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Biomedical subjects

T K Ghosh

Publications and source records attributed to T K Ghosh.

At least 91 records · Page 5Linked to original sources
PubMed1989

Epidemiology of brugian filariasis in a rural community of Kerala State.

The baseline clinico-parasitological parameters collected during the initial survey and the entomological observations made during the first year as a part of a longitudinal study undertaken in a brugian endemic rural community are presented in this paper. Out of the total (11.604) examined population, 8.1 per cent had microfilaraemia and 7.6 per cent had filarial disease. A highly significant (P less than 0.001) relationship of age was observed with microfilaraemia and the disease. The filarial disease rate showed no significant difference between two sexes while the microfilaria (Mf) rate was significantly (P less than 0.001) higher in males than females. A significant (P less than 0.001) relationship of microfilaraemia as well as of filarial disease was found with the income and the educational status of the individual. The mf and the disease rates did not differ by the family size except those families with 1-3 members. However, the relationship of family size was found to be significant (P less than 0.001) with disease and non-significant (P greater than 0.05) with microfilaraemia. The vectors were prevalent throughout the year but the infection was mostly confined to Mansonia annulifera.

Adolescent↗
PubMed1989

Feasibility of controlling lymphatic filarial diseases through primary health care system.

A study was undertaken to explore the feasibility of treatment of clinical cases of filariasis by the Village Health Guides (VHG) and to assess the impact of different dose schedules by Diethylcarbamazine (DEC) on the frequency of acute attacks. It was observed that six days treatment with DEC at a dose of 500 mg daily was the most effective regimen in controlling recurrence of filarial attacks. The VHGs can serve the community in treating filarial cases with DEC.

Community Health Workers↗
PubMed1988

Competitive, reversible, and potent antagonism of inositol 1,4,5-trisphosphate-activated calcium release by heparin.

The action of inositol 1,4,5-trisphosphate (InsP3) in releasing intracellular Ca2+ is shown to be competitively and potently antagonized by the glycosaminoglycan, heparin. Using either permeabilized cells of the DDT1MF-2 smooth muscle cell line, or an isolated microsomal membrane fraction derived from intact cells, heparin (4-6 kDa) at 10 micrograms/ml was observed to completely block the action of InsP3 in releasing Ca2+ accumulated via the ATP-dependent Ca2+ pump. In permeabilized cells, heparin had no effect on Ca2+ pump activity or on passive Ca2+ fluxes contributing to equilibrium Ca2+ accumulation. Heparin up to 100 micrograms/ml had no effect on the GTP-activated Ca2+ translocation process previously characterized in this cell line. Half-maximal inhibition of Ca2+ release activated by 10 microM InsP3 occurred with heparin at approximately 0.6 and 0.2 microgram/ml in permeabilized cells and isolated microsomes, respectively. Using microsomes, InsP3 dose-response curves in the presence and absence of 0.2 microgram/ml heparin (approximately 40 nM) revealed a 10-fold increase in apparent Km for InsP3 (0.31 microM in the absence of heparin) with no change in Vmax, indicating a competitive action of heparin. The results revealed a very high apparent affinity of heparin for the InsP3 active site, with a calculated Ki value of 2.7 nM. Heparin was shown to rapidly (within 20 s) reverse prior full activation of InsP3-mediated Ca2+ release returning the Ca2+ equilibrium back to that observed without InsP3. This reversal occurs even after prolonged (6 min) InsP3 activation. These results indicate a specific, high affinity, and competitive antagonism of the InsP3 active site by heparin. The rapidly induced reversal of InsP3-activated Ca2+ release by heparin strongly suggests that InsP3 directly activates a channel which remains open only while InsP3 is associated and closes immediately upon InsP3 dissociation.

Animals↗
PubMed1988

Calcium entry into the inositol 1,4,5-trisphosphate-releasable calcium pool is mediated by a GTP-regulatory mechanism.

Intracellular Ca2+ release activated by inositol 1,4,5-trisphosphate (InsP3) plays a pivotal role in Ca2+ signaling in cells. A controlling mechanism for InsP3-induced Ca2+ movements is suggested by results showing that the InsP3-releasable Ca2+ pool is directly modified by a specific and sensitive GTP-regulated Ca2+-translocating process. By using saponin-permeabilized N1E-115 neuroblastoma cells or DDT1MF-2 smooth muscle-derived cells, InsP3 releases 30-50% of Ca2+ accumulated through intracellular high-affinity ATP-dependent Ca2+-pumping activity. Oxalate-promoted Ca2+ uptake is reversed by InsP3, indicating oxalate permeability of the InsP3-releasable pool, which is consistent with this compartment being the endoplasmic reticulum. GTP (10 microM) activates release of 50-70% of accumulated Ca2+ from cells. In the presence of 5-10 mM oxalate, GTP induces a biphasic Ca2+ flux response; initially (1-2 min) GTP induces rapid Ca2+ release followed thereafter by a profound increase in Ca2+ uptake. Thus, GTP-activated Ca2+ influx and efflux compete for Ca2+ access to the oxalate-permeable Ca2+ pool. The nonadditive effects of InsP3 and GTP suggest that InsP3 releases Ca2+ from a subcompartment of the GTP-releasable pool. Most significantly, InsP3 is observed to block the GTP-activated uptake phase in the presence of oxalate, indicating that GTP induces Ca2+ entry into the pool from which InsP3 activates release. Hence, the results provide direct evidence that loading of Ca2+ into the InsP3-sensitive Ca2+ pool is controlled by a GTP-regulated Ca2+-translocating mechanism. Such a process could be significant in regulating the extent and duration of the InsP3-induced Ca2+ signal, a crucial step in the inositol phospholipid signaling pathway.

Animals↗
PubMed1988

Intracellular calcium translocation: mechanism of activation by guanine nucleotides and inositol phosphates.

The movements of Ca2+ within cells in response to external stimuli are complex. Internal Ca2+ release activated by inositol 1,4,5-trisphosphate (InsP3) is now widely established. However, the mechanism of InsP3-induced Ca2+ release, the identity and control of the InsP3-sensitive Ca2+ pool and its relationship to other internal and external Ca2+ pools all remain uncertain. We have characterized a highly sensitive and specific guanine nucleotide-regulatory mechanism that induces rapid and profound movements of intracellular Ca2+ via a mechanism distinct from that activated by InsP3. Using permeabilized neural or smooth muscle cells, application of submicromolar concentrations of GTP induces rapid release of Ca2+ from a compartment that contains within it the InsP3-releasable Ca2+ pool. Although of similar GTP-sensitivity as G-protein-activated events, the apparent dependence on GTP hydrolysis and blockade by GTP gamma S suggest a mechanism distinct from those mediated by known G-proteins. Recent experiments in the presence of oxalate reveal rapid and profound GTP-activated uptake of Ca2+ via a mechanism with identical nucleotide sensitivity and specificity to GTP-induced Ca2+ release. These results were interpreted to suggest that GTP induces a transmembrane conveyance of Ca2+ between different compartments distinguished by oxalate permeability; GTP-induced release probably occurs via a similar mechanism except involving transfer between closed compartments and nonclosed membranes (perhaps the plasma membrane). Recently, it has been revealed that GTP activates a translocation of Ca2+ into the Ca2+ pool from which InsP3 induces release. This is an important observation suggesting that the GTP-activated Ca2+ translocation process may control entry into and hence the size of the InsP3-releasable Ca2+ pool. Indeed, it is possible that GTP-induced Ca2+ release observed in permeabilized cells reflects a reversal of the pathway that functions in intact cells to permit external Ca2+ entry into the InsP3-releasable pool. This type of process could mediate the longer-term secretory or excitatory responses to external receptors which are known to be dependent on external Ca2+.

Animals↗
PubMed1988

Persistence of parasite antigenemia following diethylcarbamazine therapy of bancroftian filariasis.

This study was designed to reexamine the efficacy of diethylcarbamazine for bancroftian filariasis with special reference to changes in serum parasite antigen levels and antifilarial antibody titers after treatment. Patients with asymptomatic microfilaremia were treated with 6 mg/kg diethylcarbamazine daily for 12 days. Microfilaria counts fell dramatically after treatment, as expected. IgG antibody titers to adult and microfilarial antigens of B. malayi were increased 1 month after treatment in most patients. Titers fell slowly to or below pretreatment levels, but remained positive during subsequent months. Parasite antigen levels, measured by monoclonal antibody-based enzyme immunoassay, decreased to 72%, 58%, 53%, and 48% of pretreatment values 1, 3, 6, and 12 months after diethylcarbamazine treatment, respectively. Parasite antigen levels decreased similarly in subjects with and without residual microfilaremia after treatment. These results suggest that diethylcarbamazine has only partial macrofilaricidal activity against W. bancrofti with this dosage schedule. The sustained, impressive reductions in microfilaria counts after treatment despite significant persistence of parasite antigenemia may be explained by sublethal effects of the drug on adult worms. We believe that parasite antigen detection represents a valuable new approach for monitoring the efficacy of antifilarial drug therapy which we hope will lead to improved use of existing drugs and aid in the evaluation of new drugs for filariasis.

Animals↗
PubMed1987

GTP- and inositol 1,4,5-trisphosphate-activated intracellular calcium movements in neuronal and smooth muscle cell lines.

Recent evidence has revealed that a highly sensitive and specific guanine nucleotide regulatory process controls intracellular Ca2+ release within N1E-115 neuroblastoma cells (Gill, D. L., Ueda, T., Chueh, S. H., and Noel, M. W. (1986) Nature 320, 461-464). The present report documents GTP-induced Ca2+ release within quite distinct cell types, including the DDT1MF-2 smooth muscle cell line. GTP-induced Ca2+ release has similar GTP sensitivity and specificity among cells and rapidly mobilizes up to 70% of Ca2+ specifically accumulated within a nonmitochondrial Ca2+-pumping organelle within permeabilized DDT2MF-2 cells. Maximal GTP-induced release of Ca2+ is observed to be greater than inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ release (the latter being approximately 30% of total releasable Ca2+). After maximal IP3-induced release, further IP3 addition is ineffective, whereas subsequent addition of GTP further releases Ca2+ to equal exactly the extent of Ca2+ release observed by addition of GTP in the absence of IP3. This suggests that IP3 releases Ca2+ from the same pool as GTP, whereas GTP also releases from an additional pool. The effects of GTP appear to be reversible since simple washing of GTP-treated cells restores their previous Ca2+ uptake properties. Electron microscopic analysis of GTP-treated membrane vesicles reveals their morphology to be unchanged, whereas treatment of vesicles with 3% polyethylene glycol, known to enhance GTP-mediated Ca2+ release, clearly induces close coalescence of membranes. In the presence of 4 mM oxalate, GTP induces a rapid and profound uptake, as opposed to release, of Ca2+. The findings suggest that GTP-activated Ca2+ movement is a widespread phenomenon among cells, which can function on the same Ca2+ pool mobilized by IP3, and although activating Ca2+ movement by a mechanism distinct from IP3, does so via a process that does not appear to involve fusion between membranes.

Animals↗
PubMed1987

Intracellular calcium uptake activated by GTP. Evidence for a possible guanine nucleotide-induced transmembrane conveyance of intracellular calcium.

The GTP-activated Ca2+ release process we recently described (Gill, D. L., Ueda, T., Chueh, S. H., and Noel, M. W. (1986) Nature 320, 461-464) was revealed in the preceding report to operate via a mechanism likely to be induced by close membrane association but which appears not to involve membrane fusion (Chueh, S. H., Mullaney, J. M., Ghosh, T. K., Zachary, A. L., and Gill, D. L. (1987) J. Biol. Chem. 262, 13857-13864). To determine more about the GTP-activated Ca2+ translocation process, effects of GTP on cells loaded with Ca-oxalate were investigated. Using permeabilized cells of both the N1E-115 neuroblastoma and DDT1MF-2 smooth muscle cell lines, 10 microM GTP activates a profound uptake of Ca2+ in the presence of oxalate, as opposed to release observed without oxalate. GTP stimulation of Ca2+ uptake was observed at oxalate concentrations (2 mM) only slightly augmenting Ca2+ uptake without GTP; with 8 mM oxalate (which alone induces linear Ca2+ accumulation) GTP still increases the rate of uptake. GTP-activated uptake in the presence of oxalate is completely reversed by 1 mM vanadate. 3% polyethylene glycol enhances the effect of GTP although GTP-activated uptake is still observed without polyethylene glycol. The Km for GTP for activation of Ca2+ uptake is 0.9 microM. Uptake is not activated by guanosine 5'-O-(3-thio)triphosphate (GTP gamma S) or guanosine 5'-(beta, gamma-imido)triphosphate (GppNHp); however, GTP gamma S (but not GppNHp) completely blocks the action of GTP. GDP gives a delayed uptake response which is blocked by ADP, indicating its action arises from conversion to GTP. In the presence of ADP, GDP blocks the action of GTP; guanosine 5'-O-(2-thio)diphosphate, which does not activate uptake, also blocks the action of GTP. These data reveal almost exact correlation between parameters affecting GTP-activated uptake and release, strongly suggesting the same process mediates both events. To explain the opposite effects of GTP in the absence and presence of oxalate, it is proposed that GTP activates a transmembrane conveyance of Ca2+ between oxalate-permeable and -impermeable compartments.

Animals↗
PubMed1987

Angiotensin-converting enzyme in organs of air-breathing fish.

Angiotensin-converting enzyme (ACE) was measured in tissue homogenates from the African lungfish and six species of air-breathing teleosts (Heteropneustes fossilis, Clarias batrachus, Channa gachua, Anabas testudineus, Notopterus chitala, and Monopterus cuchia) using a standard spectrophotometric assay. In most species, the highest levels of ACE activity were found in the respiratory organs (gills and/or accessory respiratory organs). ACE was also found in heart and kidney tissues from most species and occasionally in liver. Converting enzyme was not found in skin or skeletal muscle from any species and only in blood from H. fossilis and brain from C. batrachus. Captopril, a potent inhibitor of mammalian ACE, inhibited enzymatic activity from all tissues except C. gachua heart and liver and A. testudineus heart. As fish make the transition from aquatic to aerial respiration the gill microcirculation is usually reduced in size and the accessory respiratory organs become elaborated and occupy a more central position in the vascular tree. The presence of ACE in accessory respiratory organs of air-breathing fish appears to greatly enhance the metabolic efficiency of this enzyme on circulating substrates.

Animals↗
PubMed1987

Effect of inhalation of xylene on intracranial self-stimulation behavior in rat.

The effect of the inhalation of xylene on intracranial self-stimulation behavior was studied in rats in a flow-through (dynamic) inhalational behavioral chamber. Rats were exposed successively to four graded concentrations (102, 192, 419 and 623 ppm) of xylene vapor during 2-hr sessions on different days. The rate of lever-pressing showed a dose-dependent decrease during exposure to 192, 419 and 623 ppm of xylene. The 4-hr exposure to the smallest concentration (106 ppm) of xylene failed to show any effect on self-stimulation behavior. During a 5-day 2 hr/day exposure, the decrease in response observed on the 1st day was further accentuated with a nadir on the 3rd day; from the 4th day onwards, the depressant effect was attenuated showing the development of tolerance.

Administration, Inhalation↗
PubMed1987

Effect of xylene inhalation on fixed-ratio responding in rats.

The effect of xylene inhalation was studied on operant behavior under a fixed-ratio (FR24) schedule in rats. Experiments were performed while rats were being exposed to xylene vapor in an inhalational (flow-through) behavioral chamber. Rats were exposed successively to three graded concentrations (113, 216 and 430 ppm) of xylene vapor each for 2 hr in range-finding studies during 6 1/4-hr sessions. The reinforcement rate which is correlated with FR responding was shown to be decreased at hr 1, hr 3 and hr 5. However at hr 2, hr 4 and hr 6 the reinforcement rate in rats increased approaching the control levels, thereby indicating development of tolerance. When rats were exposed to one of the three graded concentrations of xylene for 2 hr on separate days, they also showed a decrease in the reinforcement rate at hr 1; development of acute tolerance was also noted in this schedule. Exposure to the lowest (98.5 ppm) level of xylene used during 5-hr sessions caused no significant decrease in the reinforcement rate. This study thus attempts to identify a minimum effective concentration of xylene and indicates the development of acute tolerance to behavioral effect of xylene.

Administration, Inhalation↗
PubMed1987

A monoclonal antibody-based enzyme immunoassay for detecting parasite antigenemia in bancroftian filariasis.

We evaluated a monoclonal antibody-based enzyme immunoassay for detecting soluble parasite antigen in sera collected in an area in South India endemic for Wuchereria bancrofti. Filarial antigen was detected in sera from 56 of 57 microfilaremic patients, 9 of 64 aminofilaremic patients with clinical filariasis, and 11 of 70 endemic controls. Antigen was not detected in sera from patients from nonendemic areas who had a variety of other filarial and nonfilarial helminth infections. Parasite antigen titers were significantly correlated with microfilarial counts in night blood smears (r = .64, P less than .01). Negative antigen tests in patients with clinical filariasis may be explained in part by antibody-mediated clearance of circulating antigen. Antibodies to circulating W. bancrofti antigen were detected in 41 of 55 antigen-negative sera from patients with clinical filariasis. Despite this limitation, detecting parasite antigen by enzyme immunoassay provides significant advantages over previously available methods for diagnosing active W. bancrofti infection.

Antibodies↗