PubMed HealthSearch

Biomedical subjects

N Islam

Publications and source records attributed to N Islam.

At least 19 recordsLinked to original sources

Naturally occurring SLE anti-DNA antibodies recognize unique conformation on DNA-lysine photoadduct.

Native calf thymus DNA has been covalently modified with lysine under UV-A light. Human autoantibodies on purification through affinity column of native DNA linked to polylysyl-Sepharose 4B showed almost equal recognition of DNA and photoadduct. The recognition of DNA-lysine photoadduct by the affinity-purified autoantibodies might be helpful in understanding their origin in SLE vis-à-vis the role of positively charged amino acids in the pathogenesis of autoimmune diseases.

Animals

Enhancement of platelet reactivity and modulation of eicosanoid production by intact erythrocytes. A new approach to platelet activation and recruitment.

Erythrocytes are known to influence hemostasis. Bleeding times are prolonged in anemia and corrected by normalizing the hematocrit. We now demonstrate that intact erythrocytes modulate biochemical and functional responsiveness of activated platelets. A two-stage procedure, permitting studies of cell-cell interactions and independently evaluating platelet activation and recruitment within 1 min of stimulation, was developed. Erythrocytes increased platelet serotonin release despite aspirin treatment, enzymatic adenosine diphosphate removal, protease inhibition, or combinations thereof. The data suggested that erythrocyte enhancement of platelet reactivity can reduce the therapeutic effectiveness of aspirin. Erythrocytes metabolically modified platelet arachidonate or eicosapentaenoate release and eicosanoid formation. They promoted significant increases in cyclooxygenase and lipoxygenase metabolites upon platelet stimulation with collagen or thrombin. However, with ionophore, erythrocytes strongly reduced platelet lipoxygenation. These erythrocyte modulatory effects were stimulus-specific. Activated platelet-erythrocyte mixtures, with or without aspirin, promoted 3-10-fold increases in extracellular free fatty acid, which would be available for transcellular metabolism. Erythrocyte-induced increases in free eicosapentaenoate may contribute to antithrombotic and anti-inflammatory effects of this fish oil derivative. These results provide biochemical insight into erythrocyte contributions to thrombosis and hemostasis, and support the concept of thrombus formation as a multicellular event.

Adenosine Diphosphate

Inhibition of platelet function by an aspirin-insensitive endothelial cell ADPase. Thromboregulation by endothelial cells.

We previously reported that platelets become unresponsive to agonists when stimulated in combined suspension with aspirin-treated human umbilical vein endothelial cells. Inhibition occurred concomitant with metabolism of platelet-derived endoperoxides to prostacyclin by endothelial cells. We now demonstrate that if aspirin-treated platelets which fully respond to appropriate doses of agonists are exposed to aspirin-treated endothelial cells, they remain unresponsive despite absence of prostacyclin. Platelet inhibition is due in large part to ecto-ADPase activity on the endothelial cells. This was established by incubating aspirin-treated endothelial cells with 14C-ADP. Radio-thin layer chromatography and aggregometry demonstrated that 14C-ADP and induction of platelet activation decreased rapidly and concurrently. AMP accumulated transiently, was further metabolized to adenosine, and deaminated to inosine. The apparent Km of the endothelial cell ADPase was 33-42 microM and the Vmax 17-43 nmol/min per 10(6) cells, values in the range of antithrombotic potential. Thus, at least three complementary systems in human endothelial cells control platelet responsiveness: a cell-associated, aspirin-insensitive ADPase which functions in parallel with fluid phase autacoids such as the aspirin-inhibitable eicosanoids, and the aspirin-insensitive endothelium-derived relaxing factor.

Adenosine Diphosphate

Clinical profile: prognostic index in hepatocellular carcinoma.

A clinical study and follow-up of 77 patients (63 males and 14 females) with hepatocellular carcinoma with age range from 22 to 80 years were collected from the Institute of Post Graduate Medicine and Research and eight private hospitals from Dhaka City. Past history of transfusion was present in 16 (20.8%), Jaundice in 20 (26%) and 13 (16.9%) patients had associated cirrhosis. HBs Ag was positive in 17 (33.33%) out of 51 patients and liver ultrasound suggested hypoechogenic lesion in 44 (57.2%) patients. CT was performed in 7 (9.1%) and in one MRI was done. Eight (50%) out of 16 patients had alphafetoprotein ranging from 1000-12000 ng/ml. Space occupying lesion was detected in 25 (71.4%) out of 35 cases by isotope scan and needle biopsy was confirmatory in 25 (32.5%). Commonest presentations were abdominal lump (96.2%), weakness (79.3%), weight loss (74%), and loss of appetite (78%). Fifty six (72.2%) patients were followed weekly till death (2.9 +/- 2.4 months). The mean survival was higher under 30 years (5.9 +/- 3.7 months; P less than 0.05). Serum bilirubin above 5 mg/dl with HCC also had poor prognosis (1.6 +/- 0.8 months; P less than 0.01) Those who had prothrombin time higher than 16 seconds died earlier (1.6 +/- 0.7 months; P less than 0.01). Survival was poor in those who had the tumour size over 7 cm (2.5 +/- 0.9 months; P less than 0.01).

Adult

Pemphigoid and cancer.

To evaluate the significance of the association of malignant disease with bullous pemphigoid, we reviewed 497 consecutive cases with positive immunofluorescence tests for circulating antibodies to basement membrane. We searched the Swedish Cancer Registry, Stockholm, Sweden, for records reporting malignancies in the study population (1958 to 1985), and the expected number of malignancies was calculated on the basis of age- and sex-standardized incidence data. In 61 patients, a total of 69 malignancies were diagnosed. The expected number of malignancies was 82.6. In 25 patients, a total of 27 malignancies appeared during the same year as the onset of pemphigoid, or later. The expected number was 35.8. The median titer of circulating antibodies in the 497 patients, in the 61 patients with malignancy, and in the 25 patients with malignancy preceded by the pemphigoid, were not significantly different. We conclude that pemphigoid is not statistically associated with malignancy, and that the former hypothesis of such an association was based on age only.

Adult

Survival determinants in black patients with angiographically defined coronary artery disease.

Long-term survival of blacks with angiographically defined coronary artery disease was examined in a series of 1233 consecutive patients who underwent cardiac catheterization at a large urban municipal hospital. Vital status information was available at a mean of 86 weeks for the cohort as a whole, and 94 deaths were recorded. As noted in other angiographic series that included blacks, a high proportion of patients in this study had unobstructed coronary arteries (41%), and there was a preponderance of women (56%). Hypertension was present in 82% of the cases, whereas 68% of the sample had left ventricular hypertrophy as revealed by echocardiogram. The cumulative proportion of patients who were surviving at 5 years was 90 +/- 1 (+/- SEM), 79 +/- 4, and 70 +/- 4 for patients with no obstructive lesions, one-vessel disease, and multivessel disease, respectively. The survival rate at 3 years for patients who had undergone bypass surgery (N = 152) was only 82% (+/- 5%). Noninvasive univariate predictors of mortality included male sex, history of myocardial infarction, Q waves on electrocardiogram, exercise duration on treadmill stress testing, and left ventricular hypertrophy. Angiographic predictors included left ventricular end-diastolic pressure, the number of diseased coronary vessels, ejection fraction, and mean pulmonary artery pressure. Regression analysis showed an independent association for all the angiographic variables noted previously as well as for echocardiographically determined left ventricular hypertrophy. Survival rates for blacks with coronary artery disease in this series were considerably lower than those currently reported for whites, particularly for patients who underwent coronary bypass grafting.(ABSTRACT TRUNCATED AT 250 WORDS)

Black or African American

Smoking habit among Bangladesh Secretariat staff.

The paper assesses the smoking behaviour among the Bangladesh Secretariat Staff, Dhaka. The findings are based on interviewing 2008 respondents of whom 775 (38.6%) were reported to be smokers. Amongst the three categories of the respondents selected for interview, the prevalence of smoking was the highest (49%) for the respondents belonging to the lowest socio-economic group. The mean age at commencement of smoking was in the neighbourhood of 18 years. Majority of the smokers (76.5%) were motivated by their friends. Advertisement did not appear to have any influence of smoking. Nearly 17% were self motivated. Respondents' current age, level of education and employment status were found to have strong influence on smoking habit.

Adult

Platelet-neutrophil interactions. 12S,20- and 5S,12S-dihydroxyeicosapentaenoic acids: two novel neutrophil metabolites from platelet-derived 12S-hydroxyeicosapentaenoic acid.

Dietary marine n-3 polyunsaturated fatty acids have demonstrated an antiinflammatory potential in epidemiologic and intervention studies in humans. Proposed mechanisms, involving only leukocytes, fall short of explaining this potential completely. Enriched by dietary means with eicosapentaenoic acid (EPA), stimulated human platelets release substantial amounts of eicosapentaenoic acid and 12S-hydroxyeicosapentaenoic acid (12S-HEPE) in addition to 12S-hydroxyeicosatetraenoic acid (12S-HETE) derived from arachidonic acid. Human neutrophils metabolize 12S-HETE to 5S,12S-DiHETE when stimulated, whereas unstimulated neutrophils produce 12S,20-DiHETE. This study was undertaken to characterize metabolism of 12S-HEPE in human neutrophils. We demonstrate herein for the first time that 12S-HEPE is metabolized by human neutrophils. In unstimulated neutrophils 20-hydroxylation to 12S,20-DiHEPE occurs, whereas in stimulated neurtrophils 5-lipoxygenation to 5S,12S-DiHEPE takes place. The structures of these metabolites were characterized by their relative retention times on reversed-phase high pressure liquid chromatography, by their UV absorbance spectra, and by gas-liquid chromatography-mass spectrometry. With increasing amounts of 12S-HEPE, stimulated neutrophils produced increasing amounts of 5S,12S-DiHEPE, which is virtually inactive biologically. Concomitantly, production of the potent chemokinetic and chemoattractant arachidonic acid derivative leukotriene B4 decreased. Thus, 12S-HEPE can compete with endogenous arachidonic acid for 5-lipoxygenation in stimulated human neutrophils. 12,20-DiHEPE, LTB5, and 5S,12S-DiHEPE were detectable after coincubating EPA-enriched platelets with unenriched neutrophils, and arachidonic acid-derived 5-lipoxygenase products were decreased. We conclude that 12S-HEPE can participate in platelet-neutrophil interactions in a manner similar to 12S-HETE. By providing competing substrates for neutrophil 5-lipoxygenase, platelets might contribute to the antiinflammatory potential of dietary n-3 fatty acids through platelet-neutrophil interaction.

Anti-Inflammatory Agents, Non-Steroidal

Cell cations and blood pressure in US whites, US blacks, and west African blacks.

Differences in cell cation metabolism have been previously demonstrated between blacks and whites in the US. To investigate a potential racial/genetic basis for these differences we studied red cell sodium content (Nai) and platelet cytosolic calcium (Cai) in a group of US whites (n = 26), US blacks (n = 20) and West African blacks (n = 26) residing in Chicago, IL. Participants in all groups were primarily health professionals. The West Africans had lived in Africa until at least age 21 and subsequently resided in the US for an average of 19 months. Immunological markers were used to estimate European gene admixture among the US blacks. Red cell Nai was significantly lower in US whites (7.72 +/- 2.49 mEq/l cells) compared to both the US blacks and West African blacks (9.98 +/- 2.36 and 10.60 +/- 2.80, respectively; P less than 0.01) and Cai was higher in whites than among US blacks (P less than 0.05). No differences were noted in blood pressure (BP) levels among the three racial groups. A linear correlation existed between Nai and both systolic (SBP) and diastolic (DBP) (r = 0.378 and 0.339, respectively; P less than 0.01), which was strongest among the blacks, particularly the US blacks (SBP vs. Nai, r = 0.716, P less than 0.01). Approximately 20% European gene admixture was present among the US blacks. Based on these findings, it would appear that, compared to US whites, higher levels of RBC Nai are common to black persons native to the US and West Africa.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Severity of coronary artery disease among blacks with acute myocardial infarction.

A growing body of evidence suggests that survival after acute myocardial infarction (AMI) is considerably worse among blacks than whites. The severity of coronary artery disease (CAD), as measured by the number of diseased vessels and the degree of left ventricular dysfunction, is the major determinant of survival after AMI. To determine whether or not the severity of CAD could explain the poor prognosis in a cohort of blacks followed at this institution, cardiac catheterization was performed in a consecutive series of 51 patients less than 70 years of age. All patients were studied within 2 weeks after AMI. The mean age of the patients was 56 +/- 8 (mean +/- standard deviation) and 71% were men. A greater than or equal to 50 narrowing in 0, 1, 2 or 3 coronary arteries was noted in 5, 24, 40 and 31%, respectively. Left main stenosis was present in 3 patients (6%) and the mean left ventricular ejection fraction was 55%. In a subgroup of 20 patients echocardiographic estimates of left ventricular mass/height yielded a mean of 196 g/m, and left ventricular hypertrophy on echocardiogram was present in 74%. These data indicate that among blacks with AMI in this series CAD was only modestly more severe than expected and suggest that other factors most likely explain the high mortality in blacks after hospital discharge.

Black or African American

Platelet-neutrophil interactions. (12S)-hydroxyeicosatetraen-1,20-dioic acid: a new eicosanoid synthesized by unstimulated neutrophils from (12S)-20-dihydroxyeicosatetraenoic acid.

In the course of a cell-cell interaction, 12-HETE (12-hydroxy-5,8,10,14-eicosatetraenoic acid), the arachidonic acid lipoxygenase product released from stimulated platelets, is metabolized by a cytochrome P-450 enzyme system in unstimulated neutrophils to 12,20-DiHETE (12,20-dihydroxy-5,8,10,14-eicosatetraenoic acid). This report describes time-dependent formation of a new eicosanoid by unstimulated neutrophils exposed to 12-HETE, which is more polar than 12,20-DiHETE (reversed-phase high performance liquid chromatography). Time course studies indicated that the precursor compound of this new eicosanoid was 12,20-DiHETE. This was determined by incubation of purified 12,20-DiHETE with neutrophils, which resulted in a progressive decrease in 12,20-DiHETE as formation of the polar metabolite increased. In the absence of neutrophils, 12,20-DiHETE was quantitatively unchanged. The new metabolite of 12,20-DiHETE was identified as 12-hydroxyeicosatetraen-1,20-dioic acid, based upon its UV spectrum, co-chromatography with a chemically synthesized standard in both high performance liquid chromatography and thin layer chromatography systems, and gas chromatography-mass spectrometry. Formation of 12-HETE-1,20-dioic acid was partially inhibited by 20-hydroxy-LTB4. This indicated that the neutrophil dehydrogenase responsible for further metabolism of 12,20-DiHETE may also be involved in conversion of 20-hydroxy-LTB4 to 20-carboxy-LTB4. The 12,20-DiHETE dehydrogenase enzyme system specifically requires NAD as cofactor and has subcellular components in both cytosolic and microsomal fractions which are synergistic in their activity. These results provide additional evidence for the occurrence of multicellular metabolic events during hemostasis, thrombosis, and the inflammatory response.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid