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Biomedical subjects

A Kapur

Publications and source records attributed to A Kapur.

At least 55 records · Page 3Linked to original sources
PubMed1997

The interaction of the molecular chaperone, alpha-crystallin, with molten globule states of bovine alpha-lactalbumin.

Small heat shock proteins function in a chaperone-like manner to prevent the precipitation of proteins under conditions of stress (e. g. heat). alpha-Crystallin, the major mammalian lens protein, is a small heat shock protein. The mechanism of chaperone action of these proteins is poorly understood. In this paper, the conformational state of a protein when it forms a high molecular weight complex with alpha-crystallin is investigated by examining, using NMR spectroscopy and size exclusion high performance liquid chromatography, the interaction of alpha-crystallin with alpha-lactalbumin and its various intermediately folded (molten globule) states. The complex is formed following reduction of alpha-lactalbumin by dithiothreitol in the presence of alpha-crystallin, and this interaction has been monitored in real time by 1H NMR spectroscopy. It is concluded that alpha-crystallin interacts with a disordered molten globule state of alpha-lactalbumin while it is on an irreversible pathway toward aggregation and precipitation. alpha-Crystallin does not interact, however, with molten globule states of alpha-lactalbumin that are stable in solution, e.g. the reduced and carboxyamidated species. It is proposed that alpha-crystallin distinguishes between the various molten globule states of alpha-lactalbumin on the basis of the lifetimes of these states, i.e. the protein must be in a disordered molten globule state for a significant length of time and on the pathway to aggregation and precipitation for interaction to occur.

Animals↗
PubMed1997

GABAA-mediated IPSCs in piriform cortex have fast and slow components with different properties and locations on pyramidal cells.

GABAA-mediated IPSCs in piriform cortex have fast and slow components with different properties and locations on pyramidal cells. J. Neurophysiol. 78: 2531-2545, 1997. A recent study in piriform (olfactory) cortex provided evidence that, as in hippocampus and neocortex, gamma-aminobutyric acid-A (GABAA)-mediated inhibition is generated in dendrites of pyramidal cells, not just in the somatic region as previously believed. This study examines selected properties of GABAA inhibitory postsynaptic currents (IPSCs) in dendritic and somatic regions that could provide insight into their functional roles. Pharmacologically isolated GABAA-mediated IPSCs were studied by whole cell patch recording in slices. To compare properties of IPSCs in distal dendritic and somatic regions, local stimulation was carried out with tungsten microelectrodes, and spatially restricted blockade of GABAA-mediated inhibition was achieved by pressure-ejection of bicuculline from micropipettes. The results revealed that largely independent circuits generate GABAA inhibition in distal apical dendritic and somatic regions. With such independence, a selective decrease in dendritic-region inhibition could enhance integrative or plastic processes in dendrites while allowing feedback inhibition in the somatic region to restrain system excitability. This could allow modulatory fiber systems from the basal forebrain or brain stem, for example, to change the functional state of the cortex by altering the excitability of interneurons that mediate dendritic inhibition without increasing the propensity for regenerative bursting in this highly epileptogenic system. As in hippocampus, GABAA-mediated IPSCs were found to have fast and slow components with time constants of decay on the order of 10 and 40 ms, respectively, at 29 degrees C. Modeling analysis supported physiological evidence that the slow time constant represents a true IPSC component rather than an artifactual slowing of the fast component from voltage clamp of a dendritic current. The results indicated that, whereas both dendritic and somatic-region IPSCs have both fast and slow GABAA components, there is a greater proportion of the slow component in dendrites. In a companion paper, the hypothesis is explored that the resulting slower time course of the dendritic IPSC increases its capacity to regulate the N-methyl--aspartate component of EPSPs. Finally, evidence is presented that the slow GABAA-mediated IPSC component is regulated by presynaptic GABAB inhibition whereas the fast is not. Based on the requirement for presynaptic GABAB-mediated block of inhibition for expression of long-term potentiation, this finding is consistent with participation of the slow GABAA component in regulation of synaptic plasticity. The lack of susceptibility of the fast GABAA component to the long-lasting, activity-induced suppression mediated by presynaptic GABAB receptors is consistent with a protective role for this process in preventing seizure activity.

Animals↗
PubMed1997

Regulation of the NMDA component of EPSPs by different components of postsynaptic GABAergic inhibition: computer simulation analysis in piriform cortex.

Regulation of the NMDA component of EPSPs by different components of postsynaptic GABAergic inhibition: computer simulation analysis in piriform cortex. J. Neurophysiol. 78: 2546-2559, 1997. Physiological analysis in the companion paper demonstrated that gamma-aminobutyric acid-A (GABAA)-mediated inhibition in piriform cortex is generated by circuits that are largely independent in apical dendritic and somatic regions of pyramidal cells and that GABAA-mediated inhibitory postsynaptic currents (IPSCs) in distal dendrites have a slower time course than those in the somatic region. This study used modeling methods to explore these characteristics of GABAA-mediated inhibition with respect to regulation of the N-methyl--aspartate (NMDA) component of excitatory postsynaptic potentials. Such regulation is relevant to understanding NMDA-dependent long-term potentiation (LTP) and the integration of repetitive synaptic inputs that can activate the NMDA component as well as pathological processes that can be activated by overexpression of the NMDA component. A working hypothesis was that the independence and differing properties of IPSCs in apical dendritic and somatic regions provide a means whereby the NMDA component and other dendritic processes can be controlled by way of GABAergic tone without substantially altering system excitability. The analysis was performed on a branched compartmental model of a pyramidal cell in piriform cortex constructed with physiological and anatomic data derived by whole cell patch recording. Simulations with the model revealed that NMDA expression is more effectively blocked by the slow GABAA component than the fast. Because the slow component is present in greater proportion in apical dendritic than somatic regions, this characteristic would increase the capacity of dendritic IPSCs to regulate NMDA-mediated processes. The simulations further revealed that somatic-region GABAergic inhibition can regulate the generation of action potentials with little effect on the NMDA component generated by afferent fibers in apical dendrites. As a result, if expression of the NMDA component or other dendritic processes were enabled by selective block of dendritic inhibition, for example, by centrifugal fiber systems that may regulate learning and memory, the somatic-region IPSC could preserve system stability through feedback regulation of firing without counteracting the effect of the dendritic-region block. Simulations with paired inputs revealed that the dendritic GABAA-mediated IPSC can regulate the extent to which a strong excitatory input facilitates the NMDA component of a concurrent weak input, providing a possible mechanism for control of "associative LTP" that has been demonstrated in this system. Postsynaptic GABAB-mediated inhibition had less effect on the NMDA component than either the fast or slow GABAA components. Depolarization from a concomitant alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) component also was found to have comparatively little effect on current through the NMDA channel because of its brief time course.

2-Amino-5-phosphonovalerate↗
PubMed1997

Insulin kinetics.

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Biological Availability↗
PubMed1997

Animal insulins.

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Animals↗
PubMed1997

Candida splenic abscess in the absence of obvious immunodeficiency.

Focal hepatosplenic candidiasis has been increasingly recognized as a variant of disseminated candidiasis in immunocompromised patients. It rarely presents as Candida splenic abscess. Its occurrence in non-leukemic patients is quite rare. A patient with diabetes mellitus and previously undiagnosed sickle cell trait presented with upper gastrointestinal bleeding. Candida splenic abscess was diagnosed. She was successfully treated with percutaneous drainage and fluconazole. The clinical presentation, diagnosis, and treatment of Candida splenic abscess is reviewed, and its relationship to diabetes mellitus and sickle cell disease without major immunodeficiency is discussed.

Abscess↗
PubMed1997

Randomized, controlled comparison of two forms of preparation for screening flexible sigmoidoscopy.

OBJECTIVE: There is a paucity of data regarding the optimal form of bowel preparation for flexible sigmoidoscopy. Most endoscopists recommend enemas. A simpler preparation that is easy, acceptable, and that reduces patient encounter time would be desirable, and might be cost-effective. Our objective in this study was to evaluate a simple oral form of preparation for screening flexible sigmoidoscopy. METHODS: In this randomized, single-blind, controlled trial, we compared two forms of preparation in consecutive male patients referred for screening flexible sigmoidoscopy. The oral preparation consisted of one bottle of magnesium citrate and two "Dulcolax" tablets on the evening before flexible sigmoidoscopy. This was compared with the standard form of preparation, namely, two Fleet's enemas given on arrival at the endoscopy suite. Thirty-seven patients received the oral preparation [mean age, 62.8 +/- 8.9 (SD) yr]; 33 received enemas (mean age, 65.2 +/- 7.3 yr). Endoscopists were blinded to the preparation. RESULTS: Mean time between arrival and starting flexible sigmoidoscopy was 36 +/- 22 (SD) min for patients on oral preparation, and 62 +/- 25 min for patients receiving enemas (p < 0.0001). Mean times performing flexible sigmoidoscopy were 10 +/- 3 min and 13 +/- 4 min, respectively (p = 0.004). Mean patient satisfaction score (range 0-13) was higher for patients given the oral preparation (11.4 +/- 1.8) than for patients receiving enemas (9.6 +/- 2.4) (p = 0.001). Fifteen patients randomized to receive the oral preparation had previous flexible sigmoidoscopy with an enema preparation; all preferred the oral form. Mean technical difficulty (range 1-10) was 3 +/- 2.2 for patients given the oral preparation and 4.9 +/- 3.1 for patients receiving the enema preparation (p = 0.01). Polyps were identified in 10/37 patients who received the oral preparation and in 3/33 patients who received enemas (p = 0.05). Quality of colon preparation was judged "good" in 29, "fair" in four, and "poor" in four, among the 37 patients given the oral form; corresponding values for 33 patients given enemas were 16, 10, and 7 (p = 0.03). CONCLUSION: Patient acceptance, encounter time, technical ease, and quality of colon preparation were significantly better with the oral form of colon preparation than with the standard Fleet enema preparation.

Administration, Oral↗
PubMed1997

Recurrent acute scleroderma renal crisis complicated by thrombotic thrombocytopenic purpura.

Acute renal crisis as an early manifestation of scleroderma is underemphasized, and its recurrence after initial successful therapy is rare. We describe a 32-year-old woman who presented with scleroderma renal crisis. A second episode of apparent renal crisis, however, was complicated by thrombotic thrombocytopenic purpura, which led to pancreatitis, a large cerebral infarction, and fatal outcome despite intensive therapy. This case illustrates the complexity and severity of diffuse systemic sclerosis presenting with multiple, major organ complications.

Acute Disease↗
PubMed1996

A dendritic GABAA-mediated IPSP regulates facilitation of NMDA-mediated responses to burst stimulation of afferent fibers in piriform cortex.

Studies in a number of cortical systems have shown that the NMDA component of the EPSP is strongly regulated by GABAA-mediated inhibition. The present study explored the possibility that specificity in inhibitory circuitry could allow such regulation to occur during normal function without increasing the propensity for epileptiform bursting, which occurs with indiscriminate GABAA blockade. Specifically, the hypothesis was tested that a dendritic GABAA-mediated IPSP is present which strongly modulates the NMDA component and can be activated independently of the somatic IPSP. The experiments were performed on slices of piriform cortex in which the NMDA component of the EPSP was pharmacologically isolated by bath-applied 6,7-dinitroquinoxaline-2,3-dione. A facilitation of NMDA responses to burst stimulation of afferent fibers is described, which required GABAA blockade and served as an assay for the presence of a functionally significant GABAA input. When bicuculline was applied focally in the somatic region, the feedback IPSP was blocked with little or no increase in the NMDA component of the response to burst stimulation of afferent fibers. In contrast, when bicuculline was applied focally in the dendritic region, the NMDA-mediated response to burst stimulation was facilitated with minimal effect on the somatic IPSP, confirming the hypothesis.

Afferent Pathways↗
PubMed1996

Heated lidocaine.

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Anesthetics, Local↗
PubMed1995

Linear IgA dermatosis, coeliac disease, and extraintestinal B cell lymphoma.

Linear IgA dermatosis is a malignancy associated rare bullous disorder similar to dermatitis herpetiformis. Linear IgA dermatosis differs from dermatitis herpetiformis in that the IgA deposits in the epidermal basement membrane are linear rather than granular. A patient is presented with coeliac disease who presented with linear IgA dermatosis and anaemia caused by chronic low grade B cell lymphoma.

Aged↗
PubMed1993

Factor V inhibitor in thrombosis.

A 68-year-old previously well woman developed sudden onset of limb gangrene in association with liver dysfunction. An immediately acting inhibitor to factor V with some of the features of lupus anticoagulant was demonstrated. The patient required limb amputation within 2 weeks and activity of the anticoagulant seemed to be on the decline 6 months later.

Aged↗
PubMed1990

Effects of purified insulins on insulin requirement and metabolic control.

Seventeen diabetics requiring high insulin doses were transferred from conventional insulin to purified chromatographed porcine insulins (Actrapid and Lentard-Novo, Denmark). At the end of 8 to 12 weeks, there was a 46% reduction in insulin dosage while metabolic control improved. Some of these patients when transferred again to conventional insulins demonstrated poor metabolic control and an increase in insulin requirements. Use of purified insulin is beneficial as insulin requirement is reduced with improved metabolic control.

Adolescent↗
PubMed1989

Carbohydrate deficient transferrin: a marker for alcohol abuse.

OBJECTIVE: To assess the value of serum carbohydrate deficient transferrin as detected by isoelectric focusing on agarose as an indicator of alcohol abuse. DESIGN: Coded analysis of serum samples taken from patients with carefully defined alcohol intake both with and without liver disease. Comparison of carbohydrate deficient transferrin with standard laboratory tests for alcohol abuse. SETTING: A teaching hospital unit with an interest in general medicine and liver disease. PATIENTS: 22 "Self confessed" alcoholics admitting to a daily alcohol intake of at least 80 g for a minimum of three weeks; 15 of the 22 self confessed alcoholics admitted to hospital for alcohol withdrawal; 68 patients with alcoholic liver disease confirmed by biopsy attending outpatient clinics and claiming to be drinking less than 50 g alcohol daily; 47 patients with non-alcoholic liver disorders confirmed by biopsy; and 38 patients with disorders other than of the liver and no evidence of excessive alcohol consumption. INTERVENTION: Serial studies performed on the 15 patients undergoing alcohol withdrawal in hospital. MAIN OUTCOME measure--Determination of relative value of techniques for detecting alcohol abuse. RESULTS: Carbohydrate deficient transferrin was detected in 19 of the 22 (86%) self confessed alcohol abusers, none of the 47 patients with non-alcoholic liver disease, and one of the 38 (3%) controls. Withdrawal of alcohol led to the disappearance of carbohydrate deficient transferrin at a variable rate, though in some subjects it remained detectable for up to 15 days. Carbohydrate deficient transferrin was considerably superior to the currently available conventional markers for alcohol abuse. CONCLUSION: As the technique is fairly simple, sensitive, and inexpensive we suggest that it may be valuable in detecting alcohol abuse.

Alcoholism↗