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Biomedical subjects

M Ishaq

Publications and source records attributed to M Ishaq.

At least 19 recordsLinked to original sources
PubMed2006

Intravitreal steroids may facilitate treatment of Eales' disease (idiopathic retinal vasculitis): an interventional case series.

PURPOSE: Eales' disease is an idiopathic peripheral perivasculitis leading to proliferative vascular retinopathy, recurrent vitreous haemorrhages, and tractional retinal detachment. It is an elusive cause of blindness in young, otherwise healthy individuals. We studied the effects of intravitreal triamcinolone acetonide (IVTA) in patients of Eales' disease, which may eventually reduce the side effects and cost of management, with results equivalent to or better than oral steroids. METHODS: Ethics approval and prior patient consent were obtained. Fluorescein fundus angiograms (FFAs) of 12 eyes of 12 Eales' disease patients were taken before enrolment. These patients received 0.1 ml of 40 mg/ml (4 mg) intravitreal triamcinolone through pars plana under topical anaesthesia. Regular weekly follow-ups were initiated to ascertain Snellen visual acuity, intraocular pressure (IOP) with Goldman tonometer, and triple mirror examination. Fluorescein fundus angiography was again performed in the 8th week to monitor response to treatment. Decrease in areas of late perivascular dye extravasation on fluorescein angiography was used as marker for improvement. RESULTS: Ten out of a total of 12 (83.33%) eyes treated with IVTA showed significant reduction of late leakage from retinal vessels on fluorescein fundus angiography. Two out of 12 eyes (16.67%) did not show considerable decrease in late perivascular fluorescein dye leakage after 8 weeks of intravitreal triamcinolone injection. Two patients (16.67%) had a significant rise in IOP after IVTA. CONCLUSION: Intravitreal steroids may be advocated for management of idiopathic retinal vasculitis without complications of systemic steroids, and minimize need for more invasive procedures.

Adult↗
PubMed2006

A differential association of interferon-gamma high-producing allele T and low-producing allele A (+874 A/T) with Hashimoto's thyroiditis and Graves' disease.

Cytokines play a crucial role in the pathogenesis of autoimmune thyroid disease. The aim of this study was to investigate the relationship of the single base change polymorphic variants identified in the first intron of interferon-gamma (IFN-gamma) (+874 T/A) with susceptibility to thyroid dysfunctions. A total of 340 subjects were included in the study comprising of 190 patients (104 patients with Hashimoto's thyroiditis, 26 with non-Hashimoto's hypothyroidism and 60 Graves' disease) and 150 controls. Genotyping was done by amplification refractory mutation system-polymerase chain reaction using a set of sequence-specific primers. Statistical analysis revealed a significant association between high IFN-gamma-producing genotype TT and Hashimoto's thyroiditis compared to controls (P value < 0.001). On the other hand, the frequency of genotype TT was decreased in patients with Graves' hyperthyroidism with a significant increase in low IFN-gamma-producing genotype AA among this group (P = 0.03). To conclude the results of the study suggest a differential association of high- and low-producing alleles of IFN-gamma gene with Hashimoto's thyroiditis and Graves' disease. The high IFN-gamma-producing allele T was observed to be associated with Hashimoto's thyroiditis in the present study where as in Graves' hyperthyroidism the association was observed to be stronger with the low producing allele A.

Adenine Nucleotides↗
PubMed2005

Role of vitamins B6, B12 and folic acid on hyperhomocysteinemia in a Pakistani population of patients with acute myocardial infarction.

BACKGROUND AND AIM: Pakistani people belong to an ethnic group which has the highest rate of coronary artery disease (CAD). We investigated the possible correlation between deficiency of vitamins B6, B12 or folic acid and hyperhomocysteinemia in Pakistani patients with acute myocardial infarction (AMI). A case-control study was carried out involving 224 AMI patients (age 30-70 years; 55 females and 169 males) and 126 normal healthy subjects (age 31-70 years; 35 females and 91 males). METHODS AND RESULTS: Fasting venous blood was obtained from cases and controls. Serum was analyzed for folic acid and B12 using radioassays. Plasma was analyzed for pyridoxal phosphate (PLP; coenzymic form of B6) using a radioenzymatic assay and for total homocysteine using a fluorescence polarization immunoassay. Mean serum B12 concentration in AMI patients was found to be significantly lower than the mean for controls (241+/-185 pg/ml vs 608+/-341 pg/ml; p < 0.001). Mean serum folate level in patients was also found to be lower than controls (3.35+/-3.78 ng/ml vs 4.93+/-2.93 ng/ml), however, the differences were not statistically significant. Similarly, mean PLP concentration in plasma of cases (19.4+/-24.4 nmol/l) was lower than the concentration in controls (23.2+/-17.6 nmol/l), but the difference was not statistically significant. Mean plasma homocysteine level in AMI cases (18+/-8.36 micromol/l) was higher than the mean level in controls (16.4+/-4.9 micromol/l), but not to a significant extent. However, this mean homocysteine concentration in normal healthy subjects was among the highest reported in the literature and was significantly more than mean values reported in most Eastern and Western studies. Compared to controls, there was significantly greater deficiency of folate (32.5% vs 67.1%), B12 (3.2% vs 63.4%) and PLP (49.2% vs 74.1%) in AMI patients. Deficiencies of folate, B12 and PLP were defined as serum folate levels less than 3.5 ng/ml, serum levels of B12 less than 200 pg/ml and plasma PLP levels less than 20 nmol/l. Mean plasma homocysteine levels in smokers were found to be significantly higher in both cases and controls. Similarly, mean serum folate levels in smokers (compared to nonsmokers) were significantly lower in both cases and controls. CONCLUSIONS: Substantial nutritional deficiencies of these three vitamins along with mild hyperhomocysteinemia, perhaps through an interplay with the classical cardiovascular risk factors (highly prevalent in this population), could be further aggravating the risk of CAD in the Pakistani population.

Adult↗
PubMed2005

Efficacy of sonicated and acid-extractable antigens in the serodiagnosis of H. pylori infection in peptic ulcer patients.

Helicobacter pylori is implicated in causation of peptic ulcers and gastric cancer and plays a pivotal role in gastric pathophysiology. In the present study we evaluated the relative efficacy of sonicated and acid-extractable antigens in the serodiagnosis of H. pylori infection in peptic ulcer patients by ELISA. In the present study we evaluated the relative efficacy of sonicated and acid-extractable antigens in the serodiagnosis of H. pylori infection in peptic ulcer patients by ELISA. The two types of antigens mentioned above were prepared from H. pylori subcultures following appropriate procedures. Sera were collected from 13 subjects of whom eight were diagnosed to be suffering from duodenal ulcer (DU) and five from non-ulcer dyspepsia (NUD) and screened for the presence of anti H. pylori antibodies by ELISA. A case was considered seropositive, if the OD value was more than or equivalent to twice the mean OD value of blank. Analysis of our results showed that, with acid extractable antigen at a concentration of 2 mg/mL, 12 cases were seropositive. Contrastingly, with sonicated antigen, at a concentration of 2 mg/mL only eight cases were positive. It is concluded from this study, that the use of relatively purified antigens like acid extractable antigens enhances the sensitivity and specificity of this serodiagnostic test, indicative of its relatively higher efficacy over sonicated lysate containing multiple antigens.

Acids↗
PubMed2004

Increased levels of erythrocyte glutathione in acute myocardial infarction: an antioxidant defence.

OBJECTIVE: Glutathione (GSH) has a central role in the defence against oxidative damage. This study was carried out to investigate any change in erythrocyte GSH levels in a population of patients with acute myocardial infarction (AMI) and compare them with levels in normal healthy subjects. METHOD: GSH levels were determined in erythrocytes of one hundred and seventy six patients with AMI (age: 30-70 years; 131 males and 45 females) admitted to the National Institute of Cardiovascular Diseases, Karachi. These levels were compared with eryrocyte GSH levels obtained from 95 normal healthy subjects (controls). RESULTS: Mean +/- SD erythrocyte GSH levels in AMI patients and controls were found to be 2.34 +/- 0.62 micromol/ml of packed cells and 2.08+/- 0.62 micromol/ml of packed cells, respectively. The two values when compared with one way ANOVA were found to be significantly different (p=0.001). Age had little effect on erythrocyte GSH levels in both AMI patients and normal healthy subjects. CONCLUSION: Increased production of reactive oxygen species is a feature of cardiovascular disease, such as AMI and cells can respond to mild oxidative stress by upregulating antioxidant defence in terms of increased production of GSH.

Acute Disease↗
PubMed2001

In vivo genotoxic effect of arsenic trioxide in mice using comet assay.

Although arsenic has been the subject of toxicological research, acute in vivo genotoxic studies using relevant animal models and uniform methodology are lacking. Hence, the present study aims to study DNA damage caused by arsenic trioxide in mice in in vivo using alkaline single cell gel electrophoresis (Comet) assay. Mice were administered orally 0,0.13,0.27,0.54,1.08,2.15,4.3 and 6.45 mg/kg body weight of arsenic trioxide dissolved in distilled water. The samples of whole blood were collected at 24,48,72 h, first and second week post-treatment and the assay was carried out to determine DNA damage as represented by comet tail-length. All the doses induced significant increase in comet tail-length at 24 h post-treatment (P<0.05) showing a clear dose dependent increase from 0.13 to 2.15 mg/kg b.wt. and a dose dependent decrease in higher doses (4.3-6.45 mg/kg b.wt). At 48 h post-treatment all the doses showed a significant increase (P<0.05) in comet tail-length when compared to 24 h post-treatment. A gradual decrease in the comet tail-length was observed for all the doses from 72 h post-treatment onwards indicating a gradual repair in DNA damage. This indicates a non-linear dose and time response between DNA damage and different doses of arsenic trioxide at different time-intervals. A significant increase in comet tail-length at all the doses clearly gives evidence that arsenic trioxide cause DNA damage effectively. The study indicates that the alkaline comet assay is a reliable and effective method to detect DNA damage caused by metals.

Analysis of Variance↗
PubMed2000

Accumulation of RXR alpha during activation of cycling human T lymphocytes: modulation of RXRE transactivation function by mitogen-activated protein kinase pathways.

We have previously reported that the activation of resting human immature peripheral blood T (PBT) lymphocytes is associated with the loss of retinoid X receptor alpha (RXRalpha) expression. In the present study, we have demonstrated that, unlike resting cells, activation of cycling human mature PBT lymphocytes, and T lymphocyte leukemia cell lines is accompanied by the accumulation of RXRalpha mRNA and protein. Interestingly, cyclosporin A further augmented RXRalpha expression, indicating the involvement of calcineurin pathways in the process. 9-cis retinoic acid inhibited the accumulation, suggesting that retinoids can regulate the synthesis of their own receptors during T cell activation. Transfection analysis in Jurkat cells, using RXRE-dependent reporter assays, showed that RXRalpha accumulated during T cell activation was transcriptionally inactive. To investigate the mechanism of such inhibition, the role of two mitogen-activated protein kinase pathways, c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK), in modulating RXRE-dependent transcription, was explored. The expression of constitutively active MAP/ERK kinase kinase 1 (MEKK1) inhibited RXRE-dependent transcription, whereas dominant negative MEKK1 increased the transcription, indicating the involvement of JNK signaling pathways in the process. In contrast, expression of constitutively active MEK1, which activates ERK pathway, enhanced RXRE-dependent activation. When both were activated simultaneously, JNK pathway was dominant over ERK pathway and resulted in inhibition of RXRE-mediated transcription. These data demonstrate a dual regulatory control of RXRalpha expression during the activation of resting and cycling T lymphocytes and indicate a dynamic balance between JNK and ERK pathways in modulating RXRE-mediated transactivation.

Alitretinoin↗
PubMed1999

Renal cell carcinoma with massive osseous metaplasia and bone marrow elements.

Focal calcifications are frequently seen in renal masses and may be present in renal cell carcinomas. Metaplastic bone formation, on the other hand, is a rare event. We report a unique case of a large calcified renal cell carcinoma with massive osseous metaplasia and bone marrow elements. The clinical and pathologic differential diagnosis for this tumor is discussed along with a review of the literature on this unusual phenomenon.

Biomarkers, Tumor↗
PubMed1998

Activation-induced down-regulation of retinoid receptor RXRalpha expression in human T lymphocytes. Role of cell cycle regulation.

A 5.4-kilobase mRNA, the expression of which is down-regulated after treatment of human peripheral blood mononuclear cells (PBMCs) with various T cell-activating agents, was isolated using an mRNA differential display method. Nucleotide sequence analysis identified the 5' end of this RNA as human retinoid receptor RXRalpha mRNA. Here, we report the nucleotide sequence of 3.6 kilobases of this RNA, which represents the 3' end of RXRalpha mRNA, the sequence of which has not been previously described. Activated PBMCs also expressed lower levels of RXRalpha protein, and a DNA binding assay showed that the activation-induced loss of RXRalpha mRNA and protein expression correlated with the loss of DNA binding activity of this protein. We present evidence that the transition from G0/G1 to S phase of the cell cycle results in the down-regulation of RXRalpha expression and that cell cycle inhibitors, which block the cells in G1 phase, prevent this down-regulation. The decrease in the levels of RXRalpha mRNA was found to be regulated at the post-transcriptional level and involved new protein synthesis. These observations indicate that the levels of RXRalpha expression in T lymphocytes are coupled to cell cycle progression, and there is tight regulatory control of RXRalpha expression during the transition from G0/G1 to S phase of the cell cycle.

Base Sequence↗
PubMed1997

Value of routine pre-operative chest X-ray in patients over the age of 40 years.

The overall usefulness of routine chest X-ray, its cost benefit ratio and effect on anaesthetic management in patients over the age of 40 years was assessed. Four hundred and seventy-seven consecutive patients undergoing elective non-cardiopulmonary surgery with no cardiopulmonary diseases, having a routine preoperative chest x-ray were selected at the Aga Khan University Hospital, Karachi. Twenty five (5.2%) were excluded from the study as their chest x-ray were not available at the time of surgery. Twenty eight (8.3%) below and 33 (28.7%) above 60 years of age had abnormalities in chest x-ray but the difference in cardiac abnormalities in two age groups was insignificant. The frequency of lung field abnormalities increased with age from 3.2% in less than 60 to 15.6% in patients above 60 years of age. The difference in frequency of occurrence of lung field abnormalities was statistically significant in case of lung abnormalities. Only one case required change in anaesthetic management based on routine preoperative chest x-ray. Our study showed that the incidence of significant lung field abnormalities increased in patients aged 60 years and above with no history of chronic obstructive airway disease. We recommend routine preoperative chest x-ray be carried out only in patients over the age of 60 years.

Adult↗
PubMed1995

Purification and properties of lactate dehydrogenase from liver of Uromastix hardwickii.

Lactate dehydrogenase isoenzyme-1 was purified from liver of Uromastix hardwickii using colchicine-Sepharose and heat-inactivation methods. The crude enzyme showed four isoenzymes by agarose gel electrophoresis (AGE). The purified enzyme showed a single band after native AGE and SDS-PAGE corresponding to a molecular weight of 34 kDa. The enzyme did not bind with DEAE-Sepharose at pH 7.2. The optimum pH for forward reaction was 7.5, while for reverse reaction, the maximum activity was at pH 9.5. The Km values for pyruvate, NADH, lactate and NAD+ were 0.105, 0.045, 9.0 and 0.011 mM, respectively. The pyruvate showed maximum activity at about 150 microM and then starts showing inhibition at higher concentration. Pre-heating of enzyme showed that it was stable at 80 degrees C for 30 min and at 100 degrees C it became inactive immediately. Oxalate, glutamate, Cu2+, Co2+, Mn2+, and Mg2+ have shown inhibitory effects both for forward- and reverse-reactions. From these properties, we suggest that LDH-1 from Uromastix liver may be quite different from that of other vertebrates.

Animals↗
PubMed1994

Differential expression of mRNAs for JC virus large and small tumor antigens in brain tissues from progressive multifocal leukoencephalopathy patients with and without AIDS.

JC virus (JCV) causes progressive multifocal leukoencephalopathy (PML), the fatal demyelinating infection of oligodendrocytes, in up to 5% of AIDS patients. An intron-differential RNA PCR was developed to study the expression of alternately spliced JCV early mRNAs in brain tissues from PML patients with and without AIDS and in JCV-induced hamster brain tumors. The method utilizes primers that span the large tumor (T) and small tumor (t) antigen introns allowing amplification of specific cDNAs in the presence of contaminating viral genomic DNA. Hybridization with specific junctional probes and DNA sequence analysis confirmed the identity of the PCR products. Sequencing showed that JCV early mRNA is alternatively spliced as previously predicted by analogy to simian virus 40. Large T antigen mRNA was detected in all the brain tissues from PML patients with and without AIDS. The expression of small t antigen mRNA varied depending upon the association of PML with AIDS and upon other unknown factors. Of the 12 PML/AIDS brain tissue samples, 11 (92%) expressed small t antigen mRNA, whereas only 8 of 13 (62%) brain samples from patients with PML alone showed detectable levels of small t antigen mRNA. Human immunodeficiency virus 1 proviral DNA was detected in 10 of 12 PML/AIDS brain samples. The results indicate that alternative splicing of JCV early mRNA is regulated in the human brain and that the production of small t antigen may not be essential for the pathogenesis of PML.

Acquired Immunodeficiency Syndrome↗