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S Ganesan

Publications and source records attributed to S Ganesan.

At least 55 records · Page 3Linked to original sources
PubMed1992

Ca(2+)-cyclic AMP interactions in sustained cellular responses.

As early as 1970 it was apparent that the cyclic AMP (cAMP) and Ca2+ messenger systems often interact to regulate cellular responses. Work over the past 20 years has greatly expanded our knowledge of these interactions, and has shown that these signalling systems interact in complex ways to regulate sustained cellular responses such as aldosterone secretion, smooth muscle contraction and insulin secretion. The latter system is considered in detail because it illustrates several types of interactions, both positive and negative, which help to determine the normal response of beta-cells to physiological stimuli, and how abnormalities in secretory patterns can develop as a consequence of the prolonged stimulation of a messenger system.

Animals↗
PubMed1991

Influence of staurosporine on glucose-mediated and glucose-conditioned insulin secretion.

The effect of staurosporine, a putative inhibitor of protein kinase C (PKC), on insulin secretion induced by glucose and 4-methyl-2-oxopentanoate (KIC) was examined. In addition, the effects of staurosporine on the actions of other agonists, for which glucose acts as a conditional modifier, were also examined. At 20 nM, staurosporine caused a marked inhibition of second-phase insulin secretion, whether it was stimulated by 10 mM- or 20 mM-glucose, by 15 mM-KIC, or by carbachol or tolbutamide in islets co-perifused with 7.0 mM-glucose. In each case, the second-phase secretory response was inhibited by 70-85%. In contrast, in all cases there was no effect of staurosporine on the magnitude of the first phase of insulin secretion, nor on the time course of first-phase secretion, except when glucose alone was the secretagogue. With either 10 mM- or 20 mM-glucose, the peak of the first phase of insulin secretion was delayed. Staurosporine does not alter glucose metabolism, or the ability of glucose to activate phosphoinositide hydrolysis or to cause the translocation of alpha-PKC to the membrane. These findings support the concept that PKC activation plays an important role in fuel-induced or fuel-conditioned insulin secretion.

Alkaloids↗
PubMed1991

Effects of the phorbol ester phorbol 12-myristate 13-acetate (PMA) on islet-cell responsiveness.

Collagenase-isolated rat islets were labelled for 2 h in myo-[2-3H]inositol solution supplemented with 2.75 mM-glucose. The phorbol ester phorbol 12-myristate 13-acetate (PMA; 0.1 or 1 microM) was also present in some experiments. After labelling, islets were washed and then perifused in 2.75 mM-glucose to establish basal [3H]inositol-efflux and insulin-secretory rates. Subsequently, the responses of these islets to stimulation with various agonists were assessed. Inositol phosphate accumulation was measured at the termination of the perifusion. In separate experiments, the cellular location of protein kinase C (PKC) after PMA pretreatment was measured by quantitative immunoblotting of membrane and cytosolic fractions. The following observations were made. (1) Labelling in 0.1-1 microM-PMA had no deleterious effect on total [3H]inositol incorporation during the 2 h labelling period. However, islets labelled for 2 h in 1 microM-PMA were unable to respond, in terms of increases in insulin release, to a 1 microM-PMA stimulus during the subsequent perifusion. (2) As compared with the responses of control islets labelled in 2.75 mM-glucose alone, islets labelled in the additional presence of 1 microM-PMA displayed a significant impairment in phosphoinositide (PI) hydrolysis, but an enhancement of both first-and second-phase insulin secretion, in response to subsequent 20 mM-glucose stimulation. (3) Decreasing extracellular Ca2+ level to 0.1 mM and including the Ca(2+)-channel antagonist nitrendipine (0.5 microM) along with 1 microM-PMA during the [3H]inositol-labelling period did not alter the response of the islets to the subsequent addition of 20 mM-glucose. Glucose-induced PI hydrolysis was still inhibited and 20 mM-glucose-induced insulin release was still enhanced. (4) A markedly amplified and sustained insulin-secretory response to 200 microM-tolbutamide in the presence of 2.75 mM-glucose was also obtained from 1 microM-PMA-pretreated islets. This contrasts sharply with the small and transient response to tolbutamide noted in control islets. (5) When present only during the perifusion phase of the experiments, nitrendipine (0.5 microM) abolished the amplified insulin-secretory responses to both 20 mM-glucose and 200 microM-tolbutamide noted in PMA-pretreated islets. (6) Prior labelling in 1 microM-PMA dramatically amplified the insulinotropic effect of 25 mM-K+ or 5 microM-A23187 stimulation. The amplified insulin-secretory response to K+, but not to A23187, was abolished by inclusion of nitrendipine during the perifusion.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Effect of increased acceleration on regional pleural pressure in dogs.

The variation of pleural pressure was measured in anesthetized spontaneously breathing dogs subjected to increased acceleration (0-4 G) in a centrifuge. Two groups of animals were studied. In one group, the resultant acceleration was in a direction either ventral-to-dorsal (+Gx) or dorsal-to-ventral (-Gx), with a relatively small residual cranial-to-caudal acceleration. In the other group, the resultant acceleration was either cranial-to-caudal (+Gz) or caudal-to-cranial (-Gz), with a relatively small residual dorsal-to-ventral acceleration. Pleural liquid pressure (Ppl) was measured by two rib capsules that were separated by 7-9 cm and oriented either in the dorsal-to-ventral or cranial-to-caudal direction. At functional residual capacity, Ppl in the nondependent lung region became more negative when the acceleration was in the +Gx or +Gz direction. Thus the lung would be susceptible to damage that results from overexpansion in these acceleration directions. By contrast, acceleration in the -Gx or -Gz direction produced values of Ppl at functional residual capacity that were positive. Thus, in these acceleration directions, the respiratory muscles must provide greater force during inspiration to overcome lung compression before lung ventilation can occur. The Ppl gradients with respect to the acceleration directions increased approximately in proportion to acceleration in the +Gx, -Gx, and -Gz directions but remained relatively constant in the +Gz direction.

Acceleration↗
PubMed1990

Glucose-induced translocation of protein kinase C in rat pancreatic islets.

The role of protein kinase C (PKC) as a mediator of glucose-induced insulin secretion has been a subject of controversy. Glucose-induced translocation of PKC has not been reported, and the relevant PKC isoenzymes in islets have not been identified. To address these issues, we developed specific antibodies to the alpha, beta, and gamma isoenzymes of PKC. Western blots of homogenates of freshly isolated rat islets probed with these antibodies revealed that the major isoenzyme present is alpha-PKC. Islets were perifused for 15 min with either 2.75 mM glucose, 20 mM glucose, 20 mM glucose plus 30 mM mannoheptulose, 15 mM alpha-ketoisocaproate, or alpha-ketoisocaproate plus mannoheptulose. Quantitative immunoblotting of membrane and cytosol fractions showed that alpha-PKC translocated from the cytosol to the membrane in freshly isolated rat islets stimulated with either 20 mM glucose or 15 mM alpha-ketoisocaproate. Both the secretory response and the translocation of alpha-PKC were blocked by the addition of mannoheptulose, an inhibitor of glucose metabolism, in islets stimulated with glucose but not in islets stimulated with alpha-ketoisocaproate. These results support a role for alpha-PKC in mediating glucose-induced insulin secretion in pancreatic islets.

Amino Acid Sequence↗
PubMed1990

Physiology and pathophysiology of insulin secretion.

Mechanisms by which various classes of extracellular signals regulate insulin secretion are discussed regarding their cellular and molecular actions. Under physiological circumstances, the small postprandial changes in plasma glucose concentrations (approximately 4.4-6.6 mM) primarily serve as a conditioned modifier of insulin secretion and dramatically alter the responsiveness of islets to a combination of neurohormonal agonists. These agonists have two functions. Cholecystokinin (CCK) and acetylcholine activate the hydrolysis of polyphosphoinositides, and gastric inhibitory polypeptide (GIP) and glucagonlike peptide 1 activate adenylate cyclase. These two functional classes of neurohumoral agonists act synergistically to enhance insulin secretion when plasma glucose is greater than 6.0 mM but not when it is less than or equal to 4 mM. On the other hand, an increase in plasma glucose concentration to 8-10 mM induces an increase in insulin secretory rate in the absence of any of the neurohormonal agonists. Remarkably, high glucose leads to an increase in the same intracellular signals, as does a combination of acetylcholine and GIP. On the basis of these data, a model of how insulin secretion is regulated under physiological circumstances is proposed. This model emphasizes that the regulation of insulin secretion occurs in three stages: cephalic, early enteric, and later enteric. In this view, the crucial event occurring during the first two phases is the agonist-induced, translocation of protein kinase C (PKC) to the plasma membrane under conditions in which an increase in Ca2+ influx does not occur. PKC is now in a cellular location and a Ca2(+)-sensitive conformation such that an increase in Ca2+ influx rate occurring during the third phase leads to its immediate activation and an enhanced rate of insulin secretion. Furthermore, under physiological circumstances, an optimal insulin secretory response is dependent on a correct temporal pattern of signals arising from neural and enteric sources. If this pattern is deranged, an abnormal pattern of insulin secretion is observed. An important new insight is provided by the observation that agonists (e.g., CCK or acetylcholine) that act to stimulate the hydrolysis of phosphatidylinositides, when acting for a short period (10-20 min), induce an enhanced responsiveness of islets to glucose, i.e., proemial sensitization. However, when acting unopposed for several hours, these agonists will induce a time-dependent suppression of responsiveness to glucose and other agonists. The latter observation implies that optimal insulin secretion is dependent on periodic rather than a continuous exposure to the correct pattern of extracellular signals.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Alveolar liquid pressures in nonedematous and kerosene-washed rabbit lung by micropuncture.

We studied the relationship between alveolar interfacial pressure and lung volume in kerosene-filled lungs, nonedematous air-filled lungs on lung deflation and inflation, and air-filled lungs after washing with kerosene or the Dow Corning oil, 0.65 cs dimethyl siloxane (DC200). We used the micropipet-servonulling technique to measure alveolar liquid pressure (Pliq) in the alveolar liquid layer of isolated rabbit lungs at different airway pressures (Palv). It was not possible to measure pressure in kerosene or in DC200 by micropuncture because of its low electrical conductivity. We used the Laplace law for a spherical membrane to estimate alveolar surface tension (T). In the kerosene-filled lung, the pressure drop (delta P = Pliq - Palv) across the alveolar surfactant-kerosene interface was 1.1 cm H2O at TLC and decreased to 0.5 cm H2O at 71% TLC. These values corresponded to T values of 2.2 and 0.9 dyne/cm at TLC and 71% TLC, which were in agreement with in vitro measurements using the captive bubble technique. In the air-filled lung on inflation, delta P values were 12.7 and 15.7 cm H2O at 48% and 76% TLC. Corresponding T values were 14 and 21 dyne/cm. Thus, alveolar surface tension on lung inflation is surface area dependent. In the kerosene-washed and DC200-washed lungs, delta P values were 16 and 14.5 cm H2O at TLC and decreased to 9 and 8 cm H2O at 50-56% TLC. These values indicated a reduction of 40-60% in alveolar surface tension with lung deflation from TLC to 50% TLC. The results indicate that alveolar surface tension in both kerosene-filled and kerosene-washed air-filled lungs is surface area dependent. This is due to a surfactant-kerosene interface in the kerosene-filled lung and a surfactant-kerosene-air interface in the kerosene-washed lung.

Air↗
PubMed1989

Catastrophic stress and factors affecting its consequences among Southeast Asian refugees.

Effects on mental health of the stress of being interned in a refugee camp were assessed in a community survey of 1348 Southeast Asians. The impact on depressive mood proved significant but short-lived. Social support derived from the ethnic community and from an intact marriage moderated the risk of developing depressive symptoms, apparently by enhancing a sense of identity and belongingness. A psychological coping mechanism--avoidance of the past--buffered the impact of camp stress on depressive symptoms. While refugees brought into the country under private sponsorship were expected to have a mental health advantage compared to those admitted under government sponsorship, this hypothesis was not confirmed. Private sponsorship, carried out by individuals or groups whose religion differed from the refugees they were supporting, acted as a source of stress.

Acculturation↗
PubMed1988

Airway resistance measured in liquid-trapped guinea pig lungs by micropuncture.

We studied the relationship between bronchoconstriction and the degree of trapping in saline-filled lungs isolated from guinea pigs postmortem after rapid exsanguination. Airway resistance was measured in nine lungs, and in five lungs the site of airway narrowing was located radiographically. Animals were anesthetized with pentobarbital sodium, degassed by O2 absorption, then rapidly exsanguinated when O2 absorption was almost complete. Liquid trapping was assessed from the pressure-volume behaviour measured in saline-filled lungs. During a slow deflation from maximum volume, alveolar liquid pressure (Palv) was measured by the micropipette-servonulling method, airway opening pressure (Pao) by a strain gauge, and flow rate (Q) by weighing a reservoir connected to the airway. Airway resistance (Raw) was calculated at different lung volumes from the relationship: Raw = (Palv-Pao)/Q. In untreated lungs, Raw and fluid trapping were relatively high, and severe bronchoconstriction occurred at the level of the main stem and lobar bronchi. Nifedipine infusion reduced Raw 40-fold and decreased trapping. Raw was further reduced 10-fold and fluid trapping was minimal in lungs pretreated with nifedipine before exsanguination. Results suggest a close association between bronchoconstriction and fluid trapping in guinea pig lungs.

Airway Resistance↗
PubMed1987

Phenylmethylsulfonyl fluoride (PMSF) inhibits 17 beta-estradiol binding to estrogen receptor from human prostate.

Estrogen receptor binding studies were performed on cytosol obtained from human benign prostatic hyperplasia (BPH) tissue. Binding assays were done in the absence or presence of various concentrations of phenylmethylsulfonyl fluoride (PMSF). Saturation analysis and Scatchard plots showed that the binding of 17 beta -estradiol to the estrogen receptor (ER) was inhibited by PMSF. The nature of the inhibition appears to be uncompetitive, as determined from double-reciprocal plots. Glycerol density gradient centrifugation analysis also confirmed the results obtained with Scatchard plots. The inhibition observed in the presence of dithiothreitol (DTT) was greater than the inhibition observed in the absence of DTT. The maximum number of binding sites (Bmax) observed in our present study was 59.1 +/- 34.1 fmol/mg protein with an equilibrium dissociation constant (KD) of 2.2 +/- 2.2 nM. Our study indicates that PMSF significantly affects 17 beta -estradiol binding to ER and consequently alters the estimation of ER in Human BPH.

Centrifugation, Density Gradient↗
PubMed1986

Effect of 16 beta-ethyl-17 beta-hydroxy-4-estren-3-one (TSAA-291) on the binding of promegestone (R5020) and methyltrienolone (R1881) to hyperplastic and neoplastic human prostate.

The effect of a synthetic steroidal compound TSAA-291 (16 beta-ethyl-17 beta-hydroxy-4-estren-3-one) on the binding of methyltrienolone (R1881) and promegestone (R5020) to hyperplastic and neoplastic human prostate was investigated. TSAA-291 inhibits both androgen and progestogen binding to hyperplastic and neoplastic human prostate. Glycerol density gradient analysis revealed that the inhibition of promegestone (R5020) binding by TSAA-291 was significantly greater than that of methyltrienolone (R1881) in both hyperplastic and neoplastic human prostate. The nature of the inhibition was competitive as determined by Scatchard analysis and double reciprocal plots. Comparison of the Ki values for the inhibition by TSAA-291 of R1881 binding (3.2 X 10(-7) M) and of R5020 binding (2.0 X 10(-8) M) suggests that TSAA-291 binds to progesterone receptor with a greater affinity than to androgen receptor. Our results suggest that the effectiveness of the drug in the treatment of benign hyperplasia might be due not only to its anti-androgenic properties but also due to its ability to inhibit progesterone receptor.

Binding, Competitive↗
PubMed1983

Cloning and expression in Escherichia coli of a DNA fragment from Bacillus sphaericus coding for biocidal activity against mosquito larvae.

A 3.7 kb DNA fragment from Bacillus sphaericus 1593 was cloned and expressed in E. coli using the plasmid pHV33. The level of larvicidal activity of the hybrid plasmid, pGsp03, against two species of mosquito larvae was comparable to that found with sporulating cell suspensions of B. sphaericus. A limited restriction cleavage map of the cloned insert is given.

Animals↗
PubMed1980

5'-Nucleotide phosphodiesterase isozyme-V in health, in cancer, and in viral hepatitis.

An abnormal, fast-moving 5'-nucleotide phosphodiesterase isozyme was found in 90.0% of 20 Malaysian patients with primary hepatoma and in 23.5% of 391 Malaysian patients with various malignant diseases; it was also discovered in 42.9% of 14 Malaysian and American patients with clinically active hepatitis B infection; in 16.7% of 18 healthy American blood bank donors who were positive for hepatitis B surface antigen (HBsAg); in 13.9% of 287 healthy Malaysian blood bank donors, some positive for HBsAg; and in none of 160 healthy American donors who were negative for HBsAg. A correlation of this abnormal isozyme with hepatoma and with infectious hepatitis B is clearly evident.

Adult↗
PubMed1980

Arylesterase isoenzymes and activity in normal healthy adults and in patients with cancer and with other diseases.

Serum arylesterase isozyme patterns were studied in 184 normal healthy individuals, 290 cancer patients and 466 patients with various diseases. No abnormal patterns were seen in the normal healthy subjects. Several abnormal patterns found in the group of cancer patients and patients with various diseases are described. In the majority of patients with cancer of the liver there is an abnormal additional cathodal band. The most cathodal band in normals or the two most cathodal bands in the patients with hepatoma with double cathodal bands stained for cholinesterase as well as for arylesterase. We also studied serum arylesterase activity on the basis of the kinetic release of beta-naphthol in these groups. The mean activity in normal healthy individuals agrees with that reported earlier. In patients with cancer and with miscellaneous other diseases, the mean activity is lower but the range of values in the two groups is very wide.

Adult↗
PubMed1976

Radioimmunoassay of serum alpha-fetoprotein in patients with different maliganant tumors.

The level of serum alpha-fetoprotein (AFP) was estimated by radioimmunoassay in 153 normal healthy Malysians of different ethnic groups. The mean level was 7.5 In1/ml (SD 2.28InU/ml). Among 330 patients with malignant tumors, 11 had increased levels of AFP. The only patient who had hepatoma had a very high level of serum AFP. High levels were also found in three of four patients with dysgerminoma of the ovary, in the only two patients with carcinoma of the testis, and in one patient with secondary carcinoma of the humerus of unknown origin. Lower, but significantly increased levels were observed in one patient (of 48) with breast carcinoma, one patient (of 8) with basal cell carcinoma of the nose, one patient (0f 27) with carcinoma of the lung, and one patient (of 59) with nasopharynegeal carcinoma.

Adult↗