insulin-stimulated mitogen-activated protein kinase cascade in cultured rat skeletal muscle cells.

Tumor necrosis factor-alpha (TNF-alpha) is a proposed mediator of insulin resistance in obese/diabetic animals through its effects on tyrosine phosphorylation of the insulin receptor and its substrate, insulin receptor substrate-1. In this study, the acute effects of TNF-alpha on the mitogen-activated protein kinase (MAPK) signalling cascade were examined in cultured rat skeletal muscle cell line, L6. Insulin treatment of L6 cells resulted in a rapid increase in MAPK activity (> twofold in 5 min with 10 nM insulin). Prior treatment with TNF-alpha for 60 min blocked subsequent insulin-induced activation of MAPK in a dose- and time-dependent manner. Metabolic labelling studies with inorganic [32P]phosphate followed by immuno-precipitation of MAPK and its upstream activator, mitogen-activated protein kinase kinase, indicated decreased phosphorylation of MAPK and its kinase in response to insulin in cells exposed to TNF-alpha. This effect of TNF-alpha was not due to inhibition of insulin-stimulated p21ras-GTP loading or Raf-1 phosphorylation. Low concentrations (2 nM) of okadaic acid, a serine/threonine phosphatase inhibitor, prevented TNF-alpha-induced inhibition of MAPK and restored insulin's effect on MAPK activity, while orthovanadate (a tyrosine phosphatase inhibitor), inhibitor 2 (phosphatase-1 inhibitor) and FK506 (phosphatase-2B inhibitor) were ineffective. These results suggested an involvement of an okadaic-acid-sensitive serine/threonine phosphatase in TNF-alpha-induced blockade of insulin's effect on MAPK and/or its kinase. Therefore, we examined the effect of TNF-alpha on protein phosphatase-1 (PP-1) and protein phosphatase-2A (PP-2A) activities. As reported by us earlier, insulin rapidly stimulated PP-1 and concomitantly inhibited PP-2A activities in control cells. TNF-alpha treatment blocked insulin-induced activation of PP-1. In contrast to PP-1, TNF-alpha caused a 60% increase in PP-2A activity and insulin failed to prevent this TNF-alpha effect. The time course of PP-2A activation by TNF-alpha preceded the kinetics of inhibition of MAPK. Cell-permeable ceramide analogs mimicked the TNF-alpha effect on MAPK inhibition and PP-2A activation. We conclude that TNF-alpha abrogates the insulin effect on MAPK activation by increasing dephosphorylation of MAPK kinase via an activated phosphatase.

Animals↗
PubMed1996

Honeybee navigation en route to the goal: visual flight control and odometry

Recent research has uncovered a number of different ways in which bees use cues derived from optic flow for navigational purposes. The distance flown to a food source is gauged by integrating the apparent motion of the visual world that is experienced en route. In other words, bees possess a visually driven 'odometer' that is robust to variations in wind load and energy expenditure. Bees flying through a tunnel maintain equidistance to the flanking walls by balancing the apparent speeds of the images of the walls. This strategy enables them to negotiate narrow passages or to fly between obstacles. The speed of flight in a tunnel is controlled by holding constant the average image velocity as seen by the two eyes. This avoids potential collisions by ensuring that the bee slows down when flying through narrow passages. Bees landing on a horizontal surface hold constant the image velocity of the surface as they approach it. This automatically ensures that flight speed decreases with altitude and is close to zero at touchdown. The movement-sensitive mechanisms underlying these various behaviours seem to be different, qualitatively as well as quantitatively, from those mediating the well-investigated optomotor response.

Journal Article↗
PubMed1996

Incidence of corneal ulceration in Madurai district, South India.

OBJECTIVE: To determine the incidence of corneal ulceration in Madurai District, South India. DESIGN: Retrospective incidence study. SETTING: General community. PATIENTS: All patients who reside in Madurai District and presented to an ophthalmologist in 1993 with corneal ulceration. MAIN OUTCOME MEASURE: Cases of corneal ulceration. RESULTS: 1148 cases of corneal ulceration were recorded in the medical records of those ophthalmologists who maintained records. Based upon the recorded number of cases, the annual incidence per 10,000 population was 3.4. The ratio of male to female patients was 1.6:1.0. When the estimated number of cases from those without records was added to the total number of recorded cases the annual incidence was 11.3 per 10,000 population. CONCLUSION: Corneal ulceration is a common occurrence in South India. While the true incidence of this problem is impossible to determine because of the lack of medical records, we believe our estimation of the incidence to be close to the true incidence in this community.

Adolescent↗
PubMed1996

Glycogen synthase regulation in hyperinsulinemic/obese progeny of rats fed a high carbohydrate formula in their infancy.

OBJECTIVE: To evaluate the effects of chronic hyperinsulinemia/obesity on the proximal events leading to the activation of glycogen synthase. DESIGN: 100 d old second generation of chronically hyperinsulinemic/obese rats born to mothers which were artificially reared on a high carbohydrate (HC) milk formula in their infancy were used for this study and compared with mother-fed (MF) controls. MEASUREMENTS: Glycogen, glycogen synthase, protein phosphatase-1 (PP-1), mitogen-activated protein kinase (MAPK), insulin-stimulated protein kinase (ISPK) and protein kinase A (PKA) were measured in liver and muscle of both MF and HC rats. RESULTS: Glycogen content, glycogen synthase and PP-1 activities were significantly reduced in liver and muscle of HC rats compared to MF controls while trypsin released PP-1 activity was elevated. The activities of both MAPK and ISPK were also decreased in the HC rats. In contrast PKA activity was increased. CONCLUSIONS: Glycogen synthase activity in the basal state may be impaired in the hyperinsulinemic HC rats in two ways: (i) by a decrease in the activities of the kinases that presumably activate PP-1 and (ii) by increased activity of PKA which inactivates glycogen synthase directly by phosphorylation and indirectly by its effects on PP-1.

Animals↗
PubMed1995

Control of lamprey locomotor neurons by colocalized monoamine transmitters.

Neurons in the central nervous system (CNS) often store more than one neurotransmitter, but as yet the functional significance of this type of coexistence is poorly understood. 5-Hydroxytryptamine (5-HT) modulates calcium-dependent K+ channels (KCa) responsible for the postspike afterhyperpolarization in different regions of the CNS. In lamprey, 5-HT neurons control apamine-sensitive KCa channels in spinal locomotor network interneurons, thereby in addition regulating the duration of locomotor bursts. We report here that these spinal 5-HT neurons also contain dopamine. Like 5-HT, dopamine causes a reduction of the afterhyperpolarization, but in this case it is due to a reduction of calcium entry during the action potential, which results in a reduced activation of KCa. 5-HT and dopamine are both released from these midline neurons, and both reduce the afterhyperpolarization through two distinctly different, but complementary cellular mechanisms. The net effect of dopamine (10-100 microM) on the locomotor network is similar to that of 5-HT, and the effects of dopamine and 5-HT are additive at the network level.

Action Potentials↗
PubMed1995

In vitro characterization of the mitochondrial processing and the potential function of the 68-kDa subunit of renal glutaminase.

Rat renal mitochondrial glutaminase (GA) is initially synthesized in primary cultures of proximal tubule cells as a 74-kDa precursor and is processed via a 72-kDa intermediate to generate a heterotetrameric enzyme which contains three 66-kDa subunits and one 68-kDa subunit (Perera, S. Y., Chen, T. C., and Curthoys, N. P. (1990) J. Biol. Chem. 265, 17764-17770). The two mature subunits may be derived by either of two possible mechanisms: 1) alternative proteolytic processing or 2) initial synthesis of the 66-kDa subunit followed by its covalent modification to generate the 68-kDa subunit. An in vitro system was utilized to further characterize this unique processing pathway and to investigate the potential function of the 68-kDa subunit. In vitro transcription and translation of the GA cDNA yields a single 74-kDa precursor. Upon incubation with isolated rat liver mitochondria, the precursor is translocated into the mitochondria and processed via a 72-kDa intermediate to yield a 3:1 ratio of the 66- and 68-kDa subunits, respectively. The kinetics of the in vitro processing reaction also closely approximate the kinetics observed in cultured cells. Mitochondrial processing is blocked by o-phenanthroline, an inhibitor of the matrix processing peptidase (MPP). The 72-amino acid presequence of the 66-kDa subunit contains a large proportion of basic amino acids. Two-dimensional gel electrophoresis of mature GA established that the 68-kDa subunit is slightly more basic than the 66-kDa subunit. In addition, incubation of the 74-kDa precursor with purified MPP yields equimolar amounts of the two mature peptides. A cDNA construct, p delta GA, was created which lacks the nucleotides that encode the amino acid residues 32 through 72 of GA. When transcribed and translated in vitro, p delta GA yields a 70-kDa precursor. This precursor is processed by mitochondria to a single mature subunit with a M of 66 kDa. This observation suggests that the 68-kDa subunit is not produced by covalent modification of the 66-kDa subunit and further supports the conclusion that the two mature subunits of GA are produced by alternative processing reactions which can be catalyzed by MPP. However, the yield of products obtained in intact mitochondria may be determined by some unidentified accessory factor. Submitochondrial fractionation of imported GA and delta GA precursors suggest that the 68-kDa subunit may function to retain the mature GA within the mitochondrial matrix.

Animals↗
PubMed1995

Role of the N-terminal 118 amino acids in the processing of the rat renal mitochondrial glutaminase precursor.

Rat renal mitochondrial glutaminase (GA) is synthesized as a 74-kDa cytosolic precursor that is translocated into mitochondria and processed via a 72-kDa intermediate to yield a 3:1 ratio of mature 66- and 68-kDa subunits, respectively. The 66-kDa subunit is derived by removal of a 72-amino-acid presequence. The structural determinants necessary for translocation and proteolytic processing were further delineated by characterizing the processing of different chimeric constructs formed by fusing various segments of the N-terminal sequence of the GA precursor to chloramphenicol acetyl transferase (CAT). GA1-118 CAT is translocated and processed in isolated rat liver mitochondria or cleaved by purified mitochondrial processing peptidase (MPP) to yield an intermediate peptide and two mature subunits that are analogous to the products of processing of the GA precursor. The two reactions also occur with kinetics which are similar to those observed for processing of the GA precursor. Thus, all of the information required for the translocation and synthesis of the mature subunits of GA reside in the N-terminal 118 amino acids of the GA precursor. In contrast, GA1-72 CAT, a construct that contains the GA presequence fused to CAT, is apparently translocated and processed less efficiently. It yields only two peptides that are analogous to the intermediate and 68 kDa forms of GA. In addition, GA1-31 CAT associates with mitochondria but is not proteolytically processed and GA1-31,73-118 CAT is slowly translocated and processed to a single peptide that is analogous to the 66 kDa form of GA. The latter results suggest that the MPP cleavage reactions which yield the GA intermediate and the 66-kDa subunit depend primarily on information that is present C-terminal to the respective sites of cleavage.

Amino Acid Sequence↗
PubMed1995

Decoding Ca2+ signals to the nucleus by multifunctional CaM kinase.

Multifunctional Ca2+/calmodulin-dependent protein kinase (CaM kinase) is one of the major protein kinases coordinating cellular responses to neurotransmitters and hormones. CaM kinase transduces changes in intracellular free Ca2+ into changes in the phosphorylation state and activity of target proteins involved in neurotransmitter synthesis and release, neuronal plasticity and gene expression. Structure/function analyses of the kinase reveal the kinase is kept inactive in its basal state by a regulatory domain that is displaced by the binding of Ca2+/calmodulin. Once activated by Ca2+/calmodulin, autophosphorylation occurs if a pair of proximate subunits of the decameric kinase have calmodulin bound. The frequency of Ca2+ oscillations or spikes may be decoded by CaM kinase via this autophosphorylation. Calmodulin is essentially trapped by autophosphorylation which converts CaM kinase into a high affinity calmodulin-binding protein. Repetitive stimulation of the kinase may promote recruitment of calmodulin to the kinase so that it becomes increasingly active with each stimulus in a frequency-dependent manner. The association domain at the C-terminal end of CaM kinase contains a variable region that targets isoforms of the kinase to the nucleus or cytoskeleton and assembles the kinase into a decameric structure. Alternative splicing introduces a short nuclear localization signal that targets transfected kinase to the nucleus where it may regulate nuclear functions. The regulatory properties of CaM kinase provide for molecular potentiation of Ca2+ signals and frequency detection whereas its association domain should enable it to decode such Ca2+ fluctuations in the nucleus.

Amino Acid Sequence↗
PubMed1995

Developmental and regional expression of multifunctional Ca2+/calmodulin-dependent protein kinase isoforms in rat brain.

Multifunctional Ca2+/calmodulin-dependent protein kinase (CaM kinase) participates in diverse calcium signaling pathways in neurons. The alpha- and beta-CaM kinase isoforms are neuron-specific and highly abundant in rat brain. The variable domain of CaM kinase is a potential site for the generation of isoform diversity by alternative spicing of its N- and/or C-terminal segments. We used specific PCR primers which span the variable domain of either alpha- or beta-CaM kinase and isolated three new isoforms from rat brain, namely alpha B-, beta e- and beta'e-CaM kinase. alpha beta-CaM kinase contains 11 amino acids, likely inserted by alternative splicing, at the C-terminal segment of the variable domain. This insertion introduces a nuclear localization signal (NLS) that targets alpha B-CaM kinase to the nucleus of transfected cells; alpha-CaM kinase is excluded from the nucleus. The mRNA and the protein corresponding to this isoform are detected only in the diencephalon/midbrain regions. We have also identified two alternatively spliced isoforms of beta-CaM kinase that lack the 24 amino acid sequence at the N-terminal segment of the variable domain. Alternative splicing of these two isoforms occurs with a three base pair shift of the 3'-splice site. Our analysis shows that these new beta-CaM kinase isoforms are expressed primarily in early developmental stages, and we therefore term them beta e - (embryonic) and beta' e-CaM kinase. Recombinant alpha B-, beta e and beta' e-CaM kinase expressed in COS-7 cells exhibit characteristic Ca2+/calmodulin-dependent protein kinase activity and autophosphorylation.

Aging↗