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Biomedical subjects

M S Ali

Publications and source records attributed to M S Ali.

At least 55 records · Page 3Linked to original sources
PubMed1999

The angiotensin II-dependent association of Jak2 and c-Src requires the N-terminus of Jak2 and the SH2 domain of c-Src.

The binding of angiotensin II (Ang II) to AT1 is known to increase the kinase activity of several nonreceptor tyrosine kinases including Jak2 and c-Src. In the present study, we demonstrate that treatment of vascular smooth muscle cells with Ang II results in a rapid and transient association of Jak2 and c-Src. This association is dependent on a catalytically active Jak2 kinase, because it is blocked both by pharmacological means and by the inability of a catalytically inactive Jak2 to associate with c-Src. c-Src bound tyrosine phosphorylated Jak2 but was unable to bind an equal amount of unphosphorylated Jak2 protein, indicating that the SH2 domain of c-Src mediates this association. In vivo studies indicated that c-Src binds the N-terminus of Jak2 as expression of a Jak2 molecule lacking the initial 240 amino acids, including 16 tyrosines, and was unable to bind c-Src. Lastly, using transiently transfected COS-7 cells, we found that Ang II treatment induced an association between c-Src and wild-type Jak2 but not between c-Src and the Jak2 molecule that lacks the initial 240 amino acids. Thus, our data suggest that in addition to increasing the kinase activities Jak2 and c-Src, treatment of cells with Ang II results in the physical association of Jak2 and c-Src; an association that is mediated by the SH2 domain of c-Src and the N-terminus of Jak2.

Angiotensin II↗
PubMed1999

Bucharioside and buchariol from Salvia bucharica.

A new monoterpene-glycoside (2-exo-beta-D-glucopyranosyl-1,8-cineol) named bucharioside from the methanol-soluble part and a new sesquiterpenoid (4,10-epoxy-6alpha-hydroxyguaiane) named buchariol from the hexane-soluble part of Salvia bucharica were obtained. Their structures were elucidated with the help of NMR spectroscopy including 1D and 2D experiments.

Cyclohexane Monoterpenes↗
PubMed1999

Simultaneous determination of metronidazole benzoate, methylparaben, and propylparaben by high-performance liquid chromatography.

The simultaneous determination of metronidazole benzoate (MB), methylparaben (MP), and propylparaben (PP) in an oral suspension formulation was developed using high-performance liquid chromatography (HPLC). The method was developed using a Novapak C18 (3.9 x 150 mm, 4 microns) column, methanol-water (50:50, v/v) as the mobile phase and an ultraviolet (UV) detector at 254 nm. The peak area response versus concentration was linear in a concentration range from 40 to 400 micrograms/ml of MB, 0.8 to 8.0 micrograms/ml of MP, and 0.2 to 2.0 micrograms of PP. The correlation coefficients were 0.9997 for MB, 0.9987 for MP, and 0.9983 for PP, with relative standard errors of 1.12%, 1.28%, and 1.67%, respectively.

Anti-Infective Agents↗
PubMed1998

Angiotensin II signal transduction pathways.

It has been 100 years since the discovery of renin by Tigerstedt and Bergman. Since that time, numerous discoveries have advanced our understanding of the renin-angiotensin system, including the observation that angiotensin II is the effector molecule of this system. A remarkable aspect of angiotensin II is the many different physiological responses this simple peptide induces in different cell types. Here, we focus on the signal transduction pathways that are activated as a consequence of angiotensin II binding to the AT1 receptor. Classical signaling pathways such as the activation of heterotrimeric G proteins by the AT1 receptor are discussed. In addition, recent work examining the role of tyrosine phosphorylation in angiotensin II-mediated signal transduction is also examined. Understanding how these distinct signaling pathways transduce signals from the cell surface will advance our understanding of how such a simple molecule elicits such a wide variety of specific cellular responses.

Amino Acid Sequence↗
PubMed1998

Janus kinase 2 (Jak2) must be catalytically active to associate with the AT1 receptor in response to angiotensin II.

Angiotensin II evokes a variety of biological responses by binding to a seven transmembrane cell surface receptor termed AT1. Ligand binding to the AT1 receptor induces the physical association and activation of the intracellular kinase Jak2. To elucidate the mechanism of this association, COS-7 cells were co-transfected with the AT1 receptor and either wild type Jak2 or a catalytically inactive Jak2. AT1 receptor-Jak2 association was assessed in vitro by a GST-AT1 receptor fusion protein binding assay and in vivo by direct co-immunoprecipitation of the receptor-Jak2 complex. Both studies showed that Jak2 must be catalytically active to form a complex with the AT1 receptor, and that complex formation is associated with Jak2 tyrosine phosphorylation. These results were confirmed using the Jak2 specific inhibitor AG-490. We also found that over-expression of wild type Jak2 in COS-7 cells leads to in vivo complex formation of spontaneously autophosphorylated Jak2 with the AT1 receptor. No such complex formation was observed with a dominant negative Jak2. Thus, the physical association of Jak2 with the AT1 receptor is regulated by an angiotensin II mediated autophosphorylation event.

Angiotensin II↗
PubMed1998

Phosphorylation of p130Cas by angiotensin II is dependent on c-Src, intracellular Ca2+, and protein kinase C.

p130Cas is a signaling molecule that was initially found to be tyrosine-phosphorylated in v-Crk and v-Src transformed cells. We characterized the regulation of p130Cas tyrosine phosphorylation in vascular smooth muscle cells by angiotensin II (Ang II). This ligand induced a transient increase in p130Cas tyrosine phosphorylation, which was sensitive to the actin polymerization inhibitor cytochalasin D and to the intracellular Ca2+ chelator BAPTA-AM but not the Ca2+ channel blocker verapamil. The Ang II-induced tyrosine phosphorylation of p130Cas was also dependent on an active Src family tyrosine kinase, since it could be blocked by the Src kinase inhibitors geldanamycin and PP1. Ang II treatment resulted in the ability of p130Cas to bind at least 11 different phosphate-containing proteins. Analysis of these proteins revealed that protein kinase Calpha and the cell adhesion signaling molecule pp120 formed temporal associations with p130Cas in response to Ang II. c-Src was found to associate with p130Cas in a manner that was independent of Ang II treatment. Inhibition of protein kinase C by either calphostin C or phorbol 12-myristate 13-acetate downregulation inhibited the Ang II-induced tyrosine phosphorylation of p130Cas. These results are the first to demonstrate that the tyrosine phosphorylation of p130Cas by Ang II is transduced by the Src, intracellular Ca2+, protein kinase C signaling pathway.

3T3 Cells↗
PubMed1998

Treatment of visceral leishmaniasis with sodium stibogluconate in Sudan: management of those who do not respond.

Almost all (98%) of 1593 visceral leishmaniasis (VL) patients treated with sodium stibogluconate (Pentostam; Wellcome) in Sudan between 1989 and 1995 and follow-up responded well to treatment. However, the other 33 patients, all of whom were seronegative for HIV, showed partial or no response. The two main causes of unresponsiveness were primary drug resistance (39.3%) and low drug dosages given at peripheral dispensaries (30.3%). All of those who had been sub-optimal doses were cured when adequate doses of the drug were given. A third cause was concurrent disease, particularly pulmonary tuberculosis (18%). With treatment of the concurrent disease, patients responded well to Pentostam. Eight patients who failed to respond to repeated courses of Pentostam did not benefit from pentamidine or sterol inhibitors. Three of these patients responded to liposomal amphotericin B, two responded to splenectomy in association with Pentostam therapy, and three died. Pentostam, given in adequate doses, still appears to be the drug of choice for the treatment of VL in the Sudan Liposomal amphotericin B is a suitable second-line drug.

Adolescent↗
PubMed1997

Dependence on the motif YIPP for the physical association of Jak2 kinase with the intracellular carboxyl tail of the angiotensin II AT1 receptor.

Angiotensin II is the effector molecule of the renin-angiotensin system. Virtually all of its biochemical actions are mediated through a single class of cell-surface receptors called AT1. These receptors contain the structural features of the seven-transmembrane, G-protein-coupled receptor superfamily. Angiotensin II, acting through the AT1 receptor, also stimulates the Jak/STAT pathway by inducing ligand-dependent Jak2 tyrosine phosphorylation and activation. Here, we show that a glutathione S-transferase fusion protein containing the carboxyl-terminal 54 amino acids of the rat AT1A receptor physically binds to Jak2 in an angiotensin II-dependent manner. Deletional analysis, using both in vitro protocols and cell transfection analysis, showed that this association is dependent on the AT1A receptor motif YIPP (amino acids 319-322). The wild-type AT1A receptor can induce Jak2 tyrosine phosphorylation. In contrast, an AT1A receptor lacking the YIPP motif is unable to induce ligand-dependent phosphorylation of Jak2. Competition experiments with synthetic peptides suggest that each of the YIPP amino acids, including tyrosine 319, is important in Jak2 binding to the AT1A receptor. The binding of the AT1A receptor to the intracellular tyrosine kinase Jak2 supports the concept that the seven-transmembrane superfamily of receptors can physically associate with enzymatically active intracellular proteins, creating a signaling complex mechanistically similar to that observed with growth factor and cytokine receptors.

Amino Acid Sequence↗
PubMed1997

Angiotensin II stimulates tyrosine phosphorylation and activation of insulin receptor substrate 1 and protein-tyrosine phosphatase 1D in vascular smooth muscle cells.

Angiotensin II (Ang II) and insulin-like growth factor I (IGF I) stimulate intracellular signaling events through binding to their respective G-protein-coupled and growth factor receptors. In rat aortic vascular smooth muscle cells, IGF I (20 ng/ml) induced a sustained (>30 min) increase in the tyrosine phosphorylation of both Src-homology 2 domain-docking insulin receptor substrate 1 (IRS-1) and Src-homology 2-binding tyrosine phosphatase 1D (PTP-1D). In addition, IGF I stimulated PTP-1D phosphatase activity. Ang II (10(-7) M) also increased the tyrosine phosphorylation of IRS-1 (4-fold), PTP-1D (5-fold), and PTP-1D activity (3-4-fold), but with a more transient time course. Ang II also induced PTP-1D.IRS-1 complex formation. These Ang II-induced events were not affected by preincubation with an anti-IGF I antibody, suggesting that Ang II's actions were not mediated via the autocrine secretion of IGF I. Anti-PTP-1D antibody electroporation attenuated Ang II-induced PTP-1D.IRS-1 complex formation and PTP-1D tyrosine phosphorylation and activation. Our findings show that the tyrosine phosphorylation of IRS-1 and PTP-1D represents a convergent intracellular signaling cascade stimulated by both growth factor (i.e. IGF I) and G-protein-coupled (i.e. AT1) receptors.

Angiotensin II↗
PubMed1997

Caesalpinia bonduc (L.) Roxb. seed oil: lipid composition assessment.

Thirty different fatty acids of various classes were extracted from the non-polar fraction of the seeds of Caesalpinia bonduc (L.) Roxb. (Caesal-piniaceae). Eight among them were found to be saturated while 22 were unsaturated acids, which included nine monoenoic, five dienoic, seven trienoic and one polyenoic acid. Unsaturated fatty acids were present in a large proportion (65.76%) than the saturated ones (34.24%). Spectroscopic methods (GLC and GC-MS) were used for their characterization and identification. Hexadecadienoic acid occurred in the highest proportion (21.17%). The single polyenoic acid (tetracosapentaenoate) was rare and present in traces (0.95%).

Journal Article↗
PubMed1996

Chemical constituents from the seeds of Pongamia pinnata (L.) Pierre.

Six compounds (two sterols, three sterol derivatives and one disaccharide) together with eight fatty acids (three saturated and five unsaturated) have been isolated from the seeds of Pongamia pinnata. Their structures were elucidated with the help of physico-chemical methods and spectroscopic techniques. The metabolities, beta-sitosteryl acetate and galactoside, stigma sterol, its galactoside and sucrose are being reported for the first time from this plant. The saturated and unsaturated fatty acids (two monoenoic, one dienoic and two trienoic) were present in exactly the same amount. Oleic acid occurred in highest amount (44.24%), stearic (29.64%) and palmitic (18.58%) acids were the next in quantity. Hiragonic and octadecatrienoic acids were present in trace amounts (0.88%).

Journal Article↗
PubMed1996

Serological diagnosis of extraintestinal Sarcocystosis.

The present study was carried out on eighty patients attending Zagazig University Hospitals. Forty cases suffered idiopathic cardiac diseases (28 with cardiomyopathy, 8 with myocarditis & 4 with valvular lesions) and forty cases suffered idiopathic rheumatic diseases (30 with musculoskeletal complaints and 10 with myositis). Sera were investigated by enzyme-linked immunosorbent assay (ELISA) and indirect fluorescent antibody technique (IFAT) using Sarcocystis fusiformis antigen in order to detect the role of Sarcocystis in initiation of these diseases. Twenty positive toxoplasmic sera and sera from twenty normal individuals were considered as control group. The sera of the investigated cases were tested against Toxoplasma gondii antigen to exclude it as one of the causative agents of these idiopathic lesions. No statistical difference was found between IFAT and ELISA in diagnosis of sarcocystosis (P < 0.05). Also, there was no cross reaction between Sarcocystis and Toxoplasma. This study showed that Sarcocystis can be considered as one of the possible causes of some idiopathic diseases.

Animals↗
PubMed1995

Arginine-239 in the beta subunit is at or near the active site of bovine pyruvate dehydrogenase.

We have modified bovine pyruvate dehydrogenase (E1), the first catalytic component of the pyruvate dehydrogenase complex, with pyreneglyoxal. Treatment of E1 with pyreneglyoxal resulted in the loss of enzyme activity. Pyruvate plus thiamin pyrophosphate (TPP) afforded approximately 80% protection against this inactivation and protected two arginine residues per mol of E1 tetramer (alpha 2 beta 2) from modification. Circular dichroism spectral analysis indicated absence of any gross structural changes in the enzyme as a result of modification. Comparison of the peptide maps, monitored at 345 nm of unprotected and pyruvate plus TPP protected E1s after V8 digestion revealed that a peptide in the protected enzyme was labeled by pyreneglyoxal to a lesser extent than its counterpart in the unprotected enzyme. Sequence analysis of the peptide demonstrated that it corresponded precisely to amino-acid residues 235 to 246 in the human E1 beta sequence, with arginine residues at positions 239 and 242. Since Arg-239 is conserved in the beta-subunit of all presently known sequences of the pyruvate dehydrogenase complex and branched-chain alpha-keto acid dehydrogenase complex, it is strongly suggested that Arg-239 in the human E1 beta sequence is at or near the active site of bovine E1.

Amino Acid Sequence↗
PubMed1995

Identification of the tryptophan residue in the thiamin pyrophosphate binding site of mammalian pyruvate dehydrogenase.

The pyruvate dehydrogenase (E1) component of the mammalian pyruvate dehydrogenase complex catalyzes the oxidative decarboxylation of pyruvate with the formation of an acetyl residue and reducing equivalents, which are transferred sequentially to the dihydrolipoyl acetyltransferase and dihydrolipoamide dehydrogenase components. To examine the role of tryptophanyl residue(s) in the active site of E1, the enzyme was modified with the tryptophan-specific reagent N-bromosuccinimide. Modification of 2 tryptophan residues/mol of bovine E1 (out of 12 in a tetramer alpha 2 beta 2) resulted in complete inactivation of the enzyme. The inactivation was prevented by preincubation with thiamin pyrophosphate (TPP), indicating that the modified tryptophan residue(s) is part of the active site of this enzyme. Fluorescence studies showed that thiamin pyrophosphate interacts with tryptophan residue(s) of E1. The magnetic circular dichroism (MCD) spectral intensity at approximately 292 nm was decreased by approximately 15% for E1 + TPP relative to the intensity for E1 alone. Because this MCD band is uniquely sensitive to and quantitative for tryptophan, the simplest interpretation is that 1 out of 6 tryptophan residues present in E1 (alpha beta dimer) interacts with TPP. The natural circular dichroism (CD) spectrum of E1 is dramatically altered upon binding TPP, with concomitant induction of optical activity at approximately 263 nm for the nonchiral TPP macrocycle. From CD studies, it is also inferred that loss of activity following N-bromosuccinimide treatment occurred without significant changes in the overall secondary structure of the protein. A single peptide was isolated by differential peptide mapping in the presence and absence of thiamin pyrophosphate following modification with N-bromosuccinimide. This peptide generated from human E1 was found to correspond to amino acid residues 116-143 in the deduced sequence of human E1 beta, suggesting that the tryptophan residue 135 in the beta subunit of human E1 functions in the active site of E1. The amino acid sequence surrounding this tryptophan residue are conserved in E1 beta from several species, suggesting that this region may constitute a structurally and/or functionally essential part of the enzyme.

Amino Acid Sequence↗
PubMed1995

Comparison of dynamic hip screw and gamma nail: a prospective, randomized, controlled trial.

We report a prospective, randomized, controlled trial, comparing the results of treatment with a dynamic hip screw (DHS) and a gamma nail in 95 consecutive patients with peri-trochanteric fractures of the femur. The DHS was used in 48 patients, the gamma nail in 47. Clinical and radiological outcomes were similar, but the gamma nail was associated with a higher incidence of complications, in particular fracture of the femur below the implant in eight cases. This is consistent with previous reports, and we do not recommend the gamma nail for the treatment of peri-trochanteric femoral fractures.

Aged↗