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Biomedical subjects

A Rahman

Publications and source records attributed to A Rahman.

At least 109 records · Page 6Linked to original sources

Involvement of ethylene and gibberellin signalings in chromosaponin I-induced cell division and cell elongation in the roots of Arabidopsis seedlings.

Chromosaponin I (CSI), a triterpenoid saponin isolated from pea, stimulates the growth of roots in Arabidopsis thaliana seedlings on wetted filter paper in the light for 14 d. The growth rates of roots in Columbia (Col) and Landsberg erecta (Ler) wild-types were 0.92 and 0.26 mm d(-1), respectively, and they were accelerated to 3.46 (Col) and 2.20 (Ler) mm d(-1) by treating with 300 microM CSI. The length of mature epidermal cells was increased by 1.8-fold (Col) and 2.81-fold (Ler) compared with control and the number of epidermal cells was increased by a factor of 1.65 (Col) and 2.12 (Ler). Treatment with 2-aminoethoxyvinylglycine (AVG), an inhibitor of ethylene biosynthesis, also increased cell length but not cell number. The effects of CSI on root growth were not detected in the ethylene-insensitive mutant ein2-1. CSI did not inhibit ethylene production but stimulated the growth of roots in ctr1-1, the constitutive triple response mutant for ethylene, indicating that CSI inhibits ethylene signaling, especially downstream of CTR1. In the GA-insensitive mutant gai and the mutant spy-3, in which the basal level of GA signaling is activated, CSI did not increase cell number, although both CSI and AVG stimulated cell elongation in these mutants. These results suggest that the inhibition of ethylene signaling is the cause of CSI-induced cell elongation. A possible involvement of both GA and ethylene signalings is discussed for the CSI-induced cell division.

Aminobutyrates↗

Impact of beta-adrenoceptor antagonists on myofilament calcium sensitivity of rabbit and human myocardium.

Beta-adrenoceptor antagonists (beta-blockers) are commonly used in clinical pharmacotherapy of cardiovascular diseases. Carvedilol and nebivolol possess beneficial effects on myocardial function in situations of oxidative stress associated with intracellular calcium overload. This preservation of contractile function might be due to direct scavenging capacities or to compensation of the intracellular calcium overload through direct impact on myofilament calcium sensitivity. Accordingly, we measured the relation between calcium and force in the absence and in the presence of 10(-6) M carvedilol, nebivolol, or propranolol in skinned right ventricular trabeculae of rabbit hearts. In rabbit myocardium, nebivolol (10(-6) M) altered the pCa50% by a rightward shift (less sensitive) from 5.72 +/- 0.05 to 5.57 +/- 0.05 (p < 0.05). Maximal force development was reduced by nebivolol. In contrast, the same concentration of propranolol or carvedilol did not influence calcium sensitivity and force development. In additional experiments, we repeated this protocol in trabeculae from human failing hearts. As in rabbit trabeculae, nebivolol shifted the pCa50% by 0.16 +/- 0.04 pCa units to the right (p < 0.05). Experiments with intact rabbit trabeculae confirmed depressed contractility: when all beta-adrenoceptors were blocked by 10(-6) M propranolol, subsequent addition of 10(-6) M nebivolol reduced developed force of these muscles significantly from 3.1 +/- 0.9 to 1.7 +/- 0.4 mN/mm2. We conclude that nebivolol desensitizes cardiac myofilaments slightly, whereas neither propranolol nor carvedilol had an effect.

Actin Cytoskeleton↗

Associations between drinking water and urinary arsenic levels and skin lesions in Bangladesh.

The present study examined the associations between drinking water and urinary arsenic levels and skin lesions among 167 residents of three contiguous villages in Bangladesh. Thirty-six (21.6%) had skin lesions (melanosis, hyperkeratosis, or both), of which 13 (36.1%) occurred in subjects who were currently drinking water containing concentrations of arsenic < 50 micrograms/L. The risk for skin lesions in relation to the exposure estimates based on urinary arsenic was elevated more than 3-fold, with the odds ratios for the highest versus the lowest quartiles being 3.6 (95% confidence interval, 1.2 to 12.1) for urinary total arsenic and 3.2 (95% confidence interval, 1.1 to 10.0) for urinary creatinine-adjusted total arsenic. The risks for skin lesions in relation to the exposure estimates based on arsenic in drinking water were less strongly elevated, with the odds ratios for the highest versus the lowest quartiles of exposure being 1.7 (95% confidence interval, 0.6 to 5.1) for drinking-water arsenic and 2.3 for cumulative arsenic index. The study suggests that arsenic exposure is associated with skin lesions in the Bangladesh population and that urinary arsenic may be a stronger predictor of skin lesions than arsenic in drinking water in this population.

Adult↗

Developing child mental health services in developing countries.

There is an urgent need to pay attention to the mental health of children in developing countries. Professionals confronted with this task face a number of challenges. Services have to be planned in a rational way, keeping in mind the needs of local populations. These needs will often exceed the available resources, and it will be necessary to set priorities. Feasible and cost-effective models of service delivery then have to be developed to meet these needs. This annotation provides a framework within which mental health needs of children can be assessed, priorities established, and services organised. This is illustrated with examples of relevant activities undertaken in low-income developing countries over the last two decades.

Child↗

Protein kinase C-zeta mediates TNF-alpha-induced ICAM-1 gene transcription in endothelial cells.

We addressed the role of protein kinase C (PKC) isozymes in mediating tumor necrosis factor-alpha (TNF-alpha)-induced oxidant generation in endothelial cells, a requirement for nuclear factor-kappaB (NF-kappaB) activation and intercellular adhesion molecule-1 (ICAM-1) gene transcription. Depletion of the conventional (c) and novel (n) PKC isozymes following 24 h exposure of human pulmonary artery endothelial (HPAE) cells with the phorbol ester, phorbol 12-myristate 13-acetate (500 nM), failed to prevent TNF-alpha-induced oxidant generation. In contrast, inhibition of PKC-zeta synthesis by the antisense oligonucleotide prevented the oxidant generation following the TNF-alpha stimulation. We observed that PKC-zeta also induced the TNF-alpha-induced NF-kappaB binding to the ICAM-1 promoter and the resultant ICAM-1 gene transcription. We showed that expression of the dominant negative mutant of PKC-zeta prevented the TNF-alpha-induced ICAM-1 promoter activity, whereas overexpression of the wild-type PKC-zeta augmented the response. These data imply a critical role for the PKC-zeta isozyme in regulating TNF-alpha-induced oxidant generation and in signaling the activation of NF-kappaB and ICAM-1 transcription in endothelial cells.

Cells, Cultured↗

Activation of NF-kappaB induced by H(2)O(2) and TNF-alpha and its effects on ICAM-1 expression in endothelial cells.

Reactive oxygen species have been proposed to signal the activation of the transcription factor nuclear factor (NF)-kappaB in response to tumor necrosis factor (TNF)-alpha challenge. In the present study, we investigated the effects of H(2)O(2) and TNF-alpha in mediating activation of NF-kappaB and transcription of the intercellular adhesion molecule (ICAM)-1 gene. Northern blot analysis showed that TNF-alpha exposure of human dermal microvascular endothelial cells (HMEC-1) induced marked increases in ICAM-1 mRNA and cell surface protein expression. In contrast, H(2)O(2) added at subcytolytic concentrations failed to activate ICAM-1 expression. Challenge with H(2)O(2) also failed to induce NF-kappaB-driven reporter gene expression in the transduced HMEC-1 cells, whereas TNF-alpha increased the NF-kappaB-driven gene expression approximately 10-fold. Gel supershift assay revealed the presence of p65 (Rel A), p50, and c-Rel in both H(2)O(2)- and TNF-alpha-induced NF-kappaB complexes bound to the ICAM-1 promoter, with the binding of the p65 subunit being the most prominent. In vivo phosphorylation studies, however, showed that TNF-alpha exposure induced marked phosphorylation of NF-kappaB p65 in HMEC-1 cells, whereas H(2)O(2) had no effect. These results suggest that reactive oxygen species generation in endothelial cells mediates the binding of NF-kappaB to nuclear DNA, whereas TNF-alpha generates additional signals that induce phosphorylation of the bound NF-kappaB p65 and confer transcriptional competency to NF-kappaB.

Binding, Competitive↗

A novel beta-glucuronidase inhibiting triterpenoid from Paeonia emodi.

A novel beta-glucuronidase inhibiting triterpene (1) has been isolated from the chloroform fraction of Paeonia emodi beta-glucuronidase inhibit established ase chloroform fraction of Pa 11,beta,5alpha,23,24-pentahydroxy-30-norolean-12,20(29)-d ien-28-oic acid on the basis of spectroscopic analysis, including high resolution mass spectroscopy, one and two-dimensional NMR techniques. Oleanolic acid, betulinic acid, ethyl gallate, methyl grevillate and 1,5-dihydroxy-3-methylanthraquinone are also reported for the first time from Paeonia emodi.

Acetylation↗

Standardization and decomposition of rates: useful analytic techniques for behavior and health studies.

Standardization and decomposition are widely used analytic techniques in population studies for adjusting the impact of compositional factors on rates. This study demonstrates the application of these methods to behavior and health studies. Bootstrapping is used to estimate standard errors of the component effects and to conduct significance tests for them. The authors have developed a Windows-based computer program that is demonstrated in the study for standardization and decomposition analysis by using empirical data on HIV seropositivity rates in two injection-drug-using populations in the northeastern United States.

Data Interpretation, Statistical↗

Defective kinesin heavy chain behavior in mouse kinesin light chain mutants.

Conventional kinesin, kinesin-I, is a heterotetramer of two kinesin heavy chain (KHC) subunits (KIF5A, KIF5B, or KIF5C) and two kinesin light chain (KLC) subunits. While KHC contains the motor activity, the role of KLC remains unknown. It has been suggested that KLC is involved in either modulation of KHC activity or in cargo binding. Previously, we characterized KLC genes in mouse (Rahman, A., D.S. Friedman, and L.S. Goldstein. 1998. J. Biol. Chem. 273:15395-15403). Of the two characterized gene products, KLC1 was predominant in neuronal tissues, whereas KLC2 showed a more ubiquitous pattern of expression. To define the in vivo role of KLC, we generated KLC1 gene-targeted mice. Removal of functional KLC1 resulted in significantly smaller mutant mice that also exhibited pronounced motor disabilities. Biochemical analyses demonstrated that KLC1 mutant mice have a pool of KIF5A not associated with any known KLC subunit. Immunofluorescence studies of sensory and motor neuron cell bodies in KLC1 mutants revealed that KIF5A colocalized aberrantly with the peripheral cis-Golgi marker giantin in mutant cells. Striking changes and aberrant colocalization were also observed in the intracellular distribution of KIF5B and beta'-COP, a component of COP1 coatomer. Taken together, these data best support models that suggest that KLC1 is essential for proper KHC activation or targeting.

Animals↗

Evidence that ferric nitrilotriacetate mediates oxidative stress by down-regulating DT-diaphorase activity: implications for carcinogenesis.

Ferric nitrilotriacetate (Fe-NTA) is a known complete renal carcinogen as well as renal and hepatic tumor promoter, which acts by generating oxidative stress in the tissue. However, the mechanism by which it generates this stress is not fully understood. In this study, we show that Fe-NTA down-regulates hepatic and renal quinone reductase (QR) activity dose dependently. The maximum decrease in the activity of QR was observed at 12 h in the liver and 6 h in the kidney following Fe-NTA treatment. However, at all other time points studied, QR activity was reduced. In addition, a parallel increase in protein carbonyl content, a sensitive indicator of tissue oxidative stress was observed both in the liver and kidney. The pretreatment of animals with antioxidants, butylated hydroxyanisole and butylated hydroxytoluene, prevented the observed inhibition in the activity of QR and enhanced the formation of protein carbonyl in both organs. These studies suggest that Fe-NTA-mediated generation of oxidant free radicals down-regulates QR activity which may be responsible, at least in part, for the observed renal and hepatic injury and carcinogenic properties of Fe-NTA.

Animals↗

Thrombin-induced p65 homodimer binding to downstream NF-kappa B site of the promoter mediates endothelial ICAM-1 expression and neutrophil adhesion.

We investigated the mechanisms by which proinflammatory mediator, thrombin, released during intravascular coagulation and tissue injury, induces ICAM-1 (CD54) expression in endothelial cells. Stimulation of HUVEC with thrombin resulted in dose- and time-dependent increases in ICAM-1 mRNA and cell surface expression and in ICAM-1-dependent endothelial adhesivity toward polymorphonuclear leukocytes. Transient transfection of endothelial cells with ICAM-1 promoter luciferase reporter gene (ICAM-1LUC) constructs indicated that deletion of upstream NF-kappa B site (-533 bases from translation start site) had no effect on thrombin responsiveness, whereas mutation/deletion of downstream NF-kappa B site (-223 bases from the translation start site) prevented the activation of ICAM-1 promoter, indicating that the downstream NF-kappa B site is critical for thrombin inducibility. NF-kappa B-directed luciferase activity increased approximately 3-fold when cells transfected with the plasmid pNF-kappa BLUC containing five copies of consensus NF-kappa B site linked to a minimal adenovirus E1B promoter-luciferase gene were exposed to thrombin, indicating that activation of NF-kappa B was essential for thrombin response. Gel supershift assays demonstrated that thrombin induced binding of NF-kappa Bp65 (Rel A) to downstream NF-kappa B site of the ICAM-1 promoter. Thrombin receptor activation peptide, a 14-amino-acid peptide representing the new NH2 terminus of proteolytically activated receptor-1, mimicked thrombin's action in inducing ICAM-1 expression. These data indicate that thrombin activates endothelial ICAM-1 expression and polymorphonuclear leukocyte adhesion by NF-kappa Bp65 binding to the downstream NF-kappa B site of ICAM-1 promoter after proteolytically activated receptor-1 activation.

Cell Line↗

Structure-function analysis and the molecular origins of anti-DNA antibodies in systemic lupus erythematosus.

Patients with the autoimmune rheumatic disease systemic lupus erythematosus (SLE or 'lupus') develop a wide variety of clinical and serological manifestations including the presence of antibodies to double-stranded DNA (dsDNA), which are often diagnostic and potentially pathogenic. In this review, we have examined the links between the structure and function of anti-dsDNA antibodies, emphasising their clinical associations. We have also reviewed studies involving animal models, the analysis of human antibody sequences and studies of, and using, computer modelling and crystal structure.

Journal Article↗

Zonal allocation for thoracic organs in the united kingdom: Has it been successful? A single-center view.

OBJECTIVES: The purpose of this study was to analyze the impact of the zonal allocation system for thoracic organs on the outcome of our transplant activity. METHODS: We analyzed the results of thoracic transplants performed between 1987 and 1998. The transplants were divided into 3 groups: local donors retrieved by our team (171 hearts and 61 lungs; DL group); distant donors retrieved by our team (58 hearts and 35 lungs; DD group); and distant donors retrieved by other teams (51 hearts and 41 lungs; DX group). RESULTS: No significant differences were observed among the groups in early postoperative events for either heart or lung transplantation. Heart transplants: Cardiac index was 2.6 +/- 0.4 L/m(2) for the DL group, 2.7 +/- 0.6 L/m(2) for the DD group, and 2.5 +/- 0.7 L/m(2) for the DX group (P =.4). The 30-day mortalities were 9.1%, 9.1%, and 8.3% ( P =.5) and the 1-year survivals 83%, 80%, and 82% ( P =.4) for the DL, DD, and DX groups, respectively. Lung transplants: Alveolar-arterial oxygen gradient was 358 +/- 19 mm Hg for the DL group, 345 +/- 17 mm Hg for the DD group, and 329 +/- 21 mm Hg for the DX group (P =.07). The 30-day mortalities were 9.9%, 10.5%, and 12.8% (P =.2) and the 1-year survivals 79%, 75%, and 77% (P =.3) for the DL, DD, and DX groups, respectively. CONCLUSION: Zonal allocation for thoracic organs has been successfully applied to our program. Using donor organs retrieved by other teams, we have achieved equivalent outcomes for both heart and lung transplantation.

Actuarial Analysis↗

Bicaval and standard techniques in orthotopic heart transplantation: medium-term experience in cardiac performance and survival.

OBJECTIVE: The aim of this study was to compare the medium-term results of right heart pressures, tricuspid valve dysfunction, overall cardiac performance, and survival between the bicaval and standard techniques. METHOD: Between 1991 and 1997, 201 heart transplantations were performed in our center. Right heart catheterization was performed up to 12 months after transplantation. Echocardiography was used to assess left ventricular and tricuspid valve function. RESULT: The standard technique was used in 105 cases, and the bicaval technique was used in 96 cases. There was no difference in the age, preoperative parameters, pulmonary hemodynamics, or ischemic time between the 2 groups. Right atrial pressure (4.3 +/- 4.0 mm Hg for the bicaval vs 10.9 +/- 4.8 mm Hg for standard technique) and mean pulmonary artery pressure (17.5 +/- 5.3 mm Hg and 22.5 +/- 5.2 mm Hg, respectively) were lower for the bicaval recipients up to 12 months after the operation (P =.001 and. 01, respectively). Left ventricular ejection fraction was higher for the recipients of the bicaval technique up to the most recent measurement (P =.005). The prevalence of moderate or severe tricuspid regurgitation was higher in the recipients of the standard technique up to the most recent measurement (28% vs 7%; P =.02). The actuarial survival at 1, 3, and 5 years was 74%, 70%, and 62% for the recipients of the standard technique versus 87%, 82%, and 81% for the recipients of the bicaval technique (P <.03, <.04, and <.02, respectively). CONCLUSION: The bicaval technique maintains good left ventricular function, lower incidence and severity of tricuspid valve dysfunction, and improved survival compared with the standard technique.

Actuarial Analysis↗

Transforming growth factor beta (TGF-beta) and obliterative bronchiolitis following pulmonary transplantation.

BACKGROUND: Obliterative bronchiolitis (OB) characterised by small-airway fibrosis is a major cause of morbidity and mortality after lung transplantation. TGF-beta has been implicated in the pathogenesis of fibrosis. METHODS: We immunohistochemically examined 380 transbronchial biopsies (from 91 pulmonary transplants) using TGF-beta polyclonal antibodies. OB and interstitial fibrosis were diagnosed and graded in all biopsies. Other potential histologic and clinical risk factors for OB were analysed. RESULTS: Procedures were heart and lung (n = 32), bilateral sequential lung (n = 18), and single lung transplantation (n = 41). The incidence of OB in this group was 28.5%. In all patients with OB, TGF-beta was immunolocalized in the airways and lung parenchyma. TGF-beta expression was greater in OB patients (median score 8, range 5-12) in comparison to patients without OB (median score 4, range 1-13), p < .0001. Positive TGF-beta staining preceded the histologic confirmation of OB by 6 to 18 months. The development of OB was associated with two HLA mismatches at the A locus (p = .02); recurrent acute rejection episodes (p < .0005); lymphocytic bronchiolitis (p = .0001); and tissue eosinophilia, regardless of the rejection grade (p < .0001). CONCLUSIONS: Increased expression of TGF-beta is a risk factor for the development of OB. Other risk factors are recurrent acute rejection, lymphocytic bronchiolitis, tissue eosinophilia, and two mismatches at the HLA-A locus. This suggests that the pathogenesis of progressive small airway fibrosis characteristic of OB may be inflammatory damage, followed by an aberrant repair process due to excessive TGF-beta production following allograft injury. Hence, modulation of TGF-beta levels or function by antagonists may represent an important approach to control OB.

Adult↗

Information acquisition from audio-video-data sources: an experimental study on remote diagnosis. The LOTAS Group.

OBJECTIVE: To determine what information sources are used during a remote diagnosis task. MATERIALS AND METHODS: Experienced trauma care providers viewed segments of videotaped initial trauma patient resuscitation and airway management. Experiment 1 collected responses from anesthesiologists to probing questions during and after the presentation of recorded video materials. Experiment 2 collected the responses from three types of care providers (anesthesiologists, nurses, and surgeons). Written and verbal responses were scored according to detection of critical events in video materials and categorized according to their content. Experiment 3 collected visual scanning data using an eyetracker during the viewing of recorded video materials from the three types of care providers. Eye-gaze data were analyzed in terms of focus on various parts of the videotaped materials. RESULTS: Care providers were found to be unable to detect several critical events. The three groups of subjects studied (anesthesiologists, nurses, and surgeons) focused on different aspects of videotaped materials. CONCLUSION: When the remote events and activities are multidisciplinary and rapidly changing, experts linked with audio-video-data connections may encounter difficulties in comprehending remote activities, and their information usage may be biased. Special training is needed for the remote decision-maker to appreciate tasks outside his or her speciality and beyond the boundaries of traditional divisions of labor.

Anesthesiology↗