Biochemistry, Biophysics, and Structural Biology Commons^™

Polymorphism Of Hla-Dr And Hla-Dq In Rheumatoid Arthritis Patients And Clinical Response To Methotrexate--A Hospital-Based Study, Azra Arif I Ali, Tariq Moatter, Jawed Altaf Baig, Ahmed Iqbal, Azmat Hussain, Mohammad Perwaiz Iqbal

Department of Biological & Biomedical Sciences

Objective: To investigate the frequency and distribution of DRB1 and DQB1 alleles in Patients with rheumatoid arthritis (RA) and analyze the relationship between clinical response to methotrexate (MTX) and the HLA-DR and HLA-DQ genotypes in these patients.
Methods: In this case-control study, the HLA-DRB1 and HLA-DQB1 polymorphism in 91 RA patients and 91 healthy controls was done using polymerase chain reaction and sequence specific primers.
Results: There was no statistical difference in frequencies of HLA-DRB1*03, DRB1*04, DRB1*07, DRB1*10, DRB1*11, DRB1*12, DRB1*13, DRB1*14, DRB1*15 and DRB1*16 genotypes between patients and controls. However, DRB1*01 was found to be significantly more common (p=0.015) …

Hyperhomocysteinemia And Coronary Artery Disease In Pakistan, M Perwaiz Iqbal

Department of Biological & Biomedical Sciences

The relative risk of developing coronary artery disease (CAD) in Pakistani men is highest in early ages. Majority of those suffering from CAD belong to the lower middle socioeconomic stratum of the society. Mild hyperhomocysteinemia (concentration of plasma homocysteine between 15-25 micromol/l) is very commonly seen in Pakistani patients with acute myocardial infarction (AMI) as well as in normal healthy subjects. There appears to be a lack of association between hyperhomocysteinemia and CAD in Pakistani population. There is also no evidence of association of methylenetetrahydrofolate reductase 677C>T mutation with CAD in this population. High prevalence of deficiency of folate …

Critical Evaluation Of The Claims Made By Pharmaceutical Companies In Drug Promotional Material In Pakistan, Dileep Kumar Rohra, Anwarul Hassan Gilani, Ismail Kamal Memon, Ghazala Perven, Muhammad Talha Khan, Hina Zafar, Rakesh Kumar

Department of Biological & Biomedical Sciences

Background: In Pakistan, there is no mechanism to monitor the drug promotional campaign by pharmaceutical industry despite the fact that there is enough evidence that irrational pharmacotherapy is increasingly encountered even in the developed countries due to unethical practices of pharmaceutical promotion. Objectives. To audit the drug promotional claims made by the pharmaceutical companies in Pakistan.
Methods: Drug promotional pamphlets and brochures containing claims for the drugs, which were circulated by the pharmaceuticalrepresentatives were collected from 122 general practitioners (GPs) from Karachi and Larkana cities of the Sindh Province. The claims were critically analyzed and audited with the help of …

[3120+1kbdel86kb]+[Pn1303k] Genotype In An Emirati Cystic Fibrosis Patient: Indication Of A Founder Mutation In Palestinian Arabs, Danish Saleheen, Philippe M. Frossard, Emmanuelle Girodon

Department of Biological & Biomedical Sciences

Cystic fibrosis (CF) is the most common life-limiting autosomal recessive disorder in Caucasian population. The disease was initially considered to be rare in Middle Eastern countries. 95% of CF in Emirati families is due to two mutations only--p.S549R(T > G) and p.F508del. We report here the case of a patient referred to CF and Respiratory Clinic at Tawam Hospital for cystic fibrosis transmembrane regulator (CFTR) gene screening to ascertain the diagnosis of CF, who was found to carry a unique genotype, signifying the importance of retrieving ancestral histories of patients with monogenic disorders.

Hiv-1 Subtype A Infection In A Community Of Intravenous Drug Users In Pakistan, Saeed Khan, Mohammad A. Rai, Mohammad R. Khanani, Muhammad N. Khan, Syed H. Ali

Department of Biological & Biomedical Sciences

Background: Data on the subtypes of HIV in a population help in predicting the potential foci of epidemic, tracking the routes of infection and following the patterns of the virus' genetic divergence. Globally, the most prevalent HIV infection is the HIV-1 subtype C. In Asia, predominant subtypes of HIV-1 are B, C, and CRF-01AE. During the last few years, HIV prevalence in Pakistan has taken the form of a concentrated epidemic in at least two high risk groups, namely, Intravenous Drug Users (IDUs) and Male Sex Workers (MSWs). Factors that have facilitated the proliferation of HIV infection include transmission through …

Fractals Analysis Of Cardiac Arrhythmias, Mohammed Saeed

Department of Biological & Biomedical Sciences

Heart rhythms are generated by complex self-regulating systems governed by the laws of chaos. Consequently, heart rhythms have fractal organization, characterized by self-similar dynamics with long-range order operating over multiple time scales. This allows for the self-organization and adaptability of heart rhythms under stress. Breakdown of this fractal organization into excessive order or uncorrelated randomness leads to a less-adaptable system, characteristic of aging and disease. With the tools of nonlinear dynamics, this fractal breakdown can be quantified with potential applications to diagnostic and prognostic clinical assessment. In this paper, I review the methodologies for fractal analysis of cardiac rhythms and …

Lack Of Association Of Methylenetetrahydrofolate Reductase 677c>T Mutation With Coronary Artery Disease In A Pakistani Population, M Perwaiz Iqbal, Tasneem Fatima, Siddiqa Parveen, Farzana A. Yousuf, Majid Shafiq, Naseema Mehboobali, Abrar H. Khan, Iqbal Azam, Philippe M. Frossard

Department of Biological & Biomedical Sciences

Pakistanis belong to the South Asian population which has the highest known rate of coronary artery disease. Folic acid deficiency also appears to be highly prevalent in this population. Methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism decreases the activity of this enzyme and can be associated with mild to moderate hyperhomocysteinemia in homozygotes, particularly when there is folic acid deficiency, as well as with coronary artery disease. To assess the value of genotyping the MTHFR 677C>T dimorphism, we carried out a case-control study of dimorphism 677C>T for putative association with myocardial infarction (MI) among Pakistani nationals. We investigated a …

Variability In Lipid Profile Before And After Coronary Artery Bypass Grafting (Cabg), M Perwaiz Iqbal, Hasanat Mohammad Sharif, Naseema Mehboobali

Department of Biological & Biomedical Sciences

Objective: To investigate changes in total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, and triglycerides in serum of Pakistani patients before, immediately after and 5 days post CABG.
Method: Serum samples from 31 consecutive Pakistani angina patients undergoing CABG at the Aga Khan University Hospital were analyzed for total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides using kit methods.
Results: Immediately after CABG, there is a significant decline in the mean levels of serum cholesterol, LDL cholesterol, HDL cholesterol and triglycerides. However, 5 days post CABG, there is a significant increase in the concentrations of total …

Biochemical Screening For The Prediction Of Preeclampsia, Dileep Kumar Rohra, Nazia Qidwai

Department of Biological & Biomedical Sciences

No abstract provided.

Gene Markers And Complex Disorders: A Review, M S. Mahmood, N Kureshi, P M. Frossard

Department of Biological & Biomedical Sciences

No abstract provided.

Variability In Lipid Profile In Patients With Acute Myocardial Infarction From Two Tertiary Care Hospitals In Pakistan, M P. Iqbal, M Shafiq, N Mehboobali, S P. Iqbal, K Abbasi

Department of Biological & Biomedical Sciences

Objective: To investigate changes in total cholesterol, high density lipoprotein (HDL)-cholesterol, low density lipoprotein (LDL)-cholesterol and triglycerides in serum of Pakistani patients with AMI due to age, gender, body mass index (BMI), diabetes, hypertension, and smoking, and also find out the prevalence of hypercholesterolemia, hypertriglyceridemia, "low HDL-cholesterol" and "isolated low-HDL cholesterol" in them.
Patients and Methods: Serum samples from 451 consecutive AMI patients (250 from National Institute of Cardiovascular Diseases, Karachi and 201 from Armed Forces Institute of Cardiology, Rawalpindi) were analyzed for total cholesterol, HDL-cholesterol and triglycerides using kit methods. LDL-cholesterol was determined using the Friedewald formula.
Results: Mean …

Cystic Breast Lymphangioma, S N. Waqar, H Khan, S F. Mekan, N Kayani, A J. Raja

Department of Biological & Biomedical Sciences

No abstract provided.

Immunity In Medicine, M Saeed

Department of Biological & Biomedical Sciences

No abstract provided.

Involvement Of Thromboxane A2 And Tyrosine Kinase In The Synergistic Interaction Of Platelet Activating Factor And Calcium Ionophore A23187 In Human Platelet Aggregation, Huma Rasheed, Sheikh Arshad Saeed

Department of Biological & Biomedical Sciences

The present study was carried out to examine the mechanisms of the synergistic interaction of PAF and A23187 mediated platelet aggregation. We found that platelet aggregation mediated by subthreshold concentrations of PAF (5 nM) and A23187 (1 mM) was inhibited by PAF receptor blocker (WEB 2086, IC50 = 0.65 mM) and calcium channel blockers, diltiazem (IC50 = 13 mM) and verapamil (IC50 = 18 mM). Pretreatment of platelets with PAF and A23187 induced rise in intracellular calcium and this effect was also blocked by verapamil. While examining the role of the down stream signaling pathways, we found that platelet aggregation …

Increased Levels Of Erythrocyte Glutathione In Acute Myocardial Infarction: An Antioxidant Defence, M P. Iqbal, M Ishaq, N Mehboobali

Department of Biological & Biomedical Sciences

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 …

Association Study Of The Angiotensin-Converting Enzyme (Ace) Gene G2350a Dimorphism With Myocardial Infarction, M Perwaiz Iqbal, Saeed Mahmood, Naseema Mehboobali, Mohammad Ishaq, Tasnim Fatima, Saddiqa Parveen, Philippe Frossard

Department of Biological & Biomedical Sciences

The angiotensin converting enzyme (ACE) is a strong candidate gene for myocardial infarction (MI). Insertion-deletion dimorphism in intron 16 of this gene has been inconclusively found to be associated with it. Several new polymorphisms in the ACE gene have been identified and among these, a dimorphism in exon 17, ACE G2350A, has a significant effect on plasma ACE concentrations. To assess the value of genotyping the ACE G2350A dimorphism in a genetically homogeneous population, we carried out a case-control study of dimorphism G2350A for a putative association with MI among Pakistani nationals. We investigated a sample population of 370 Pakistanis, …

Core Concepts In Biochemistry And Molecular Biology In An Integrated Mbbs Curriculum, M P. Iqbal

Department of Biological & Biomedical Sciences

No abstract provided.

Blood Lead Levels During Pregnancy And Pregnancy Outcome In Karachi Women, A Rahman, A Hakeem

Department of Biological & Biomedical Sciences

objective: To evaluate association of blood lead levels with pregnancy outcome in the obstetrics and gynaecology unit.
Methods: Blood lead levels were measured in 73 pregnant women at the time of delivery and assessed its association with pregnancyoutcome.
Results: Mean maternal lead level was 9.91+/-4.44 mg/dL (range 2.28-36.35 mg/dL). Mothers of boys had significantly higher (p=0.013, one-tailed t test) blood lead levels (11.05+/-5.19) when compared to mothers of girls (8.74+/-3.18 mg/dL.
Conclusion: Maternal lead levels at the time of delivery showed no association with gestational age, birth weight, recumbent length, or head circumference.

Topographical Expression Of Class Ia And Class Ii Phosphoinositide 3-Kinase Enzymes In Normal Human Tissues Is Consistent With A Role In Differentiation, Soha Salama El Sheikh, Jan Domin, Prakitpunthu Tomtitchong, Paul Abel, Gordon Stamp, El-Nasir Lalani

Department of Pathology and Laboratory Medicine

Background: Growth factor, cytokine and chemokine-induced activation of PI3K enzymes constitutes the start of a complex signalling cascade, which ultimately mediates cellular activities such as proliferation, differentiation, chemotaxis, survival, trafficking, and glucose homeostasis. The PI3K enzyme family is divided into 3 classes; class I (subdivided into IA and IB), class II (PI3K-C2α, PI3K-C2β and PI3K-C2γ) and class III PI3K. Expression of these enzymes in human tissue has not been clearly defined.

Methods: In this study, we analysed the immunohistochemical topographical expression profile of class IA (anti-p85 adaptor) and class II PI3K (PI3K-C2α and PI3K-C2β) enzymes in 104 formalin-fixed, paraffin embedded …

N-Acetyl-Beta-D-Glucosaminidase In Acute Myocardial Infarction, M Perwaiz Iqbal, Khawar A. Kazmi, Hasan R. Jafri, Naseema Mehboobali

Department of Biological & Biomedical Sciences

The objective of the study was to investigate whether the lysosomal enzyme, N-Acetyl-beta-D-glucosaminidase (NAG) activity is increased in plasma of patients with acute myocardial infarction (AMI) and to determine if there is any association between plasma levels of NAG and severity of myocardial infarction (MI). NAG activity in plasma was monitored in 69 patients with AMI and 135 normal healthy subjects using a spectrofluorimetric method. A modified Aldrich ST elevation score was used to gauge the severity of MI in terms of size of the infarct. Plasma NAG levels in AMI patients and normal healthy subjects were found to be …

Cardiac Acceleration As A Marker Of Vagal Withdrawal In Heart Rate Control During Exercise In Humans, S S I Bokhari, H R. Ahmad, M M F Subhan, S A. Ali, M N. Khan

Department of Biological & Biomedical Sciences

Objective: To investigate whether the time rate of change in heart rate i.e. cardiac acceleration, during aerobic exercise in human subjects could be used to differentiate vagal withdrawal from sympathetic stimulation.Methods: Fifteen male subjects exercised on a bicycle ergometer at 50 Watts (Step 1), then 100 Watts (Step 2), for 2 minutes each.Results: Heart rate (HR) was monitored from a resting value (mean +/- SD) of 80.3 +/- 12.9 to 113.8 +/- 13.6 beats min-1 in Step 1. In Step 2 exercise, HR increased from 113.8 +/- 13.6 to 145 +/- 20 beats min-1. At the initiation of Step 1, …

Enzymatic Method For Assaying Calcium In Serum With Ca++ -Atpase, Masood-Ul-Hassan Javed, Francesco Michelangeli

Department of Biological & Biomedical Sciences

A kinetic assay for total calcium in serum was developed which is based on the activation of Ca(++)-ATPase by free Ca(++) [Ca(++)](f) maintained by EGTA in the reaction mixture. The concentration of Ca(++)(f) was dependent on total reference calcium added or serum calcium. Ca(++)-ATPase activity was coupled to the reduction of NADH by pyruvate kinase (PK) and lactate dehydrogenase (LDH) and monitored by change in absorbance at 340 nm. The calcium in normal serum was 10.08 +/- 0.24 mg/dl (n = 35) by our method while with o-cresolphthalein complexone (CPC) method, the total calcium in the same 35 serum samples …

Methylene Tetrahydrofolate Reductase Gene And Coronary Artery Disease, M P. Iqbal, P M. Frossard

Department of Biological & Biomedical Sciences

Abstract is not provided by the author/publisher

Renal Cortical Necrosis: A Case Series Of Nine Patients & Review Of Literature, Syed Sohail Ali, Syed Zulfiqar Rizvi, Suhail Muzaffar, Aasim Ahmad, Akhtar Ali, Sheema H. Hassan

Department of Biological & Biomedical Sciences

Background: The purpose of this study is to review cases of renal cortical necrosis (RCN) which we came across during a period of five years, confirmed on needle biopsy specimens, with literature available so far.
Methods: All renal biopsy records between January 1996 to December 2001 at the Aga Khan University Hospital, Karachi, Pakistan were reviewed to identify patients with histologically proven renal cortical necrosis. Seven patients were also referred by the department of Nephrology, Lady Reading Hospital, Peshawar, Pakistan. Patients' medical records were reviewed for demographic, clinical, and follow up data.
Results: There were total of nine patients identified …

Molecular Mechanisms Involved In Human Platelet Aggregation By Synergistic Interaction Of Platelet-Activating Factor And 5-Hydroxytryptamine, B H. Shah, H Rasheed, I H. Rahman, A H. Shariff, F L. Khan, H B. Rahman, S Hanif, S A. Saeed

Department of Biological & Biomedical Sciences

Our recent studies have shown that co-activation of Gq and Gi proteins by 5-hydroxytryptamine (5-HT) and adrenaline show synergism in human platelet aggregation. This study was conducted to examine the mechanism(s) of synergistic interaction of 5-HT and platelet activating factor (PAF) in human platelets. We show that PAF, but not 5-HT, increased platelet aggregation in a concentration-dependent manner. However, low concentrations of 5-HT (2 microM) potentiated platelet aggregation induced by subthreshold concentration of PAF (40 nM) indicating a synergistic interaction between the two agonists and this synergism was blocked by receptor antagonists to either 5-HT or PAF. 5-HT also potentiated …

Problem-Based Learning Variant: Transition Phase For A Large Institution, I Khan, A Fareed

Department of Biological & Biomedical Sciences

Objective: To compare students' test scores and perceptions of problem-based learning (PBL) and lecture-based learning (LBL) by applying a PBL-variant.
Method: For the transition from LBL to PBL, PBL was varied for one discipline only and for a large group of students. Two hundred forty nine second year medical students were taught a topic of Biochemistry by the LBL method and then 141 of these were taught another topic by the PBL-variant. At the conclusion of each topic an MCQ test was given. One week later a 9 item questionnaire was given to the 50 students now attending classes to …

An Enzymatic Method For The Detection Of Human Serum Albumin, M U. Javed, S N. Waqar

Department of Biological & Biomedical Sciences

Albumin is the most abundant protein in human serum. A dye-binding method is commonly used in clinical laboratories for its estimation using different types of dyes. However, all these dye methods were interfered by a variety of compounds. Here we present a method for the detection of albumin in human serum and other biological fluids. The principle is based on the fact that lactate dehydrogenase isoenzyme-5 (LDH-5) binds specifically to Dextran-Blue (DB). Albumin inhibits the binding of LDH-5 with DB. Absence of LDH activity in DB fraction after gel filtration indicates the presence of albumin in sample and vice versa.

Induction Of White Cell Proliferation Due To Haematopoietic Growth Factors Is Associated With An Increase In Multiple Forms Of Dihydrofolate Reductase In Non-Neutropenic Cancer Patients, M P. Iqbal, I A. Burney, F Sultana, N Mehboobali

Department of Biological & Biomedical Sciences

Objective: Granulocyte-colony stimulating factor (G-CSF) and granulocyte macrophage-colony stimulating factor (GM-CSF) are frequently used in cancer patients to overcome the granulocytopenic effects of chemotherapy, and also to mobilize the stem cells. The mobilized stem cells are collected from the peripheral blood and used for transplantation following high doses of chemotherapy. However, the molecular mechanism by which these colony stimulating factors (CSFs) bring about proliferation of myeloid precursor cells is not clearly known. Dihydrofolate reductase (DHFR), which has an established role in DNA synthesis, could be a link between administration of CSF and stem cell proliferation. The purpose of this study …

Nitric Oxide Mediated Effect Of Cyclo-Oxygenase Inhibitors, M Mahmood, H S. Zuberi, M K. Ashfaq

Department of Biological & Biomedical Sciences

Objectives: Non-Steroidal anti-inflammatory drugs (NSAIDS) have long been used as anti-inflammatory agents, yet their mode of action is not entirely clear. The inhibitory effects of NSAIDS on prostaglandin production can only partly explain their anti-inflammatory actions. This study was aimed at defining the role of cycl-oxygenase (COX) inhibitors on nitric oxide (NO) production in murine macrophages in vitro.
Methods: Murine macrophages were obtained from the peritoneum and after exposure, in vitro to lipopolysaccharide (LPS) produced nitrite, measured after 24 hours by Griess reaction. The macrophages were pre-incubated with aspirin or indomethacin before activation with LPS.
Results: Treatment with aspirin resulted …

Increased Levels Of Multiple Forms Of Dihydrofolate Reductase In Peripheral Blood Leucocytes Of Cancer Patients Receiving Haematopoietic Colony-Stimulating Factors: Interim Analysis, M P. Iqbal, I A. Burney, F Sultana, N Mehboobali, T Siddiqui

Department of Biological & Biomedical Sciences

The precise mechanism whereby granulocytes proliferate when haematopoietic colony stimulating factors (CSFs) are used in neutropenic cancer patients is poorly understood. The purpose of this study was to investigate whether these cytokines bring about leucocyte proliferation by increasing the levels of multiple forms of dihydrofolate reductase (DHFR). Blood samples were collected from 36 cancer patients (25 males and 11 females) with chemotherapy-induced neutropenia. One sample of blood from each patient was obtained before therapy either with CSF, such as granulocyte colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF) or with placebo, and another one at the time of …