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Biomedical subjects

R Ahmad

Publications and source records attributed to R Ahmad.

At least 19 recordsLinked to original sources
PubMed2006

Inhibition of interleukin 1-induced matrix metalloproteinase 13 expression in human chondrocytes by interferon gamma.

BACKGROUND: Despite well-documented immunomodulation by interferon gamma (IFNgamma), its role and mechanism of regulation of matrix metalloproteinase 13 (MMP13) gene expression in human chondrocytes is unknown. OBJECTIVE: To investigate the ability and mechanism of IFNgamma to suppress interleukin 1 (IL1)-induced MMP13 expression in articular chondrocytes. METHODS: Human chondrocytes were treated with IFNgamma or IL1beta alone or in combination. MMP13 mRNA was analysed by semiquantitative reverse transcriptase-PCR. MMP13 protein, phospho-signal transducer and activator of transcription 1 (STAT1) and p44/42 mitogen-activated protein kinase levels were measured by western blotting. MMP13 promoter luciferase, cytomegalovirus cyclic AMP response element-binding protein (CBP)/p300 plasmids and STAT1 small interfering RNA (siRNA) were transfected by the calcium phosphate method. IFNgamma receptor was also neutralised. Activator protein (AP) 1 activity was monitored by the TransAM transcription factor kit. STAT1-CBP/p300 interaction was studied by immunoprecipitation. RESULTS: IFNgamma potently suppressed IL1-induced expression of MMP13 and promoter activity. Blockade with neutralising IFNgamma R1 antibody revealed that MMP13 inhibition by IFNgamma is mediated by the IFN receptor. IFNgamma-stimulated activation of STAT1 was directly correlated with MMP13 suppression. Knockdown of the STAT1 gene by specific siRNA or its inhibition with fludarabine partially restored the IL1beta induction of MMP13 expression and promoter activity. IFNgamma did not alter AP1 binding ability but promoted physical interaction of STAT1 and CBP/p300 coactivator. p300 overexpression reversed IFNgamma inhibition of endogenous MMP13 mRNA expression and exogenous MMP13 promoter activity. CONCLUSION: IFNgamma, through its receptor, activates STAT1, which binds with CBP/p300 coactivator, sequesters it from the cell system, and thus inhibits transcriptional induction of the MMP13 gene in chondrocytes. IFNgamma and its signalling pathways could be targeted therapeutically for diminishing IL1-induced cartilage degradation by MMP13 in patients with arthritis.

Blotting, Western↗
PubMed2006

MUC1 oncoprotein is targeted to mitochondria by heregulin-induced activation of c-Src and the molecular chaperone HSP90.

The MUC1 heterodimeric transmembrane glycoprotein is aberrantly overexpressed by most human carcinomas. The MUC1 C-terminal subunit localizes to mitochondria and blocks stress-induced activation of the intrinsic apoptotic pathway. How MUC1 is delivered to mitochondria is not known. The present studies demonstrate that MUC1 forms intracellular complexes with HSP70 and HSP90. We show that the MUC1 cytoplasmic domain binds directly to HSP70 in vitro. By contrast, binding of MUC1 to HSP90 in vitro is induced by c-Src-mediated phosphorylation of the MUC1 cytoplasmic domain. c-Src also increases binding of MUC1 to HSP90 in cells. In concert with these results, we show that heregulin (HRG), a ligand for ErbB receptors, activates c-Src and, in turn, stimulates binding of MUC1 to HSP90. We also show that inhibitors of c-Src or HSP90 block HRG-induced targeting of MUC1 to mitochondria and integration of MUC1 into the mitochondrial outer membrane. These findings indicate that MUC1 is delivered to mitochondria by a mechanism involving activation of the ErbB receptor-->c-Src pathway and transport by the molecular chaperone HSP70/HSP90 complex.

Amino Acid Sequence↗
PubMed2005

A Comparative study of Fe(II) and Fe(III) interactions with DNA duplex: major and minor grooves bindings.

The involvement of the Fe cations in autoxidation in cells and tissues is well documented. DNA is a major target in such reaction, and can chelate Fe cation in many ways. The present study was designed to examine the interaction of calf-thymus DNA with Fe(II) and Fe(III), in aqueous solution at pH 6.5 with cation/DNA (P) (P = phosphate) molar ratios (r) of 1:160 to 1:2. Capillary electrophoresis and Fourier transform infrared (FTIR) difference spectroscopic methods were used to determine the cation binding site, the binding constant, helix stability and DNA conformation in Fe-DNA complexes. Structural analysis showed that at low cation concentration (r = 1/80 and 1/40), Fe(II) binds DNA through guanine N-7 and the backbone PO(2) group with specific binding constants of K(G) = 5.40 x 10(4) M(1) and K(P) = 2.40 x 10(4) M(1). At higher cation content, Fe(II) bindings to adenine N-7 and thymine O-2 are included. The Fe(III) cation shows stronger interaction with DNA bases and the backbone phosphate group. At low cation concentration (r = 1:80), Fe(III) binds mainly to the backbone phosphate group, while at higher metal ion content, cation binding to both guanine N-7 atom and the backbone phosphate group is prevailing with specific binding constants of K(G) = 1.36 x 10(5) M(-1) and K(P) = 5.50 x 10(4) M(-1). At r = 1:10, Fe(II) binding causes a minor helix destabilization, whereas Fe(III) induces DNA condensation. No major DNA conformational changes occurred upon iron complexation and DNA remains in the B-family structure.

Animals↗
PubMed2005

Bone marrow abnormalities in HIV disease.

Bone marrow abnormalities are frequently observed in HIV infected individuals at all stages of the disease. The most common abnormal finding is dysplasia affecting one or more cell lines. Erythroid dysplasia is the most common type of dysplasia and is recognized in over 50% of HIV infected patients, abnormal granulocytic and megakaryocytic development is encountered in one-third of patients. Plasma cells are strikingly increased in bone marrow of HIV infected patients. It may represent a physiological response to antigenic stimulation by viruses, other infective agents or secondary to dysregulated B-cell proliferation due to HIV. Herein we present a review discussing the various bone marrow abnormalities associated with the HIV disease.

AIDS-Related Complex↗
PubMed2004

Synthesis of alpha-mannosylated phenolics as alpha-glucosidase inhibitors.

BF3OEt2-catalysed glycosidation of phenolic compounds 3 and 6 with the mannofuranosyl glycosyl donor 2 separately gave the corresponding alpha-mannofuranosyl derivatives 4 and 7 in good yield, and the latter on selective deacetonation (hydrolysis) with 2% aqueous HCl afforded 5 and 8 respectively. Compounds 4 and 7 inhibited rat intestinal alpha-glucosidase more effectively than a standard drug acarbose.

Animals↗
PubMed2004

HIV disease presenting as parotid lymphoepithelial cysts: a presumptive diagnosis of diffuse infiltrative lymphocytic syndrome (DILS).

Diffuse infiltrative lymphocytic syndrome (DILS), is a rare manifestation of human immunodeficiency virus (HIV) disease which is characterized by a diffuse visceral CD8 lymphocytic infiltration, a persistent CD8 lymphocytosis, bilateral parotid swelling and cervical lymphadenopathy. We describe a case of a HIV positive female, who had bilateral parotid swelling and CD8 lymphocytosis, to illustrate this rare clinical entity.

Adult↗
PubMed2003

Synthesis and bioevaluation of glycosyl ureas as alpha-glucosidase inhibitors and their effect on mycobacterium.

Glycosyl amino esters (2-13) on reaction with different isocyanates resulted in quantitative conversion to glycosyl ureas (14--32). Few of the selected ureas (15-20, 22-28, 30 and 32) on cyclative amidation with DBU/TBAB/4 A MS gave respective dihydropyrimidinones in fair to good yields (33-47). The compounds were screened for alpha-glucosidase inhibitory activity and two (19 and 23) of them showed strong inhibition against rat intestinal alpha-glucosidase. The compounds were also screened against Mycobacterium aurum, however, only one (19) of them exhibited marginal antitubercular activity.

Animals↗
PubMed2003

Synthesis and antifilarial evaluation of N1,Nn- xylofuranosylated diaminoalkanes.

A series of N(1),N(n)-xylofuranosylated diaminoalkanes (3-9 and 11-18) has been synthesized either by reductive amination of deoxy xylouloses (2a, 2b) with amines followed by one pot reduction with NaBH(4) or NaCNBH(3); or by 1,4-conjugate addition of amines to glycosyl olefinic esters (10a, 10b). The compounds were screened for their interference with filarial worms' glutathione metabolism, a potential target for chemotherapeutic attack. Interestingly, these compounds affected intracellular glutathione, gamma-glutamyl cysteine synthetase, glutathione reductase and glutathione-S-transferase(s) of bovine filarial worms to varying degrees. Some of the compounds though effected the motility and MTT reduction potential of filarial worms Brugia malayi, however, little microfilaricidal and macrofilaricidal were noted with compounds at 50mg/kg oral dose. Compounds 6, 16 and 17 were evaluated also for in vivo activity.

Alkanes↗
PubMed2003

A comparative study of DNA complexation with Mg(II) and Ca(II) in aqueous solution: major and minor grooves bindings.

Although structural differences for the Mg-DNA and Ca-DNA complexes are provided in the solid state, such comparative study in aqueous solution has been less investigated. The aim of this study was to examine the bindings of Mg and Ca cations with calf thymus DNA in aqueous solution at physiological pH, using constant concentration of DNA (1.25 or 12.5 mM) and various concentrations of metal ions (2 microM-650 microM). Capillary electrophoresis, UV-visible, and Fourier transform infrared spectroscopic methods were used to determine the cation-binding modes, the binding constants, and DNA structural variations in aqueous solution. Direct Ca-PO(2) binding was evident by major spectral changes (shifting and splitting) of the backbone PO(2) asymmetric stretching at 1222 cm(-1) with K = 4.80 x 10(5) M(-1), whereas an indirect Mg-phosphate interaction occurred (due to the lack of shifting and splitting of the phosphate band at 1222 cm(-1)) with K = 5.6 x 10(4) M(-1). The metal-base bindings were directly for the Mg with K = 3.20 x 10(5) M(-1) and indirectly for the Ca cation with K = 3.0 x 10(4) M(-1). Both major and minor groove bindings were observed with no alteration of the B-DNA conformation.

Binding Sites↗
PubMed2003

Virus load correlates inversely with the expression of cytotoxic T lymphocyte activation markers in HIV-1-infected/AIDS patients showing MHC-unrestricted CTL-mediated lysis.

Cytotoxic T lymphocytes (CTL) are key players to suppress viral load (VL) but CTL responses become compromised with progression of HIV-infection/AIDS. Some progressors develop MHC-unrestricted CTL with anti-CD4+ cytocidal activity. Immune activation status of these CTL and its significance in disease progression are unknown. To determine the relationship between VL and T cell activation, a cross-sectional study was carried out using blood samples from 13 HIV-1-infected/AIDS patients at various stages of progression and seven age-matched seronegative controls. We examined expression of HLA-DR and CD38 activation markers on purified CTL. MHC-unrestricted killing by these CTL was also evaluated against uninfected, allogeneic CD4+ T cells as well as several human cell lines. The expression of activation markers correlated inversely (rs = - 0.91, P < 0.0001) with VL of the subjects. CTL effectors of these patients killed targets expressing or lacking CD4+, independently of MHC class I recognition. Interestingly, the patients with higher VL showed an increased number of gammadeltaTCR-bearing CTL in blood and their MHC-unrestricted killing activity was blocked significantly (P < 0.01) by gammadeltaTCR-specific monoclonal antibody. CD3+ T counts of these patients were also consistently subnormal. Inverse correlation between VL and CD8+ T cell activation markers seems to be an indicator of CTL-associated immunopathogenesis in HIV patients with elevated gammadeltaCTL in the peripheral blood.

Acquired Immunodeficiency Syndrome↗
PubMed2003

A clinical review of large cerebello pontile angle tumors.

The study was designed as retro-prospective and the study period was 3.5 years. A total of 66 (42 prospective and 24 retrospective) consecutive patients were included in the study. The commonest tumor in CPA is the Schwannoma (76%) followed by Meningioma (13.3%) and Epidermoid (4.44%). Unusual forms are Ependymoma and Hemangiopericytoma. Amongst the troublesome clinical features headache, hearing loss, vertigo and imbalance, vomiting and tinnitus were more important besides visual failure and features of lower cranial nerve involvement. The objective of the study is to "Review the Large Cerebello Pontile Angle tumors clinically". In this study 66 large CPA tumors were included and analyzed. Analysis of variance (ANOVA) was implied for the test of significance. On the whole, n=66 Schwannoma represents 76.70% and Meningioma 15.38%. Of these there are 45 cases with histological verification. The most common presenting (average duration is 1.3 years) symptoms were Headache (94.54%) and Hearing loss of varying grade (85.45%). Vertigo or imbalance was present in 67.27% cases. Vomiting was found in 54.54% of the times and difficulties in deglutition or voice change were complained of in 29.09% cases. Tinnitus was found only in 27.27% cases and it was the complaint mostly in lower diameter tumors. By maximum diameter, there were 24 cases measuring 3-4 cm, 15 more than 4 cm and only one case <3 cm sized tumors. Volume-wise tumors with volume <10 cc were 5 cases, 10-20 cc were 10, 20-30 cc were 13, 30-40 cc were 6 and >40 cc were 6. Similarly tumor volume and posterior fossa volume ratio was as follows: <10% were 6 cases, 10-20% were 15 cases, 20-30% were 7 cases and >30% were 6 cases. Amongst the schwannomas, the consistency of the tumor has been shown to be important factor for LCN involvement. The softer variety involved LCN more often than the harder (p<0.05). The involvement of the different groups of lower cranial nerve ranged from 7% to 92%.

Adult↗
PubMed2003

Reversible leg ulcer due to hydroxyurea in a case of chronic myeloid leukemia.

The cutaneous side effects of hydroxyurea are lesser known complication of long term hydroxyurea therapy in myeloproliferative disorders. We report a non-diabetic patient, who developed hydroxyurea dermopathy (leg ulcers) during long-term treatment with hydroxyurea for chronic myeloid leukemia (CML). The time course of the development of ulcers and its healing suggests that these resulted from the direct toxicity of hydroxyurea. We aim to increase clinical awareness of this problem.

Adult↗
PubMed2002

Influence of dehydration effects on the optical spectra of H4PVMo11O40 in the visible and near infrared range: intra- and intercenter optical transitions in the V-Mo cluster.

UV-Vis-NIR diffuse reflectance spectra of heteropoly acids of the type of H4PVMo11O40.xH2O were recorded with improved spectroscopic equipment for different times on helium stream at room temperature. A broad asymmetric absorption band with a maximum at 740-780 nm in the visible range and a shoulder at 900-1000 nm in the near infrared range is identified. With increasing time on stream the intensity of this band grows appreciably: simultaneously, the water peaks at 1430 and 1925 nm decrease. Focusing on a single mixed-valence V4+-Mo6+-cluster, a model is suggested for the description of the experimental results. The model takes into account electron transfer, low symmetry crystal fields and vibronic interaction. The absorption band shape calculation is performed within the semiclassical limits. The band shape is shown to be determined both by the optical d-d transitions in V4+ and Mo5- and the intervalence V4+-Mo6+ optical transition. Appreciable changes in the band intensity are attributed to the increase in the electron transfer parameter due to water loss. Quite good agreement with the experiment was found for a reasonable set of transfer and vibronic parameters.

Biophysical Phenomena↗