Biochemistry Commons^™

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 …

Effect Of Amino Acids On Inhibition Of Lactate Dehydrogenase-X By Gossypol, M H. Javed, M A. Khan

Department of Biological & Biomedical Sciences

Gossypol acetic acid (GAA) has been shown to have male antifertility effects, but there are pronounced differences among animal species. In the search of endogenous effector molecules, which interfere with the functions of GAA, we have studied the in vitro effect of various amino acids on the inhibition of the purified LDH-X by GAA. Histidine, cysteine and glycine were shown to block the effect of GAA. The effects of these amino acids were concentration dependent. Histidine and glycine protection was found to be complex type in which both the Km and Vmax were decreased compared to control. Arginine, glutamic acid, …

Atherosclerosis And Plaque Rupture: An Update, M N. Afzal, S A. Saeed, B H. Shah

Department of Biological & Biomedical Sciences

No abstract provided.

Accumulation Of Methotrexate In Human Tissues Following High-Dose Methotrexate Therapy, M P. Iqbal

Department of Biological & Biomedical Sciences

Methotrexate concentration was analyzed in a number of tissues of a patient of osteogenic sarcoma who had been on high-dose methotrexate therapy for nearly 6 months. Gall bladder and kidney contained the highest concentration of the drug, followed by testis, small intestine, skeletal muscle, bone marrow, lung, spleen, heart and liver. Although, compared to kidney the liver contained relatively small amount of the drug, yet nearly 1/5th of the total drug in liver was in bound form. This bound form of methotrexate is most likely associated with multiple forms of dihydrofolate reductase. The total concentration of methotrexate in kidney is …

Urinary N-Acetyl-Beta-D-Glucosaminidase In Rheumatoid Arthritis, M P. Iqbal, A A. Ali, M A. Waqar, N Mehboobali

Department of Biological & Biomedical Sciences

Excretion of urinary N-acetyl beta-D-glucosaminidase (NAG) and its isoenzyme patterns were studied in two groups of patients with rheumatoid arthritis (RA) and in normal control subjects. Urine samples were collected from 30 seropositive RA patients, 19 seronegative RA patients, and 15 normal healthy subjects. All the patients and normal subjects were assessed to have normal liver and kidney functions. A small portion of the urine sample was dialyzed against 0.01 M phosphate buffer, pH 7.0 and NAG activity was monitored. Mean +/- SD values of urinary NAG in seropositive RA patients, in seronegative RA patients and in normal healthy subjects …

Diphtheria Toxin Fusion Proteins, Frank Foss, Mansoor Saleh, James Krueger, John Nichols, John Murphy

Haematology and Oncology, East Africa

Two different approaches have been undertaken to develop targeted biomolecules for therapeutics. The first was the construction of immunotoxins consisting of monoclonal antibodies chemically linked through a disulfide bond to a plant or bacterial toxin or radionuclide. Instability of the chemical conjugation of some of the earlier immunotoxins led to the concept of using protein engineering and recombinant DNA to assemble fusion genes combining the sequences for the enzymatically active and translocation domains of a toxin with those of a specific targeting ligand. From the outset, the prospect of using recombinant DNA methods to assemble the structural genes encoding bacterial …

Basic Medical Research As A Means Of Solving National Health Problems, M. Perwaiz Iqbal, M Anwar Waqar

Department of Biological & Biomedical Sciences

No abstract provided.

Severe Bone Marrow Suppression In A Patient With Rheumatoid Arthritis On Methotrexate, M P. Iqbal, A A. Ali, A A. Alvi

Department of Biological & Biomedical Sciences

No abstract provided.

Appearance Of A Methotrexate Binding Plasma Protein During High Dose Methotrexate Therapy, M P. Iqbal, I Malik, N Mehboobali

Department of Biological & Biomedical Sciences

No abstract provided.

Methotrexate As An Alternative To Surgery In Ectopic Pregnancy: A New Role For An Old Drug, M P. Iqbal

Department of Biological & Biomedical Sciences

Abstract is not provided by the author/publisher

Estimation And Separation Of N-Acetyl-Beta-D-Glucosaminidase Isoenzymes In Urine, M H. Javed, A N. Hussain, M A. Waqar

Department of Biological & Biomedical Sciences

N-acetyl-beta-D-glucosaminidase is a lysosomal enzyme made up of two isoenzymes (A and B). It has been used extensively as a marker for kidney damage. However, its estimation in urine has not been standardized. We have established a method for the estimation and separation of NAG isoenzymes by ion-exchange chromatography. In 19 experiments done so far, this method has given reproducible results. The significance of this method is that with a single experiment, one can estimate total as well as individual isoenzyme activity. Furthermore, urine constituents do not appear to interfere in this assay.

Heterogeneity Of Methotrexate Binding In Human Colon Tumor Cells, M P. Iqbal, N Mehboobali, M A. Waqar, M Ahmed

Department of Biological & Biomedical Sciences

[3H]-methotrexate binding at pH 5.0 and pH 7.2 by the cytosol of tumor tissues and the surrounding normal areas of the gastrointestinal tract of patients suffering from colon or gastric cancer has been used to identify in these cells the presence of a binder of methotrexate having low-affinity for this drug in addition to the enzyme dihydrofolate reductase. Scatchard analysis of the [3H]-methotrexate binding data by a colon tumor sample also reveals that there are two binders of this drug present in the cytosol of these cells. The association constant (Kass) for one binder of methotrexate is = 5.6 x …

Pharmacokinetics, Immune Response, And Biodistribution Of Iodine-131-Labeled Chimeric Mouse/Human Igg1, K 17-1a Monoclonal Antibody, Ruby Meredith, Albert Lobuglio, Walter Plott, Roger Orr, Ivan Brezovich, Charles Russell, Elizabeth Harvey, Michael Yester, Mansoor Saleh

Haematology and Oncology, East Africa

Pharmacokinetics,immunogenicity,and biodistributionof a 131I-Iabeledmouse/human chimenc monoclonal antibody (C17-1A) was studiedin six metastaticcoloncancerpatients. Pharmacokinetics obtalned from serum radioactivity or chi mera concentration were identical after 5 mCi of 131I(>17-1A withmeanalphahalf-livesof 17.6±2.3 and19.7±2.9 and meanbeta half-livesof 100.9±16.1 and 106.4±14.1 hr, respectively. HPLC analysis documented the monomeric chi rneiic17-lA withoutevidenceof immunecomplexesorfree 1311 None of the patients developed antibody after ‘31I-chi merle17-1A exposure.Radiolocalizationoccurredin known areas of disease >4 cm in all patients. The half-life of total body radioactivity was 58 ±7 hr by whole-body counts and 64 ±13 hr by urine measurements. Whole-body and bone marrow dose estimates ranged from 0.75-1 .03 and …

Mega Doses Of Methotrexate In The Treatment Of Osteosarcoma, M P. Iqbal, I A. Malik

Department of Biological & Biomedical Sciences

Abstract is not provided by the author/publisher

Trace Element Studies On Karachi Populations Part V: Blood Lead Levels In Normal Healthy Adults And Grammar School Children, W W. Manser, R Lalani, S Haider, M A. Khan

Department of Biological & Biomedical Sciences

Blood lead levels of healthy Karachi population were estimated. Mean levels for males, females, soldiers and school children were 34.4, 31.8, 29.9 and 38.2 micrograms/dl respectively. About 93% cases of either sex had elevated lead levels, of whom 30% males and 10% females had levels above the safety limits (40 micrograms/dl). Soldiers living in relatively pollution free area though had levels lower than the rest of the population but 91% had levels over 25 micrograms/dl and only two had acceptable levels. Ninety-two percent children showed levels above 25 micrograms/dl with a large number having levels over 40 micrograms/dl. A very …

Lectins, El-Nasir Lalani, M Wells

Department of Pathology and Laboratory Medicine

No abstract provided.