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Biomedical subjects

A Mahmood

Publications and source records attributed to A Mahmood.

At least 91 records · Page 5Linked to original sources
PubMed1996

Generation of hydroxyl radicals by nucleohistone-bound metal-adriamycin complexes.

A recently developed method has been utilized to demonstrate the generation of hydroxyl radicals (HO.) in the immediate proximity of DNA by copper(II)/iron(III)-adriamycin in the presence of ascorbate and hydrogen peroxide. SECCA, a succinylated derivative of coumarin, generates the fluorescent 7-hydroxy-SECCA following reaction with HO.. SECCA was coupled to polylysine or to histone H1 and then complexed to DNA. When HO. was generated in the proximity of DNA by polylysine-coupled iodine-125, which emits short range Auger electrons, 7-hydroxy-SECCA was produced. DMSO was only moderately efficient in reducing the fluorescence induction, demonstrating the "local" generation of HO. in this system. Copper(II)/iron(III)-adriamycin in the presence of ascorbate and hydrogen peroxide generated the fluorescent 7-hydroxy-SECCA both when SECCA was free in solution and when SECCA was DNA-conjugated. With SECCA free in solution, the fluorescence induction was almost eliminated in the presence of HO. scavengers (ethanol, tert-butanol or DMSO) and the relative efficiency of the scavengers in reducing the fluorescence followed their rate constant with HO.. Furthermore, SECCA incubated with a single oxygen-generating compound demonstrated no fluorescence induction. When SECCA was positioned in close proximity to DNA as a SECCA-histone-H1-DNA complex, the relative efficiency of the scavengers in reducing the fluorescence still followed their rate constant with HO.; overall however the scavengers were much less effective in reducing the fluorescence, due presumably to the formation of HO. radical in the immediate vicinity of DNA. These data suggest that copper(II)/iron(III)-adriamycin produces HO. in the presence of ascorbate and hydrogen peroxide whether unbound or bound to DNA and suggest that in the latter case scavengers would not prevent HO. from attacking chromatin. In addition, the ability of DMSO to trap HO. was shown to decrease as the conformation of the H1-DNA complex becomes more compact indicating the strong dependence of the trapping ability on chromatin conformation.

Chemical Phenomena↗
PubMed1996

Modulation of the cytochrome P450 system as a mechanism of chemoprotection.

The cytochrome P450-dependent mono-oxygenase system has evolved as one of our primary defences against toxic chemicals present in our environment. This multi-enzyme system functions as an adaptive response to environmental challenge in that exposure to specific toxic agents induces the expression of cytochrome P450 isozymes active in their metabolism. In most cases, such metabolism leads to an increased rate of chemical detoxification, but in certain cases it can also lead to an increased rate of chemical activation to toxic products. The induction of cytochrome P450s leading to cytoprotection is a major mechanism of chemoprotection, and it is well documented that this pathway prevents a large number of toxic reactions. Incredibly, despite the importance of this metabolic pathway, the effects of a wide range of chemoprotective agents with different mechanisms of action on the expression of specific cytochrome P450 isozymes remains poorly understood. In this chapter, we discess the ability of different chemical compounds to modulate cytochrome P450 both at the transcriptional and post-transcriptional levels, in a way which affects its ability to metabolize or detoxify chemical carcinogens.

Animals↗
PubMed1996

Changes in tubular membrane glycosylation in diabetic, insulin and thyroxin treated rat kidneys.

The effect of insulin, thyroxine and alloxan induced diabetes has been studied on brush border membrane glycosylation in rat kidneys. Expressed on dry weight basis, the membrane protein was elevated in insulin, thyroxine and diabetic membranes compared to the control group. Sialic acid content of the membranes was significantly reduced in insulin and thyroxine injected animals whereas fucose level was unaffected under these conditions. Brush border fucose content was significantly reduced in diabetic animals but sialic acid content was unaffected. Membrane hexose and hexosamines levels were unaltered by hormone treatments, but in diabetic rats hexosamine level was significantly reduced. The binding of radiolabelled UEA, WGA, PNA to purified brush borders corroborated changes in membrane saccharides. These findings suggest the role of hormones in membrane glycosylation of rat kidney tubules.

Animals↗
PubMed1996

Isatin (2,3-dioxoindole): a competitive inhibitor of Na(+)-dependent lysine uptake in rat instestine.

Isatin (2,3-dioxoindole) competitively inhibited (27-40%) Na(+)-dependent L-lysine uptake in rat intestine. The value of Kt was increased from 3.04 mM in control to 5.88 mM in presence of 10 mM isatin. Effect of isatin on the Na(+)-independent amino acid uptake was insignificant (12-18%). The inhibitory constant (Ki) was 2.8 mM under these conditions. The observed inhibition was unaffected by -SH group reacting agents. Isatin (1-10 mM) inhibited Na+, K(+)-ATPase activity in intestine in vitro, the maximum inhibition (66%) being at 10 mM isatin concentration. But the drug had no effect on enzyme activity under in vivo conditions.

Animals↗
PubMed1995

Two rat intestinal alkaline phosphatase isoforms with different carboxyl-terminal peptides are both membrane-bound by a glycan phosphatidylinositol linkage.

Two cDNAs encode rat intestinal alkaline phosphatases having completely different carboxyl-terminal peptides; one is hydrophobic and fulfills the consensus requirements for glycan phosphatidylinositol linkage, and the other is neither hydrophobic nor hydrophilic, but contains a small amino acid domain (-NSASS-) just distal to a region of 17 threonine residues. Constructs were created using 80% of the amino-terminal portion of one alkaline phosphatase and the carboxyl-terminal portions of each of the isoforms. Both of the carboxyl-terminal peptides supported glycan phosphatidylinositol linkage as demonstrated by the following criteria: 1) plasma membrane targeting in transfected COS-1 cells, 2) release of transfected alkaline phosphatase by phosphatidylinositol-specific phospholipase C, 3) appearance of the trypanosome variable glycoprotein cross-reacting determinant after phospholipase C treatment, 4) ethanolamine incorporation into newly synthesized enzyme, 5) loss of phospholipase C release after mutation of the omega and omega + 2 positions in the putative linkage site, -NSA-, and 6) evidence of surface membrane localization by immunofluorescence using antibody against rat intestinal alkaline phosphatase. These data demonstrate that a predicted hydrophobic carboxyl-terminal sequence is not essential for glycan phosphatidylinositol linkage. Moreover, because both isomers are membrane-bound, the origin of soluble enzyme in the serum is likely to arise from the action of serum phosphatidylinositol-specific phospholipase C.

Alkaline Phosphatase↗
PubMed1995

IGF-II dependent autocrine growth in cell lines derived from renal tumours of childhood.

Aims-To determine the role of insulin-like growth factors (IGF) in the proliferation of tumour cells, by studying the mitogenic response to IGFs of three cell lines of differing phenotype established from both malignant rhabdoid and Wilms tumour, representing a range of cell types (GOS 4, G401, and T3/73).Methods-Production of IGF-II and IGF-I was measured by radioimmunoassay, and the presence of IGF binding protein complexes was observed by gel exclusion chromatography. Following growth analyses in serum-free media to ascertain the dependence of the cell lines on exogenous IGFs, the generation of autocrine growth was measured by a density dependence assay of proliferation in culture. Receptors were measured by radioligand cross linking and autocrine growth through these receptors assayed by the use of blocking antibodies.Results-While GOS 4 and G401 were able to proliferate in serum-free medium over a period of 5 d, T3/73 showed an absolute dependence on IGFs added daily at 1-10 ng/ml. Plating at clonal density showed that cell growth was directly density dependent in serum-free medium. The serum independent proliferation of G401 and GOS 4 was blocked by the addition of an antibody to the type 1 IGF receptor (alpha-IR3) suggesting that the effects of autocrine factors are mediated through type 1 IGF receptors. S1 nuclease protection analysis indicated that all three cell lines produced significant amounts of mRNA derived mainly from the P3 IGF-II promoter, but transcripts for IGF-I were undetectable. Radioimmunoassay of IGFs from conditioned media showed that all the lines made assayable IGF-II (8.6, 8.4, and 6.1 ng/ml/24 h/10(6) cells for GOS 4, G401, and T3/73 respectively). The presence of species consistent with both type 1 and type II IGF receptors was demonstrated using radioligand binding to cell membranes followed by cross linking.Conclusions-Autocrine IGF-II may contribute to the serum independence of GOS 4 and G401 cells, whereas T3/73 may depend on exogenous IGF-II for proliferation.

Journal Article↗
PubMed1995

Appearance of surfactant-like particles in apical medium of Caco-2 cells may occur via tight junctions.

Intestinal alkaline phosphatase (AP) is secreted by Caco-2 cells bound to surfactant-like particles (SLP), which can be localized by electron microscopy to the basolateral space and the intestinal lumen, especially over tight junctions. To investigate the hypothesis that SLP are secreted basolaterally and enter the lumen through the tight junction, Caco-2 cells were incubated with agents known to increase permeability at tight junctions. Cytochalasin D and phorbol 12-myristate 13-acetate increased Caco-2 cell monolayer permeability and the appearance of particles in apical medium two- to threefold, as monitored by mannitol movement and AP activity, respectively. Blocking the apical secretory pathway by nocodazole or colchicine had no effect on either parameter. Estimation of SLP content demonstrated an increase in apical media particles similar to that determined by AP activity. Quantitative image analysis established that apical SLP content increased 4-10 times, whereas total cell particle content remained unchanged. These data indicate that SLP may be secreted initially into the basolateral space and then transported to the intestinal lumen through the tight junctions.

Adenocarcinoma↗
PubMed1995

Effect of chronic ethanol administration and dietary protein regimens on intestinal absorption of macromolecules in rats.

The effect of feeding ethanol daily for 40 days has been studied on intestinal absorption of bovine serum albumin (BSA) and gamma-globulin (IgG) in rats fed a low (8%) protein (LP) or a high (30%) protein (HP) diet. Feeding the LP diet enhanced the tissue uptake of BSA (p < 0.05) and absorption of BSA and IgG into serum (p < 0.001) as compared with controls. Feeding the HP diet also augmented the uptake of IgG (p < 0.001) by the intestinal tissue and significantly enhanced serum levels of BSA and IgG. Ethanol feeding to rats for 40 days enhanced the uptake of BSA and IgG (24-84%) and their absorption into serum (p < 0.001) as compared with the controls. Ethanol administration to rats fed LP or HP diets did not alter the uptake of these proteins as compared with their respective controls. Luminal degradation of BSA and IgG was higher in ethanol-administered (48-50% and 36-39%, respectively) and LP-fed rats (50 and 38%, respectively). It was reduced by 17-21% in HP-fed rats as compared with the control group. This indicated that the observed increase in protein absorption is not related to the luminal degradation of the proteins under these conditions. These findings suggest that the absorption of macromolecules from intestine in response to ethanol feeding is influenced by the dietary status of the animals.

Animals↗
PubMed1995

The construction of mobilizable YACs and their direct conjugative transfer from E. coli to yeasts.

YAC, yeast artificial chromosome, consists of Saccharomyces cerevisiae's ARS, CEN and nutrient requirement genes and TEL from Tetrahymena with ori and ampicillin resistant genes of pBR322. we have constructed two mobilizable pAY-YACs plasmids by inserting oriT at different positions. pAY-YAC-B (12.2 kbp) containes oriT in between two telomeres, whereas in pAY-YAC-E (14 kbp) oriT has been inserted at the cloning site of pYAC4. Both plasmids were mediated from E.coli to S.cerevisiae and S.kluyveri with the aid of helper plasmid pRH220 which resides mob and tra genes. The results of conjugal transmission, restriction enzyme digestion and Southern blotting analyses indicated that both plasmids were able to maintained their size and structure, thus reflected the faithfull accomplishment of nicking and resealing of plasmids during conjugation. The direct transformation of plasmid DNA into yeast showed that pAY-YACs plasmids, may be due to their small size, have tendency of circularization.

Chromosomes, Artificial, Yeast↗
PubMed1994

Inhibition of glucose transport in human erythrocytes by 2,3-dioxoindole (isatin).

10 mM isatin (2,3-dioxoindole) inhibited glucose influx into human erythrocytes by over 30%. The inhibition is of the competitive type, where the affinity constant (Kt) was increased from 5.71 (control) to 11.11 mM in the presence of isatin with no change in Vmax (130 nmol/min/ml packed cells). The observed inhibition of sugar transport by isatin was not mediated through membrane -SH groups accessible to iodoacetate, iodoacetamide, DTNB, DNP or sodium arsenite. Isatin inhibited sugar transport in the presence of 2 mM harmaline, an alkaloid inhibitor of Na+, K(+)-ATPase activity. The inhibition was non additive which suggests that these two compounds interact with the same or a similar site on the erythrocyte membrane.

Arsenites↗
PubMed1994

Intracranial meningiomas: analysis of recurrence after surgical treatment.

Recurrence of intracranial meningiomas after surgery has long been recognized, but there is still no consensus about factors responsible for recurrence. To better understand such factors, we analysed data on 276 patients with meningiomas who were treated at our institution from 1976 to 1990 (mean follow-up = 5.1 years). Effects of sex, tumour histology, tumour site, and radiotherapy on recurrence were closely studied. Using World Health Organization criteria to define malignancy, 254 of the tumours were benign and 22 were atypical or malignant. For data analysis, distinction was made between "recurrence"(i.e., reappearance of tumour after total resection) and "regrowth" (i.e., tumour enlargement after subtotal removal). Recurrence was seen in 2 of 183 benign meningiomas and in 10 of 16 malignant meningiomas. Recurrence and regrowth rates for malignant meningiomas far exceeded those for benign meningiomas (p = 0.001). Neither sex nor tumour site was associated with subsequent recurrences in patients whose tumours had been completely resected. The influence of radiotherapy was studied in terms of its effects on benign versus malignant meningiomas, whether given after complete or incomplete resection, and whether given after primary resection or on reoperation. We found that radiotherapy did not decrease "recurrence" or "regrowth" regardless of when administered, either at first resection or on recurrence. This was true for benign as well as malignant meningiomas. However, due to the small number in our series, we cannot conclude that radiotherapy has no beneficial role in the treatment of meningiomas.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Novel technetium ligands with affinity for the muscarinic cholinergic receptor.

The synthesis and preliminary biological characterization of two isomeric technetium labeled complexes (2,5,5,9-tetramethyl-4,7-diaza-7-(3' (R)-quinuclidinylcarboxymethyl)-2,9-decanedithiolato oxo 99/99mtechnetium(V), [99/99mTc]-1 and [99/99mTc]-2) designed to exhibit affinity to muscarinic cholinergic receptors are described. In vitro binding assays were conducted in mouse brain homogenates (whole brain-cerebellum) at 37 degrees C by the centrifugation method, where non-specific binding was defined by atropine (1 microM). The measured affinity (KD) of [99Tc]-1 for mAChR was 1.9 +/- 0.5 microM (mean +/- SEM; n = 3) and [99Tc]-2 was 4.5 +/- 0.5 microM (mean +/- SEM; n = 3). Scatchard analysis indicated that Bmax values were 10.6 +/- 0.5 and 16.9 +/- 0.5 pmol/mg tissue, respectively. In competition assays, [99Tc]-1 exhibited an apparent affinity (KI) of 16.5 microM (n = 2) against [125I] iododexetimide, whereas [99Tc]-2 exhibited an affinity (KI) of 105 microM. In vivo, 0.3% of the injected dose of [99mTc]-1 and [99mTc]-2 accumulated in the brain at 5 min after injection. These values indicate technetium analogues of neuroreceptor binding ligands can be synthesized and retain some affinity for the receptor.

Animals↗
PubMed1994

Treatment options in sulfamethoxazole-trimethoprim-induced thrombocytopenic purpura.

We describe two female patients who had severe sulfamethoxazole-trimethoprim-induced thrombocytopenic purpura. One case occurred shortly after initiating therapy, whereas the other began on the seventh day of treatment. Both patients presented a platelet count below 5,000/microL, extensive purpura, and significant vaginal bleeding. Treatment with systemic corticosteroids resulted in rapid resolution of the thrombocytopenia in the first patient, but had no immediate effect in the other. High-dose intravenous immunoglobulin was effective in correcting the thrombocytopenia in this second instance. Both patients were discharged with a tapering 4-week course of oral prednisone and have remained well since.

Adult↗
PubMed1994

A possible role for rat intestinal surfactant-like particles in transepithelial triacylglycerol transport.

To further examine whether surfactant-like particles (DeSchryver-Kecskemeti, K., R. Eliakim, S. Carroll, W. F. Stenson, M. A. Moxley, and D. H. Alpers. 1989. J. Clin. Invest. 84:1355-1361) were involved in the transepithelial transport of lipid, alkaline phosphatase activity and surfactant-like particle content were measured in apical mucosal scrapings, enterocytes, lamina propria, and serum after inhibition of chylomicron transport. Serum triacylglycerol levels were decreased 60-76% by Pluronic L-81, fenfluramine, and choline deficiency compared with fat-fed controls. 5 h after triacylglycerol feed, alkaline phosphatase activity in all three experimental groups was decreased compared with controls by 52-69% in mucosal scrapings and by 33-72% in serum. A parallel decline (60%) in alkaline phosphatase activity occurred in the lamina propria of Pluronic-treated animals. Total particle content (measured by an ELISA using antiserum against purified particle) after Pluronic treatment was decreased in mucosal scrapings, lamina propria, and serum by 16, 22, and 29% at 3 h and by 33, 40, and 8%, respectively, at 5 h after fat feeding. In contrast, particle content was increased in enterocytes by 29% 3 h and by 8% 5 h after fat feeding. By electron microscopy, enterocytes from Pluronic- and fenfluramine-treated animals exhibited a two- to threefold increase in large intracellular cytoplasmic lipid globules and the appearance of lamellae in apposition, with a marked decrease in the number of surfactant-like particles overlying the brush border. These changes, produced by inhibition of chylomicron transport, in the distribution of surfactant-like particles and particle-bound alkaline phosphatase are consistent with a role for these particles in transepithelial triacylglycerol transport across and out of the enterocyte.

Animals↗
PubMed1994

Dural arteriovenous malformation of the skull base with intraosseous vascular nidus. Report of two cases.

Intracranial arteriovenous malformations (AVM's) have been classified as pure pial, pure dural, and mixed pial and dural. Dural AVM's are relatively uncommon, with 377 cases documented up to 1990. These lesions were believed to be situated within the walls of the sinuses, but during the last decade researchers discovered a small subgroup of dural AVM's in extrasinusal locations such as the skull base and tentorium. Two of the 17 patients who were studied between 1976 and 1993 had dural AVM's that were entirely intraosseous except for their venous drainage, which was via the dural venous sinuses. Although such intraosseous dural AVM's have not been previously described, the authors elected to group these malformations with dural AVM's because their venous drainage was intracranial and angiograms revealed identical features.

Cerebral Angiography↗
PubMed1994

Inhibition of brush border sucrase by indoline 2,3-dione (isatin) in rat small intestine.

Isatin (15-25 mM) inhibited rat brush border sucrase by 40% in presence of Na+ and the inhibition was enhanced to over 60% in sodium free medium. Sucrase inhibition by isatin was dependent on pH. Kinetic analysis revealed a pure capacity type (Vmax-effect) inhibition of sucrase activity by isatin in presence of sodium. But it changed to affinity type (K-effect) in sodium free medium. The value of Ki was around 20-25 mM under these conditions. Enzyme inhibition by isatin was alleviated by increasing Na+ or sucrose concentrations. Other monovalent cations like K+, Li+ and Cs+ were also effective in restoring the enzyme activity to control levels. The effectiveness of the metal ions in alleviating the enzyme inhibition was in the order of Na+ > Cs+ > K+ > Li+.

Animals↗
PubMed1994

In vivo effects of isatin on certain enzymes, lipids & serotonergic system of rat brain.

Isatin (10 microM) strongly inhibited the activity of rat brain monoamine oxidase-B (MAO-B) in vitro. At millimolar concentrations (1-10 mM) it inhibited brain acetylcholinesterase (AChE) and sodium, potassium-adenosine triphosphatase (Na+, K(+)-ATPase) activity also. However, isatin did not affect these enzymes after both acute and chronic treatments in vivo. Administration of isatin to rats at 300 mg/kg body weight for 2 and 6 h significantly raised brain serotonin levels. Chronic treatment for 20 days resulted in enhanced brain glycolipids and plasmalogen levels. There was no change in the levels of 5-hydroxy indole acetic acid (5 HIAA), phospholipids, cholesterol and gangliosides under these conditions.

Animals↗