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Biomedical subjects

K George

Publications and source records attributed to K George.

At least 19 recordsLinked to original sources
PubMed1992

Effects of acute vs. chronic phorbol ester exposure on transepithelial permeability and epithelial morphology.

In previous experiments we have shown that acute (30 minutes) exposure to phorbol esters or other protein kinase C activators causes increased transepithelial permeability, specifically by the increased paracellular permeability through tight junctions. However, the role of protein kinase C activators in carcinogenesis is predicted upon a chronic exposure of an effective dose at frequent intervals for a prolonged period of time. We therefore sought to determine the effect of chronic phorbol ester exposure on transepithelial permeability by exposing cells of the polar renal epithelial cell line, LLC-PK1, to phorbol esters for time periods as long as 16 weeks. The following changes ensued: (1) after the initial drop in transepithelial resistance due to phorbol ester exposure, i.e., an increase in transepithelial permeability (in the acute phase of exposure), an adaptive response occurs as transepithelial resistances in chronically exposed cultures recover to approximately 50% of control values, (2) the cell sheets in chronically exposed cultures lose their acute responsiveness of transepithelial permeability to phorbol ester exposure, (3) cell sheet architecture changes as cells occasionally multilayer and actual polyp-like cell masses appear at high frequency, and (4) cytosolic protein kinase C activity decreases to 50% of control level with acute exposure and then is further decreased to less than 1% of control level in chronically treated cells; membrane-associated PKC activity is not as sharply decreased. The possible role of transepithelial permeability in carcinogenesis and the value of chronically treated epithelial cell cultures as a model for two-stage carcinogenesis are discussed.

Animals↗
PubMed1992

Chromosomal abnormalities associated with a single umbilical artery.

A single umbilical artery was seen in 10 out of 117 cytogenetically abnormal pregnancies. The abnormal karyotypes found to be associated with a single umbilical artery were trisomy 18 (n = 5), monosomy X (n = 2), triploidy (n = 1), sex chromosome (47,XYY; n = 1) and translocation (46t(X,5)(q13p15);n = 1). With the exception of the translocation case, all cases with a single umbilical artery had anatomical defects which were detectable ultrasonographically. This suggests that a single umbilical artery alone is not an indication for prenatal fetal karyotyping.

Chromosome Aberrations↗
PubMed1992

Regulation of expression of the reovirus receptor on differentiated HL60 cells.

The reovirus receptor on mammalian cells has not been fully characterized and controversy exists over the nature of this receptor. We report here that the expression of this receptor is dependent on the differentiation status of a human promyelocytic leukaemia cell line (HL60). Phorbol treatment of HL60 cells for 24 h, at a concentration range of 160 nM down to 1 nM, led to differentiation of these cells towards monocytes and a loss of approximately 80% of their ability to bind reovirus in a fluorescence assay. These cells also lost their susceptibility to T1 and T3 reovirus infection. DMSO treatment for 24 h at a concentration of 1.25% (v/v) led to differentiation towards granulocytes. This was accompanied by an increase of approximately 15% in binding of reovirus to these cells. After being infected by T1 or T3 reovirus, the granulocytes produced higher titres of progeny virus than did untreated HL60 cells. Similar differences were noted when virus binding to HL60 cells was assayed using radiolabelled reovirus. These effects were not detected when murine L fibroblasts were treated with DMSO or phorbol. ATCC-derived murine R1.1 cells did not bind reovirus. Competition data indicated that there may be two reovirus receptors on HL60 cells, and that T1 can bind to only one receptor whereas T3 can bind to both receptors. Our data also suggested that the beta-adrenergic receptor was unlikely to act as the reovirus receptor on HL60 cells.

Animals↗
PubMed1992

The effect of consanguinity on pregnancy-induced hypertension.

The aetiology of pregnancy induced hypertension (PIH) is unknown. Either an immunological or a genetic disorder are considered likely, with possibly an interaction between the two. If this were true, homozygosity would play an important role. Though consanguinity is believed to play a protective role, the effect of inbreeding on PIH has been inadequately studied. In South India consanguinity is common (26%). We prospectively studied 814 primigravidas of whom 213 had consanguineous marriages. The proportion of women who developed PIH was compared in the 2 groups of women with consanguineous and nonconsanguineous marriages. The odds of a patient with PIH being consanguineous was 1.12 with a 95% confidence interval of 0.72-1.75. Our observations suggest that consanguinity does not influence the incidence of PIH.

Adult↗
PubMed1991

Ca(2+)-independent form of protein kinase C may regulate Na+ transport across frog skin.

Activators of protein kinase C (PKC) stimulate Na+ transport (JNa) across frog skin. We have examined the effect of Ca2+ on PKC stimulation of JNa. Both the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) and the diacyl-glycerol sn-1,2-dioctanoylglycerol (DiC8) were used as PKC activators. Blocking Ca2+ entry into the cytosol (either from external or internal stores) reduced the subsequent natriferic effect of the PKC activators. This negative interaction did not simply reflect saturation of activation of the apical Na+ channels, since the stimulations produced by blocking Ca2+ entry and adding cyclic AMP were simply additive. The Ca2+ dependence of the natriferic effect could have reflected either a direct action of cytosolic Ca2+ on PKC or an indirect action on the final receptor site (the Na+ channel). To distinguish between these possibilities, the TPA- and phospholipid-dependent kinase activity of broken-cell preparations was assayed. The kinase activity was not stimulated by physiological levels of Ca2+, and in fact was inhibited at millimolar concentrations of Ca2+. We conclude that the effects of Ca2+ on the natriferic response to PKC activators are indirect. Reducing cytosolic uptake of Ca2+ may have stimulated Na+ transport by a chemical modification of the apical channels observed in other tight epithelia. The usual stimulation of Na+ transport produced by PKC activators in frog skin may reflect the operation of a nonconventional form of PKC. This enzyme is Ca2+ independent and seems related to the nPKC or PKC epsilon observed in other systems.

Amiloride↗
PubMed1991

Abdominal obesity and physical inactivity as risk factors for NIDDM and impaired glucose tolerance in Indian, Creole, and Chinese Mauritians.

OBJECTIVE: We wanted to determine whether obesity, abdominal fat distribution, and physical inactivity act similarly and independently as risk factors for noninsulin-dependent diabetes mellitus (NIDDM) and impaired glucose tolerance (IGT) in Hindu and Muslim Asian Indians, African-origin Creoles, and Chinese Mauritians. RESEARCH DESIGN AND METHODS: We examined a population-based random cluster sample of 5080 adult subjects from the Indian Ocean island of Mauritius. Glucose tolerance was assessed with a 75-g oral glucose tolerance test and World Health Organization criteria. RESULTS: Univariate data and multiple logistic regression models indicated that age, family history of diabetes, body mass index (BMI), waist-hip ratio (WHR), and physical inactivity conveyed similar risk for NIDDM (and IGT) in each ethnic group. After adjusting for all other factors, Hindu ethnicity conferred additional risk for NIDDM (but not IGT) in men, but in women there were no clear ethnic differences. Although BMI and WHR were independently significant risk factors, WHR conveyed relatively stronger risk for NIDDM than BMI in women, whereas the converse was true in men. For ethnic groups combined, the independent odds ratios for IGT associated with moderate and low physical activity scores (relative to high) were 1.56 and 1.71 (P less than 0.05), respectively, in men and 1.32 and 1.69 (P less than 0.05) in women. In subjects with asymptomatic NIDDM diagnosed during the survey, the independent odds ratios were 1.96 and 2.00 (P less than 0.05) in men and 1.73 and 2.70 (P less than 0.05) in women. CONCLUSIONS: These data indicate that BMI, abdominally distributed fat, and physical inactivity are important independent risk factors for both IGT and NIDDM in diverse ethnic groups. Attributable risk fractions for Mauritius suggest that populationwide modification of levels of these risk factors could potentially result in substantially lower occurrence of NIDDM (and IGT). Such interventions should be attempted in high-risk populations.

Activities of Daily Living↗
PubMed1990

The role of intrahousehold contact in the transmission of leprosy.

This study examines the role of intrahousehold contact in the transmission of leprosy using the case control methodology. The study was done in the leprosy control area of the Community Health and Development (CHAD) Programme of the Christian Medical College. Three age, sex and village matched controls were selected for each case. This study shows that persons with intrahousehold contact with leprosy have a higher risk of acquiring leprosy compared with those who did not (RR 2.509; 95% confidence limits 1.23-5.109).

Adolescent↗
PubMed1989

Optical urethrotomy--experience in Oman.

Over a 4-year period 170 men with urethral strictures were treated with optical urethrotomy; 80% required no further treatment during the 2-year follow-up; 2 patients with urethral fistulae associated with stricture were also treated successfully.

Follow-Up Studies↗
PubMed1989

Interactions of TPA and insulin on Na+ transport across frog skin.

The phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) activates protein kinase C (PKC) and produces an early stimulation of Na+ transport across frog skin. The ionic basis for this stimulation was studied with combined transepithelial and intracellular electrical measurements. In an initial series of experiments, TPA approximately doubled the amiloride-sensitive short-circuit current (ISC), apical Na+ permeability (PapNa), and apical membrane conductance without affecting the basolateral membrane conductance. The apical effects led to a marked depolarization of the short-circuited skin and a small increase in intracellular Na+ concentration. TPAs increase of PapNa was sufficient to explain the stimulation of basolateral Na+ transport when both the voltage and substrate dependence of the pump were taken into account. After the early stimulation, TPA later depressed ISC. Added at this point (congruent to 1-2 h after TPA administration), insulin had no effect on ISC, whereas a partial response to vasopressin was still observed. Measured either early or late after TPA addition, the phorbol ester reduced insulin binding by congruent to 40%. Insofar as 60% of the specific binding is retained, the abolishment of insulin's natriferic response is unlikely to result from the TPA-induced reduction in hormonal binding. The data provide further support for the concept that activation of PKC produces an early stimulation of Na+ transport by increasing apical Na+ permeability, and that part of insulin's natriferic effect may be mediated by PKC activation.

Amiloride↗
PubMed1988

Protein kinase C and membrane transport: divergent responses of Na+/K+/Cl- cotransport and sugar transport to exogenous diacylglycerol.

Even though the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) is known to bind to and activate protein kinase C (PKC), it is still not certain that all cellular responses to phorbol esters are necessarily mediated by PKC. In BALB/c 3T3 preadipose cells, TPA has previously been shown to rapidly inhibit Na+K+Cl- -cotransport activity, stimulate 2-deoxyglucose uptake and induce ornithine decarboxylase activity. The cell-permeable diacylglycerol sn-1,2-dioctanoylglycerol (DiC8) was used in order to distinguish between PKC-dependent and -independent responses of BALB/c 3T3 cells. DiC8 modulated 86Rb+ fluxes in BALB/c 3T3 cells in the same manner as TPA: furosemide-sensitive 86Rb+ influx and efflux was inhibited, while in cotransport-defective cells no effect was observed. In contrast, DiC8 did not stimulate 2-deoxyglucose uptake in either parental or cotransport-defective cell lines, even though TPA is a very effective inducer of this transport system in both cell types. Pretreatment of cells with DiC8 did not substantially alter the subsequent induction of 2-deoxyglucose uptake by TPA, although a slight but reproducible reduction in the magnitude of the response was observed in DiC8-pretreated cells. The PKC-dependent phosphorylation of an acidic 80-kDa protein was stimulated by both TPA and DiC8 in parental and cotransport-defective cell lines, suggesting that a gross defect in the primary effector system used by both TPA and diacylglycerols cannot explain any of our results. Ornithine decarboxylase was induced by DiC8 and the K1/2 was approximately the same as that for inhibition of Na+/K+/Cl- cotransport in these cells. Thus, our results suggest that PKC is clearly essential for some phorbol ester membrane transport responses (such as inhibition of Na+/K+/Cl- cotransport), but our results do not allow us to conclude that other responses (such as stimulation of 2-deoxyglucose uptake) necessarily require PKC activation.

Animals↗
PubMed1988

Fine-needle aspiration of metastatic atrial myxoma.

Atrial myxoma is the most common primary neoplasm of the heart, but "metastatic" or embolic phenomena are rare. The first reported case of "metastatic" atrial myxoma diagnosed by fine-needle aspiration biopsy is presented. It occurred in a 54-yr-old woman with multiple metastatic lesions. The cytologic and histologic findings of the fine-needle aspiration biopsy and subsequent surgical excision are presented as is a discussion of the incidence, origin, and clinical findings of atrial myxoma and the characteristics of its emboli.

Biopsy, Needle↗
PubMed1988

Suppression of puerperal lactation using jasmine flowers (Jasminum sambac).

The efficacy of jasmine flowers (Jasminum Sambac) applied to the breasts to suppress puerperal lactation was compared that of Bromocriptine. Effectiveness of both regimens was monitored by serum prolactin levels, clinical evaluation of the degree of breast engorgement and milk production and the analgesic intake. While both bromocriptine and jasmine flowers brought about a significant reduction in serum prolactin, the decrease was significantly greater with bromocriptine. However, clinical parameters such as breast engorgement, milk production and analgesic intake showed the 2 modes of therapy to be equally effective. The failure rates of the 2 regimens to suppress lactation were similar; however, rebound lactation occurred in a small proportion of women treated with bromocriptine. Jasmine flowers seem to be an effective and inexpensive method of suppressing puerperal lactation and can be used as an alternative in situations where cost and nonavailability restrict the use of bromocriptine.

Bromocriptine↗
PubMed1986

Use of intrathecal hyaluronidase in the management of tuberculous meningitis with hydrocephalus.

A preliminary study to evaluate the efficacy of intrathecal hyaluronidase was carried out in nine children suffering from tuberculous meningitis with communicating hydrocephalus. This was followed by a randomized trial in which five cases were treated with intrathecal hyaluronidase, while six cases were treated by the insertion of a ventriculoperitoneal shunt. No untoward reaction of any significance was noted. The results were judged in terms of improvement in the sensorium and mentation, in specific neurological deficit (e.g., visual impairment and hemiparesis), and in overall functional performance. Although most of the patients receiving hyaluronidase showed some improvement in the sensorium, only one of the nine preliminary cases and one of the five cases in the randomized trial showed a total recovery of function. Two of the six shunted patients, however, showed complete recovery. Shunt insertion led to further improvement in two of the nine preliminary cases who had failed to respond to treatment with hyaluronidase. This preliminary study shows that intrathecal hyaluronidase does, in most cases, lead to an improvement in the sensorium but does not offer any particular advantage over shunt insertion in terms of regression of specific neurological deficit or overall functional improvement.

Antitubercular Agents↗