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Biomedical subjects

A Ansari

Publications and source records attributed to A Ansari.

At least 19 recordsLinked to original sources

Implementation of a mass measles campaign in central Afghanistan, December 2001 to May 2002.

In Afghanistan health services have been disrupted by 23 years of conflict and 1 of 4 children die before age 5 years. Measles accounts for an estimated 35,000 deaths annually. Surveillance data show a high proportion of measles cases (38%) among those >/=5 years old. In areas with complex emergencies, measles vaccination is recommended for those aged 6 months to 12-15 years. From December 2001 to May 2002, Afghan authorities and national and international organizations targeted 1,748,829 children aged 6 months to 12 years in five provinces in central Afghanistan for measles vaccinations. Two provinces reported coverage of >90% and two >80%. Coverage in Kabul city was 62%. A subsequent cluster survey in the city found 91% coverage (95% confidence interval [CI], 0.85-0.91) among children 6-59 months and 88% (95% CI, 0.87-0.95) among those 5-12 years old. Thus, this campaign achieved acceptable coverage despite considerable obstacles.

Afghanistan↗

Effect of carboxymethyl cellulose and ionic strength on stability of mineral suspensions in potash ore flotation systems.

The adsorption of sodium carboxymethyl cellulose from aqueous solutions varying in ionic strength from that of distilled water to 50% NaCl/KCl brine (about 3.5 mol/dm(3)) onto illite and dolomite has been studied. The purpose of this work was to investigate the solvency effects in the phenomena underlying the potash flotation process that is carried out in saturated brine. Based on viscosity measurements, the adsorption results were analyzed in terms of a simple model of polymer macromolecules in solution. Suspension stability measurements carried out concomitantly with adsorption tests showed the ranges of carboxymethyl cellulose concentration over which the tested suspensions either were aggregated or were restabilized.

Adsorption↗

Thiopurine methyltransferase activity and the use of azathioprine in inflammatory bowel disease.

BACKGROUND: Azathioprine therapy is discontinued in one-third of patients with inflammatory bowel disease because of toxicity or a lack of clinical response. Patients with thiopurine methyltransferase (TPMT) deficiency are intolerant to azathioprine, whilst carriers are at increased risk of side-effects. AIM: To evaluate the importance of TPMT activity in the management of azathioprine therapy in inflammatory bowel disease. METHODS: Clinical response, adverse effects and haematological parameters were determined and correlated with TPMT enzyme activity and genotype in 106 patients with inflammatory bowel disease. RESULTS: Ninety-six patients had high TPMT activity, and 10 had intermediate activity. Nineteen patients (18%) were intolerant to azathioprine. Fifteen (16%) of those with high TPMT activity were intolerant, compared with five (50%) with intermediate activity [odds ratio (OR), 5.4; 95% confidence interval (CI), 1.5-19.8]. Complete remission was achieved in 63% of cases, and complete or partial remission in 79%. Interestingly, very high TPMT activity (> 14 units/mL red blood cells) was significantly associated with non-response, irrespective of the time on azathioprine (OR, 0.21; 95% CI, 0.07-0.68). TPMT gene mutations correlated with TPMT activity. CONCLUSIONS: Inflammatory bowel disease patients with intermediate TPMT activity have an increased risk of azathioprine toxicity. Conversely, very high TPMT activity predicts treatment failure. TPMT genotype predicted TPMT phenotype in this study.

Adult↗

Anorexic behaviour and attitudes among female medical and nursing students at a private university hospital.

OBJECTIVE: To study the anorexic behaviour and attitude among female medical and nursing students in a tertiary care hospital. SUBJECTS AND METHODS: A cross-sectional survey to determine the proportion of anorexic behaviour among female medical and nursing students at The Aga Khan University Hospital Karachi was conducted. A multistaged sampling technique was utilized in which our study population was first divided according to field of enrollment (medical or nursing school) and then stratified by class. Within each stratum, we used convenience sampling due to time and availability constraints. We utilized a modified Eating Attitudes Test (EAT-26) to collect data. The Eating Attitude Test is probably the most widely used standardized measure of symptoms characteristic of eating disorders, including anorexia nervosa. RESULTS: A total of 180 female students were interviewed. Ninety-four (52.2%) were medical students and 86 (47.8%) were nursing students. Among the 94 medical students, 26 (27.7%) were from first year, 14 (14.9%) from second year, 15 (16.0%) from third year, 20 (21.3%) from fourth year and 19 (20.2%) from the final year of medical college. Among the 86 nursing students 34 (39.5%) were from first year, 23 (26.7%) from second year, 27 (31.4%) from third year and 2 (2.4%) from fourth year. The proportion of anorexic behaviour among medical students was 8.0%, 7.1% and 20.0% in first, third and fourth years respectively. No individuals with anorexic behaviour were found in second and fifth years. The total proportion of anorexic behaviour among female health care students was 21.7%. CONCLUSION: Results showed a 21.7% prevalence of anorexic behaviour, a figure much higher than that reported in similar studies conducted in Asia. We also found that the proportion was much higher among female nursing students as compared to female medical students. A previous visit to a psychiatrist for reasons other than eating disorders was found to be associated with anorexic behaviour.

Adult↗

Characterization of thermal stability of the Escherichia coli Fapy-DNA glycosylase.

Thermal stability of Escherichia coli Fpg protein was studied using far-UV circular dichroism and intrinsic fluorescence. Experimental data indicate that Fpg irreversibly aggregates under heating above 35 degrees C. Heat aggregation is preceded by tertiary conformational changes of Fpg. However, the secondary structure of the fraction that does not aggregate remains unchanged up to approximately 60 degrees C. The kinetics of heat aggregation occurs with an activation enthalpy of approximately 21 kcal/mol. The fraction of monomers forming aggregates decreases with increasing urea concentration, with essentially no aggregation observed above approximately 3 M urea, suggesting that heat aggregation results from hydrophobic association of partially unfolded proteins. With increasing urea concentration, Fpg unfolds in a two-state reversible transition, with a stability of approximately 3.6 kcal/mol at 25 degrees C. An excellent correlation is observed between the unfolded fraction and loss of activity of Fpg. A simple kinetic scheme that describes both the rates and the extent of aggregation at each temperature is presented.

Circular Dichroism↗

Immunoreactivity of organic mimeotopes of the E2 component of pyruvate dehydrogenase: connecting xenobiotics with primary biliary cirrhosis.

In primary biliary cirrhosis (PBC), the major autoepitope recognized by both T and B cells is the inner lipoyl domain of the E2 component of pyruvate dehydrogenase. To address the hypothesis that PBC is induced by xenobiotic exposure, we took advantage of ab initio quantum chemistry and synthesized the inner lipoyl domain of E2 component of pyruvate dehydrogenase, replacing the lipoic acid moiety with synthetic structures designed to mimic a xenobiotically modified lipoyl hapten, and we quantitated the reactivity of these structures with sera from PBC patients. Interestingly, antimitochondrial Abs from all seropositive patients with PBC, but no controls, reacted against 3 of the 18 organic modified autoepitopes significantly better than to the native domain. By structural analysis, the features that correlated with autoantibody binding included synthetic domain peptides with a halide or methyl halide in the meta or para position containing no strong hydrogen bond accepting groups on the phenyl ring of the lysine substituents, and synthetic domain peptides with a relatively low rotation barrier about the linkage bond. Many chemicals including pharmaceuticals and household detergents have the potential to form such halogenated derivatives as metabolites. These data reflect the first time that an organic compound has been shown to serve as a mimeotope for an autoantigen and further provide evidence for a potential mechanism by which environmental organic compounds may cause PBC.

Amino Acid Sequence↗

Configurational diffusion down a folding funnel describes the dynamics of DNA hairpins.

Elucidating the mechanism of folding of polynucleotides depends on accurate estimates of free energy surfaces and a quantitative description of the kinetics of structure formation. Here, the kinetics of hairpin formation in single-stranded DNA are measured after a laser temperature jump. The kinetics are modeled as configurational diffusion on a free energy surface obtained from a statistical mechanical description of equilibrium melting profiles. The effective diffusion coefficient is found to be strongly temperature-dependent in the nucleation step as a result of formation of misfolded loops that do not lead to subsequent zipping. This simple system exhibits many of the features predicted from theoretical studies of protein folding, including a funnel-like energy surface with many folding pathways, trapping in misfolded conformations, and non-Arrhenius folding rates.

DNA↗

Anatomy and clinical significance of ventricular Thebesian veins.

An injection study was carried out in sheep hearts to compare the anatomy and distribution of Thebesian veins (venae cordis minimae) in the ventricles. The left azygos, middle cardiac, small cardiac, and anterior cardiac veins were ligated in 36 hearts, and India ink was injected into the right coronary artery or the left coronary artery or the coronary sinus. Examination revealed foramina Thebesii in both of these cardiac chambers. Myocardial tissue samples were taken, and 12 were subsequently studied histologically to confirm the presence of Thebesian veins. A greater number of Thebesian veins were observed in the right ventricle than in the left (P < 0.05). To identify any larger communications between the coronary arteries and cardiac chambers (arterioluminal), and between the coronary veins and cardiac chambers (venoluminal), gelatine was injected in 16 hearts. Arterioluminal vessels were identified only in the right ventricle, whereas venoluminal vessels were present in both ventricles. Venoluminal vessels are most likely responsible for the non-nutritive shunting of cardioplegic solutions delivered via the coronary sinus during surgery. Thebesian veins play a role in the drainage of blood, contributing towards right to left shunting of deoxygenated blood. It has also been suggested, although not proven, that they are able to supply blood to the myocardium in coronary arterial occlusion, thus acting as a natural form of nutrient channel. Thebesian veins may be confused with artificial nutrient channels constructed by transmyocardial laser revascularization, a possibility that should be considered during histological evaluation of this technique.

Animals↗

Increased expression of mXBP-1 (TREB-5) in thymic B cells in New Zealand mice.

New Zealand Black mice as well as several other murine models of murine lupus are well known for premature degeneration of thymus and development of autoimmunity. To focus on molecular events unique to murine lupus, we performed differential display using arbitrary primer pairs to distinguish NZB versus BALB/c thymus at 5 weeks of age. Following an extensive analysis of DNA bands that were either consistently up or downregulated and from studies of expression pattern of thymic genes by in situ nucleic acid hybridization, we focused on one clone that was consistently differentially expressed between NZB and BALB/c thymus. This clone was isolated, sequenced, and identified as the murine homologue of the human X box binding protein (hXBP-1), also known as TREB 5. mXBP-1 was found to be consistently upregulated in B cells in the thymic cortex of NZB and (NZBxNZW)F1, but not BALB/c, C3H/HeJ or C57BL/6 mice. In addition, it was dramatically elevated in MRL/ lpr but not MRL/++ mice; similarly, it was increased in BXSB/ Yaa male but not BXSB female thymic cortex. Of particular interest was an absence of mXBP-1 expression in the thymus of NZB/ Bln- Igh6(null)homozygotes. mXBP-1 has several putative functions, including the regulation of MHC class II expression and by virtue of its ability to recognize CRE-like elements shown to be involved in HTLV-1 transcription.

Animals↗

The greening of engineers: a cross-cultural experience.

Experience with a group of mechanical engineering seniors at the University of Colorado led to an informal experiment with engineering students in India. An attempt was made to qualitatively gauge the students' ability to appreciate a worldview different from the standard engineering worldview--that of a mechanical universe. Qualitative differences between organic and mechanical systems were used as a point of discussion. Both groups were found to exhibit distinct thought and behavior patterns which provide important clues for sensitizing engineers to environmental issues in future educational initiatives. Cross-cultural and global dimensions of these initiatives are discussed.

Colorado↗

A semiflexible polymer model applied to loop formation in DNA hairpins.

A statistical mechanical "zipper" model is applied to describe the equilibrium melting of short DNA hairpins with poly(dT) loops ranging from 4 to 12 bases in the loop. The free energy of loop formation is expressed in terms of the persistence length of the chain. This method provides a new measurement of the persistence length of single-stranded DNA, which is found to be approximately 1.4 nm for poly(dT) strands in 100 mM NaCl. The free energy of the hairpin relative to the random coil state is found to scale with the loop size with an apparent exponent of > or = 7, much larger than the exponent of approximately 1.5-1.8 expected from considerations of loop entropy alone. This result indicates a strong dependence of the excess stability of the hairpins, from stacking interactions of the bases within the loop, on the size of the loop. We interpret this excess stability as arising from favorable hydrophobic interactions among the bases in tight loops and which diminish as the loops get larger. Free energy profiles along a generalized reaction coordinate are calculated from the equilibrium zipper model. The transition state for hairpin formation is identified as an ensemble of looped conformations with one basepair closing the loop, and with a lower enthalpy than the random coil state. The equilibrium model predicts apparent activation energy of approximately -11 kcal/mol for the hairpin closing step, in remarkable agreement with the value obtained from kinetics measurements.

Base Composition↗

Peripartum cardiomyopathy: National Heart, Lung, and Blood Institute and Office of Rare Diseases (National Institutes of Health) workshop recommendations and review.

OBJECTIVE: Peripartum cardiomyopathy (PPCM) is a rare life-threatening cardiomyopathy of unknown cause that occurs in the peripartum period in previously healthy women. In April 1997, the National Heart, Lung, and Blood Institute (NHLBI) and the Office of Rare Diseases of the National Institutes of Health (NIH) convened a Workshop on Peripartum Cardiomyopathy to foster a systematic review of information and to develop recommendations for research and education. PARTICIPANTS: Fourteen workshop participants were selected by NHLBI staff and represented cardiovascular medicine, obstetrics, immunology, and pathology. A representative subgroup of 8 participants and NHLBI staff formed the writing group for this article and updated the literature on which the conclusions were based. The workshop was an open meeting, consistent with NIH policy. EVIDENCE: Data presented at the workshop were augmented by a MEDLINE search for English-language articles published from 1966 to July 1999, using the terms peripartum cardiomyopathy, cardiomyopathy, and pregnancy. Articles on the epidemiology, pathogenesis, pathophysiology, diagnosis, treatment, and prognosis of PPCM were included. RECOMMENDATION PROCESS: After discussion of data presented, workshop participants agreed on a standardized definition of PPCM, a general clinical approach, and the need for a registry to provide an infrastructure for future research. CONCLUSIONS: Peripartum cardiomyopathy is a rare lethal disease about which little is known. Diagnosis is confined to a narrow period and requires echocardiographic evidence of left ventricular systolic dysfunction. Symptomatic patients should receive standard therapy for heart failure, managed by a multidisciplinary team. If subsequent pregnancies occur, they should be managed in collaboration with a high-risk perinatal center. Systematic data collection is required to answer important questions about incidence, treatment, and prognosis.

Cardiomyopathies↗

Fetal microchimerisms in the mother: immunologic implications.

The previously held concept that the fetus is completely separated from the mother, especially by trophoblasts that line the outer layer of the placenta, has recently been questioned. It has recently been shown that fetal cells are detectable not only in the peripheral blood, but also in maternal skin and liver. Although the migration of fetal cells into the maternal circulation has been given a great deal of attention because of its implication in the prenatal diagnosis of genetic diseases, the potential role of such placental transfer of fetal cells in the pathogenesis of autoimmune diseases has only recently been considered. In patients with scleroderma, fetal cell-derived DNA was detected more frequently in the peripheral blood of patients than controls. This finding of a limited number of fetal cells in maternal tissues leading to microchimerism has been proposed to have a role in the induction of scleroderma. Although evidence for microchimerism has also been confirmed in a high frequency of liver tissues from patients with primary biliary cirrhosis (PBC), a similar high frequency was noted in control patients, which suggests that microchimerism by itself is unlikely to fully account for the pathogenesis of PBC. The finding of such a high frequency of fetal microchimerism in the liver suggests that this is a very common event, raising the possibility that the migration of fetal cells may be important in the induction and subsequent maintenance of tolerance against the fetus during pregnancy. In addition, it is clearly possible that such microchimerism could contribute to the pathogenesis of select autoimmune diseases.

Autoimmunity↗

Comparative immunoreactivity of anti-trifluoroacetyl (TFA) antibody and anti-lipoic acid antibody in primary biliary cirrhosis: searching for a mimic.

Previous studies documenting the existence of cross-reactivity between the lipoated (but not unlipoated) forms of the inner lipoyl domain (E2L2) of PDC-E2 [the major autoantigen in Primary biliary cirrhosis (PBC)] and trifluoroacetylated (TFA) proteins, led us to hypothesize that PBC may be due to an initial insult with an environmental agent that cross-reacts with TFA. Therefore, we performed a comparative study of the reactivity of rabbit anti-TFA antibody and anti-lipoic acid (LA) antibody against the mitochondrial autoantigens of human PBC and various TFA and LA conjugated proteins. Whereas both anti-TFA and anti-LA reacted with PDC-E2, the wild-type lipoated form of E2L2, OGDC-E2, E3-BP and LA-KLH, neither reacted with BCOADC-E2 or the non-lipoated form of E2L2. Of interest was that while anti-TFA reacted with PDC-E2, TFA-RSA and LA-KLH, it failed to inhibit PDC-E2 enzyme function. In contrast, anti-LA demonstrated cytoplasmic and mitochondrial staining, and inhibited PDC enzyme activity. Hence, although considerable cross reactivity exists between anti-TFA and anti-LA, the molecular nature of the interaction is clearly different. One of 14 PBC sera reacted weakly with TFA-albumin, whereas four of 14 PBC sera reacted with LA-KLH. Immunohistochemically, both anti-TFA and anti-LA antibodies reacted focally with periportal hepatocytes and bile ducts in both PBC and controls. However, anti-LA produced much stronger focalized staining of the bile ducts of diseased liver. This study suggests that while anti-TFA antibody recognizes lipoic acid-linked enzymes and proteins, the epitope recognized differs from that of anti-LA antibody and PBC autoantibodies. It is unlikely that a response to TFA is the triggering event in PBC. Anti-LA antibodies share a higher degree of similarity to PBC sera providing suggestive evidence that anti-LA antibodies or anti-LA like antibodies (mimotopes) may help define the initiator of the autoimmune response.

Animals↗

Genotypic analysis of hepatitis C virus in blood donors in Indonesia.

A study was conducted to describe the genetic diversity of hepatitis C virus (HCV) in a population of positive blood donors from throughout Indonesia. Repeat analysis by reverse transcription-polymerase chain reaction (RT-PCR) of 102 anti-HCV positive samples showed that 67 gave HCV-specific positive signals by the PCR for the 5'-untranslated genomic region of HCV. Further genotypic analysis on 64 HCV RNA-positive samples indicated that 57 belonged to the following individual genotypes: 1a, 1b, 2a, 2b, and 3b. The predominant HCV genotypes in this donor population were 1b (57.8%), 2a (17.2%), and 3b (10.9%). The core sequences of the 4 indeterminate samples when aligned with published sequences of various HCV genotypes showed a range of homology from 16.16% to 78.67%. Comparative analysis of genotypic representation from other anti-HCV-positive study populations, including polytransfused pediatric and adult renal dialysis groups, is now being carried out to determine the potential genotypic association with mechanistic HCV spread.

5' Untranslated Regions↗