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Biomedical subjects

S Ali

Publications and source records attributed to S Ali.

At least 235 records · Page 13Linked to original sources
PubMed1994

Adenosine receptor-mediated bronchoconstriction and bronchial hyperresponsiveness in allergic rabbit model.

Recently, there has been an increasing interest in adenosine as a potential mediator of allergic asthma. In the present study, we have employed an allergic rabbit model of late-phase asthma to characterize the adenosine receptor subtype in the asthmatic airways. The allergic rabbit model has physiological characteristics and pharmacological sensitivity comparable to human asthma. Adenosine causes a dose-dependent bronchoconstriction in allergic, but not in normal, rabbits. This adenosine-induced bronchoconstriction is significantly inhibited by theophylline, an adenosine receptor antagonist, thus suggesting the involvement of adenosine receptor(s). 5'-(N-ethylcarboxyamido) adenosine (NECA), a nonselective agonist, 2-[p-(2-carboxyethyl)-phenethylamino]-5'-(N-ethylcarboxamido)-aden osine (CGS-21680), an A2-selective receptor agonist, and cyclopentyl adenosine (CPA), an A1-selective agonist, were used to characterize the adenosine receptor subtype in the airways of allergic rabbits, respectively. The PC50 (concentration of agonist in mg/ml required to reduce the dynamic compliance 50% from the baseline) values for adenosine, CGS-21680, NECA, and CPA were 9.25 +/- 0.86, 6.8 +/- 0.69, 3.90 +/- 0.27, and 1.45 +/- 0.26 mg/ml, respectively. Thus the potency profile for the bronchoconstrictor of adenosine in this model is a typical A1-receptor subtype (CPA > NECA > CGS-21680 > adenosine). Adenosine also induced further bronchial hyperresponsiveness (BHR) at 1 but not at 24 h following aerosol challenge.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1994

Tyrosine kinase inhibition prevents deformation-stimulated vascular smooth muscle growth.

The goal of this study was to determine the role of tyrosine phosphorylation in transducing deformation-stimulated vascular smooth muscle growth. Rat aorta-derived vascular smooth muscle cells were cultured on flexible silicone elastomer membranes and subjected to cyclic deformation (15 cycles per minute, deformed 2 seconds, relaxed 2 seconds). Deformation significantly increased proto-oncogene expression, [3H]thymidine incorporation, [3H]leucine incorporation, and cell number. Time course studies showed an 8-hour lag between initiation of cell deformation and onset of [3H]thymidine incorporation, with peak levels achieved after 18 to 24 hours. Western analysis of protein blots from deformed cells (10 minutes) demonstrated increased levels of phosphotyrosine-containing proteins having molecular weights of 110 to 130 and 70 to 80 kD. Deformation-stimulated tyrosine phosphorylation was prevented by the tyrosine kinase inhibitor Herbimycin A. Tyrosine kinase inhibition also prevented deformation-stimulated vascular smooth muscle cell growth as measured by [3H]thymidine incorporation. Cyclic deformation stimulates vascular smooth muscle proliferation through activation of tyrosine kinases. Inhibition of tyrosine phosphorylation is an effective means of preventing deformation-induced vascular smooth muscle growth in vitro.

Animals↗
PubMed1994

Dissociation of vasoconstrictor-stimulated basic fibroblast growth factor expression from hypertrophic growth in cultured vascular smooth muscle cells. Relevant roles of protein kinase C.

Thromboxane A2 (TXA2) and angiotensin II (Ang II) stimulate vascular smooth muscle hypertrophy by upregulating endogenous synthesis of basic fibroblast growth factor (bFGF). Because mitogenic phorbol esters can also stimulate bFGF formation, we investigated the role of protein kinase C (PKC) in vascular smooth muscle cell (VSMC) bFGF formation and hypertrophy. Preliminary characterization of PKC isoform expression in VSMC by use of polymerase chain reaction identified PKC alpha, delta, epsilon, and zeta. Western analysis confirmed the presence of these isoforms in cultured VSMC lines and demonstrated downregulation of PKC alpha, delta, and epsilon by phorbol 12-myristate 13-acetate (PMA) but not TXA2 or Ang II. PKC activation with 100 nmol/L PMA stimulated VSMC mitogenesis measured as incorporation of [3H]leucine and [3H]thymidine and increased cell number. Like TXA2 and Ang II, PMA increased endogenous VSMC bFGF in a time-dependent manner, whereas an inactive phorbol ester had no such effect. Addition of an antisense oligodeoxynucleotide against bFGF prevented PMA-stimulated bFGF expression and inhibited PMA-stimulated growth, suggesting that bFGF synthesis is necessary for VSMC growth stimulated by PMA. To clarify the role of PKC in vasoconstrictor-stimulated VSMC production of bFGF and hypertrophy, PKC was down-regulated by prolonged exposure to PMA or was inhibited with calphostin C or staurosporine before the addition of TXA2 or Ang II. PKC inhibition prevented TXA2-stimulated and Ang II--stimulated VSMC hypertrophy without attenuating the observed increase in bFGF expression. Furthermore, PKC inhibition with calphostin C inhibited VSMC mitogenesis stimulated by exogenous bFGF.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1994

Receptor domains involved in signal transduction of prolactin and growth hormone.

Prolactin (PRL) and growth hormone (GH) receptors are members of a superfamily that include receptors for a number of cytokines. GH and its receptor form an unusual homodimer consisting of one molecule of GH and two molecules of receptor. A similar homodimer of the PRL receptor is probably required for biological effects to be seen. Using specific assays to measure the functional activity of PRL and GH receptors, a 25 amino acid juxtamembrane region has been identified as essential but not sufficient for normal action. More detailed studies have limited the region to eight amino acids, rich in prolines, that is highly conserved in many members of the receptor superfamily. Finally, GH and PRL have been shown to induce the rapid tyrosine phosphorylation of an associated kinase, Janus kinase 2, and of the receptor itself.

Animals↗
PubMed1994

Histological changes in reptilean spinal cord transection: correlation with functional recovery.

The study of spinal cord regeneration in the phylogenetic scale is likely to help us in the understanding of the problem in the human situation. After spinal transection in lizards, histological changes in the spinal cord were studied and correlated with functional recovery. Some changes in spinal cord, suggestive of regeneration between the two stumps were observed. The recovery of function did not appear to be dependent on synaptic continuity.

Animals↗
PubMed1994

Incidence of cancer breast at Aligarh.

Breast cancer is a worldwide problem but its frequency varied from place to place. One hundred twenty-four breast cancer cases were reported during the ten years of survey at Aligarh constituting 12.4% of all malignant lesions. Peak incidence was found between the age of 41 and 50 years. More patients were from lower socio-economic group belonging to both Hindu as well as Muslim communities. Nearly 90% of cases had their menarche by the age of 14 years. Male breast cancer was 4%. Right breast was more commonly affected than that of the left. The upper and outer quadrant was involved in more than one-third cases and more than half the lesions occurred in upper half. There were 97.6% of epithelial and 2.4% of stromal tumours. Among epithelial tumours, highest incidence (72.38%) was that of invasive duct carcinoma followed by medullary, colloid and Paget's disease.

Adult↗
PubMed1994

Cloning and pharmacologic characterization of a thromboxane A2 receptor from K562 (human chronic myelogenous leukemia) cells.

Pharmacologic and molecular evidence conflicts in regard to the existence of tissue-specific subtypes of thromboxane A2 receptors (TXR). The full length TXR complementary DNA (cDNA) was cloned from a platelet-like cell line. It was expressed and its pharmacology was characterized. Northern analysis of TXR transcripts in multiple tissues showed strong hybridization to K562 chronic myelogenous leukemia messenger RNA. Therefore, a K562 cDNA library was screened and a full-length TXR cDNA (K562TXR) was isolated. K562TXR encodes a protein identical to the previously characterized placenta TXR cDNA, except for a single amino acid substitution (Glu21-->Lys). Similar to thromboxane receptors on K562 cells, K562TXR transiently expressed in HEK 293 cells (K562TXR/293) bound the thromboxane agonist 125I-labeled [1S-(1 alpha,2 beta(5Z),3 alpha-(1E,3S),4 alpha]-7-[3-(3-hydroxy-4-(p- iodophenoxy)-1-butenyl)-7-oxabicyclo-[2.2.1]heptane-2-yl]-5- heptenoic acid ([125I]BOP) with a Kd of 5.5 +/- 1.1 nM, a Bmax of 289,056 +/- 60,220 sites/cell and a Hill coefficient of -0.94 +/- 0.01 (n = 6). K562TXR/293 cells also demonstrated concentration-dependent increases in intracellular calcium in response to the thromboxane agonist (15S-hydroxy-11 alpha,9 alpha(epoxymethano)-prosta-5Z,13E-dienoic acid. In contrast to the single [125I]BOP binding site observed in K562TXR/293, [125I]BOP binding to placental membranes resulted in a Hill coefficient significantly less than unity with a statistically superior two-site model for binding [KdH 0.63 +/- 0.18 nM and KdL of 12.5 +/- 5.0 nM, with Bmaxs of 29 +/- 9 and 212 +/- 41 fmol/mg of protein, respectively (n = 7)].(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1994

Adenosine-induced bronchoconstriction and contraction of airway smooth muscle from allergic rabbits with late-phase airway obstruction: evidence for an inducible adenosine A1 receptor.

Recently, there has been an increasing interest in adenosine as a potential mediator of allergic asthma. In the present study, we used the allergic rabbit model developed in our laboratory to study the airway responses to adenosine and receptor binding in allergic lung vs. normal. Neonatal, pathogen-free rabbit litter mates were injected intraperitoneally within 24 hr of birth with ragweed pollen extract (1 mg/ml) to produce preferentially allergen-specific immunoglobulin E. Immunization produced bronchial airway hyperresponsiveness. Aerosolized adenosine (0.156-10 mg/ml) caused a dose-dependent bronchoconstriction (PC50 adenosine = 1.64 +/- 0.84 mg/ml). 9-Chloro-2-(2-furyl)[1,2,4]triazole[1,5- c]quinazolin-5-amine (CGS-15943), a nonxanthine adenosine receptor antagonist, significantly inhibited the adenosine-induced airway obstruction in term of dynamic compliance (P < .05). Adenosine also increased the lung resistance in a dose-dependent manner which was significantly inhibited by CGS-15943 (P < .05). Nonimmunized, pathogen-free, age-matched rabbits (control) did not respond to adenosine at these same concentrations. Adenosine also produced a concentration-dependent (10(-9)-10(-4) M) contraction of isolated tracheal and bronchial airway rings in vitro from allergic rabbits but had no detectable effect on normal rabbit airway smooth muscle. Peripheral airway smooth muscles (secondary and tertiary) were more responsive to adenosine than central (tracheal) airways. The contraction produced by 10(-4) M adenosine in primary, secondary and tertiary airways was 90, 135 and 265% of the contraction produced by 50 mM KCl, respectively. CGS-15943 (10(-7) M) significantly inhibited the adenosine-induced contraction (P < .05) shifting the dose-response curve to the right.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1993

Acyl structure regulates galactosylceramide's interfacial interactions.

Galactosylceramides (GalCer) with homogeneous acyl chains containing zero, one, or two cis double bonds have been synthesized and characterized at an argon-aqueous buffer interface using a Langmuir film balance. Both surface pressure and surface potential were measured as a function of molecular area at 24 degrees C. N-Lignoceroylgalactosylsphingosine (N-24:0-GalSph), N-stearoylgalactosylsphingosine (N-18:0-GalSph), and N-palmitoylgalactosylsphingosine (N-16:0-GalSph) form condensed films that are similar to that of bovine brain GalCer, which contains long saturated and mono-unsaturated acyl chains, almost half being hydroxylated. In contrast, a bovine brain GalCer subfraction (NFA-GalCer) that is devoid of the hydroxylated acyl chains displays an apparent two-dimensional phase transition near 9.0 mN/m at 54 A2/molecule. To determine the role of acyl unsaturation in regulating NFA-GalCer's surface behavior, GalCer derivatives containing different mono-unsaturated acyl residues were investigated. N-Nervonoyl-galactosylsphingosine (N-24:1 delta 15-GalSph) and N-docosenoylgalactosylsphingosine (N-22:1 delta 13-GalSph) show liquid-expanded to -condensed phase transitions in their force-area isotherms at 10 and 35 mN/m, respectively. Introduction of acyl chains that are short and saturated [e.g., N-decanoylgalactosylsphingosine (N-10:0-GalSph)] or that are long but contain two cis double bonds [e.g., N-linoleoylgalactosylsphingosine (N-18:2 delta 9,12-GalSph)] causes GalCer to display only liquid-expanded behavior at 24 degrees C. The surface potentials (delta V) of the condensed GalCer derivatives with long saturated acyl residues were quite similar and were over 100 mV higher than that of bovine brain GalCer.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Thromboxane A2 stimulates vascular smooth muscle hypertrophy by up-regulating the synthesis and release of endogenous basic fibroblast growth factor.

We have shown previously that thromboxane A2 stimulates hypertrophy of cultured rat aortic smooth muscle cells defined as protooncogene expression and protein synthesis without DNA synthesis or cellular proliferation (Dorn, G.W., II, Becker, M.W., Davis, M.G. (1992) J. Biol. Chem. 267, 24897-24905). Since endogenous growth modulators could possibly regulate vascular smooth muscle growth to this vasoconstrictor, we tested the hypothesis that thromboxane-stimulated vascular smooth muscle hypertrophy was due to increased expression of endogenously produced basic fibroblast growth factor (bFGF). The thromboxane mimetic (15S)-hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5Z,13E-dienoic acid (U46619) (1 microM) increased cultured rat aorta derived smooth muscle cell immunoreactive bFGF content by 331 +/- 40% over untreated controls after 24 h. Co-incubation of vascular smooth muscle cells with a specific antisense oligodeoxynucleotide (AS) against codon 60 of bFGF coding sequence reduced thromboxane-stimulated bFGF expression by 72 +/- 5% and prevented thromboxane-stimulated hypertrophy (nonsense oligonucleotide had no effects). Addition of exogenous bFGF (20 ng/ml) restored growth to AS-treated/thromboxane-stimulated vascular smooth muscle cells. Furthermore, addition to the culture medium of neutralizing antibody against bFGF inhibited U46619-stimulated vascular smooth muscle hypertrophy by 69 +/- 17%, whereas nonimmune IgG had no effect. Since protein tyrosine phosphorylation is a cell signal associated with growth, thromboxane-stimulated tyrosine phosphorylation was also examined. Exposure to 1 microM U46619 for 10 min increased vascular smooth muscle immunoreactive phosphotyrosine content of 130-144-, 86-, 80-, 75-, and 58-kDa proteins. The tyrosine kinase inhibitor herbimycin A (5 microM) prevented thromboxane-stimulated tyrosine phosphorylation, but not thromboxane-stimulated hypertrophy, suggesting that tyrosine phosphorylation was not required for thromboxane-stimulated vascular smooth muscle growth. These results indicate that increased expression and release of endogenous bFGF, but not direct tyrosine phosphorylation, mediates the hypertrophic vascular smooth muscle response to thromboxane.

Animals↗
PubMed1993

Hydrolysis of short acyl chain inositol lipids by phospholipase C-delta 1.

We investigated the relationship between substrate aggregation and activation of phosphoinositide-specific phospholipase C-delta 1 (PLC-delta 1), isolated from bovine brain cytosol. The inositol lipids 1,2-dibutyryl-sn-glycero-3-phosphoinositol (di-C4-PI), 1,2-dihexanoyl-sn-glycero-3-phosphoinositol (di-C6-PI), and 1,2-dioctanoyl-sn-glycero-3-phosphoinositol (di-C8-PI) were prepared from synthetic cytidine diphosphate diglyceride analogs in a reaction with myo-inositol catalyzed by yeast phosphatidylinositol synthase. All three lipids served as substrates for PLC-delta 1 at concentrations significantly below their critical micelle concentration (cmc). Under these conditions, steps that might limit the reaction rate, such as membrane adsorption or penetration into the phospholipid surface, were eliminated. Below the cmc, the concentration of lipid substrate required to produce hydrolysis followed the order: di-C8-PI < di-C6-PI << di-C4-PI. Calcium was essential for hydrolysis of the short chain substrates at all lipid concentrations tested. The dependence of the reaction on calcium suggests that this ion activates PLC-delta 1 at a step other than adsorption to or penetration of the membrane surface. As the concentration of di-C8-PI was raised above the cmc, the reaction velocity increased 2-3-fold. These results are consistent with the idea that micellar or bilayer aggregates of phosphoinositol are not required for PLC-catalyzed hydrolysis, although the reaction rate is enhanced by micelle formation.

Animals↗
PubMed1993

Different TBP-associated factors are required for mediating the stimulation of transcription in vitro by the acidic transactivator GAL-VP16 and the two nonacidic activation functions of the estrogen receptor.

The estrogen receptor (ER) contains two nonacidic transcriptional activation functions, AF-1 and AF-2 (formerly TAF-1 and TAF-2). In this study we show that AF-1 and AF-2 are able to stimulate transcription in vitro in a HeLa cell system when fused to the DNA binding domain of the yeast activator GAL4. We also demonstrate that a factor(s) required for the function of the ER AFs is chromatographically separable from a factor(s) necessary for the activity of the acidic activation domain of VP16. Moreover, immunoprecipitation experiments using a monoclonal antibody directed against the TATA box binding protein (TBP) indicate, that these different factors are associated with TBP in distinct TFIID complexes.

Amino Acid Sequence↗
PubMed1993

Modulation of transcriptional activation by ligand-dependent phosphorylation of the human oestrogen receptor A/B region.

Using a transient co-transfection system, we show that the human oestrogen receptor (hER) becomes phosphorylated in the presence of oestradiol (E2) as well as in the presence of the anti-oestrogens 4-hydroxy-tamoxifen (OHT) and ICI 164, 384 (ICI), although at lower efficiencies than with E2. There are multiple sites of phosphorylation in hER; using deletion and point mutants one of these sites has been mapped in the N-terminal A/B region at serine 118. Mutation of this serine to alanine caused, in a number of cell types, a significant reduction in transcriptional activation by hER from reporter genes containing an oestrogen response element (ERE), but did not affect the DNA binding properties or nuclear localization of hER. Thus phosphorylation of serine 118 is important for the action of the transcription activation function 1 (AF-1) located in the A/B region of the oestrogen receptor.

Amino Acid Sequence↗
PubMed1993

Protein characterization of Babesia equi piroplasms isolated from infected horse erythrocytes.

Proteins of Babesia equi piroplasms were characterized. The piroplasms of B. equi were purified by lysis of infected horse erythrocytes with N2 gas cavitation followed by separation in Percoll density-gradient centrifugation. The relative molecular weights (Mr) of major proteins separated by two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis were 18, 28, 30, 41, 43, 54, 66.5, and 96 kDa. Immunoblot analysis using serum from an experimentally infected horse revealed six immunodominant proteins of 15, 18, 28, 30, 41, and 96 kDa. Two immunodominant proteins of 18 and 28 kDa were membrane-bound proteins as revealed by Triton X-114 phase partitioning.

Animals↗
PubMed1993

The effects of bilirubin on the thermal properties of phosphatidylcholine bilayers.

The thermotropic properties of multilamellar vesicles of dimyristoylphosphatidylcholine (DMPC), dipalmitoylphosphatidylcholine (DPPC), and distearoylphosphatidylcholine (DSPC), as a function of the concentration of bilirubin in the range of 0.1 to 1 mol%, were measured. The exact effects of bilirubin depended on the chain length of the polymethylene chains. But the general effects of bilirubin were the same in all systems. At the lowest concentrations tested (0.1 mol bilirubin/100 mol phospholipid (0.1 mol%)), bilirubin broadened and shifted to higher temperatures the main phase transitions of all bilayers. For DPPC and DSPC, but not DMPC, this concentration of bilirubin was associated with a new transition at 25 degrees C (DPPC) or 34 degrees C (DSPC). Bilirubin at 0.2 mol% was required for the detection of a similar transition (at 13.7 degrees C) in DMPC. Higher concentrations of bilirubin (> 0.2 mol%) suppressed completely the main phase transitions in all bilayers but increased the enthalpy of the new transition. Maximal values of delta H for these transitions were reached at 0.5, 0.25, and 0.2 mol% bilirubin in DMPC, DPPC, and DSPC, respectively. Values of delta H and delta S for these transitions were far larger than for the corresponding gel-to-liquid crystal transitions in pure lipid bilayers but were equal to those expected for a transition between crystalline and liquid crystalline phases.

Bilirubin↗
PubMed1993

Manipulation of the repertoire of digestive enzymes secreted into the gastrointestinal tract of transgenic mice.

In non-ruminant livestock the energy which can be derived from dietary cellulose and xylan is limited by the inefficient microbial fermentation of these polymers in the hind-gut. Furthermore, in poultry, cereal-derived plant structural polysaccharides impair normal digestive function through the formation of gel-like structures, which trap nutrients rendering them unavailable to the animal. The nutrition of non-ruminant livestock could be significantly improved by the depolymerization of plant structural polysaccharides, through the introduction of cellulase activity into the small intestines of these animals. Here we describe the expression of Clostridium thermocellum endoglucanase E in the exocrine pancreas of transgenic mice. A non-glycosylated active enzyme is secreted into the small intestines, and is resistant to proteolytic inactivation, demonstrating the feasibility of generating non-ruminant animals with the endogenous capacity to depolymerize plant structural polysaccharides in the small intestines.

Animals↗