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Biomedical subjects

M M Khan

Publications and source records attributed to M M Khan.

211 records · Page 12Linked to original sources

Insulin and glucagon releasing activity of coleonol (forskolin) and its effect on blood glucose level in normal and alloxan diabetic rats.

Colenol, a diterpenoid isolated from the roots of Coleus forskohlii stimulates the release of insulin and glucagon from the islets both in vitro and in vivo. Colenol-stimulated release of glucagon from islets in vitro is much more pronounced as compared to that of insulin. Glucose concentration of 5.6 mM in the medium is required for the colenol stimulation of insulin release. Feeding of coleonol to alloxan diabetic rats cause 36.5% increase in blood glucose level as compared to alloxan diabetic control. Oral feeding of coleonol for 7 days to normal rats causes increase in blood glucose, serum insulin, glucagon and free fatty acid levels with corresponding increase in glucose-6-phosphatase activity and depletion of liver glycogen. Predominant stimulation of A-cells by coleonol is suggested for the above effects.

Animals↗

Forskolin and prostaglandin E2 regulate the generation of human cytolytic T lymphocytes.

In this paper we examine the characteristics of human cytolytic T lymphocytes (CTL) generated in the presence of forskolin and PGE2. Forskolin and PGE2 suppressed the generation of class-I-specific CTL. The CTL generated in the presence of forskolin and PGE2 had different characteristics which included their ability to proliferate in response to the alloantigen and their lectin-mediated cytolytic activity. The CTL generated in the presence of forskolin had normal proliferative response to the alloantigen, whereas the CTL generated in the presence of PGE2 showed a suppressed proliferative ability to the alloantigen. The two groups of CTL were then tested for their activity in the process of lectin-dependent cell-mediated cytotoxicity. After the addition of PHA into the chromium release assay the CTL generated in the presence of forskolin normally lysed the nonspecific targets, whereas the CTL generated in the presence of PGE2 did not show the normal response in lysing the nonspecific targets. The results suggest that the cytolytic machinery was intact when the CTL were generated in the presence of forskolin but CTL were not able to either recognize or lyse the target cell. However, the CTL generated in the presence of PGE2 did not share the same characteristics as the CTL generated in the presence of forskolin because the CTL generated in the presence of PGE2 were unable to kill even in the presence of lectin. It appears that the inhibitory effects of forskolin were mediated by cAMP and not by its effects on the potassium channels because the 1,9-dideoxy derivative of forskolin which did not activate adenylate cyclase also did not suppress the generation of CTL. However, it was not established whether the diverse effects of PGE2 on the generation of CTL were mediated by cAMP-dependent, -independent or by both mechanisms.

Antigens, Differentiation, T-Lymphocyte↗

Cyclic AMP is not a direct regulator of calcium flux and hydrolysis of phosphoinositides in human lymphocytes.

The regulatory effects of adenosine 3',5'-cyclic monophosphate (cAMP) on Ca2+ flux and phosphatidylinositol (PI) turnover in human lymphocytes were studied. cAMP did not affect the intracellular accumulation of Ca2+ induced by phytohemagglutinin (PHA) and histamine-trifluoromethyl toluidide derivative (HTMT) in peripheral blood lymphocytes (PBL). In addition, cAMP also did not alter Ca2+ flux induced by PHA, anti-CD3, or PAF in T cells, or by anti-IgM and HTMT in non-rosetted cells. Similarly, cAMP did not inhibit IP accumulation induced by HTMT in PBL, anti-CD3 in T cells, and by anti-IgM or HTMT in non-rosetted cells. The only exception was the synthesis of IP induced by PHA in T cells that was inhibited by cAMP. Furthermore, prolonged treatment of T cells with cholera toxin inhibited Ca2+ accumulation in response to CD3. The degree of inhibition of Ca2+ and IP responses was not proportional to the levels of intracellular cAMP generated.

Antibodies, Anti-Idiotypic↗

A histamine derivative increases intracellular calcium mobilization and oxidative metabolism in HL-60 cells.

Past work in our laboratory has shown that a derivative of histamine, histamine-trifluoromethyl-toluidide (HTMT), has surprising tissue specificity on lymphocytes and can produce remarkable immunosuppression. This study focuses on the effects of HTMT on Ca2+ mobilization and oxidative metabolism in undifferentiated and DMSO-differentiated HL-60 cells. HTMT caused two phases of increases in intracellular calcium concentrations ([Ca2+]i) in HL-60 cells. The responses were dose dependent, with similar EC50 values (1.7 x 10(-5) M for undifferentiated and 1.5 x 10(-5) M for differentiated cells). The increase in [Ca2+]i in differentiated cells was much greater than in undifferentiated cells. The maximum responses were observed after the undifferentiated cells were incubated with DMSO for 7 days. The increase in [Ca2+]i induced by HTMT in both types of cells was competitively antagonized by high concentrations of histamine but not by classic histamine receptor antagonists (H1, H2, or H3). The inhibitory effects of histamine on [Ca2+]i accumulation in differentiated cells were partially reversed by histamine H2 receptor antagonist ranitidine, whereas in undifferentiated cells, the effects of histamine on Ca2+ mobilization were not affected by ranitidine. Other cAMP elevating agents did not inhibit increases in [Ca2+]i in undifferentiated cells but did affect [Ca2+]i in differentiated cells. The enhanced response in [Ca2+]i mobilization after differentiation of HL-60 cells appeared to be the result of an increase in the expression/function of receptors for HTMT. One interesting feature of this regulation was the fact that cAMP per se did not regulate HTMT induced Ca2+ mobilization in undifferentiated cells but inhibited the mobilization in differentiated cells. HTMT caused the generation of reactive oxygen species in both undifferentiated and differentiated HL-60 cells as measured by chemoluminescence and the levels of generation correlated with the mobilization of [Ca2+]i. In addition, the EC50s for the HTMT induced calcium mobilization and the generation of reactive oxygen species were similar, as was the case for histamine induced inhibition (Ki) in both cell types. The data imply a second messenger role for Ca2+ in HTMT induced neutrophil activation.

Binding Sites↗

Trace element levels in human alcoholic brain.

Copper, magnesium, zinc and manganese levels in the temporal cortex of human alcoholic and control brains were measured by atomic absorption spectrophotometry using both the flame and graphite furnace. All of the 21 alcoholics were male with a mean age of 54.1 years; the 19 male controls had a mean age of 60.2 years. The only statistically significant change in ion levels was an increase in manganese concentration (expressed both as microgram/g wet weight and ng/mg protein) in the alcoholic group when compared to the control group. Five of the alcoholics had malignancies, while 16 of the controls had systemic malignancies. Covariance analysis showed there was no effect of age on the level of manganese in the temporal cortex.

Adult↗

Mantle cell lymphoma presenting as solitary polypoid colonic lesions.

Mantle cell lymphoma of the intestine is rare, usually presenting as multiple small polyps. We report three men with colonic mantle cell lymphoma in the form of single large polypoid mass. The clinical picture suggested adenocarcinoma; the diagnosis was made at histology and immunohistochemistry of the colectomy specimens.

Adult↗

Effect of maternal anaemia on fetal parameters.

BACKGROUND: A cohort study of anaemic pregnant women was carried out at the Department of Obstetrics and Gynecology, Women and Children Hospital, Abbottabad, from November 30, 1992 to March 30, 1993, to determine the effects of antenatal maternal anaemia on the newborn babies. METHODS: 34 pregnant women with anaemia and 39 non-anaemic pregnant women were included in the study. Parameters studied were Hemoglobin levels, RBC morphology, Foetal birth weights, Foetal gestational ages, and Foetal APGAR score (at birth and after 10 months). RESULTS: Out of 34 anaemic women, 6 delivered at 7 or 7+ months, 7 at 8 or 8+ months and 21 at 9 or 9+ months, as compared to 39 non-anaemic, one of whom delivered at 7 or 7+ months, 2 at 8 or 8+ months and 36 at 9 or 9+ months. Fetal mortality rate for anaemic women was 50% at 7 or 7+ months, 28.7% at 8 or 8+ months and 23.80% 9 or +9 months. For all non-anaemic women, it was 0%. Mean fetal birth weight in anaemic group was 1.4 +/- 0.66 kg at 7 or 7+ months, 1.93 +/- 0.53 kg at 8 or 8+ months and 2.61 +/- 0.31 kg at 9 or 9+ months. Among non-anaemic group, it was 2.8 kg at 7+ months, 3.75 +/- 0.55 kg at 8 or 8+ months and 3.65 +/- 0.66 kg at 9 or 9+ months. CONCLUSIONS: These findings show that mothers with nutritional or iron deficiency anaemias tend to deliver prematurely with low birth weight babies and a high mortality rate or stillbirths, as compared to non-anaemic mothers.

Anemia, Iron-Deficiency↗

Aetiologic agents of diarrhoeal diseases in hospitalised children in Rawalpindi, Pakistan.

The causes of diarrhoea were diagnosed in 250 children and 250 controls, a sample of 3,500 children who reported to the Rawalpindi General Hospital, Pakistan between May 1983 and April 1984. The pathogens identified in children with diarrhoea were enteropathogenic Escherichia coli (EPEC) (43.2%), enterotoxigenic E. coli (14%), rotavirus (9.6%), Shigella spp (3.6%), Salmonella spp (3.2%) and Giardia lamblia (1.2%). Mixed infections were found in 2.4% of patients. The following pathogens were detected in controls: EPEC (14.0%), rotavirus (7.6%), G. lamblia (6.8%) and Entamoeba histolytica (3.2%). The serotypes of E. coli were determined.

Bacteria↗

Microvascular abnormalities as possible predictors of disease subsets in Raynaud phenomenon and early connective tissue disease.

In vivo capillary examination was performed on 80 patients included in a prospective study of Raynaud phenomenon (RP): 40 RP only (RPO), 20 undifferentiated connective tissue disease (UCTD) and 20 systemic scleroderma (SD) of less than 5 years' duration. On initial examination, SD-pattern capillary abnormalities were found in 7/40 patients with RP alone, 18/20 with UCTD and 19/20 with SD. On follow-up a change of diagnosis into a definite connective tissue disease occurred in 4 patients with UCTD; one patient with RP alone died with symptoms of myositis and fulminant pulmonary vasculitis. All five showed SD-pattern capillary abnormalities of the "active" type on initial examination. A significant correlation between the "slow" capillary pattern and the presence of anticentromere antibodies was also observed. Only one patient of 25 RPO with normal capillaries available for follow-up showed any change in clinical status.

Antibodies, Antinuclear↗

A study of ocular complications in leprosy.

A total of 380 leprosy patients were studied in four different leprosy hospitals. The involvement of eye was found in 18.95% of cases in which 10.97% in lepromatous leprosy and 8.16% in non-lepromatous leprosy cases. In total cases studied 52.63% were of lepromatous leprosy and 47.37% of non lepromatous leprosy cases. Among them 11.05% were males and 18.95% were females. In 72 cases of ocular involvement, males constituted 80.56% and females 19.44% of cases. Maximum cases (52.78%) of ocular involvement were in leprosy patient with 5 to 10 years of duration. Blindness among the total leprosy patients studied was 1.84% which was mainly due to corneal opacity following exposure keratitis and ulceration, iridocyclitis and its complications.

Adolescent↗