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Biomedical subjects

M Akbar

Publications and source records attributed to M Akbar.

31 records · Page 2Linked to original sources

Transfected human somatostatin receptor type 2, SSTR2, not only inhibits adenylate cyclase but also stimulates phospholipase C and Ca2+ mobilization.

COS-7 cells were transfected with human somatostatin (SRIF) receptor type 1 and 2 (human SSTR1 and SSTR2, respectively) cDNAs. In human SSTR2-expressing cells, SRIF not only inhibited forskolin-induced cAMP accumulation but also stimulated phospholipase C and Ca2+ mobilization. While the inhibition of cAMP accumulation was completely reversed by pertussis toxin (PTX) treatment of the cells, SRIF-induced activation of phospholipase C and Ca2+ mobilization was partially but not completely inhibited by the toxin treatment. In human SSTR1-expressing cells, however, SRIF induced only slight inhibition of cAMP accumulation and stimulation of phospholipase C-Ca2+ system. We conclude that the transfected SSTR2 can couple to phospholipase C as well as adenylate cyclase in a stimulatory and inhibitory manner, respectively. Both PTX-sensitive and -insensitive GTP-binding proteins may be involved in the SSTR2 signal transduction mechanisms.

Adenosine Triphosphate↗

A single species of A1 adenosine receptor expressed in Chinese hamster ovary cells not only inhibits cAMP accumulation but also stimulates phospholipase C and arachidonate release.

Chinese hamster ovary cells were transfected with both A1 adenosine receptor and muscarinic type 3 acetylcholine receptor cDNAs. The muscarinic receptor agonist carbachol stimulated phospholipase C activity, resulting in Ca2+ mobilization and arachidonate release. N6-Cyclopentyladenosine (CPA), an A1 receptor agonist, did not activate Ca(2+)-related signal transduction systems by itself but instead inhibited cAMP accumulation. In the presence of carbachol, however, the A1 receptor agonist enhanced muscarinic receptor agonist-induced phospholipase C/Ca2+ responses. In addition, the arachidonate release caused by Ca2+ ionophores or thapsigargin was also amplified by CPA, without a change in phospholipase C activity. Thus, CPA augments Ca(2+)-mediated phospholipase A2 activation in addition to and separate from its ability to amplify phospholipase C-mediated Ca2+ mobilization. Because the permissive actions of CPA on phospholipase C and phospholipase A2 activation were each reversed by pertussis toxin treatment, in a manner similar to that of the CPA-induced inhibition of cAMP accumulation, we conclude that a single species of A1 receptor expressed in Chinese hamster ovary cells can couple to multiple signal transduction systems stemming from phospholipase C stimulation, phospholipase A2-mediated and Ca(2+)-dependent arachidonate release, and inhibition of cAMP accumulation. A pertussis toxin-sensitive G protein (or proteins) mediates the permissive actions of the A1 receptor in the stimulation of phospholipase C- and phospholipase A2-mediated arachidonate release.

Adenosine↗

Haemolytic uraemic syndrome in children.

Of the 4070 children admitted in the department of paediatrics, 830 (24%) presented with diarrhoea. Eleven of these had haemolytic ureamic syndrome (HUS) characterised by microangiopathic haemolytic anaemia, thrombocytopenia and acute renal failure. Only 3 had positive stool cultures (E. Coli 2, shigella dysenteriae 1). Two children expired while the rest recovered with conservative management and peritoneal dialysis. Thus HUS should be remembered as a complication of diarrhoea and a cause of acute renal failure in children.

Child, Preschool↗

Effect of saline soil on grain quality of rices differing in salinity tolerance.

Four varieties of rice, differing in salinity tolerance and grown in saline soil (electrical conductivity 5-6 dS/m) at Sadhoke, Punjab, Pakistan, had lighter grain and higher Na content than control samples. Grains of three out of the four rices grown on saline soils had higher brown rice protein (higher nutritional value), less translucent grain, lower starch and amylose content, and lower K than their control samples, but these differences were not related to salinity tolerance. Alkali spreading value and gel consistency were not affected by culture in saline soil. Cooked rice Instron hardness increased in saline culture in two higher-protein samples of the four rices. Amylograph peak viscosity was suppressed by saline culture.

Agriculture↗

Acute respiratory infections in children: a case management intervention in Abbottabad District, Pakistan.

Between 1985 and 1987, a community-based case-management programme for acute lower respiratory infection (ALRI) was conducted in a rural district of northern Pakistan. The impact on infant and child mortality of this programme, which included active case-finding and maternal health education, was evaluated. In 1985-86, the ALRI-specific mortality rate among children less than 5 years old in 31 intervention villages was 6.3 deaths per 1000 children per year, compared with 14.4 in seven control villages (P = 0.0001). Within one year of the interventions being extended to the control villages in 1987, the ALRI-specific mortality rate in these villages dropped by 55% to 6.5 per 1000 children per year (P = 0.06). The total child mortality rate in 1985-86 was 29.0 per 1000 children per year in the intervention villages and 39.4 per 1000 children in the control villages, a difference of 26% (P = 0.01). With the interventions in 1987, the total child mortality rate in the control villages declined by 29% to 27.8 per 1000 children per year (P = 0.09). Similar intervention-associated declines in the infant mortality rate were also observed. Case management of acute respiratory infection by village-level community health workers backed up by local health centre staff appeared to significantly reduce both ALRI-specific and total infant and child mortality rates in this setting.

Acute Disease↗

Cyclic changes in cytosol progesterone receptor of human fallopian tube.

The binding of progesterone (P) to a specific cytoplasmic receptor was studied in cytosol fractions prepared from oviducts obtained from women who elected to undergo sterilization either during a normal menstrual cycle, after the first trimester of pregnancy, or in the puerperium. The in vitro cytosol incubations with [3H]P included cortisol, which eliminated binding to corticosteroid-binding globulin. The relative binding affinities for the cytosol receptor were P > R5020 > > corticosterone = estradiol = testosterone. The P-binding protein had a sedimentation coefficient of 7-8S. Specific [3H]P binding was approximately 4.0 x 10(-13) mol/mg protein at all of the reproductive stages included in this study, except for a 4- to 5-fold increase (approximately 18.0 x 10(-13) mol/mg protein) during the middle and late follicular phases of the menstrual cycle. The sharp decline in P receptor observed during the ealy luteal phase coincided with the luteal rise of serum P. Also, cytosol receptor was replenished when serum P was essentially undetectable.

Cytosol↗

Cyclic changes in ciliation, secretion and cell height of the oviductal epithelium in women.

Oviducts were obtained from women who elected to undergo sterilization either during a normal menstrual cycle, after the first trimester of pregnancy, or in the puerperium. The percent of ciliated cells, cell height and morphology of the fimbria and ampulla were determined and correlated with the stage of the reporductive cycle and plasma levels of the ovarian steroids. Mature ciliated and secretory cells were observed only at mid-cycle. Atrophy, deciliation and loss of secretory activity coincided with elevated levels of serum progesterone. These degenerative processes continued during pregnancy. Ciliation, hypertrophy, and restoration of secretory activity occurred when serum progesterone was essentially undetectable and estradiol relatively low. During each menstrual cycle the secretory cells were observed to undergo a complete cycle of dedifferentiation-differentiation, whereas 10--12% of the ciliated cells lost and regenerated their celia. Ciliogenic cells were frequently present in the epithelium obtained from women in the mid-follicular phase. Fibrous granules, deuterosomes, procentrioles and ciliary buds were observed in the apex of these cells. Plasma levels of estradiol were higher during periods of atrophy and deciliation than they were during periods of hypertrophy and reciliation. It appears that the serum levels of estradiol were adequate to maintain a mature epithelium at all the reproductive stages included in this study. However, progesterone, when present, blocked the growth-promoting effect of estradiol in the oviduct.

Cilia↗

Dissociation between TSH and prolactin dynamics in treated thyrotoxicosis.

TSH and prolactin secretory patterns in thyroid disease have generally been reported as concordant. We studied TSH and prolactin responses to TRH infusion (500 mug) in euthyroid individuals previously treated for thyrotoxicosis with 131I or antithyroid drugs. The 131I-treated group (seven men, twenty women) had been clinically and biochemically euthyroid (normal serum thyroxine and triiodothyronine levels) for 6 months to 4-5 years (kappa +/- SD = 17-1 +/- 4-1 months). Based on maximal TSH increment (deltaTSH), three patient groups were identified: Group 1 [normal deltaTSH, n = 6]: delta prolactin was normal in two, blunted in one and exaggerated in three. Group 2 (exaggerated TSH response, n = 8): delta prolactin was normal in two, blunted in one and exaggerated in five. Group 3 (TSH nonresponders, n = 13): delta prolactin was normal in five, blunted in three, and exaggerated in five. Eleven patients (three men, eight women) were studied after 6 months antithyroid-drug treatment. All were clinically and biochemically euthyroid. All but one showed a blunted TRH-TSH response. All three men showed an exaggerated delta prolactin as did four of eight women. Three women showed a blunted delta prolactin and in one, delta prolactin was normal. Thus, TRH-induced TSH and prolactin response patterns in treated thyrotoxicosis are not uniformly concordant, and, while a blunted or absent TSH response commonly persists long after euthyroidism has been restored, this is most frequently accompanied by a normal or exaggerated prolactin response.

Adult↗

Regulation of thyroid ornithine ornithine decarboxylase (ODC) by thyrotropin. I. The rat.

We studied the effects of TSH on rat thyroid ornithine decarboxylase (ODC) activity. After 1 day of goitrogen treatment, there was an abrupt fall in serum triiodothyronine (T3) a rise in circulating TSH, and a dramatic increase in thyroid ODC activity. Despite the continued rise in TSH and progressive increase in thyroid gland size with further treatment, thyroid ODC activity declined on the third day and remained at submaximal levels. Thyroid ODC activity was also stimulated in a dose-related manner by administration of exogenous TSH. Little TSH effect was noted before 3 h. Maximal ODC activity occurred between 4 and 5 h. The TSH stimulation of ODC could be inhibited by pretreatment with actinomycin D or cycloheximide, suggesting that the increase in ODC activity requires new RNA and protein synthesis. Although pretreatment with agents that alter microtubule structure (e.g., colchicine and vinblastine) prevent stimulation of ODC activity by TSH, additional data suggest, but do not confirm, that hrmone secretion and ODC activation may be dissociable. Further studies were undertaken to determine whether cyclic AMP (cAMP) or prostaglandins played any role in the regulation of thyroidal ODC activity. Dibutyryl cAMP, alone, or together with aminophylline, did not stimulate thyroidal ODC activity in dosages which concomitantly stimulated adrenal enzyme activity. Likewise, prostaglandin E2 (PGE2) did not stimulate thyroidal ODC activity, but did stimulate adrenal enzyme activity in a dose-related manner. However, pre-treatment of rats with inhibitors of prostaglandin synthesis prevented the activation of thyroidal ODC BY TSH. One inhibitor, indomethacin, attenuated the TSH stimulation of enzyme activity in a dose-related manner. Indomethacin pretreatment also resulted in approximately a 10-fold decrease in thyroidal prostaglandin levels. Exogenous PGE9, in dosages as high as 500 pg, did not overcome the inhibitory effect of indomethacin on ODC activation. Although the precise role for endogenous prostaglandins remains to be defined, it does appear that a reduction in thyroidal prostaglandins prevents activation of the enzyme by TSH.

Animals↗

Prospects of breeding for salt tolerance in rice.

Variations with regard to salt tolerance were observed in rice varieties, Blue bonnet, IR-8, Jhona-349, and Magnolia. Crosses (F1) between relatively salt-resistant (Jhona-349) and salt-sensitive (Magnolia) varieties were highly resistant to salinity. The F2 population resulted in some salt-resistant combinations. In the F3 and F4 populations, some desirable salt-resistant progenies were selected. Results obtained suggest that selection for salt tolerance may be possible within hybrid populations.

Genetic Engineering↗

Inhibition of neuronal apoptosis by polyunsaturated fatty acids.

The effect of polyunsaturated fatty acids (PUFAs), docosahexaenoic acid (22:6n-3; DHA) and arachidonic acid (20:4n-6; AA), on apoptotic cell death was evaluated based on DNA fragmentation and caspase-3 activity induced by serum starvation using Neuro-2A and PC-12 cells. The presence of 20:4n-6 in the medium during serum starvation decreased DNA fragmentation and this initial protective effect was diminished with prolonged serum starvation. The observed protective effect of 20:4n-6 was not affected by the inhibitors of cyclooxygenase (COX) and lipoxygenase. Conversely, 22:6n-3 became protective only after the enrichment of cells with this fatty acid at least for 24 h prior to the serum deprivation. DNA fragmentation as well as caspase-3 activity was reduced in 22:6n-3 enriched cells with a concomitant decrease in protein and mRNA levels. During the enrichment period, 22:6n-3 steadily increased its incorporation into PS leading to a significant increase in the total PS content; the protective effect of 22:6n-3 paralleled the PS accumulation. Neither direct exposure of cells to nor enrichment with 18:1n-9 had any protective effect. In conclusion, it is proposed that 20:4n-6 prevents neuronal apoptosis primarily due to the action of nonesterified 20:4n-6 but 22:6n-3, at least in part, through PS accumulation.

Animals↗