Authorities overstretched as earthquake death toll increases.
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Disasters↗
Biomedical subjects
S Kumar
Publications and source records attributed to S Kumar.
Roles of the C termini of alpha -, beta -, and gamma -subunits of epithelial Na+ channels (ENaC) in regulating ENaC and mediating its inhibition by cytosolic Na+.
The amiloride-sensitive epithelial Na(+) channels (ENaC) in the intralobular duct cells of mouse mandibular glands are inhibited by the ubiquitin-protein ligase, Nedd4, which is activated by increased intracellular Na(+). In this study we have used whole-cell patch clamp methods in mouse mandibular duct cells to investigate the role of the C termini of the alpha-, beta-, and gamma-subunits of ENaC in mediating this inhibition. We found that peptides corresponding to the C termini of the beta- and gamma-subunits, but not the alpha-subunit, inhibited the activity of the Na(+) channels. This mechanism did not involve Nedd4 and probably resulted from the exogenous C termini interfering competitively with the protein-protein interactions that keep the channels active. In the case of the C terminus of mouse beta-ENaC, the interacting motif included betaSer(631), betaAsp(632), and betaSer(633). In the C terminus of mouse gamma-ENaC, it included gammaSer(640). Once these motifs were deleted, we were able to use the C termini of beta- and gamma-ENaC to prevent Nedd4-mediated down-regulation of Na(+) channel activity. The C terminus of the alpha-subunit, on the contrary, did not prevent Nedd4-mediated inhibition of the Na(+) channels. We conclude that mouse Nedd4 interacts with the beta- and gamma-subunits of ENaC.
Amiloride↗
The Nedd4-like protein KIAA0439 is a potential regulator of the epithelial sodium channel.
The amiloride-sensitive epithelial sodium channel (ENaC) plays a critical role in fluid and electrolyte homeostasis and consists of alpha, beta, and gamma subunits. The carboxyl terminus of each ENaC subunit contains a PPxY, motif which is believed to be important for interaction with the WW domains of the ubiquitin-protein ligase, Nedd4. Disruption of this interaction, as in Liddle's syndrome, where mutations delete or alter the PPxY motif of either the beta or gamma subunits, has been proposed to result in increased ENaC activity. Here we present evidence that KIAA0439 protein, a close relative of Nedd4, is also a potential regulator of ENaC. We demonstrate that KIAA0439 WW domains bind all three ENaC subunits. We show that a recombinant KIAA0439 WW domain protein acts as a dominant negative mutant that can interfere with the Na(+)-dependent feedback inhibition of ENaC in whole-cell patch clamp experiments. We propose that KIAA0439 and Nedd4 proteins either play a redundant role in ENaC regulation or function in a tissue- and/or signal-specific manner to down-regulate ENaC.
Animals↗
Theories of musculoskeletal injury causation.
Based on the scientific evidence in published literature about precipitation of musculoskeletal injuries in the workplace, four theories have been proposed to explain these afflictions. Central to all theories is the presupposition that all occupational musculoskeletal injuries are biomechanical in nature. Disruption of mechanical order of a biological system is dependent on the individual components and their mechanical properties. These common denominators will be causally affected by the individual's genetic endowment, morphological characteristics and psychosocial makeup, and by the occupational biomechanical hazards. This phenomenon is explained by the Multivariate Interaction Theory. Differential Fatigue Theory accounts for unbalanced and asymmetric occupational activities creating differential fatigue and thereby a kinetic and kinematic imbalance resulting in injury precipitation. Cumulative Load Theory suggests a threshold range of load and repetition product beyond which injury precipitates, as all material substances have a finite life. Finally, Overexertion Theory claims that exertion exceeding the tolerance limit precipitates occupational musculoskeletal injury. It is also suggested that while these theories may explain the immediate mechanism of precipitation of injuries, they all operate simultaneously and interact to modulate injuries to varying degrees in different cases.
Biomechanical Phenomena↗
Inhibition of p38 mitogen-activated protein kinase provides neuroprotection in cerebral focal ischemia.
Mitogen-activated protein kinases (MAPKs) are involved in many cellular processes. The stress-activated MAPK, p38, has been linked to inflammatory cytokine production and cell death following cellular stress. Here, we demonstrate focal ischemic stroke-induced p38 enzyme activation (i.e., phosphorylation) in the brain. The second generation p38 MAPK inhibitor SB 239063 was identified to exhibit increased kinase selectivity and improved cellular and in vivo activity profiles, and thus was selected for evaluation in two rat models of permanent focal ischemic stroke. SB 239063 was administered orally pre- and post-stroke and intravenously post-stroke. Plasma concentration levels were achieved in excess of those that effectively inhibit p38 activity. In both moderate and severe stroke, SB 239063 reduced infarct size by 28-41%, and neurological deficits by 25-35%. In addition, neuroprotective plasma concentrations of SB 239063 that reduced p38 activity following stroke also reduced the stroke-induced expression of IL-1beta and TNFalpha (i.e., cytokines known to contribute to stroke-induced brain injury). SB 239063 also provided direct protection of cultured brain tissue to in vitro ischemia. This robust SB 239063-induced neuroprotection emphasizes a significant opportunity for targeting MAPK pathways in ischemic stroke injury, and also suggests that p38 inhibition be evaluated for protective effects in other experimental models of nervous system injury and neurodegeneration.
Animals↗
Sesamin a potent antifeedant principle from Piper mullesua.
Sesamin, a major lignan of Piper mullesua of Manipur origin, exhibited significant antifeedant activity and moderate growth inhibition towards 4th instar larvae of Spilarctia obliqua. No larval toxicity of sesamin could be established in topical bioassay experiments. Its effective dose for 50% feeding deterrence (ED(50)) and growth inhibition (GI(50)) were found to be 3856 and 6212 ppm, respectively.
Animals↗
IL-1- and TNF-induced bone resorption is mediated by p38 mitogen activated protein kinase.
We have previously shown that p38 mitogen-activated protein kinase (MAPK) inhibitors, which block the production and action of inflammatory cytokines such as tumor necrosis factor (TNF) and interleukin-1 (IL-1), are effective in models of bone and cartilage degradation. To further investigate the role of p38 MAPK, we have studied its activation in osteoblasts and chondrocytes, following treatment with a panel of proinflammatory and osteotropic agents. In osteoblasts, significant activation of p38 MAPK was observed following treatment with IL-1 and TNF, but not parathyroid hormone, transforming growth factor-beta (TGF-beta), 1,25(OH)(2)D(3), insulin-like growth factor-1 (IGF-1), or IGF-II. Similar results were obtained using primary bovine chondrocytes and an SV40-immortalized human chondrocyte cell line, T/C28A4. SB 203580, a selective inhibitor of p38 MAPK, inhibited IL-1 and TNF-induced p38 MAPK activity and IL-6 production (IC(50)s 0.3--0.5 microM) in osteoblasts and chondrocytes. In addition, IL-1 and TNF also activated p38 MAPK in fetal rat long bones and p38 MAPK inhibitors inhibited IL-1- and TNF-stimulated bone resorption in vitro in a dose-dependent manner (IC(50)s 0.3--1 microM). These data support the contention that p38 MAPK plays a central role in regulating the production of, and responsiveness to, proinflammatory cytokines in bone and cartilage. Furthermore, the strong correlation between inhibition of kinase activity and IL-1 and TNF-stimulated biological responses indicates that selective inhibition of the p38 MAPK pathway may have therapeutic utility in joint diseases such as rheumatoid arthritis (RA).
Animals↗
Early changes in neuropeptide mRNA expression in the striatum following reserpine treatment.
Chronic dopamine depletion produces neurochemical changes within the striatum as well as enhanced behavioral and metabolic responses to dopamine agonists. Changes in striatal neuropeptides have been consistently described, including increased expression of preproenkephalin mRNA and decreased expression of preprotachykinin and prodynorphin mRNA. Acute dopamine depletion following treatment with reserpine also produces enhanced behavioral and metabolic responses to agonist treatment which develop rapidly. In the present study, we used in situ hybridization histochemistry to investigate whether acute neurochemical changes occur following reserpine treatment. We evaluated neuropeptide mRNA expression in the striatum and nucleus accumbens at several time points from 6 to 120 h following single doses of reserpine and AMPT. The aim of these studies was to determine if changes in neuropeptide mRNA expression occur following acute dopamine depletion and whether such changes are specific to the striatum. Changes in striatal neuropeptide mRNA expression developed rapidly. Preproenkephalin mRNA expression by striatopallidal neurons was unchanged at 48 h, but increased by 44% at 120 h. Preprotachykinin mRNA expression in striatonigral neurons was increased at 6 h and then fell, with a maximal decrease of 45% at 48 h and partial recovery by 120 h. Prodynorphin mRNA expression was unchanged. Expression of preproenkephalin and preprotachykinin mRNA was also examined in subregions of the striatum and the nucleus accumbens. Expression of preproenkephalin mRNA was uniform in the striatum and higher in the core than the shell of the nucleus accumbens. Preprotachykinin mRNA expression in the striatum was higher in the lateral quadrants and was higher in the shell than in the core of the nucleus accumbens. The changes in neuropeptide mRNA following treatment with reserpine were only found in the striatum. These data provide further evidence for early alterations in neuronal function in the striatum following acute dopamine depletion and suggest that neuropeptide expression by striatonigral neurons may be more rapidly regulated in response to changes in dopamine levels.
Adrenergic Uptake Inhibitors↗
Role of LLD, a new locus for leaflet/pinna morphogenesis in Pisum sativum.
Properties of a mutant at the LLD (LEAF-LET DEVELOPMENT) locus in pea Pisum sativum L. are reported in this paper. Plants homozygous for the Mendelian recessive mutation lld bear leaves in which a few to many leaflets are incompletely developed. Opposite pinnae of rachis nodes often formed fused incompletely developed leaflets. The lld mutation was observed to abort pinna development at almost all morphogenetic stages. The lld mutation demonstrated high penetrance and low expressivity. The phenotypes of lld plants in tl, tac, tl tac, tl af and tl af tac backgrounds suggested that LLD function is involved in the separation of lateral adjacent blastozones differentiated on primary, secondary and tertiary rachides and lamina development in leaflets. The aborted development of tendrils and leaflets in lld mutants was related to deficiency in vascular tissue growth. The morphological and anatomical features of the leaflets formed on a tl lld double mutant permitted a model of basipetal leaflet development. The key steps of leaflet morphogenesis include origin of the lamina by splitting of a radially symmetrical growing pinna having abaxial outer surface, opposite to the vascular cylinder, through an invaginational groove, differentiation of adaxial surface along the outer boundary of split tissue in the groove and expansion of the lamina ridges so formed into lamina spans.
Genes, Plant↗
Pleiotropic morphological and abiotic stress resistance phenotypes of the hyper-abscisic acid producing Abo- mutant in the periwinkle Catharanthus roseus.
The pleiotropic properties of a abo abo (Abo-) gamma-ray induced mutant of Catharanthus roseus cv. Nirmal, selected among the M2 generation seeds for ability to germinate at 45 degrees C, are described. The mutant produced seeds possessing tricotyledonous embryos, unlike the typically dicotyledonous embryos present in the wild type Abo+ seeds. In comparison to Abo+ adults, the mutant plants had short stature and lanceolate leaves. The vascular bundles in the leaves and stem were poorly developed. Leaf surfaces were highly trichomatous, epidermal, cortex and mesophyll cells were small sized and a large majority of stomata were closed. Besides high temperature, the mutant was salinity and water-stress tolerant. The abscisic acid (ABA) content in the leaves was about 500-fold higher. The genetic lesion abo responsible for the above pleiotropy was recessive and inherited in Mendelian fashion. The seedlings and adult plants of the mutant accumulated higher proline than Abo+ plants. The phenotypes of abo abo mutants permitted the conclusions that (i) the mutant synthesizes ABA constitutively, (ii) both ABA-dependent and ABA independent pathways for proline and betaine accumulation are functional in the mutant, and (iii) cell division, elongation and differentiation processes in embryo and adult plant stages are affected in the mutant
Abscisic Acid↗
Epidemiology of undernutrition.
OBJECTIVE: The present study was undertaken to find out the magnitude of the problem of under nutrition among the children under 5 years of age and also to identify the important factors influencing the nutritional status of the children. METHODS: 30 cluster sampling technique had been applied in the study. A total of 600 children below five years of age were covered. Twenty under five children from each cluster were chosen for the study which was carried out during January to February '97. As per IAP criteria a total of 60.29% children were undernourished and 3.92% were severely undernourished. According to NCHS standard 46.57% & 6.86% children had weight below-2SD and -3SD respectively. RESULTS: A statistically significant relationship was found between the different age groups and nutritional status of under 5 children. Severe degree of malnutrition had highest prevalence under two years of age. The influence of variables like age, sex, religion, literacy status of parents and morbidity of the children were significantly associated with malnutrition. CONCLUSION: Practice of exclusive breast feeding, introduction of timely complementary feeding, education for maintaining personal hygiene, proper implementation of UIP immunization, periodic deworming, standard case management of diarrhoea and ARI as well as continuation of feeding during illness may reduce malnutrition of under-five children.
Age Distribution↗
Fetal gastrointestinal malformations.
In an audit to evaluate fetal gastrointestinal (GIT) malformations, case sheets of all mothers who gave birth to newborns with GIT malformations were analysed regarding the maternal history, prenatal ultrasound and the postnatal structural malformations and perinatal management. In 1999, eleven babies were born with gastrointestinal malformations, one was a still birth. Nine had associated malformations of other systems, two had trisomy 21. Eight babies were operated in the immediate newborn period, 5 survived. Ultrasound was not very accurate in the diagnosis of GIT anomaly in this series. In view of associated chromosomal and structural anomaly a fetal ECHO and genetic amniocentesis is warranted. Most of these babies require immediate surgery after birth, so they need to be delivered in a centre which is equipped with good neonatal and pediatric surgery care.
Adult↗
How do thermophilic proteins deal with heat?
Recent years have witnessed an explosion of sequence and structural information for proteins from hyperthermophilic and thermophilic organisms. Complete genome sequences are available for many hyperthermophilic archaeons. Here, we review some recent studies on protein thermostability along with work from our laboratory. A large number of sequence and structural factors are thought to contribute toward higher intrinsic thermal stability of proteins from these organisms. The most consistent are surface loop deletion, increased occurrence of hydrophobic residues with branched side chains and an increased proportion of charged residues at the expense of uncharged polar residues. The energetic contribution of electrostatic interactions such as salt bridges and their networks toward protein stability can be stabilizing or destabilizing. For hyperthermophilic proteins, the contribution is mostly stabilizing. Macroscopically, improvement in electrostatic interactions and strengthening of hydrophobic cores by branched apolar residues increase the enthalpy change between the folded and unfolded states of a thermophilic protein. At the same time, surface loop deletion contributes to decreased conformational entropy and decreased heat capacity change between the folded and unfolded states of the protein.
Archaea↗
Impact of distillery effluent on physiological consequences in the freshwater teleost Channa punctatus.
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Animals↗
Exstrophy of bladder associated with unilateral renal agenesis and bicornuate uterus: a case report.
Upper urinary tract anomalies are rare in patients with classic exstrophy of the urinary bladder. We report a case of bladder exstrophy associated with unilateral renal agenesis and bicornuate uterus in a female patient. The embryological basis for this rarity and its management are discussed.
Adult↗
Spontaneous pneumomediastinum and subcutaneous emphysema complicating bronchiolitis obliterans after allogeneic bone marrow transplantation--case report and review of literature.
Chronic graft-versus-host disease occurring in the setting of allogeneic bone marrow transplantation (BMT) can affect many organ systems, is a cause of significant morbidity, and contributes to late deaths. Bronchiolitis obliterans is a form of obstructive airway disease; when seen in the post-BMT setting, it is considered a manifestation of chronic graft-versus-host disease. Air-leak syndromes including pneumothoraces, pneumomediastinum and subcutaneous emphysema are rare complications of bronchiolitis obliterans. Here we describe a patient who developed pneumomediastinum, pneumopericardium, subcutaneous emphysema and pneumothorax secondary to severe bronchiolitis obliterans complicating the post bone marrow transplantation course.
Adult↗
Entrapment and transection of the median nerve associated with minimally displaced fractures of the forearm: case report and review of the literature.
Complete transection of the median nerve associated with minimally displaced fractures of forearm bones is described in a 20-year-old woman. An end-to-end epineural repair was performed. There was good sensory and motor recovery of the median nerve in the hand.
Adult↗
Isometric axial rotation of the trunk in the neutral posture.
The purpose of this study was to measure the torque, the magnitude of the electromyogram (EMG) signal and the phase relationship of 14 muscles during trunk axial rotation. Fifty normal healthy volunteers (27 males and 23 females) with no lower-back injury participated in the study. The subjects were seated in an upright position in the axial rotation tester (AROT) after applying surface electrodes bilaterally to the following muscles: pectoralis major, rectus abdominis, external oblique, internal oblique, latissimus dorsi, and erector spinae at T10 and L3. They were stabilized from the hip down, and the shoulder harness of the AROT was applied to their shoulders. These subjects performed maximal isometric axial rotations to the left and right in a random order. The torque and 14 channels of EMG were monitored, and their magnitude, slope of the increase in magnitude, and timing of the anticipation and onset activity were determined. The results revealed that the females produced 65% of the torque of their male counterparts. The pattern and magnitude of EMG in performing these tasks were significantly different between males and females (P<0.01). Males generated the greatest activity in their ipsilateral latissimus dorsi followed by their contralateral external oblique muscles. In the females, maximal EMG activity was observed in their contralateral pectoralis muscle. Thus, under the current experimental conditions, the females employed a different muscle recruitment strategy compared to the males. Each muscle involved in axial rotation was significantly different from the other (P < 0.01). The timing pattern for these activities was inconsistent, implying that there is no fixed-order phasic recruitment of the torso muscles during maximal isometric axial rotation.
Adolescent↗