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Biomedical subjects

M N Khan

Publications and source records attributed to M N Khan.

72 records · Page 4Linked to original sources
PubMed1985

Insulin and insulin receptor uptake into rat liver. Chloroquine action on receptor recycling.

In the present study, the effect of chloroquine on both insulin and receptor distribution was examined in vivo. Insulin injection (25 nmol/100 g body wt) caused a marked accumulation of both insulin and its receptor in purified hepatic Golgi fractions by 15 min postinjection. Percoll fractionation of parent Golgi fractions resolved two endocytic components of low (rho = 1.040-1.050) and high (rho = 1.053-1.064) density in which the relative distribution of insulin binding sites was unaltered by chloroquine. Chloroquine significantly accumulated in the high-density region of the Percoll gradient consistent with this being a low pH compartment. 125I-insulin accumulated first in the low-density (1 min) and subsequently in the high-density region (5-10 min) of Percoll-subfractionated Golgi fractions. Chloroquine treatment caused marked accumulation of 125I-insulin in the high-density compartment with substantial retention of radiolabel therein at 20 min postinjection. 125I-insulin extracted from the Percoll fractions was comparably intact in control and chloroquine-treated rats. These data suggest that the chloroquine-accumulating, high-density compartment of hepatic Golgi fractions is the site of dissociation of internalized insulin-receptor complexes before degradation of the ligand and receptor recycling.

Animals↗
PubMed1984

In vivo uptake of insulin into hepatic Golgi fractions: application of the diaminobenzidine-shift protocol.

The hypothesis that insulin is internalized into the hepatic Golgi apparatus was tested by the diaminobenzidine-shift protocol of Courtoy et al. (1984, J. Cell Biol. 98, 870). Highly purified Golgi fractions were isolated after the coinjection of [125I]insulin and the synthetic ligand, galactose-bovine serum albumin-horseradish peroxidase. Golgi fractions were subsequently reacted in the presence or absence of diaminobenzidine, then subjected to Percoll gradient centrifugation. For incubations carried out in the absence of diaminobenzidine, [125I]insulin-containing components were found at a low density (peak density congruent to 1.042) identical to that of the Golgi marker enzyme galactosyltransferase. However after incubations carried out in the presence of diaminobenzidine, the majority of [125I]insulin-containing components was shifted to a higher density of greater than 1.06 while that of galactosyltransferase remained unchanged (peak congruent to 1.042). These observations indicate that the majority of internalized insulin is not located in galactosyltransferase-containing Golgi components.

3,3'-Diaminobenzidine↗
PubMed1984

Kinetics and mechanism of the alkaline hydrolysis of maleimide.

The kinetics of hydrolysis of maleimide was carried out within the [OH-] range of 2.46 X 10(-6) to 2.0 M at 30 degrees C. The observed pseudo-first-order rate constants, kobs, follow the empirical equation: kobs = (A1[OH-] + A2[OH-]2)/(1 + A3[OH-]). Both ionized and un-ionized forms of maleimide have been suggested to be involved in hydrolysis. The nucleophilic attacks by hydroxide ion at the carbonyl carbon of both ionized and un-ionized maleimide and by water at the carbonyl carbon of ionized maleimide to form tetrahedral intermediates are considered to be the rate-determining steps. The observed results obtained at different 1,4-dioxane-water compositions have revealed an increase in kobs with a decrease in 1,4-dioxane content which could be attributed to the higher polarity of the transition state compared with the reactant state.

Alkalies↗
PubMed1984

Adrenocorticotropin radioimmunoassay: properties of antisera against synthetic ACTH(1-24) and its clinical application.

Two antisera against synthetic ACTH(1-24) developed in rabbit showed strikingly different affinities toward the ACTH molecule. Both antisera (A-6 and A-7) were highly specific for the COOH-terminal region of ACTH(1-24). Antisera A-6 recognized ACTH(1-39) poorly. Radioimmunoassays (RIAs) using these antisera permitted the rapid (less than or equal to 18 h) quantitation of ACTH(1-24) (A-6) or ACTH(1-39) (A-7) at picogram levels. ACTH levels were determined on silicic acid extracts of rat and human plasma samples by the RIA specific for mid-region of ACTH(1-39) (A-7) and compared with that obtained by an ACTH(34-39) (C-terminal) RIA. In nearly all cases the C-terminal/mid-region ACTH ratios were less than 1.0, indicating that C-terminus of ACTH is more readily degraded by tissue or blood peptidases than are internal sequences. A solid-phase immunoadsorbent RIA specific for the extreme COOH-terminus of ACTH(1-24) was developed by coupling antiserum (A-6) to Sepharose 4B. This assay exhibited the same specificity as the soluble antiserum, yet tolerated relatively high concentrations of protein. Although the assay was suitable for rapid quantitation of ACTH(1-24), a decrease in sensitivity was observed in comparison to a conventional assay.

Adrenocorticotropic Hormone↗
PubMed1981

Intracellular hormone receptors: evidence for insulin and lactogen receptors in a unique vesicle sedimenting in lysosome fractions of rat liver.

Previous studies have established the presence of polypeptide hormone receptors in Golgi fractions from rodent liver. In this study we attempted to identify peptide hormone receptors in other intracellular elements, particularly lysosomes. Tritosomes were prepared by a standard procedure, and highly purified secondary lysosomes were prepared by fractionating the L fraction of rat liver in a discontinuous metrizamide gradient into subfractions L1 to L4. Binding of 125I-labeled insulin and 125I-labeled somatotropin was studied with membranes prepared from osmotically shocked fractions. The L2 and L3 fractions, virtually devoid of galactosyltransferase (UDP galactose:2-acetamido-2-deoxy-D-glucosylglycopeptide galactosyltransferase, EC 2.4.1.38) but highly enriched in acid phosphatase [orthophosphoric-monoester phosphohydrolase (acid optimum), EC 3.1.3.2], appeared as classical secondary lysosomes by electron microscopy. When compared with Golgi fractions, the level of specific binding per 50 micrograms of protein of 125I-labeled somatotropin in L2 and L3 was 1/3, whereas that of 125I-labeled insulin was comparable. L1, which was reduced in acid phosphatase and increased in galactosyltransferase activities, showed higher hormone binding than did L2 and L3. This was not attributable to Golgi fraction contamination, as evident by specific binding/galactosyltransferase ratios. Binding to tritosome membranes could be largely accounted for by variable contamination with Golgi fractions as judged by specific binding/galactosyltransferase ratios. To clarify the distribution of receptor sites in lysosomal preparations, we fractionated the entire L fraction on a continuous Percoll gradient. Acid phosphatase and galactosyltransferase activities were segregated to the high and low density ranges of the gradient, respectively; however, the fractions enriched in hormone binding were of intermediate density, distinct from Golgi and lysosomal biochemical markers. We conclude that intracellular receptors are found not only in galactosyltransferase-containing very low density lipoprotein-marked Golgi vesicles but also in a unique vesicle of intermediate density between classical Golgi and lysosomal structures.

Animals↗
PubMed1981

Blood-borne adrenocorticotropin binds specifically to the median eminence-arcuate region of the rat hypothalamus.

The quantitative light microscope radioautographic approach was utilized to locate specific binding sites for blood-borne 125I-labeled ACTH1-24 in the rat brain. Specific binding occurred exclusively in the external zone of the median eminence, adjacent to the primary portal plexus, and to a lesser extent in the ventral arcuate nucleus. This localization may indicate that the hypophysiotropic median eminence is a new target site for circulating adrenocorticotropin. Alternatively, ACTH binding sites in the median eminence-arcuate region may provide the hypothalamus with a hormone-selective capacity to concentrate pituitary ACTH for possible retrograde transport and redistribution within the central nervous system.

Adrenal Cortex↗
PubMed1981

Application of a sequence-specific radioimmunoassay for the carboxyl-terminal region of corticotropin.

The carboxyl terminal region of corticotropin (ACTH), (Ala34-Phe-Pro-Glu-Leu-Phe39), a region of the hormone conserved during evolution, served as an antigen for the production of a sequence-specific antiserum. In a radioimmunoassay, peptides that extend toward the amino terminal from Ala34, such as [Tyr,Gly]-ACTH34-39, ACTH18-39, and ACTH, had greater affinity for the antibody, which suggests that the antiserum recognizes the peptide bond preceding the alanyl residue. The assay readily detects 30 to 50 pmol of ACTH per liter with an incubation of only 3 h, and the antiserum cross reacts with larger molecular mass forms of the hormone. The amount of immunoreactive ACTH extracted by adsorption onto silicic acid from rat and human plasma was only 0.36 to 0.79 of that detected by a mid-region ACTH assay, which suggests proteolytic degradation at the carboxyl terminus of ACTH.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

Ulcerative colitis in Karachi.

Experience of 189 patients with non-specific ulcerative colitis has been reviewed. The majority of patients was in the 21-30 year age group, and neither sex predominated. Seventy-two percent had mild to moderate disease. The disease was mainly confined to the left colon (60%) and 13% had total colitis.

Adult↗
PubMedDate not supplied

The role of white cell count and C-reactive protein in the diagnosis of acute appendicitis.

BACKGROUND: Despite recent advances in diagnostic medicine, the diagnosis of appendicitis is still doubtful in a number of cases. Majority of the clinicians rely on their clinical examination strengthened by the laboratory tests. This study was carried out to find out the specificity and sensitivity of white cell count (WCC) and C-Reactive Protein (CRP) in diagnosing appendicitis in patients presenting with right iliac fossa pain. METHODS: A total of 259 patients were included in this study that presented in the hospital with acute right iliac fossa pain and later on operated and had appendicectomy. The histopathology data was collected to find out the frequency of negative appendicectomy. According to the histopathology reports these patients were grouped into three sub-groups as normal appendix, inflamed appendix or perforated/gangrenous appendix. A record was kept of the WCC and CRP levels of these patients on admission. RESULTS: A total of 259 patients were included in this study and out of them 37 had a normal appendix giving an over all negative appendicectomy rate of 14.3%. Out of these 11 were male and 26 were female, male to female ratio being 1:2.3. The age range was 12-73 with a median age of 24. Among the 222 patients who had appendicitis, 96 had a ruptured/perforated appendix and 126 had an inflamed appendix. Over all the WCC was elevated in 185 patients and CRP was elevated in 168 cases. The cut off value for white cell count was 11 x 10(6)/L. The C reactive protein levels were calculated by immunoturbidimetric test and the cut off value was taken as 1.7 mg/dl. The sensitivity and specificity of WCC in this study was 83% and 62.1% and that for CRP was 75.6% and 83.7 %. CONCLUSION: Both the inflammatory markers i.e. WCC and C-reactive protein can be helpful in the diagnosis, when measured together as this increases their positive predictive value.

Acute Disease↗