Bibliography on diarrhoeal diseases.
Explore the source record for details and available documents.
Diarrhea↗
Biomedical subjects
M S Khan
Publications and source records attributed to M S Khan.
Bibliography on diarrhoeal diseases.
Explore the source record for details and available documents.
Animals↗
Delineation and synthesis of the membrane receptor-binding domain of sex hormone-binding globulin.
Sex hormone-binding globulin (SHBG) is a plasma glycoprotein which binds certain steroids. It, in turn, binds to a specific receptor on cell membranes. This work was undertaken to identify, isolate, sequence, and synthesize the region of SHBG that interacts with its membrane receptor. To accomplish this, highly purified human SHBG was digested with trypsin. The SHBG-derived tryptic peptides were separated by high performance liquid chromatography. They were evaluated for their ability to compete with 125I-SHBG for binding to the SHBG receptor solubilized from human prostatic membranes. Only a single peptide, corresponding to residues 48-57 of the known sequence of human SHBG, inhibited receptor binding. A synthetic decapeptide with this amino acid sequence also competitively inhibited SHBG binding.
Amino Acid Sequence↗
Histidine 235 of human sex hormone-binding globulin is the covalent site of attachment of the nucleophilic steroid derivative, 17 beta-bromoacetoxydihydrotestosterone.
This article deals with the elucidation of the steroid-binding site of human sex hormone-binding globulin (SHBG). 17 beta-Bromoacetoxydihydrotesterone (BA-DHT) reacted with highly purified SHBG in a time-dependent and irreversible fashion. The interaction could be totally inhibited by the simultaneous addition of an excess of dihydrotesterone. At the completion of the reaction, the molar ratio of BA-DHT to SHBG was approximately unity. SHBG was affinity labeled with [14C]BA-DHT and submitted to acid hydrolysis. The released amino acids were evaluated on high performance liquid chromatography, and virtually all of the 14C was identified as 3-[14C]carboxymethylhistidine. Furthermore, [14C]BA-DHT-labeled SHBG was digested with trypsin, followed by isolation of the released tryptic peptides by reverse-phase high performance liquid chromatography. The 14C was localized to a single tryptic peptide. It contained 2' histidyl residues, corresponding to residues 235 and 251 in the known amino acid sequence of SHBG. Although most of the 3-[14C]carboxymethylhistidine, or its phenylthiohydantoin derivative, was trapped on the filter of the amino acid sequenator, sufficient radioactivity emerged to identify histidyl residue 235 as the labeled amino acid.
Affinity Labels↗
The control of the interaction of sex hormone-binding globulin with its receptor by steroid hormones.
Sex hormone-binding globulins (SHBG) is a plasma glycoprotein that binds certain steroids. It, in turn, binds to a specific receptor on cell membranes. This work was undertaken to investigate the role of steroids in the interaction of SHBG with its receptor. Because the probe for the interaction of SHBG with its receptor is 125I-SHBG, we first showed that 125I-SHBG binds [3H]dihydrotestosterone (DHT) at 4 degrees C and 37 degrees C with KD values similar to those published previously for pure radioinert SHBG. 125I-SHBG could be prevented from binding to its receptor by a variety of steroids whose relative inhibitory activity (dihydrotestosterone much greater than 2-methoxyestradiol greater than testosterone greater than estradiol much greater than methyltrienolone greater than cortisol) was almost identical to their relative ability to bind to SHBG. Because significant binding of [3H]DHT to the SHBG receptor could not be demonstrated, steroid inhibition of SHBG binding must be noncompetitive. If steroids bound to SHBG prevent binding to the SHBG receptor, then liganded SHBG should have a higher apparent KD for its receptor than unliganded SHBG. This is the case. The KD was 0.86 +/- 0.25 nM for the high affinity receptor site using liganded SHBG and 0.19 +/- 0.024 nM for unliganded SHBG. Thus, only liganded SHBG assumes a conformation that prohibits interaction with the SHBG receptor. However, when unliganded SHBG was prebound to its receptor, it retained its ability to bind [3H] DHT. The model that emerges from these observations is as follows. Unliganded SHBG can bind either steroids or receptor in a reversible reaction; SHBG bound to a steroid cannot bind to the receptor, but unliganded SHBG that first binds to the receptor can subsequently bind steroids.
Binding Sites↗
Endogenous insulin secretion in newly diagnosed diabetic patients in Saudi Arabia.
Diabetes mellitus is a major health problem in Saudi Arabia. The evaluation of endogenous insulin secretion at diagnosis has not yet been studied in this population. We have therefore studied fasting and post-glucagon stimulation levels of glucose, insulin and C-peptide in 216 newly diagnosed untreated diabetic patients. The mean +/- SD fasting insulin and C-peptide levels were 14.0 +/- 1.8 microU/ml and 1.8 +/- 0.4 ng/ml, while post-glucagon stimulation levels were 21.1 +/- 3 microU/ml and 2.4 +/- 0.4 ng/ml. There were significant post-stimulatory increment levels for insulin, from 4.9 to 13.7 microU/ml, and C-peptide from 0.2 to 1.3 ng/ml (P less than 0.001). Such increments did not affect specified age distribution. We found a significant correlation between the fasting levels and post-stimulation levels of C-peptide and insulin. Obesity correlated with higher basal and post-stimulation levels of both hormones (r = 0.67, P less than 0.001). The mean +/- SD fasting insulin and C-peptide levels were 18.5 +/- 9.1 microU/ml and 2.4 +/- 0.8 ng/ml for obese patients and 11.5 +/- 5.1 microU/ml and 1.9 +/- 1.1 ng/ml for non-obese patients. The type of diabetes among the Saudi adult diabetic patients studied is characterized by high basal C-peptide and insulin levels which increase significantly with stimulation, suggesting diminished but present endogenous B-cell function.
Adolescent↗
The rat hepatic corticosteroid-binding globulin receptor: distinction from the asialoglycoprotein receptor.
This investigation was undertaken to ascertain whether rat liver cells contained a receptor for corticosteroid-binding globulin (CBG) that could be differentiated clearly from the asialoglycoprotein receptor. To do this, [125I]CBG, [125I] asialo-CBG, and [125I]asialofetuin were used as probes to differentiate the binding activities of the two receptors. On hepatic membranes, CBG bound to a single set of sites with a Kd of 0.74 microM, asialofetuin bound to a single set of sites with a Kd of 0.018 microM, asialo-CBG bound to two sets of sites with Kd values of 0.004 and 1.4 microM and in the presence of 1 microM asialofetium, asialo-CBG bound to a single set of sites with a Kd of 0.53 microM, not different (P greater than 0.2) from the Kd of CBG. Cross-competition studies using the three 125I-labeled ligands and allowing each to compete with the three radioinert ligands indicated the existence of two separate receptors. Desialylation of hepatic membranes differentially affected the binding of CBG and asialofetuin. Finally, whole cells bound CBG specifically, but internalized it to only a minimal extent (less than 10%). This observation does not support a role for the CBG-receptor system in the entry of steroids into cells.
Animals↗
Biologically active steroids activate receptor-bound human sex hormone-binding globulin to cause LNCaP cells to accumulate adenosine 3',5'-monophosphate.
The binding of human sex hormone-binding globulin (SHBG) to a human prostatic cancer cell line (LNCaP) and the results of that binding were examined. Membranes derived from LNCaP cells bound unliganded SHBG on two sets of sites whose affinities were: Ka1 = 3.1 +/- 1.6 x 10(10) M-1 and Ka2 = 8.7 +/- 4.3 x 10(6) M-1. Intact cells also bound SHBG, but even after 6 h, less than 10% of specifically bound SHBG was internalized. This observation speaks against a role for the membrane binding of SHBG in steroid transport across cell membranes. When LNCaP cells were prebound with SHBG, addition of dihydrotestosterone or estradiol resulted in a dose-dependent increase in intracellular cAMP. SHBG in the absence of steroids or dihydrotestosterone in the absence of SHBG was without effect. 2-Methoxyestradiol, a steroid metabolite without biological activity, but which binds to SHBG more tightly than does estradiol, was also without effect. These observations demonstrate a potentially important role for SHBG as a regulator of cell function. They also demonstrate an additional mode of action of steroid hormones, one that does not require that the steroid interact with a steroid receptor.
2-Methoxyestradiol↗
Health sciences libraries and information services in Bangladesh.
Basic problems relating to the status of health sciences libraries and information centers in Bangladesh are highlighted and discussed; strategies for improving the country's health sciences information services are suggested. A survey of libraries is reported, the country's national science and technology information policy is defined, and recommendations for action are proposed.
Bangladesh↗
Obesity and major metabolic indices in newly diagnosed Saudi diabetic patients.
Metabolic indices were assessed in 217 Saudi diabetic patients and 57 control subjects in relation to Body Mass Index (BMI). Patients with BMI values greater than or equal to 27 in male and greater than or equal to 25 in female were considered obese. Obesity was found more frequent in females (82.7%) than in males (40.9%) (p less than 0.01). Basal glucose and HbA1C levels were lower in obese males than in females. C-peptide levels were higher (p less than 0.01) in the obese subjects than in the non-obese. Within the obese group c-peptide levels were higher in males than in females. Triglycerides and total lipids were also higher in the obese group. Our result suggests that a varying degree of obesity influences the rate of both beta cell secretion, insulin resistance and impaired lipid metabolism.
Adult↗
Solubilization and partial characterization of the sex hormone-binding globulin receptor from human prostate.
The sex hormone-binding globulin (SHBG) receptor was solubilized from the membranes of human prostate glands with the zwitterionic detergent CHAPS (3-[(3-cholamidopropyl)dimethylammonio]-1-propane-sulfonic acid). The binding activity of the soluble receptor was measured by allowing it to bind to 125I-SHBG and precipitating the complex with polyethylene glycol-8000. The binding activity was stable for at least 4 months at -20 degrees C and had a half-life of 23 days at 4 degrees C. Like the membrane-bound receptor, Scatchard analysis revealed two sets of binding sites for the soluble one. At equilibrium (24 h), the high affinity site had an association constant (KA) of 6.8 x 10(8) M-1 and a binding capacity of 1.4 pmol/mg protein, whereas the low affinity site had a KA of 4.7 x 10(6) M-1 and a binding capacity of 43 pmol/mg protein. At 37 degrees C, the association rate constant (k1) was 8.37 x 10(5) M-1 min-1 and the dissociation rate constant (k2) was 3.43 x 10(-4) min-1. The soluble receptor was retarded on Sepharose CL-6B and had an apparent Mr = 167,000.
Cholic Acids↗
Epididymo-orchitis and Brucellosis.
A series of 40 patients presented with epididymo-orchitis between January 1983 and August 1985. In 14 brucellosis was diagnosed. In 10 of these (72%) both testis and epididymis were involved and 1 had bilateral disease. All patients with brucella epididymo-orchitis were treated with streptomycin and tetracycline and complete resolution occurred in 8 (57%).
Adolescent↗
Glycaemic responses to three different honeys given to normal and alloxan-diabetic rabbits.
Blood glucose levels of normal and diabetic rabbits were determined after oral administration of graded doses of three different types of honeys; namely honeys of Apis florea (Small-Bee) and Apis dorsata (Large-Bee) and an adulterated commercial honey. The chemical analysis showed that commercial honey was adulterated with a saturated sucrose solution as it contained lower ash but higher nonreducing sugar levels than the natural ones. Oral administration of pure small or large-bee honeys in 5 ml/kg/doses could not produce a significant (P greater than 0.05) increase in glucose levels in normal and alloxan-diabetic rabbits whereas the adulterated honey significantly raised the blood glucose levels in normal and hyperglycaemic rabbits even at this low dosage. In higher doses of 10 ml/kg and 15 ml/kg body weight, all the three honeys produced a significant (P less than 0.05 or P less than 0.001) rise in blood glucose levels of normal as well as alloxan-diabetic rabbits. It may, therefore, be suggested that pure natural honeys in low doses may be recommended as a source of carbohydrates and even as a sweetening agent in place of sucrose to the human patients suffering from diabetes mellitus (JPMA 39: 107, 1989).
Administration, Oral↗
Induction of adenylate cyclase in a mammary carcinoma cell line by human corticosteroid-binding globulin.
Corticosteroid-Binding globulin (CBG) is a plasma protein that binds certain steroid hormones, mainly cortisol and progesterone. It has been demonstrated recently that specific binding sites for this protein exist on cell membranes. In this communication we establish that binding to these sites results in the induction of adenylate cyclase activity and the accumulation of cAMP in MCF-7 cells. These events are critically dependent upon a steroid being bound to CBG. These data are consistent with the hypothesis that CBG is a prohormone which is activated when cortisol is bound to it.
Adenylyl Cyclases↗
Cyclopentenylcytosine. A carbocyclic nucleoside with antitumor and antiviral properties.
Cyclopentenylcytosine (CPE-C, 2), a pyrimidine analogue of the fermentation derived carbocyclic nucleoside neplanocin A, has been synthesized from the optically active cyclopentenylamine 3b by two synthetic routes. CPE-C demonstrates significant antitumor activity against both the sensitive and ara-C resistant lines of L1210 leukemia in vivo. Multiple long term survivors are produced in both tumor models. The compound also gives 100% growth inhibition of the solid human A549 lung and MX-1 mammary tumor xenografts grown in athymic mice. Good activity is also observed against a third human tumor xenograft model, metastatic LOX melanoma. CPE-C has significant activity against both DNA and RNA viruses in vitro. Potent activity is observed against HSV-1 (TK+ and TK-), HSV-2, vaccinia, cytomegalovirus, and varicella-zoster virus. Good activity is also found against a strain of influenza virus (Hong Kong flu), vesicular stomatitis virus, Japanese encephalitis virus, and Punta Toro virus.
3-Deazauridine↗
Are corticosteroid-binding globulin and sex hormone-binding globulin hormones?
Because it no longer seemed reasonable to us that the sole function of the steroid-binding proteins in plasma was to serve as a buffer reservoir for steroid hormones, we conducted experiments which sought out other possibilities. Both CBG and SHBG bind to cell membranes, and this interaction partakes of the general characteristics of peptide hormone-membrane receptor systems. Additionally, human CBG has the ability to cause an increase in the activity of membrane-bound adenylate cyclase in MCF-7 cells, and this, in turn, results in an increase in cellular cAMP content. Thus, CBG appears to be a protein hormone. As a first consideration, one might presume that because CBG's half-life is measured in days, it would be counted among the hormones which, for the most part, are tonic in their effects, e.g., thyroid hormone. However, two important considerations tend to believe this presumption: (1) CBG which is unoccupied by steroid is not hormonally active (Figure 5): (2) Depending upon the time of day, circulating CBG is approximately 0-60% occupied in normal humans. These observations result in a circumstance in which a substantial portion of circulating CBG is available for activation by bursts of cortisol secretion. It seems prudent to speculate that, because steroids are essential for CBG's activity, the hormonal role of CBG may be entwined with, or complementary to the steroids which it binds. Finally, we should comment on the impact that our model of CBG as a hormone has on the view that only unbound steroid can be hormonally active. First, it should be stated that we have not addressed this question experimentally. Although there is evidence that CBG may be required for cortisol action, we feel that an obligate role for it is not documented adequately. At this time, we believe that CBG's hormonal role is compatible with a hypothesis that encompasses the view that unbound steroid hormones can diffuse into cells in some tissues and that both free and bound steroid can enter cells in others. Obviously, the final word on these important topics, as always, awaits the proper experiments.
Binding Sites↗