Biomedical subjects
K Narasimhan
Publications and source records attributed to K Narasimhan.
Switching the hippocampus off and on
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Creating teetotaler mice.
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Inositol-1,4,5-trisphosphate receptor-mediated Ca mobilization is not required for cerebellar long-term depression in reduced preparations.
Inositol-1,4,5-trisphosphate receptor-mediated Ca mobilization is not required for cerebellar long-term depression in reduced preparations. J. Neurophysiol. 80: 2963-2974, 1998. Cerebellar long-term depression (LTD) is a cellular model system of information storage in which coincident parallel fiber and climbing fiber activation of a Purkinje neuron (PN) gives rise to a sustained attenuation of parallel fiber-PN synaptic strength. Climbing fiber and parallel fiber inputs may be replaced by direct depolarization of the PN and exogenous glutamate pulses, respectively. The parallel fiber-PN synapse has a high-density of mGluR1 receptors that are coupled to phosphoinositide turnover. Several lines of evidence indicated that activation of mGluR1 by parallel fiber stimulation is necessary for the induction of cerebellar LTD. Because phosphoinositide hydrolysis has two initial products, 1, 2-diacylglycerol and inositol-1,4,5-trisphosphate (IP3), we wished to determine whether IP3 signaling via IP3 receptors and consequent Ca mobilization were necessary for the induction of cerebellar LTD. First, ratiometric imaging of free cytosolic Ca was performed on both acutely dissociated and cultured PNs. It was determined that the threshold for glutamate pulses to contribute to LTD induction was below the threshold for producing a Ca transient. Furthermore, the Ca transients produced by depolarization alone and glutamate plus depolarization were not significantly different. Second, the potent and selective IP3 receptor channel blocker xestospongin C was not found to affect the induction of LTD in either acutely dissociated or cultured PNs at a concentration that was sufficient to block mGluR1-evoked Ca mobilization. Third, replacement of mGluR activation by exogenous synthetic diacylglycerol in an LTD induction protocol was successful. Taken together, these results suggest that activation of an IP3 signaling cascade is not required for induction of cerebellar LTD in reduced preparations.
Acute appendicitis: the myths of migratory pain and gradual onset of symptoms.
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ACEP chest pain policy: emergency physician awareness.
STUDY OBJECTIVE: To assess emergency physician knowledge of and effect on clinical practice of the ACEP "Clinical Policy for Management of Adult Patients Presenting With a Chief Complaint of Chest Pain, With No History of Trauma." METHODS: We conducted a written survey of attending physicians by mail and in person at emergency medicine meetings. Residents were surveyed at their academic departments. The survey recipients were emergency physicians and residents from university, community teaching, urban, and rural hospitals. RESULTS: Of the 338 surveyed physicians, 163 (48%; 95% confidence interval [CI], 43% to 54%) said that they were aware of the policy. Fifty-four percent of ACEP members said they were aware of the policy, compared with 24% of nonmembers. Of the physicians who said they were aware of the policy, 63% did not know that the policy contains rules. Seventy-one percent of the physicians who were aware of the policy incorrectly believed the policy requires treatment with thrombolytic therapy in certain cases of myocardial infarction. Physicians said they learned about the policy by reading it (42%), by word of mouth (16%), or in department/quality assurance meetings (13%). Twelve percent of physicians believe the policy has changed their clinical practice. CONCLUSION: Fewer than half the emergency physicians we surveyed were aware of the policy. Of the physicians who said they had been aware of the policy, most did not know important specifics of the policy.
Defining a minimal computational unit for cerebellar long-term depression.
In cerebellar long-term depression (LTD), conjunctive stimulation of parallel and climbing fiber inputs to a Purkinje neuron (PN) results in a selective depression of parallel fiber-PN synaptic strength. A similar phenomenon may be induced in the cultured PN when glutamate pulses and PN depolarization, which mimic the effects of parallel and climbing fibers, respectively, are coapplied. Here, we show that LTD can be induced in two very reduced preparations of the postsynaptic neuron; an acutely dissociated preparation and a perforated outside-out macropatch of dendritic membrane. LTD in these preparations retains properties of that seen in an intact cultured PN in that it is not induced by either glutamate pulses or depolarization alone and requires calcium influx, mGluR activation, and PKC activation for induction. As both of these preparations lack dendritic spine compartments, these findings suggest that the associative nature of LTD induction does not require this level of morphological organization.
Protoporphyrins modulate voltage-gated Ca current in AtT-20 pituitary cells.
1. Zinc-protoporphyrin-IX (ZnPP-IX) is an inhibitor of the enzyme heme-oxygenase-2 (HO-2) and consequently has been used to examine the role of carbon monoxide production in neural tissues. We have measured voltage-gated Ca current in AtT-20 pituitary cells using the whole-cell patch-clamp technique and have assessed the effects of extracellularly applied ZnPP-IX and related compounds. 2. Ca currents evoked by depolarizing steps from a holding potential of -90 mV were of the high-threshold, slowly inactivating type. Fifty-six percent of this current was blocked by 10 microM nifedipine and 16% by 3 microM omega-conotoxin with the remainder resistant to both drugs in combination, suggesting that the total Ca current was a mixture of L, N, and possibly P-type conductances. 3. Bath application of ZnPP-IX resulted in an irreversible, dose-dependent attenuation of Ca current. Five micromolar ZnPP-IX produced a 62% reduction of peak current amplitude with no shift in the current-voltage relation, 0.5 microM produced a 19% reduction, and 0.05 microM produced a variable response, either a small transient attenuation or potentiation. 4. The attenuation of Ca current by 5 microM ZnPP-IX could be nearly completely blocked by co-application of superoxide dismutase in the bath (90 U/ml) but not by addition of an inhibitor of cGMP-dependent protein kinase to the internal saline (KT5823, 1 microM). 5. Other inhibitors of heme-oxygenase with similar potency such as tin-protoporphyrin-IX (Sn-PP-IX) and Zn-deuteroporphyrin-bis-glycol (ZnBG) did not attenuate Ca current when applied at 5microM.(ABSTRACT TRUNCATED AT 400 WORDS)
Tension pneumothorax associated with hyperbaric oxygen therapy.
The authors present three patients who developed a tension pneumothorax while receiving emergent hyperbaric oxygen therapy for acute carbon monoxide poisoning. Each patient was intubated and received closed chest compressions for cardiac arrest prior to hyperbaric oxygenation. Despite the apparent absence of pneumothorax prior to hyperbaric therapy, tension pneumothorax was detected soon after decompression. These cases illustrate the need for vigilance in detecting and addressing pneumothorax prior to hyperbaric decompression in obtunded patients. Serial physical examinations, arterial blood gas determinations, properly positioned chest radiographs, and a high index of suspicion for pneumothorax in the setting of emergent hyperbaric therapy are recommended.
Jack o'lantern mushroom poisoning.
The cases of seven adults who ingested jack o'lantern mushrooms are presented. All patients experienced nausea and vomiting associated with abdominal cramping, and three reported diarrhea. Four of the seven complained of weakness and dizziness. Two were diaphoretic on physical examination. All seven were given IV fluids and oral activated charcoal in a local emergency department and admitted overnight for observation. Laboratory studies showed three of the seven patients to have mildly elevated liver function tests. One patient had hypokalemia requiring potassium supplementation. All were discharged the following day with normal follow-up examinations and laboratory studies. We recommend that all patients presenting with jack o'lantern mushroom poisoning be observed and rehydrated and have baseline liver function tests and potassium levels obtained.
Immobilization of a primary amine-containing drug, adriamycin. Coupling to crosslinked polyvinyl alcohol and mechanistic comparison of hydrolytic stability.
Literature reports have described the covalent coupling of the primary amine-containing anticancer drug, adriamycin, to polymeric supports through the amine group on the drug. These reports also have described drug mechanism studies with the immobilized adriamycin, where the release of the drug would undermine the validity of the conclusions. In the present paper, detailed experimental conditions are given for preparation of nonwater-soluble particles of polyvinyl alcohol by crosslinking water-soluble polyvinyl alcohol with 1,4-benzenedicarboxaldehyde, and for activation with cyanuric chloride and covalent attachment of adriamycin. The expected stability of this drug-support linkage against hydrolytic cleavage is compared mechanistically to that expected for less stable coupling through a carbamate linkage or for less stable coupling via an azomethine link.
Immobilized flavin coenzyme electrodes for analytical applications.
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Application of Fourier transform infrared (FTIR) spectroscopy to the study of protein-ligand interactions.
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Site-specific immobilization of flavin adenine dinucleotide on indium/tin oxide electrodes through flavin adenine amino group.
A Mannich-type reaction was used to attach flavin adenine dinucleotide (FAD) covalently to aminosilane derivatized indium/tin oxide-coated glass plates. The aminosilane was activated with formaldehyde to give an intermediate that attached specifically to the adenine amino group of FAD. The presence of the intermediate also was demonstrated by coupling hydroquinone to the formaldehyde activated support. The immobilized FAD and hydroquinone were characterized by cyclic or differential pulse voltammetry. The immobilized FAD was shown to reduce the overpotential for NADH oxidation by 180 mV. In keeping with results for FAD on glassy carbon, FAD attached to indium/tin oxide at the adenine amino group did not lead to reconstitution of activity with apoglucose oxidase.
Action of singlet oxygen on elastoidin.
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Studies on chemical constituents of swine and bovine semen.
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