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Biomedical subjects

A Gautam

Publications and source records attributed to A Gautam.

At least 19 recordsLinked to original sources
PubMed1992

Effects of Ca2+ agonists on cytosolic Ca2+ in isolated hepatocytes and on bile secretion in the isolated perfused rat liver.

The effects of increases in cytosolic Ca2+ on hepatocyte bile secretion are unknown. A number of agents that alter levels of cytosolic Ca2+ in the hepatocyte also produce hepatic vasoconstriction and activate protein kinase C, which complicates interpretations of their effects on bile secretion. To better understand the role of cytosolic Ca2+ in bile secretion, we examined the effect of the Ca2+ ionophore A23187 (0.1 mumol/L), the Ca2+ agonist vasopressin (10 nmol/L) and the Ca(2+)-mobilizing agent, 2,5-di(tert-butyl)-1,4-benzohydroquinone (25 mumol/L) on cytosolic Ca2+ in isolated hepatocytes and on bile flow in the isolated perfused rat liver, using vasodilators and inhibitors of protein kinase C and Ca2+ influx. Single-pass perfused livers were used, and cytosolic Ca2+ was measured by luminescent photometry in isolated hepatocytes loaded with the Ca(2+)-sensitive photoprotein aequorin. After A23187 perfusion, a sustained 74% +/- 10% (mean +/- S.D.) decrease in bile flow and a sustained 271% +/- 50% increase in perfusion pressure was observed. Simultaneous pretreatment with the vasodilator papaverine (25 mumol/L) and the protein kinase C inhibitor H-7 (50 mumol/L) abolished the pressure increase but not the decrease in bile flow, whereas pretreatment with Ni2+ (25 mumol/L) to block the influx of extracellular Ca2+ markedly reduced both the pressure increase and the decrease in bile flow. Vasopressin produced a transient (mean = 6 min) 75% +/- 4% decrease in bile flow and a sustained 7% +/- 4% increase in perfusion pressure. Pretreatment with H-7 alone corrected the vasopressin-induced pressure increase but also failed to eliminate the decrease in bile flow, whereas pretreatment with Ni2+ decreased the magnitude of the decrease by two-thirds without affecting the increase in perfusion pressure, 2,5'-di(tert-butyl)-1,4-benzohydroquinone produced a transient 65% +/- 20% decrease in bile flow and a transient 56% +/- 15% increase in perfusion pressure. In isolated hepatocytes, bromo-A23187, the nonfluorescent form of the ionophore, produced a sustained 56% +/- 32% increase in the cytosolic Ca2+ signal, whereas vasopressin resulted in a transient 241% +/- 75% increase and 2,5-di(tert-butyl)-1,4-benzohydroquinone resulted in a sustained 149% +/- 66% increase. The ionophore-induced increase in Ca2+ was abolished completely by pretreatment of the hepatocytes with Ni2+, whereas the vasopressin-induced increase was reduced by 38%.(ABSTRACT TRUNCATED AT 400 WORDS)

Aequorin↗
PubMed1992

Hormonal regulation of paracellular permeability in isolated rat hepatocyte couplets.

Many hormones and drugs exert their effects on cells by increasing cytosolic Ca2+ (Cai2+) and activating protein kinase C (PKC). Each of these actions results in cholestasis in the isolated perfused rat liver, but the responsible mechanisms are unclear. We used isolated rat hepatocyte couplets to observe the direct effects of increased Cai2+ and PKC activation on permeability of the hepatocyte tight junction and canalicular volume, two possible determinants of hepatocyte bile secretion. Couplets were stimulated with the Ca2+ agonist vasopressin (10(-8) M) in the absence and presence of the Ca2+ influx antagonist Ni2+ (5 x 10(-3) M) or with the PKC activator phorbol dibutyrate (10(-6) M). Cai2+ was determined by ratio microspectrofluorometry of indo-1, permeability of the couplet tight junctions was assessed by exclusion of horseradish peroxidase from the canalicular space, and changes in canalicular volume over time were measured directly by optical planimetry. Canalicular volume increased by 1.6 +/- 2.5%/min (mean +/- SD) under basal conditions. In response to vasopressin, there was a rapid 15-fold increase in Cai2+, followed first by an increase in paracellular permeability, then by canalicular collapse (15.9 +/- 5.9%/min). Pretreatment with Ni2+ markedly decreased the vasopressin-induced increase in Cai2+ and abolished both the increase in paracellular permeability and the canalicular collapse. Phorbol dibutyrate also increased paracellular permeability but resulted in neither increased Cai2+ nor canalicular collapse. The PKC inhibitor H-7 reversed the effects of both vasopressin and phorbol dibutyrate on tight junction permeability. Bile secretory pressure, measured in isolated perfused rat liver preparations, was acutely increased by vasopressin, but the increase was augmented rather than inhibited by Ni2+.(ABSTRACT TRUNCATED AT 250 WORDS)

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1992

Lymphocyte macrophage interactions: peripolesis of human alveolar macrophages.

Peripolesis is a phenomenon in which a lymphocyte attaches itself to another cell, usually a macrophage or veiled cell, and proceeds to circle around it. In emperipolesis, a related phenomenon, the lymphocyte invaginates the target cell so deeply that it appears to be intracytoplasmic. Lung cells in bronchoalveolar lavage fluids from 20 patients were observed in the living state and filmed. Peripolesis of the alveolar macrophages was recorded in six cases. These patients included one case each of carcinoma of the bronchus, tuberculosis, sarcoidosis and asthma, while two patients had no detectable lung disease. Five out of the six positive cases were females. In every instance there was a high number of lymphocytes in the washing. The peripolesed macrophages were not injured, but temporary alteration of the cell membrane was noted in a minority of film sequences. The peripolesing cells were also examined by transmission and scanning electron microscopy. The lymphocyte was found to be closely attached to the surface of the macrophage, with no invagination and its ultrastructure was that of a small lymphocyte. Peripolesis is probably a physiological mechanism concerned with regulation of the immune response in the lung.

Adult↗
PubMed1991

Competitive inhibition of antigen presentation in animal models of autoimmune disease.

Competition between peptides for binding to class II major histocompatibility complex (MHC) molecules has been demonstrated both in vitro and in vivo. Peptide competition may provide a way to interfere with T cell activation in the treatment of autoimmune diseases. It may be possible to provide a substitute 'blocking' peptide to compete for presentation of an autoantigenic peptide to T cells. The approach described is a general one, which may be applicable to a number of T cell mediated MHC-linked autoimmune diseases, and to other undesirable immune responses. So far, peptide competitors have only been successfully used in the prevention of experimental autoimmune encephalomyelitis (EAE). Whether or not this approach will work in treating spontaneous disease models remains to be tested, although work in other test systems is encouraging.

Animals↗
PubMed1990

Combined time-lapse cinematography and immuno-electron microscopy.

A method was developed to record interactions between mobile non-adherent immunocytes by time-lapse cinematography and then to study the same cells by immuno-electron microscopy, using monoclonal antibodies against surface components. For this purpose a modified stage was designed to fit an inverted microscope. The attachment included a device to cool the culture chamber with N2 gas, a micro-injector for monoclonal antibody and immuno-gold treatment, and two pairs of washing needles to change the medium without disturbance. The technique was first employed to study the formation of aggregates around the antigen-presenting cells in cultures containing cells from hyper-immunized animals. Recently peripheral blood cells from normal subjects and patients with immune deficiency syndromes were stimulated with pokeweed mitogen, cluster formation was recorded, and the cells were processed for immuno-electron microscopy.

Animals↗
PubMed1989

Impact of a pilot acute respiratory infection (ARI) control programme in a rural community of the hill region of Nepal.

A prospective study was conducted to determine the magnitude of morbidity and mortality caused by acute respiratory infections (ARI) among children under 5 years of age and to assess the feasibility of reducing mortality owing to ARI by the use of community health workers. Villages selected for this study were situated on the south-west edge of Kathmandu Valley, about 24 km from the city centre. The study group consisted of 1019 children under the age of 5 years at the beginning of the study and followed for 3 years. During the 1st year, baseline information was collected. During the 2nd and 3rd years, intervention measures (health education, immunization and antibiotics for children with signs suggesting pneumonia) were taken and their effect assessed. There was a 59% reduction in the ARI-specific death rate among study children between surveillance year and intervention year I and a further 25% reduction in the ARI-specific death rate between intervention years I and II. Despite a substantial reduction in ARI mortality with the interventions, there was still an unacceptably high mortality from chronic diarrhoea, malnutrition and other factors. This implies that the programme to control ARI, diarrhoea, malnutrition and immunizable diseases should be integrated into one, within the framework of a primary health care strategy.

Child, Preschool↗
PubMed1989

Quantitative assessment of canalicular bile formation in isolated hepatocyte couplets using microscopic optical planimetry.

Isolated rat hepatocyte couplets (IRHC) are primary units of bile secretion that accumulate fluid in an enclosed canalicular space with time in culture. We have quantitated the rate of canalicular secretion in IRHC cultured for 4-8 h by measuring the change in canalicular space volume by video-microscopic optical planimetry using high resolution Nomarski optics. Electron microscopic morphometric studies revealed significant increases in canalicular membrane area after 4-6 h in culture. Canalicular secretion in basal L-15 medium (3.8 +/- 1.3 fl/min) increased significantly with the choleretic bile salts (10 microM), taurocholate, and ursodeoxycholate (14 +/- 7 fl/min each). Secretion rates after exposure to bile acids correlated directly with the canalicular surface area before stimulation. In contrast, expansion times after stimulation varied inversely with initial canalicular volumes. Ursodeoxycholic acid failed to produce a hypercholeresis at 10-, 100-, or 200-microM concentrations compared with taurocholate, either in normal or taurine-depleted IRHC. The present findings establish that rates of canalicular bile secretion can be quantitated in IRHC by serial optical planimetry, both in the basal state and after stimulation with bile acids. Furthermore, ursodeoxycholate does not acutely induce hypercholeresis at the canalicular level in this model. Rather, both taurocholic and ursodeoxycholic acids induced secretion in proportion to the surface area of the canalicular membrane. The IRHC are a useful model to identify canalicular choleretics and for studies of canalicular bile formation.

Animals↗
PubMed1988

Mechanisms of bile secretion: insights from the isolated rat hepatocyte couplet.

This article reviews recent studies that have characterized the isolated rat hepatocyte couplet as a primary unit of canalicular bile formation. This cell culture system is proving to be particularly useful for identifying primary canalicular choleretics and for elucidating mechanisms of canalicular bile formation by electrophysiologic, fluorescent, and quantitative microscopic techniques.

Animals↗
PubMed1988

Epidemiological study of tobacco smoking behaviour among adults in a rural community of the hill region of Nepal with special reference to attitude and beliefs.

This study, designed to examine adult smoking behaviour, attitudes and norms was carried out in the hill villages of Alapot and Bhadrabas, Nepal, using the WHO standardized survey questionnaire. Some 1506 adults were interviewed. The overall prevalence of daily smokers is 73.7%. The majority of people, though aware of hazards of smoking, are not concerned with its possible effects on their own or other people's health. More males than females endorse public action against smoking. Both the endorsement of public action against smoking and awareness of social norms discouraging smoking increase with educational attainment. The motives for not smoking and endorsement of public actions against smoking have been ranked. Based on these findings strategies for a national smoking control programme have been recommended.

Adult↗
PubMed1985

The role of dendritic cells in the initiation of immune responses to contact sensitizers. I. In vivo exposure to antigen.

Twenty-four hours after skin painting mice with picryl chloride (PIC) there was a four- to fivefold increase in the numbers of dendritic cells (DC) isolated from the lymph nodes. These DC initiated primary proliferative and cytotoxic responses when added to cultures of normal syngeneic lymph node cells. The proliferative response was enhanced when the donors of the responding lymph node cells were sensitized with the same antigen. Contact sensitivity developed in syngeneic mice injected into the footpads with 30,000-50,000 DC from lymph nodes of mice painted with picryl chloride 1 day previously. Thus, 1 day after skin painting mice, there were dendritic cells in the draining lymph nodes which were able both to initiate primary stimulation of lymphocytes in vitro and to sensitize recipient mice to give specific delayed hypersensitivity reactions.

Animals↗
PubMed1985

Domestic smoke pollution and respiratory function in rural Nepal.

A study was conducted to see the effect of domestic smoke pollution on respiratory function by using vitalograph Model 20.400 S-type dry portable spirometer in 150 randomly selected female subjects aged 30-44 years from a rural area situated in the outskirts of Kathmandu valley at an altitude of 4,800 ft. above sea level. The area is totally free from industrial and atmospheric pollution. Women spend considerable time near the fireplace, which serves both cooking and heating purposes and emits smoke from wood and other biomass fuel. Domestic smoke pollution is considerable because dwellings are ill-ventilated and without chimnies. The selected sample comprised of 6 groups-25 subjects each of 3 exposure levels to domestic smoke pollution amongst smokers and non-smokers. All the spirometric tests (FVO, FEV1 and FMEF 25-75) were performed in a standard way as recommended by American Thoracic Society in Snowbird Meeting in 1979. Variation of age, height, arm-span and weight between the three different levels of exposure to domestic smoke in both the smokers and non-smokers were compared and results revealed no significant variation in all the variables mentioned above. There was a fall of mean FVC, FEV1 and FMEF 25-75 as duration of exposure increased. This decline was found to be statistically significant amongst the smokers but not amongst the non-smokers. Similar results was found even after adjusting for age & height.

Adult↗
PubMed1976

In vitro effects of certain neurohumors on ultrastructural change of the chick embryonic thyroid gland.

In vitro effects of certain neurohumors, on ultrastructure of 14 days old chick embryonic thyroid gland, has been studied. When the chick embryonic thyroid gland was cultivated in vitro, in the medium containing neurohumors like acetylcholine, adrenaline and histamine for a definite period in a particular sequence and dose, has resulted almost similar ultrastructural changes as seen in the hyperactive thyroid gland.

Acetylcholine↗
PubMed1976

Histological response of various endocrine glands after administration of certain neurohumors in chicks.

Histological response of various endocrine glands like pituitary, adrenal, testes and pancreas after administration of certain neurohumors like acetylcholine, adrenaline and histamine in a particular dose and sequence, has been carried out in white leghorn chicks. Result of this study revealed that administration of these neurohumors produced definite changes in various endocrines. Histological changes are more prominent in pituitary and adrenal glands, whereas, pancreas and testes did not reveal much influence of these neurohumors.

Acetylcholine↗