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Biomedical subjects

A Rahman

Publications and source records attributed to A Rahman.

At least 127 records · Page 7Linked to original sources
PubMed1999

Antisense raf oligodeoxyribonucleotide is a radiosensitizer in vivo.

Raf-1, a cytosolic protein serine/threonine kinase, plays important roles in cell growth, proliferation, transformation, and cell survival. The aim of the present study was to evaluate the radiotherapeutic efficacy of a fully phosphorothioated and well-characterized antisense raf oligodeoxyribonucleotide (ODN) corresponding to the 3'-untranslated region of human c-raf-1 mRNA (ISIS 5132/5132). Using our recently developed liposome encapsulation of ODN approach, we first compared the pharmacokinetic parameters of a liposomal formulation of 5132 (LE-5132) and 5132. The peak plasma concentrations 5 minutes after ODN administrations (30 mg/kg i.v.) were 28.5 microg/ml and 13.5 microg/ml for LE-5132 and 5132, respectively. The decrease in plasma concentration of LE-5132 and 5132 followed a biexponential pattern, with initial distribution half-lives (t1/2alpha) of 34.8 minutes and 21.6 minutes, respectively. The terminal half-lives (t1/2beta) with LE-5132 and 5132 were 14.5 hours and 4.3 hours, respectively. The area under the plasma concentration-time curve (AUC) was 5.8 times higher with LE-5132 than with 5132. Significantly higher intact ODN levels could be measured in most organs within 48 hours of administration of LE-5132 compared with 5132 (liver 18.4-fold, spleen, 31-fold, heart 3-fold, lungs 1.5-fold). In kidneys, the level was lower with LE-5132 (0.77-fold). LE-5132 composition, unlike 5132, did not affect clotting time in vitro. Significant decline in the level of Raf-1 protein was observed in vitro in relatively radioresistant human laryngeal squamous cell carcinoma cells (SQ-20B) treated with LE-5132 compared with SQ-20B cells treated with equimolar concentration of 5132 or liposome-encapsulated mismatched 5132 (0.5 microM LE-5132, 71.3%+/-22.5%; 1.0 microM LE-5132, 79.6%+/-16.7%). In addition, LE-5132 appeared to be a more potent antitumor compound than 5132 (p < 0.001). These data established the suitability of LE-5132 for in vivo radiotherapeutic efficacy studies. Intravenous administration of LE-5132 into SQ-20B tumor-bearing athymic mice inhibited Raf-1 expression in tumor tissue compared with blank liposome-treated or untreated control groups. LE-5132 or ionizing radiation (IR) treatment alone caused significant but transient inhibition of SQ-20B tumor growth but not tumor regression. Remarkably, a combination of LE-5132 and IR treatments led to significant and sustained tumor regression for at least 27 days after the last treatment (< 0.001). Histopathologic examination of tumor samples revealed a significant proportion of cells containing fragmented chromatin in the LE-5132 + IR treatment group as compared with single agent and untreated control groups. These in vivo data support the notion that Raf-1 has proliferative and survival functions and advance the scientific and technologic bases for the use of antisense raf ODN in the management of radioresistant malignancies.

3' Untranslated Regions↗
PubMed1999

Unofficial fees in Bangladesh: price, equity and institutional issues.

The widespread collection of unofficial fees at health facilities is a common form of rent-seeking behaviour in Bangladesh. Typically, unofficial fees come in the form of cash payments for the performance of required services, for direct purchase of drugs and medical-surgical requisites, and for service access. Using observational and interview methods, this study explores linkages between official and unofficial fees at three Bangladesh health facility levels; primary care Thana Health Complexes, secondary or district hospitals, and medical college hospitals. The study estimates payment levels for different income classes and different payor types at these facilities, thereby highlighting potential equity, price and institutional questions associated with unofficial fees. Not only does the practice have clear income and equity effects, there also appear to be direct effects upon patient satisfaction, perception of quality, and the ability to pay for health services. The article concludes with a discussion of 'rent capture' processes at Bangladesh facilities and the effect of unofficial fees in six areas of health sector reform: displaced official policies, reduced merit goods production, upward income redistribution, distorted human resource development, growth of facility inefficiency, and obstruction of market reforms.

Bangladesh↗
PubMed1999

Nutritional rickets without vitamin D deficiency in Bangladesh.

To understand nutritional rickets in Bangladesh better, 14 rachitic and 13 'unaffected' children were evaluated. Seventy per cent of children with active rickets had no evidence of either vitamin D deficiency or familial rickets. Rickets in Bangladesh is probably related to calcium deficiency. Abnormalities in 'unaffected' children suggest that subclinical calcium insufficiency is common.

Bangladesh↗
PubMed1999

Purification and molecular genetic characterization of ZPU1, a pullulanase-type starch-debranching enzyme from maize.

This study identified and purified specific isoamylase- and pullulanase-type starch-debranching enzymes (DBEs) present in developing maize (Zea mays L.) endosperm. The cDNA clone Zpu1 was isolated based on its homology with a rice (Oryza sativa L.) cDNA coding for a pullulanase-type DBE. Comparison of the protein product, ZPU1, with 18 other DBEs identified motifs common to both isoamylase- and pullulanase-type enzymes, as well as class-specific sequence blocks. Hybridization of Zpu1 to genomic DNA defined a single-copy gene, zpu1, located on chromosome 2. Zpu1 mRNA was abundant in endosperm throughout starch biosynthesis, but was not detected in the leaf or the root. Anti-ZPU1 antiserum specifically recognized the approximately 100-kD ZPU1 protein in developing endosperm, but not in leaves. Pullulanase- and isoamylase-type DBEs were purified from extracts of developing maize kernels. The pullulanase-type activity was identified as ZPU1 and the isoamylase-type activity as SU1. Mutations of the sugary1 (su1) gene are known to cause deficiencies of SU1 isoamylase and a pullulanase-type DBE. ZPU1 activity, protein level, and electrophoretic mobility were altered in su1-mutant kernels, indicating that it is the affected pullulanase-type DBE. The Zpu1 transcript levels were equivalent in nonmutant and su1-mutant kernels, suggesting that coordinated regulation of ZPU1 and SU1 occurs posttranscriptionally.

Amino Acid Sequence↗
PubMed1999

Neutrophil inhibitory factor abrogates neutrophil adhesion by blockade of CD11a and CD11b beta(2) integrins.

We studied the basis of inhibition of polymorphonuclear leukocyte (PMN) adhesion induced by neutrophil inhibitory factor (NIF), a 41-kDa CD11/CD18 beta(2) integrin-binding protein isolated from the canine hookworm (Ancylostoma caninum). NIF blocked PMN adhesion in a concentration-dependent manner with complete blockade occurring at approximately 10 nM NIF. Because CD11a and CD11b beta(2) integrins are functionally active on stimulated PMNs, and yet NIF is postulated to inhibit only CD11b integrin by binding to its I domain, we evaluated the contributions of CD11a and CD11b beta(2) integrins in the mechanism of inhibition of PMN adhesion to endothelial cells. We observed an additive inhibitory effect (>90% inhibition) of PMN adhesion to endothelial cells when NIF was used in combination with anti-CD11b monoclonal antibodies, which alone at saturating concentrations reduced PMN adhesion by only 50%. NIF also prevented aggregation of phorbol ester-stimulated JY lymphoblastoid cells that expressed only the functionally active CD11a, suggesting that NIF also can inhibit CD11a-dependent response. We transduced the NIF cDNA into human dermal microvessel endothelial cells in which NIF synthesis and release prevented PMN adhesion to the transduced human dermal microvessel endothelial cells. These data indicated that the potent antiadhesive effect of NIF may be the result of inhibition of CD11a and CD11b beta(2) integrins on PMNs. Moreover, the strategy of NIF release from transduced endothelial cells suggests the feasibility of blocking the CD11a- and CD11b beta(2) integrin-dependent PMN adhesion and PMN migration responses specifically at sites of endothelial cell activation.

Animals↗
PubMed1999

Evaluation of HIV risk reduction intervention programs via latent growth model.

The latent growth model (LGM) has drawn increasing attention in behavioral studies using longitudinal data. The LGM captures the level and trajectory of behavior change, variation in both the initial status and the trend of behavior change, as well as the time-ordered covariation between the initial status and change. This study demonstrates how the LGM can be applied in the evaluation of intervention programs targeting HIV risk behavior among drug users. Multi-group piecewise latent growth models were fit to longitudinal data with three repeated response measures.

Female↗
PubMed1999

Glyceryl trinitrate, a nitric oxide donor, suppresses renal oxidant damage caused by potassium bromate.

Nitric oxide (NO) is a short-lived, readily diffusible intracellular messenger molecule associated with multiple organ-specific regulatory functions. Endogenous stimulation or exogenous administration of NO have been shown to inhibit production of reactive oxygen species (ROS) and expression of oxidant-mediated molecular or tissue injury. Potassium bromate (KBrO3) is one such potent renal oxidant that acts through generation of ROS-mediated lipid peroxidation, and causes increased ornithine decarboxylase activity, enhanced rate of DNA synthesis and depletion of the antioxidant armoury of the tissue. In this study, we elucidate the effect of exogenous NO administration, using the NO donor glyceryl trinitrate (GTN), on KBrO3-induced nephrotoxicity, oxidative stress and cell proliferation. KBrO3 administration at a dose of 125 mg/kg body weight results in significant (P < 0.001) depletion in renal glutathione (GSH) content, and glutathione reductase (GR) activity with a concomitant increase in microsomal lipid peroxidation, and blood urea nitrogen (BUN) and creatinine levels. Parallel to these changes, we found significant enhancement in ornithine decarboxylase (ODC) activity and rate of renal DNA synthesis. Subsequent administration of GTN resulted in dose-dependent amelioration of GSH content and GR activity with concomitant inhibition of lipid peroxidation, and BUN and creatinine levels. In addition, GTN administration to KBrO3-intoxicated rats resulted in significant dose-dependent down regulation of enhanced ODC activity and rate of [3H]-thymidine incorporation in renal DNA, providing support for the protective role of NO in attenuation of KBrO3-induced oxidative stress and cell proliferation. Enhancement of oxidative tissue injury and cell proliferation on administration of the NO inhibitor, L-NAME, further demonstrates the protective efficacy of endogenous NO. These data suggest that NO inhibits KBrO3-induced tissue injury, oxidative stress and proliferative response in the rat kidney.

Animals↗
PubMed1999

Ellagic acid ameliorates nickel induced biochemical alterations: diminution of oxidative stress.

Nickel, a major environmental pollutant is known for its clastogenic, toxic and carcinogenic potentials. The present investigation shows that ellagic acid proves to be exceptional in the amelioration of the nickel-induced biochemical alterations in serum, liver and kidney. Administration of nickel (250 micromol Ni/kg body wt) to female Wistar rats, resulted in increase in the reduced glutathione (GSH) content [kidney (*P<0.05) and liver (**P<0.001)] and Glutathione-S-transferase (GST) and glutathione reductase (GR) activities [kidney and liver, (**P<0.001)]. Ellagic acid treatment to the intoxicated rats leads to the formation of soluble ellagic acid-metal complex which facilitates excretion of nickel from the cell or tissue, thus ameliorating nickel-induced toxicity, as evident from the down regulation of GSH content, GST and GR activities with concomitant restoration of glutathione peroxidase (GPx) activity in liver and kidney. Our data shows that ellagic acid maintains cell membrane integrity through sequestration of metal ions from the extracellular fluid, as evident from the alleviated levels of serum glutamate oxaloacetate transaminase, (SGOT), serum glutamate pyruvate transaminase (SGPT) and lactate dehydrogenase (LDH) when compared to nickel treated group. Similarly, the enhanced blood urea nitrogen (BUN) and serum creatinine levels that are indicative of renal injury showed a reduction of about 45 and 40%, respectively. The data also show that treatment of ellagic acid after 30 min of nickel administration exhibits maximum inhibition in a dose-dependent manner. In summary, our data suggests that ellagic acid act as an effective chelating agent in suppressing nickel-induced renal and hepatic biochemical alterations.

Animals↗
PubMed1999

Protein kinase C-activated oxidant generation in endothelial cells signals intercellular adhesion molecule-1 gene transcription.

We tested the hypothesis that activation of protein kinase C (PKC) and generation of oxidants are critical sequential signals mediating tumor necrosis factor (TNF)-alpha-induced activation of nuclear factor-kappaB (NF-kappaB) and transcription of the intercellular adhesion molecule (ICAM)-1 gene. Stimulation of human pulmonary artery endothelial (HPAE) cells with TNF-alpha (100 U/ml) induced the activation of PKC and, subsequently, generation of oxidants. Pretreatment with calphostin C, a specific PKC inhibitor, prevented oxidant generation after TNF-alpha stimulation, indicating that PKC activation mediated the production of oxidants in HPAE cells. In contrast, pretreatment of HPAE cells with N-acetylcysteine, an antioxidant and a precursor of glutathione, failed to prevent PKC activation, indicating that PKC activation was not secondary to the oxidant production. These findings suggest that oxidant generation in endothelial cells occurs downstream of PKC activation. However, both PKC activation and oxidant generation were necessary for ICAM-1 mRNA expression because the pretreatment of HPAE cells with either calphostin C or N-acetylcysteine inhibited the TNF-alpha-induced activation of NF-kappaB and prevented the activation of ICAM-1 promoter. Prolonged exposure of HPAE cells to the phorbol ester, phorbol-12-myristate-13-acetate, which is known to deplete all except atypical PKC isozymes, failed to prevent TNF-alpha-induced ICAM-1 mRNA expression. We conclude that TNF-alpha-induced oxidant generation secondary to the activation of a phorbol ester-insensitive PKC isozyme signals the activation NF-kappaB and ICAM-1 gene transcription.

Cells, Cultured↗
PubMed1999

Central and eastern Europe: recent trends in abortion law.

The authors analyze recent developments in the abortion laws in seven countries in central and eastern Europe, Albania, Bulgaria, the Czech and Slovak Republics, Hungary, Poland and Romania, first country by country, then thematically, comparing the ways these countries' laws deal with gestational age limitations, specifications about the practitioners who may perform abortions and the facilities in which they may be performed, third-party authorization and notification requirements, mandatory counseling requirements, restrictions on the availability of abortion information, fees for abortion services and the question of fetal rights. At the conclusion of their discussion of each of these thematic issues, they recommend ways in which these laws might be made better and fairer, in form and in practice, for the women in these countries who find it necessary to consider having abortions.

Abortion, Legal↗
PubMed1999

Control of smooth muscle cell proliferation--the role of the basement membrane.

In atherogenesis and in response to vessel injury, arterial smooth muscle cells (SMCs) are activated from a quiescent, differentiated state into an actively proliferating and synthetic phenotype which migrate into the intima where the cells participate in the formation of a fibrous plaque or intimal hyperplasia. The mechanisms involved in the control of SMC function are not clear and no preventive therapy against SMC activation is available. Interactions between SMCs and the extracellular matrix have been shown to influence SMC structure and function through integrin-mediated signaling processes. The SMC basement membrane is a specific form of extracellular matrix which seems to be crucial for the maintenance of SMC quiescence and the disruption of these interactions is part of cellular activation after atherogenic or traumatic stimuli. This concept of "negative growth control" may constitute a future target for the development of new strategies in the prevention of SMC activation in atherogenesis and restenosis formation.

Animals↗
PubMed1998

Randomised trial of impact of school mental-health programme in rural Rawalpindi, Pakistan.

BACKGROUND: A school mental-health programme has been developed as a component of the community mental-health programme in Rawalpindi, Pakistan. It has the objective of improving the understanding of disorders of mental health in the rural community. We aimed to assess the impact of a school mental-health programme on the awareness of schoolchildren, their parents, friends who were not attending school, and neighbours. METHODS: We chose two secondary schools for boys and two for girls that were similar in terms of size, staff-pupil ratio, and drop-out rates. 100 children aged 12-16 years (25 girls and 25 boys in each of the study and control groups), 100 parents (one for each child), 100 friends who did not attend school (one for each child), and 100 neighbours (one for each child) were given a 19-item questionnaire before and after the study group had had a 4-month programme of mental-health education. The maximum score for the questionnaire was 16 points. FINDINGS: Before the school mental-health programme the awareness of mental-health issues was poor (mean score 5.7-7.6) in the four groups of participants. In the study group there was a significant improvement in the mean scores after the school programme in the schoolchildren (mean improvement 7.6 [95% CI 6.7-8.5], p<0.01), their parents (5.3 [4.5-6.1], p<0.01), friends (5.1 [4.1-6.1], p<0.01), and neighbours (3.4 [2.6-4.2], p<0.01). In the control group the difference in awareness was significant only in schoolchildren (1.5 [0.5-2.3], p=0.01) and their friends (0.8 [0.3-1.3], p<0.01). INTERPRETATION: The school programme succeeded in improving awareness of mental health in schoolchildren and the community. The schoolchildren were receptive to the programme, and shared their new understanding with family, friends, and neighbours. Mental-health planners who wish to improve community awareness of mental health, particularly in areas with low literacy rates, should consider setting up school mental-health programmes.

Child↗
PubMed1998

Chromosomal localization reveals three kinesin heavy chain genes in mouse.

Kinesin-related proteins constitute a superfamily of microtubule-dependent motors that play important roles in organelle transport and cell division. These molecules share a conserved motor region of approximately 340 amino acids, which is attached to diverse "tail" or cargo-binding domains. The kinesin superfamily was first defined by kinesin heavy chain, which is the principal component of "true" kinesin. Invertebrates appear to possess only a single gene encoding kinesin heavy chain. Mammals appear to have two or more genes encoding kinesin heavy chain, although the precise situation has been unclear. Here we definitively demonstrate that mouse has three kinesin heavy chain genes, Kif5a, Kif5b, and Kif5c. Kif5a, Kif5b, and Kif5c map to mouse chromosomes 10, 18, and 2; Kif5a and Kif5c appear to be expressed only in neuronal tissues by Northern blot analysis while Kif5b appears to be ubiquitous in its expression.

Animals↗
PubMed1998

Two kinesin light chain genes in mice. Identification and characterization of the encoded proteins.

Native kinesin consists of two light chains and two heavy chains in a 1:1 stoichiometric ratio. To date, only one gene for kinesin light chain has been characterized, while a second gene was identified in a genomic sequencing study but not analyzed biochemically. Here we describe new genes encoding kinesin light chains in mouse. One of these light chains is neuronally enriched, while another shows ubiquitous expression. The presence of multiple kinesin light chain genes in mice is especially interesting, since there are two kinesin heavy chain genes in humans (Niclas, J., Navone, F., Hom-Booher, N., and Vale, R. D. (1994) Neuron 12, 1059-1072). To assess the selectivity of kinesin light chain interaction with the heavy chains, we performed immunoprecipitation experiments. The data suggested that the light chains form homodimers with no specificity in their interaction with the two heavy chains. Immunofluorescence and biochemical subfractionation suggested differences in the subcellular localization of the two kinesin light chain gene products. Although both kinesin light chains are distributed throughout the central and peripheral nervous systems, there is enrichment of one in sciatic nerve axons, while the other shows elevated levels in olfactory bulb glomeruli. These results indicate that the mammalian nervous system contains multiple kinesin light chain gene products with potentially distinct functions.

Amino Acid Sequence↗