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Biomedical subjects

S A Ahmed

Publications and source records attributed to S A Ahmed.

At least 19 recordsLinked to original sources
PubMed2006

Effect of temperature on heavy metal toxicity to juvenile crayfish, Orconectes immunis (Hagen).

The acute toxicity of four selected heavy metals to juvenile crayfish Orconectes immunis (Hagen) (1-2 g wet body wt. each) at room temperature increased in the following order: cadmium (x3) < copper (x10) < zinc (x2) < lead. The toxicity of these metals to crayfish acclimated at 17, 20, 23/24, and 27 degrees C increased with temperature (by 7-20% between 20 and 24 degrees C and 14-26% between 20 and 27 degrees C) as judged by the lowering of LT(50) (time to kill 50% of test animals at a fixed concentration) values. A 4 degrees C rise in temperature (from 20 to 24 degrees C), which increased the toxicity of copper by about 7%, increased the rate of oxygen consumption by about 34%. Heavy metals inhibited the rate of oxygen consumption at all temperatures. In 20 degrees C-acclimated crayfish, copper caused about 17% inhibition of oxygen consumption compared to about 7-12% by other metals including the most toxic cadmium. A 3-4 degrees C rise in temperature tripled the inhibitory effect of copper (20%), cadmium and zinc (26 and 18%, respectively), but not of lead, on oxygen consumption. A 7 degrees C-rise in temperature (from 20 to 27 degrees C) increased the inhibitory effect of heavy metals, including lead, on oxygen consumption by up to 54% in the case of copper. The data indicate that rising global temperatures (currently 0.60 degrees C) associated with climate change can have the potential to increase the sensitivity of aquatic animals to heavy metals in their environment.

Animals↗
PubMed2006

Temporal lobe involvement in Japanese encephalitis: problems in differential diagnosis.

BACKGROUND AND PURPOSE: On MR imaging and CT, Japanese encephalitis (JE) shows lesions in the thalami, substantia nigra, basal ganglia, cerebral cortex, cerebellum, brain stem, and white matter, whereas temporal lobe involvement is characteristically seen in Herpes simplex encephalitis (HSE). Temporal lobe involvement in JE may cause problems in differentiating it from HSE. We undertook this study to show the temporal lobe involvement pattern in JE and highlight differentiating features from temporal lobe involvement in HSE. METHODS: Sixty-two patients with JE underwent CT or MR imaging or both. MR imaging was done in 53 and CT in 53. The diagnosis of JE was confirmed by cerebrospinal fluid (CSF) IgM enzyme-linked immunosorbent assay. RESULTS: Eleven (17.7%) patients showed temporal lobe involvement with abnormal MR imaging in all. All the patients showed hippocampal involvement. Two patients showed extension of lesions into the amygdala and uncus with insular involvement in 1. The rest of the temporal lobe was spared. All patients had thalamic and substantia nigra involvement with basal ganglia involvement in 7. Six of 9 CT scans were abnormal and the temporal lesions were seen in 2. CONCLUSIONS: The temporal lobe involvement pattern is fairly characteristic and mostly involves the hippocampus, usually sparing the rest of the temporal lobe. This and the concurrent involvement of the thalami, substantia nigra (SN), and basal ganglia allow differentiation from HSE. However, if the temporal lobe involvement is more severe, laboratory tests may be the only way to differentiate it from HSE, and it may be prudent to start antiviral therapy in the interim period.

Adolescent↗
PubMed2006

Thalassemia among blood donors at the Hospital Universiti Sains Malaysia.

The aim of this study was to screen and identify the types of thalassemia among blood donors at the Hospital Universiti Sains Malaysia (HUSM). Thalassemia screening was performed by hemoglobin electrophoresis. A total number of 80 blood samples were obtained from donors at the Transfusion Medicine Unit, HUSM. The ethnic origins of the donors were Malays (n=73, 91.3%) and non-Malays (n=7, 8.75%). Males comprised 88.1% of the donors. Thalassemia was detected in 16.25% (n=13) of the blood donors. Of those with thalassemia, 46.2% (6/13) were anemic. Microcytosis and hypochromia were detected in 84.6% (n=l1) and 84.6% (n=l1) of these donors, respectively. The types of thalassemias detected were Hb E, 11.25% (n=9/80) and beta thalassemia trait, 5% (n=4/80). Among the thalassemias detected, the Hb E hemoglobinopathy was comprised of Hb E/ alpha-thalassemia (38.5%: n=5), Hb E /beta-thalassemia (23.1%: n=3), Hb E trait (7.6%: n=1) and beta-thalassemia (30.8%: n=4). In conclusion, screening for thalassemia trait should be included as part of a standard blood testing before blood donation. Further studies are required to look at the effects of donated thalassemic blood.

Blood Donors↗
PubMed2006

The prevalence of human cytomegalovirus seropositivity among blood donors at the Unit of Blood Transfusion Medicine, Hospital Universiti Sains Malaysia.

Human cytomegalovirus (HCMV) is a species-specific DNA virus of the Herpetoviridae family. After a primary infection, HCMV persists in a latent form most probably in bone marrow progenitor cells or in peripheral blood monocytes. The virus can reactivate to result in shedding of the virus leading to virus dissemination and new infections. Immunocompromized patients are the ones most vulnerable to serious diseases occasionally acquired in blood transfusions. In a human population, HCMV seropositivity increases steadily with age to become approximately 100% in adults. This study was performed to detect seropositivity among regular blood donors in The Hospital of the Universiti Sains Malaysia, in the state of Kelantan. Using an enzyme immunoassay, it was found that 97.6% of blood donors were HCMV-positive. HCMV is highly prevalent and may be endemic in Kelantan. Hence, long-term strategies are required for the reduction of disease dissemination, and to prevent the exposure of immunocompromized patients to the virus.

Adolescent↗
PubMed2003

Expression, purification, and efficacy of the type A botulinum neurotoxin catalytic domain fused to two translocation domain variants.

Clostridial neurotoxins are potent inhibitors of synaptic function, with the zinc-dependent proteolytic light chain (LC) portion of the toxin cleaving one of three neural SNARE proteins. In nature, the LC is expressed as a part of a much larger toxin and hemagglutinin complex, protecting it from environmental degradation and preserving its catalytic activity. We developed forms of the LC of type A botulinum neurotoxin (BoNT-A) with parts of the larger toxin gene, for use as reagents in high-throughput assays to screen for potential LC antagonists, to further elucidate the toxin's mechanism of action, and to study immunological responses to the toxin. Three BoNT-A constructs were engineered and expressed: the LC, LC with translocation region (LC+H(n)), and the LC with the belt portion of the translocation region (LC+Belt). Purification was optimized to a two-step process, with relatively high yields of all three constructs obtained. Activity assays showed all three constructs to be active, with the LC being the most active. Immunogenic protection against native BoNT-A toxin challenge was observed for all three constructs, with the best protection observed with the LC+H(n) and LC+Belt proteins.

Animals↗
PubMed2001

Enzymatic autocatalysis of botulinum A neurotoxin light chain.

Highly purified recombinant zinc-endopeptidase light chain of the botulinum neurotoxin serotype A underwent autocatalytic proteolytic processing and fragmentation. In the absence of added zinc, initially 10-28 residues were cleaved from the C-terminal end of the 448-residue protein followed by the appearance of an SDS-stable dimer and finally fragmentation near the middle of the molecule. In the presence of added zinc, the rate of fragmentation was accelerated but the specificity of the cleavable bond changed, suggesting a structural role for zinc in the light chain. The C-terminal proteolytic processing was reduced, and fragmentation near the middle of the molecule was prevented by adding the metal chelator TPEN to the light chain. Similarly, adding a competitive peptide inhibitor (CRATKML) of the light-chain catalytic activity also greatly reduced the proteolysis. With these results, for the first time, we provide clear evidence that the loss of C-terminal peptides and fragmentation of the light chain are enzymatic and autocatalytic. By isolating both the large and small peptides, we sequenced them by Edman degradation and ESIMS-MS, and mapped the sites of proteolysis. We also found that proteolysis occurred at F266-G267, F419-T420, F423-E424, R432-G433, and C430-V431 bonds in addition to the previously reported Y250-Y251 and K438-T439 bonds.

Amino Acid Sequence↗
PubMed2001

Expression of a novel protein by regenerating hepatocytes and peripheral blood lymphocytes.

Regeneration and tolerance factor (RTF) is a protein with immunosuppressive activity and is normally present in the thymus and placenta. RTF was measured in the livers of patients with regenerating nodules due to alcoholic cirrhosis and hepatitis C. RTF was expressed in the regenerating nodules of 26 patients with alcoholic cirrhosis. All patients with chronic hepatitis C without cirrhosis failed to express RTF. Flow cytometry revealed upregulation of RTF on the lymphocytes from alcoholic cirrhosis and downregulation in hepatitis C disease.

ADP-ribosyl Cyclase↗
PubMed2000

The immune system as a potential target for environmental estrogens (endocrine disrupters): a new emerging field.

It is now well known that natural (17beta-estradiol) and synthetic (e.g. diethylstilbestrol) estrogens not only affect the reproductive system, but also markedly influence the immune system. Recently, a new class of estrogens that is abundant in the environment (in industrial chemicals, pesticides, and surfactants) has been recognized. Some of these estrogenic chemicals (which are a large subgroup of endocrine disrupters) have also been shown to influence the immune system. This review assimilates growing evidence in wildlife, laboratory animals and to a limited extent in humans, which suggests that environmental chemicals may also affect the immune system. Further studies are needed to ascertain the immunological consequences of exposure to environmental estrogens, especially in humans. At the present time, it is not known whether the human immune system responds to a low dose of environmental estrogens or if environmental estrogens influence certain subsets of human populations, rather than the general population. Conceivably, an alteration of the immune system by environmental estrogens could affect the individuals' ability to mount well-regulated immune responses to microbial and vaccine antigens, allergens, self and tumor antigens. Possible changes in the immune system must be investigated routinely in toxicity studies. A comprehensive mechanistic understanding of potential immunomodulatory chemicals is needed. In this regard, relevant laboratory animals may be especially useful in identifying susceptible periods of life, whether both genders are equally affected, in analysis of changes in target lymphoid organs, and to determine the immunological effects of mixtures of chemicals.

Animals↗
PubMed2000

Light chain of botulinum A neurotoxin expressed as an inclusion body from a synthetic gene is catalytically and functionally active.

Botulinum neurotoxins, the most potent of all toxins, induce lethal neuromuscular paralysis by inhibiting exocytosis at the neuromuscular junction. The light chains (LC) of these dichain neurotoxins are a new class of zinc-endopeptidases that specifically cleave the synaptosomal proteins, SNAP-25, VAMP, or syntaxin at discrete sites. To facilitate the structural and functional characterization of these unique endopeptidases, we constructed a synthetic gene for the LC of the botulinum neurotoxin serotype A (BoNT/A), overexpressed it in Escherichia coli, and purified the gene product from inclusion bodies. Our procedure can provide 1.1 g of the LC from 1 L of culture. The LC product was stable in solution at 4 degrees C for at least 6 months. This rBoNT/A LC was proteolytically active, specifically cleaving the Glu-Arg bond in a 17-residue synthetic peptide of SNAP-25, the reported cleavage site of BoNT/A. Its calculated catalytic efficiency kcat/Km was higher than that reported for the native BoNT/A dichain. Treating the rBoNT/A LC with mercuric compounds completely abolished its activity, most probably by modifying the cysteine-164 residue located in the vicinity of the active site. About 70% activity of the LC was restored by adding Zn2+ to a Zn2+-free, apo-LC preparation. The LC was nontoxic to mice and failed to elicit neutralizing epitope(s) when the animals were vaccinated with this protein. In addition, injecting rBoNT/A LC into sea urchin eggs inhibited exocytosis-dependent plasma membrane resealing. For the first time, results of our study make available a large amount of the biologically active toxin fragment in a soluble and stable form.

Amino Acid Sequence↗
PubMed2000

Evidence for a vesicle-mediated maintenance of store-operated calcium channels in a human embryonic kidney cell line.

Direct microinjection of the clostridial neurotoxins botulinum neurotoxin A light chain or tetanus neurotoxin into cells of a human embryonic kidney cell line significantly reduced calcium entry after depletion of internal calcium stores by cyclopiazonic acid, a reversible inhibitor of the sarcoplasmic-endoplasmic reticular calcium-ATPases. Botulinum neurotoxin A light chain specifically hydrolyzes a synaptosomal-associated protein of 25 kilodaltons (SNAP-25), and tetanus neurotoxin specifically hydrolyzes synaptobrevin-2 (vesicle-associated membrane protein 2, VAMP-2) and cellubrevin (vesicle-associated membrane protein 3, VAMP-3). Since these substrate proteins are required for vesicle docking and fusion, inhibition of store-operated calcium entry by botulinum neurotoxin A light chain and tetanus neurotoxin supports a model in which vesicle fusion is a prerequisite for activation of store-operated calcium entry. Brefeldin A, a fungal metabolite that interferes with vesicle traffic, partially reduced calcium entry following store depletion. The size of the reserve pool of vesicles or parallel vesicle recycling pathways employing brefeldin A-sensitive and brefeldin A-insensitive ADP-ribosylation factors may explain the failure of brefeldin A to completely inhibit store-operated calcium entry.

Botulinum Toxins, Type A↗
PubMed2000

Induced minor malformations in the neocortex of normal mice do not alter immunological functions.

The interactive relationship between the CNS and the immune system is well established. Major lesions in the brain have been shown to affect immune response. However, whether minor, focal lesions (ectopias), as seen in autoimmune mice, may induce alterations in the immune system is unknown. To address this point, ectopic lesions in the neocortex were induced in neonatal DBA/2 mice (Induced minor malformations; IMM) and their immune capabilities were assessed at adulthood. Serum was collected from each animal and analyzed for the presence of autoantibodies. In addition, splenic lymphocytes and thymocytes were collected to ascertain proliferative capabilities and to assess for possible phenotypic changes in lymphocyte subsets. Mice with IMM did not manifest IgG autoantibodies against cardiolipin, dsDNA or brain membrane antigens. Total lymphocyte cellularity was not affected. The induction of cerebrocortical ectopias did not impair the ability of splenic and thymic lymphocytes to proliferate in response to anti-CD3 antibodies or Concanavalin-A (Con-A) as determined by non-radioactive (Alamar Blue) and radioactive (3H-thymidine) assays. Moreover, no difference in proliferation of unstimulated and anti-CD3-stimulated splenic lymphocytes exposed to rIL-2 or rIL-7 was observed. Flow cytomeric analysis of a variety of cell surface antigens, indicated that there was no difference in lymphocyte subsets between control and IMM groups. Therefore, we conclude that induced IMM lesions in the CNS of normal DBA/2 mice do not alter immune functions.

Animals↗
PubMed2000

Recommendations for water supply in arsenic mitigation: a case study from Bangladesh.

Arsenic problems have been observed in several countries around the world. The challenges of arsenic mitigation are more difficult for developing and poor countries due to resource and other limitations. Bangladesh is experiencing the worst arsenic problem in the world, as about 30 million people are possibly drinking arsenic contaminated water. Lack of knowledge has hampered the mitigation initiatives. This paper presents experience gained during an action research on water supply in arsenic mitigation in rural Singair, Bangladesh. The mitigation has been implemented there through integrated research and development of appropriate water supply options and its use through community participation. Political leaders and women played key roles in the success of the mitigation. More than one option for safe water has been developed and/or identified. The main recommendations include: integration of screening of tubewells and supply of safe water, research on technological and social aspects, community, women and local government participation, education and training of all stakeholders, immediate and appropriate use of the available knowledge, links between intermediate/immediate and long term investment, effective coordination and immediate attention by health, nutrition, agriculture, education, and other programs to this arsenic issue.

Arsenic↗
PubMed1999

Comparison of multiple assays for kinetic detection of apoptosis in thymocytes exposed to dexamethasone or diethylstilbesterol.

BACKGROUND: Techniques to measure apoptosis are used to study a wide spectrum of conditions, from acquired immune deficiency syndrome (AIDS) to cancer to autoimmune diseases. Therefore, a critical comparison of common assays for apoptosis is warranted. METHODS: The kinetics of apoptosis induction in dexamethasone (DEX)-exposed thymocytes was examined after 2, 4, 8, 12, 26-28, and 48-50 h of culture. An additional aim was to ascertain whether a similar thymic atrophy-inducing hormone, diethylstilbestrol (DES), also directly induces thymocyte apoptosis. Apoptosis was evaluated by flow cytometric examination of cells stained with propidium iodide (PI), 7-aminoactinomycin D (7-AAD), or fluorescein isothiocyante (FITC)-annexin; by forward-and side-scatter (FS, SS) analysis, cell-size analyzer; and through cytopathologic examination. RESULTS: After 4 h of DEX exposure, apoptosis was evident by 7-AAD, annexin, and cytopathological assays, but no cells with sub-diploid DNA content were evident by PI analysis. Maximal apoptosis was evident by all the above flow cytometric techniques at 12 h after DEX exposure. The 7-AAD and annexin assays, which allow discrimination between early apoptosis and late apoptosis/necrosis, were comparable and identified similar apoptotic populations. Appearance of a FSlow/SSincreased population was evident only after 12 h of DEX exposure. Apoptosis could not be detected by any of the above assays in thymocytes exposed to various doses of DES. CONCLUSION: Two of the six assays, 7-AAD and annexin, were similar in detecting apoptosis at an early kinetic time point. Results of both assays were comparable at all time points studied. Our studies imply that DEX and DES induce thymic atrophy, in vivo, by different mechanisms.

Animals↗
PubMed1999

Species, interindividual, and tissue specificity in endocrine signaling.

The activity of endocrine-active agents exhibits specificity at many levels. Differential responsiveness to these agents has been observed between different species and extends to interindividual differences within a species and between different tissues as well. In cases where they have been identified, the biologic and molecular mechanisms underlying this specificity are quite diverse. Determinants of species specificity include differences that exist in receptor binding, gene transcription, and cellular responses to endocrine-active compounds between species. Interindividual differences in responsiveness may be determined at the level of genetic polymorphisms in hormone-metabolizing enzymes, hormone receptors, and in those genes that are transactivated by these receptors, as well as during changing windows of susceptibility that occur as a function of age, such as prenatal and postmenopausal exposures. Extrinsic factors such as diet can also impact individual susceptibility to endocrine-active agents. Tissue-specific determinants of susceptibility are well documented, but little is known regarding the mechanisms underlying these different responses. Differences in the expression of accessory proteins for steroid hormone receptors and different patterns of receptor expression, estrogen receptor alpha and estrogen receptor beta; for example, may contribute to tissue specificity, as may differences in the pattern of expression of other genes such as hormone-metabolizing enzymes. The use of animal model systems and development of appropriate mathematical models has the potential to yield additional valuable information for elucidating the role of these determinants of specificity at low-dose exposures and for improved risk assessments for the adverse health effects of endocrine-active compounds.

Age Factors↗
PubMed1999

Gender and risk of autoimmune diseases: possible role of estrogenic compounds.

A striking common feature of many autoimmune diseases in humans and experimental animals, despite differences in pathology, is that females are highly susceptible to autoimmune conditions compared to males. In several animal models, estrogens promote, whereas androgens abrogate, B-cell-mediated autoimmune diseases. To understand mechanisms by which estrogens regulate autoimmunity, it is first necessary to decipher estrogen effects on the normal immune system. Estrogen treatment of nonautoimmune mice diminished lymphocyte numbers in both developmental and mature lymphoid organs. Estrogen dysregulated T- and B-cell balance by inducing selective T-cell hypoactivity and B-cell hyperactivity. Even though estrogen did not alter the relative percentages of splenic T-cell subsets, splenic lymphocytes had a reduced proliferative response to T-cell stimulants and were refractory to rescue from activation-induced apoptosis compared to cells from placebo-treated mice. In contrast, estrogen induced B-cell hyperactivity (promoted autoantibodies to double-stranded DNA and phospholipids, increased numbers of plasma cells, and increased autoantibody yield per B cell). Note that treatment of normal mice with estrogen can alter T- and B-cell regulation and overcome B-cell tolerance to result in autoimmunity in normal individuals. Could environmental estrogens promote some human autoimmune disorders? Is there a link between environmental estrogens and autoimmune disorders, especially since these disorders are reported possibly more frequently? These provocative questions warrant investigation. Our findings on immunomodulatory effects may serve as a benchmark to examine whether endocrine-disrupting chemicals will have similar immunologic effects.

Animals↗
PubMed1999

Role of cortisol in the deterioration of glucose tolerance in Sudanese pregnant women.

OBJECTIVE: To study the state of insulin resistance which occurs in pregnancy and the possible role of cortisol in augmentation of this state. DESIGN: Case-control study. SETTING: Khartoum teaching hospital, Khartoum north hospital, Soba hospital, Ibrahim Malek hospital, maternity hospital and Fath-Elbasheer referral centre from January to August 1996. SUBJECTS: Thirty pregnant women with gestational diabetes mellitus(GDM) and thirty pregnant women with impaired glucose tolerance(IGT) were compared with thirty control pregnant women with normal glucose tolerance. RESULTS: The GDM and the IGT groups were found to have significantly higher levels of serum cortisol than that of the control group [937.2 +/- 79.4 nmol/l (mean +/- S.E.) and 794.2 +/- 60.5 vs 597.3 +/- 30.9 respectively, p < 0.0006]. CONCLUSION: Cortisol has a great role to play in the deterioration of glucose tolerance in pregnancy.

Adult↗
PubMed1998

Estrogen increases the number of plasma cells and enhances their autoantibody production in nonautoimmune C57BL/6 mice.

The immunological consequences of chronic estrogen exposure in normal individuals are not known, particularly in relation to B cells. In this study, by employing ELIspot, image cytometry, flow cytometry, cytology, and ELISA, we show that long-term exposure of normal mice to estrogen activates B cells to produce higher numbers of not only immunoglobulin-producing cells, but also autoantibody-producing cells. Estrogen promoted a decrease in B220(+) splenic lymphocytes, but resulted in a 10-fold increase in plasma cells. Further, the output of immunoglobulins including autoantibodies from individual plasma cells from estrogen-exposed mice was markedly increased, suggesting B cell hyperactivity. Importantly, our findings show that treatment of normal mice, solely with estrogen, can override B cell tolerance and promote autoreactive B cells in normal individuals.

Animals↗