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Biomedical subjects

S Ahmad

Publications and source records attributed to S Ahmad.

At least 163 records · Page 9Linked to original sources
PubMed1998

Bronchopulmonary infection due to Moraxella (Branhamella) catarrhalis at a specialist hospital in Saudi Arabia.

Moraxella (Branhamella) catarrhalis is now considered as one of the most important causative organisms responsible for respiratory tract infection. Specimens of tracheal aspirates from inpatients at King Fahd specialist hospital, Buraidah, Saudi Arabia were collected over a period of 18 months to determine prospectively the frequency of Moraxella catarrhalis and its antimicrobial susceptibility. Moraxella catarrhalis was isolated in pure culture from 3.8% of the tracheal aspirates collected from patients with symptoms of acute respiratory tract infections. It was the third most important pathogen after Haemophilus influenzae and Streptococcus pneumoniae; 76% of the patients had an underlying chronic obstructive pulmonary disease (COPD). The significance of the findings is discussed.

Adolescent↗
PubMed1998

Role of iron and copper during benzene toxicity.

Role of transition metal ions in expression of benzene toxicity has been suggested. Intraperitoneal administration of benzene to female albino rats daily for 10 days resulted in accumulation of iron in liver nuclei, without any change in copper content. Incubation of hydroquinone (HQ), one of the principal metabolites of benzene with rat liver nuclei resulted in formation of thiobarbituric acid reactive products (TBAR). However, presence of bathocuproine, a copper chelator and EDTA, an iron chelator caused significant inhibition of TBAR release. Thus, the present study revealed that iron accumulation and involvement of copper in nuclear damage induced by HQ.

Animals↗
PubMed1998

Visceral leishmaniasis in District Dir, NWFP.

Visceral leishmaniasis is endemic in District Dir, NWFP. We evaluated 10 patients with visceral leishmaniasis at DHQ Hospital Timergara District Dir, N.W.F.P. All patients were in the age range 2 to 10 years. The predominant clinical features in these were chronic fever (10), splenomegaly (10), hepatomegaly (10), weight loss (10) and abdominal distention (5). Lymphadenopathy was absent. Common laboratory abnormalities included anaemia (10), leucopenia (7), thrombocytopenia (10) and hypergammaglobulinaemia (10). Formal Gel test was positive in all patients (100%) and all had positive bone marrow smears for Leishmania Donovani (L.D.) bodies (10). The response to stibogluconate (Glucantime Sodium) therapy was good with a 100 percent cure rate.

Abdomen↗
PubMed1997

The type I interferon receptor mediates tyrosine phosphorylation of the CrkL adaptor protein.

Interferon (IFN) alpha induces rapid and transient tyrosine phosphorylation of the Src homology 2/Src homology 3 (SH2/SH3)-containing CrkL adaptor protein in a time- and dose-dependent manner. Such phosphorylation is most likely regulated by the Type I interferon receptor (IFNR)-associated Tyk-2 kinase, as suggested by the detection of Type I IFN-dependent tyrosine kinase activity in anti-CrkL immunoprecipitates and the IFNalpha-dependent association of CrkL with Tyk-2 in intact cells. Two other Type I IFNs, IFNbeta and IFNomega, also induce tyrosine phosphorylation of CrkL, suggesting that the protein is involved in the signaling pathways of several different Type I IFNs. In the IFNalpha-sensitive U-266 and Daudi cell lines, CrkL interacts via its N terminus SH3 domain with the guanine exchange factor C3G that regulates activation of Rap-1, a small G-protein that exhibits tumor suppressor activity. Thus, tyrosine phosphorylation of CrkL links the functional Type I IFNR complex to the C3G-Rap-1 signaling cascade that mediates growth inhibitory responses.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Modulation of transcription factor Sp1 by cAMP-dependent protein kinase.

Transcription factor Sp1 is a phosphoprotein whose level and DNA binding activity are markedly increased in doxorubicin-resistant HL-60 (HL-60/AR) leukemia cells. The trans-activating and DNA binding properties of Sp1 in HL-60/AR cells are stimulated by cAMP-dependent protein kinase (PKA) and PKA agonists and inhibited by PKA antagonists as well as by the PKA regulatory subunit. Reporter gene activity under the control of the Sp1-dependent SV40 promoter is stimulated in insect cells transiently expressing Sp1 and PKA, and the DNA binding activity of recombinant Sp1 is activated by exogenous PKA in vitro. These results indicate that Sp1 is a cAMP-responsive transcription factor and that Sp1-dependent genes may be modulated through a cAMP-dependent signaling pathway.

Cyclic AMP↗
PubMed1997

Angiotensin receptor antagonists delay nitric oxide-deficient stroke in stroke-prone rats.

We investigated whether chronic deficiency of nitric oxide (NO) in stroke-prone spontaneously hypertensive rats (SHRSP) precipitates stroke and whether exogenous nitrates and other pharmacological agents can prevent stroke. Groups of five-week-old male SHRSP rats chronically received saline, L-nitro-arginine methyl ester (L-NAME) in saline, L-NAME along with pharmacological agents (L-arginine, isosorbide dinitrate, enalapril maleate and L-158,809; angiotensin receptor antagonist; 5,7-dimethyl-2-ethyl-3(-)[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]meth yl]-imidazo[4,5-b]pyridine) in saline to drink. The development of visible neurological deficits following various treatments was considered as an occurrence of stroke. Within hours following onset of stroke, the rats were anesthetized, catheterized and attached to a Cardiomax blood pressure recorder. SHRSP treated with L-NAME (10+/-2 mg/day) developed stroke in 11+/-2 days while no neurological deficit was seen in animals receiving saline till the end of the study period (35 days). Blockade of the renin-angiotensin system with enalapril or L-158,809 significantly delayed the onset of stroke (19+/-2 and 20+/-2 days, respectively), but caused only slight reductions in mean arterial blood pressure. These results suggest that chronic inhibition of NO synthase in SHRSP is associated with the development of stroke and such stroke appears to be renin-angiotensin system-dependent.

Adaptation, Physiological↗
PubMed1997

Signal transduction pathways involved in the mitogenic activity of pleiotrophin. Implication of mitogen-activated protein kinase and phosphoinositide 3-kinase pathways.

Pleiotrophin (PTN) is a developmentally regulated protein which exhibits neurite-outgrowth, mitogenic, and angiogenic properties. It has also been shown to be involved in tumor growth and metastasis. Here we used primary BEL (bovine epithelial lens) cells to investigate the signal transduction pathways involved in the mitogenic activity of recombinant PTN. PTN was purified from conditioned media of SW-13 cells transfected with the human PTN cDNA. We show that inhibitors of tyrosine kinase, mitogen-activated protein kinase, or phosphoinositide (PI) 3-kinase inhibit DNA synthesis stimulated by PTN. Analysis of tyrosine-phosphorylated proteins following PTN stimulation showed phosphorylation of two novel 190- and 215-kDa proteins in addition to SHC, ERK1, and ERK2. A mobility shift of phosphorylated ERK1 and ERK2 was detected with a panERK antibody confirming the phosphorylation of the two ERKs. Furthermore, in vitro immunocomplex kinase assay with Akt1, a natural substrate of PI 3-kinase, showed an activation of the kinase following PTN stimulation and a reversal by the PI 3-kinase inhibitor wortmannin. We conclude that the mitogenic activity of PTN is dependent on tyrosine kinase activation and utilizes the mitogen-activated protein kinase and the PI 3-kinase pathways to transduce a mitogenic signal.

Animals↗
PubMed1997

Phage display of Bacillus thuringiensis CryIA(a) insecticidal toxin.

The display of proteins or peptides on the surface of filamentous phages or phagemids has been shown to be a very powerful technology for the rescue of specific binders from large combinatorial libraries, as well as to select derivatives of known proteins with altered binding properties. The Bacillus thuringiensis (Bt) crystal proteins are a large family of insecticidal toxins which bind to receptors found on the brush border of larval midgut cells, different crystal toxins having different larval specificities. Here we describe the display of different CryIA(a) toxin regions on the surface of phagemids using the display vector pHEN1, the purpose being the identification of toxin sequences suitable for mutagenesis and selection using phage display. We show that CryIA(a) domain II, in which the receptor binding activity is located, is efficiently displayed as well as being secreted as soluble protein into the periplasm of bacterial cell. This forms the basis of a simple means for the modification of toxin specificity and the selection of toxin proteins with novel or expanded host ranges.

Bacillus thuringiensis↗
PubMed1997

Reduction of peridural fibrosis after lumbar laminotomy and discectomy in dogs by a resorbable gel (ADCON-L).

STUDY DESIGN: A canine lumbar laminotomy and discectomy model was used to evaluate the effects of a resorbable gel, ADCON-L (Gliatech Inc., Cleveland, OH), in reducing peridural scar formation and to assess the healing progress of immediately adjacent normal structures. OBJECTIVES: To compare peridural scar formation and anulus fibrosis healing with and without the use of ADCON-L in an animal model that closely replicates the common human surgical procedure. SUMMARY OF BACKGROUND DATA: ADCON-L has been shown to reduce the development of peridural scars in rat, rabbit, and canine laminectomy models in previous investigations; discectomies were not performed in these previous studies, however, and thus anular healing could not be assessed. METHODS: Seven adult mongrel dogs underwent a three-level unilateral lumbar hemilaminotomy and anular fenestration. In each dog, the ADCON-L was applied to two randomly assigned sites around the discectomy, the nerve roots, and the hemilaminotomy. The third site underwent surgery, but was left untreated (sham surgery only). The canines were killed 8 weeks after surgery, and a gross anatomic assessment of scar formation was done using microdissection by an observer blinded to treatment. A numerical rating system was developed to assess the relative amount and tenacity of the anterior scarring (discectomy site) and posterior scarring (hemilaminotomy site). The healing of the anular defect was assessed histologically. RESULTS: ADCON-L significantly reduced peridural fibrosis in this lumbar discectomy model compared with the sham treated sites (p < 0.05). Further, the superficial layers, the posterior longitudinal ligament, and the anulus fibrosus healed well in the ADCON-L treated sites. CONCLUSIONS: ADCON-L reduced local peridural fibrosis after lumbar laminotomy and discectomy without impacting the healing of the surrounding tissues.

Animals↗
PubMed1997

Modeling, chemistry, and biology of the benzolactam analogues of indolactam V (ILV). 2. Identification of the binding site of the benzolactams in the CRD2 activator-binding domain of PKCdelta and discovery of an ILV analogue of improved isozyme selectivity.

Protein kinase C (PKC) is a complex enzyme system comprised of at least 11 isozymes that serves to mediate numerous extracellular signals which generate lipid second messengers. The discovery of isozyme-selective activators and inhibitors (modulators) of PKC is crucial to ascertaining the role of the individual isozymes in physiological and pathophysiological processes and to manipulating their function. The discovery of such small molecule modulators of PKC is at present a largely unmet pharmacological need. Herein we detail our modeling studies which reveal how the natural product indolactam V (ILV) and its 8-membered ring analogue, the benzolactam 15, bind to the CRD2 activator domain of PKC. These modeling studies reveal that not all PKC ligands possess a common pharmacophore, and further suggest an important role of specific hydrophobic contacts in the PKC-ligand interaction. The modeling studies find strong experimental support from mutagenesis studies on PKC alpha that reveal the crucial role played by the residues proline 11, leucine 20, leucine 24, and glycine 27. Next, we describe the synthesis of two 8-substituted benzolactams starting from L-phenylalanine and characterize their isozyme selectivity; one of the two benzolactams exhibits improved isozyme selectivity relative to the n-octyl-ILV. Lastly, we report inhibition of cellular proliferation of two different breast carcinoma cell lines by the benzolactam 5 and show that the compound preferentially down-regulates PKCbeta in both cell lines.

Antineoplastic Agents↗
PubMed1997

Protein-tyrosine phosphatase SHP2 is positively linked to proteinase-activated receptor 2-mediated mitogenic pathway.

Proteinase-activated receptor-2 (PAR2), a new member of family of the G protein-coupled receptors, is activated by proteolytic cleavage of its extracellular amino terminus, a mechanism similar to that used by the thrombin receptor. It has been suggested that PAR2 has a potential role in the late phases of the acute inflammatory response and in tissue repair and/or skin-related disorders. Here we demonstrate that the agonist peptide (SLIGRL) stimulated c-fos-mediated mitogenic activation and tyrosine phosphorylation of cellular proteins. One of the tyrosine-phosphorylated proteins was identified as an Src homology-2 domain-containing protein-tyrosine phosphatase, SHP2. The stimulatory effect of the agonist peptide on early gene transcription was markedly blocked by pertussis toxin treatment whereas the induced tyrosine phosphorylation of SHP2 was completely abolished by the drug. More importantly, while expression of wild-type SHP2 enhanced the agonist-stimulatory mitogenic activity, overexpression of a catalytically inactive mutant of SHP2 strongly suppressed the stimulatory effect of the agonist peptide on both early gene transcription and DNA synthesis. These results suggest that SHP2 acts as a positive regulator linked to the PAR2-mediated mitogenic pathway coupled to a pertussis toxin-sensitive heterotrimeric G protein. Demonstration of SHP2 as a positive mediator in a G protein-coupled, receptor-mediated signaling adds to our understanding of the function of both SHP2 and PAR2 in the signaling pathway.

Animals↗
PubMed1997

Transforming growth factor-beta negatively modulates T-cell responses in sepsis.

Sepsis is associated with depressed T-cell functions and increased circulating levels of immunosuppressive agents. TGF-beta is a potential anti-inflammatory cytokine that can modify T-cell growth and differentiation. The up-regulation of TGF-beta and the mechanism of its action on the T-cells during septic injury have not been resolved. We hypothesized that in sepsis TGF-beta produced by macrophages acts on T-cells in a paracrine manner to suppress interleukin (IL)-2 production and proliferation. In this study, we examined the circulating TGF-beta levels in a rat model of Gram-negative bacterial sepsis, and compared the abilities of adherent and non-adherent splenocytes to produce TGF-beta. Additionally, we investigated the causal relationships of hrTGF-beta to concanavalin A (ConA)-induced T-cell responses and the intracellular mechanism of the generation of these responses in normal splenic rat T-cells. Sepsis was induced in rats by intraabdominally implanting fecal pellets containing Escherichia coli (150 CFU) and Bacteroides fragilis (10000 CFU). Adherent and non-adherent splenocytes were isolated by differential adherence using Ficoll gradient centrifugation. T-cells were purified by use of Nylon wool columns. We observed a 3-6-fold increase in the circulating levels of TGF-beta in sepsis. Western blots and ELISA determinations revealed a 2.5-3-fold increase in cell-associated TGF-beta protein levels in adherent splenic cells. Northern analyses also showed a marked increase in TGF-beta mRNA expression in adherent cells during sepsis. On the other hand, a significant change was not observed in the TGF-beta protein and mRNA expression in non-adherent splenocytes. Pretreatment of control rat T-cells with hrTGF-beta decreased both ConA-induced proliferation (by 35-40%) and IL-2 mRNA expression (by > 50%). Further, whereas incubation of control rat T-cells with either ConA or TGF-beta for 24 h resulted in a 10-15-fold increase in cAMP generation, the addition of hrTGF-beta along with ConA resulted in a 50-60-fold increase in cAMP. These results suggest that in sepsis, TGF-beta produced by splenic macrophages can act in a paracrine manner on T-cells to depress their IL-2 mRNA expression, IL-2 production and proliferation after up-regulation of cAMP which can interfere with T-cell signaling for proliferation.

Animals↗
PubMed1997

Relation Between Age and Heavy Metal Content in the Otoliths ofPomadasys stridens Forskal 1775 Collected from the Arabian Gulf

A total of 216 otolith samples (89 male, 127 female) fromPomadasys stridens (Forskal 1775), a common fish of the ArabianGulf, were analyzed for the concentrations of heavy metals. Standard length,age, sex, body, and otolith weight were recorded for each fish. Otolithweight from male fish was found in the range of 0.047-0.143 g with a meanvalue 0.101 +/- 0.023 g, whereas, mean otolith weight from female fishsamples was 0.111 +/- 0.019 in the range of 0.062-0.151 g. Averageconcentration of zinc, copper, manganese, nickel, cadmium and lead was found0.965, 0.229, 0.195, 0.122, 0.100, and 0.119 μg per otolith in case of malefish and in females it was 1.371, 0.241, 0.297, 0.133, 0.089, and 0.123 μgper otolith, respectively. At the age of two to three years, concentrationsof all the analyzed elements, except for Cd, were found higher in otoliths offemale fish samples, but at the age of four years this difference becomesminimum and mostly opposite, i.e., otoliths of male fish have littlehigher concentrations as compared to otoliths from females. The concentrationvariation of different elements was different in males and in females, butwas not statistically significant. The otolith weight at the age two yearswas significantly different with other age group samples and among bothsexes.

Journal Article↗
PubMed1997

5 alpha reductase activity in human gingiva and gingival fibroblasts in response to bacterial culture supernatants, using [14C]4-androstenedione as substrate.

5 alpha-Reduction of androgen substrates is increased in inflamed gingiva. It was therefore relevant to study the effect of bacterial culture supernatants derived from Prevotella intermedius (P.i), Porphyromonas gingivalis (P.g) and Actinobacillus actinomycetemcomitans (A.a) on the metabolism of [14C]4-androstenedione to 5 alpha-dihydrotestosterone (DHT) in gingival tissue and cultured fibroblasts. Chronically inflamed human gingival tissue and cultured gingival fibroblasts from the same source were incubated in duplicate with [14C]4-androstenedione and optimal concentrations of P.i, P.g. and A.a culture supernatants in Eagle's minimal essential medium in a CO2 incubator for 24 h at 37 degrees C. The metabolites were then extracted, separated and quantified using a radioisotope scanner. There were 87, 50 and 6% increases in DHT synthesis by human gingival tissue in response to the culture supernatants of P.i, P.g and A.a, respectively, over control incubations (n = 3; p < 0.01: Wilcoxon signed-ranked statistic for paired observations). With the cells in culture, all four fibroblast cell lines produced DHT and testosterone from [14C]4-androstenedione in varying amounts. The production of DHT was enhanced in the presence of each the bacterial culture supernatants to varying degrees (P.i 40%, P.g 35% and A.a 40%; p < 0.01). Combinations of the bacterial extracts: (P.i + P.g), (P.i + A.a), (P.g + A.a) and (P.i + P.g + A.a) showed intermediate or suppressor effects on DHT formed compared with individual incubations. Culture supernatants of these pathogens can influence DHT synthesis in fibroblasts, and effect that is modulated by baseline androgen metabolism and the proportion of virulent pathogens present. This may have some bearing on host susceptibility on host and the progression of the periodontal lesion.

Adult↗
PubMed1997

Increased mediastinal pressure and decreased cardiac output during laparoscopic Nissen fundoplication.

BACKGROUND: Laparoscopic Nissen fundoplication (LNF) is gaining popularity. Although the hemodynamic effects of the typical pneumoperitoneum have been studied, the additional consequences of the hiatal dissection necessary for LNF have not. METHODS: Seven female pigs were anesthetized, intubated, and ventilated with a volume ventilator and hemodynamic and mechanical pressure monitoring devices were placed. Pressures were recorded every 15 minutes for 1 hour after each of four interventions: (1) anesthesia induction, (2) CO2 pneumoperitoneum (15 mm Hg), (3) LNF, and (4) release of pneumoperitoneum (and removal of ports). RESULTS: Right atrial, inferior vena caval, mediastinal, pleural, airway, and pulmonary capillary wedge pressures all increased after pneumoperitoneum (p < 0.05). Only mediastinal pressure (8.6 vs 13.7 mm Hg, pneumoperitoneum vs LNF; p < 0.05) and pleural pressure (2.6 vs 3.5 mm Hg, pneumoperitoneum vs LNF; p < 0.05) showed a further significant increase after LNF. In addition, cardiac output fell significantly after LNF (5.9 vs. 4.6 L/min; p < 0.05). Mediastinal pressure and cardiac output remained significantly altered after the release of pneumoperitoneum. CONCLUSIONS: Surgical disruption of the esophageal hiatus during LNF causes both increased mediastinal and pleural pressure and a significant reduction in cardiac output. These findings uncover a previously unsuspected physiologic detriment that may occur during LNF.

Anesthesia, General↗
PubMed1997

Cloning and in situ hybridization analysis of the expression of polysialyltransferase mRNA in the developing and adult rat brain.

Polysialyltransferase (PST) is an enzyme that catalyzes the addition of polysialic acid (PSA), a homopolymer of alpha-2,8-linked sialic acid residues, onto neural cell adhesion molecule (NCAM). The expression of PSA-NCAM in the brain is developmentally regulated and is of critical importance; however, the temporal and spatial developmental expression of brain PST, a potential key player in the control of PSA-NCAM levels, remains unclear. In the present study, we have cloned the coding region of rat PST cDNA by reverse transcription-polymerase chain reaction, using primers based on the hamster PST-1 cDNA sequence. A 39-mer oligonucleotide complementary to rat PST cDNA was synthesized to investigate the distribution of its mRNA in the developing and adult rat brain by Northern blot and in situ hybridization. In the embryonic rat brain, PST mRNA was detected abundantly throughout the neuroepithelia of most brain regions. At post-natal days 1 and 14, PST was detected throughout the neocortex, in the pyramidal cells (PC) of the hippocampus proper, the granule cell layer (GCL) of the dentate gyrus, the anterior ventral nucleus of the thalamus (AVNT) and the GCL and external germinal layer of the cerebellum. Finally, from PD21 until adulthood, expression of PST mRNA was restricted to the PC layer of the hippocampus proper, the GCL of the dentate gyrus, the AVNT, the GCL of the cerebellum and the dorsal and lateral nucleus of the anterior olfactory bulb. The developmental profile of PST mRNA is paralleled in some structures by that of the PSA-NCAM, there are, however, notable exceptions. Therefore, our results demonstrate that expression of rat PST mRNA is developmentally regulated, is present in the adult rat brain in restricted areas and may be involved in regulating temporal and spatial expression of PSA-NCAM.

Aging↗
PubMed1997

Expression of gamma interferon by simian immunodeficiency virus increases attenuation and reduces postchallenge virus load in vaccinated rhesus macaques.

Simian immunodeficiency virus (SIV) infection of macaques is a model for human immunodeficiency virus (HIV) infection. We have previously reported the construction and characterization of an SIV vector with a deletion in the nef gene (SIV(delta nef)) and expressing gamma interferon (SIV(HyIFN)) (L. Giavedoni and T. Yilma, J. Virol. 70:2247-2251, 1996). We now show that rhesus macaques vaccinated with SIV(HyIFN) have a lower viral load than a group similarly immunized with SIV(delta nef). Viral loads remained low in the SIV(HyIFN)-vaccinated group even though SIV expressing gamma interferon could not be isolated after 6 weeks postimmunization in these animals. All immunized and two naive control macaques became infected when challenged with virulent SIV(mac251), at 25 weeks postvaccination. In contrast to the two naive controls that died by 12 and 18 weeks postchallenge, all vaccinated animals remained healthy for more than 32 weeks. In addition, postchallenge cell-associated virus load was significantly lower in SIV(HyIFN)-immunized animals than in the group vaccinated with SIV(delta nef). These findings indicate that cytokine-expressing viruses can provide a novel approach for development of safe and efficacious live attenuated vaccines for AIDS.

Animals↗