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Biomedical subjects

N Islam

Publications and source records attributed to N Islam.

At least 91 records · Page 5Linked to original sources
PubMed1995

Thrombosis and inflammation as multicellular processes: significance of cell-cell interactions.

Platelet activation as a result of vascular injury provokes endothelial cells to respond in a manner which limits or reverses the occlusive consequences of platelet accumulation. If the agonistic forces are strong, platelet accumulation is irreversible. In vitro data from our laboratory have repeatedly demonstrated that platelets become unresponsive to all agonists when in proximity to endothelial cells. This unresponsiveness is due to at least three separate endothelial "thromboregulatory" systems: eicosanoids, endothelium-derived relaxing factor (EDRF/NO), and most importantly an endothelial cell ecto-nucleotidase which metabolizes released platelet adenosine diphosphate (ADP) with consequent restoration of platelets to the resting state. This nucleotidase is operative in the complete absence of EDRF/NO and eicosanoids, indicating that the latter two are dispensable thromboregulators. We have solubilized the human endothelial cell ectoADPase, as well as that from placental tissue. Candidate proteins from a purified ADPase fraction are now being studied in further detail. An understanding of the molecular biology of the ADPase gene may lead to development of therapeutic agents such as soluble forms of the enzyme as well as approaches toward up-regulation of ectoADPase activity. This could result in "early thromboregulation", i.e. prevention and/or reversal of platelet accumulation at sites of vascular damage via immediate metabolic removal of the prime platelet agonist-ADP.

Adenosine Diphosphate↗
PubMed1994

Anodal polarization induces protein kinase C gamma (PKC gamma)-like immunoreactivity in the rat cerebral cortex.

Protein kinase C gamma (PKC gamma)-like immunoreactivity was examined in the rat brain, employing the monoclonal antibody 36G9 raised against purified PKC gamma, after an application of weak anodal direct current to the surface of the sensorimotor cortex. Anodal polarization with 3.0 microA for 30 min resulted in a pronounced increase in the number of PKC gamma-like-positive neurons in accordance with the intensity of PKC gamma-like immunostaining in the neocortex, cingulate cortex and piriform cortex ipsilateral to the polarization. The number of PKC gamma-like-positive neurons began to increase at 1 h after polarization, peaked at 3 h, and thereafter decreased to the control levels by 72 h. The increase in expression of PKC gamma-like immunoreactivity in specific areas of the cerebral cortex is suggested to serve as a basis for the long-lasting hyperexcitability in situ following anodal polarization.

Animals↗
PubMed1994

An analysis of Xenopus tyrosine kinase genes and their expression in early development.

Xenopus laevis and X. borealis were screened for tyrosine kinase genes using the polymerase chain reaction (PCR) and reverse transcriptase (RT)-PCR and 34 X. laevis and 23 X. borealis tyrosine genes were identified. Eighteen of the genes represented novel tyrosine kinase family members. The rest could be classified into known tyrosine kinase subfamilies, of which however only three have been previously identified in Xenopus. Eight clones, including bFGFR (xFGFR1) and potential Trk, Ins R., Fak, Fyn, and Abl homologs, were used to probe temporal and spatial gene expression in early development. Quantitative RT-PCR and whole-mount and in situ hybridization showed that most of these mRNAs were present throughout development and were broadly distributed, mainly in ectodermal and mesodermal derived tissues. At the blastula stage, bFGFR mRNA was detected within the ectoderm and a gradient of expression was noted within the invaginating mesoderm. The unexpected promiscuous expression of many tyrosine kinase genes in early development is discussed.

Amino Acid Sequence↗
PubMed1994

Repeated application of anodal direct current produces regional dominance in histamine-elicited cyclic AMP accumulation in rabbit cerebral cortex.

A unilateral 30-min application of anodal direct current to the promotor cortex of rabbits was repeated 10 times, and cyclic AMP accumulation in response to histamine was investigated in slices of different cortical areas. Polarization with 1.0 microA decreased the cyclic AMP accumulation in the cortical area contralateral to the polarization, by which regional dominance in cyclic AMP accumulation was produced in the polarized cortex. In contrast, the regional difference in cyclic AMP accumulation was reversed when 10.0 or 30.0 microA was applied. The histamine-elicited accumulation of cyclic AMP was almost completely inhibited by the selective H2-receptor antagonist cimetidine. These results suggest that repeated anodal polarization regionally alters H2-receptor-mediated cyclic AMP generation in the cortex depending on the intensity of the polarizing currents and this pattern of cyclic AMP accumulation is responsible for the characteristic motor behavior induced by anodal polarization.

Animals↗
PubMed1994

Appearance of dark neurons following anodal polarization in the rat brain.

An anodal direct current of 3.0 microA or 30.0 microA was unilaterally applied for 30 min or 3 h to the surface of the sensorimotor cortex of rats, and the effects of polarization on the morphology of brain cells were examined by light microscopy. After five repeated anodal polarization trials, dark neurons appeared mainly in the polarized neocortex regardless of the intensity and duration of the polarizing currents. Such dark neurons were scarce in the control animals or the animals receiving only one trial of polarization. The dark neurons were most abundant in the second to fourth layers of the ipsilateral superior-lateral convexity of the frontal cortex, but a few were present in the contralateral cortex. The dark neurons began to appear 24 h after the last polarization; thereafter almost all of these neurons gradually reverted to their normal morphological profiles through a transitory state within 1 month of the last trial of repeated polarization. No morphological changes were apparent in any of the brain structures other than the cerebral cortex. These findings indicate that repeated anodal polarization has reversible morphological effects on the cortical neurons, suggesting that the appearance of dark neurons after anodal polarization is an important index for evaluation of cortical plastic change induced by polarization.

Animals↗
PubMed1994

Induction of N-methyl-D-asparate receptor mediated c-fos protein in the rat brain by incomplete ischaemia.

The expression of c-fos protein was examined by means of immunocytochemistry in the rat brain following incomplete ischaemia, to elucidate the molecular mechanisms of post-ischaemic neuronal death and of the modulated neurotransmission of surviving neurons. Incomplete ischaemia was produced by permanent unilateral or bilateral common carotid artery (CCA) occlusion. After 1 h of unilateral occlusion, the level of c-fos protein-like nuclear immunoreactivity increased in cortical neurons ipsilateral to the insult, especially in cingulate and piriform cortices. The reactivity peaked at 3-6 h, and was undetectable after 3 days. A number of scattered immunostained neurons in the ipsilateral subiculum, CA 1 and dentate gyrus became visible after 1 day. The effect reached a peak between 1-3 days, then returned to basal levels by 7 days. Bilateral CCA occlusion showed a similar distribution of immunoreactivity, but on both hemispheres. Immunoreactive neurons were more numerous and intensely stained but more transient. The induction of c-fos was completely blocked or reduced by treatment with MK-801. Our results suggest that c-fos expression after CCA occlusion is NMDA receptor mediated, and that it has a specific role in neurons after ischaemic insult.

Animals↗
PubMed1993

Characterization of adenosine receptor-mediated generation of cyclic AMP in slices of rat cerebral cortex with chronic epileptic activity.

Cyclic AMP accumulations elicited by adenosine analogues 2-chloroadenosine (2-CADO), R-N6-phenylisopropyladenosine (R-PIA), and N6-cyclohexyladenosine (CHA) were investigated in cortical slices of chronic iron-induced epileptic rats. Cyclic AMP accumulation was elicited 9- to 18-fold by 2-CADO and it was elicited 5- to 7-fold by either R-PIA or CHA; 2-CADO was more potent than R-PIA or CHA in eliciting cyclic AMP accumulation. The adenosine analogues elicited cyclic AMP accumulation in a dose-dependent manner, and the elicitation was inhibited by the adenosine antagonist 8-phenyltheophylline. The 2-CADO-elicited accumulation of cyclic AMP was greatly increased in the cortical region on the primary epileptic side, while the R-PIA- or CHA-elicited accumulation did not change in any cortical region. The deviation detected only in the 2-CADO-elicited accumulation of cyclic AMP may be due to the difference in relative potency for adenosine receptors of the adenosine analogues. The results suggest that adenosine receptor-mediated generation of cyclic AMP is altered in the primary region of iron-induced epileptic cortex, in which heterogeneous alterations in different adenosine receptor subtypes may occur in the epileptic process.

2-Chloroadenosine↗
PubMed1993

The diagnosis of Poncet's disease.

Two cases of polyarthritis in young people with extra-articular tuberculosis are described. The clinical features were consistent with the concept of Poncet's disease. After synovial biopsy one patient proved to have tuberculous peripheral arthritis. This observation raised doubts about the diagnosis in the other patient. Multiple joints may be simultaneously infected with Mycobacterium tuberculosis and Poncet's disease, if it exists, should not be entertained in the absence of synovial biopsy.

Adolescent↗
PubMed1993

Does squatting reduce pelvic floor descent during defaecation?

Neurogenic faecal and urinary incontinence result from a stretch-induced injury to the pelvic nerves, from difficult childbirth or from chronic straining at stool. It has been suggested that the condition occurs less frequently in societies where the squatting position is used during defaecation, and that squatting may minimize pelvic floor descent. This is a prospective study which evaluates the position of the pelvic floor during defaecation straining in 52 patients. The position of the perineum was measured at rest and during maximal defaecation straining using a perineometer, with the patient in the left lateral, sitting and squatting positions. There was a significant difference in the position of the perineum at rest and on straining between the left lateral position and both the sitting and squatting positions. However, there was no significant difference at rest or on straining between the sitting and squatting positions. These results show that squatting does not reduce pelvic floor descent during defaecation straining, and imply that squatting would not help reverse stretch-induced pudendal nerve damage.

Defecation↗
PubMed1993

Downregulation of human platelet reactivity by neutrophils. Participation of lipoxygenase derivatives and adhesive proteins.

Unstimulated neutrophils inhibited activation and recruitment of thrombin- or collagen-stimulated platelets in an agonist-specific manner. This occurred under conditions of close physical cell-cell contact, although biochemical adhesion between the cells as mediated by P-selectin was not required. Moreover, in the presence of monoclonal P-selectin antibodies that blocked biochemical platelet-neutrophil adhesion, thrombin-stimulated platelets were more efficiently downregulated by neutrophils. This suggested a prothrombotic role for P-selectin under these circumstances. The neutrophil downregulatory effect on thrombin-stimulated platelets was amplified by lipoxygenase inhibition with 5,8,11,14-eicosatetraynoic acid. In contrast, the neutrophil inhibitory effect on platelets was markedly reduced by platelet-derived 12S-hydroxy-5,8-cis, 10-trans, 14-cis-eicosatetraenoic acid (12S-HETE), as well as by the platelet-neutrophil transcellular product, 12S,20-dihydroxy-5,8,10,14-eicosatetraenoic acid (12S,20-DiHETE), but not by another comparable metabolite, 5S,12S-dihydroxy-6-trans, 8-cis, 10-trans, 14-cis-eicosatetraenoic acid (5S,12S-DiHETE), or the neutrophil-derived hydroxy acid leukotriene B4. The neutrophil downregulatory effect on thrombin-induced platelet reactivity was enhanced by aspirin treatment. This may represent a novel action of aspirin as an inhibitor of platelet function. These results provide in vitro biochemical and functional evidence for the thromboregulatory role of neutrophils and emphasize the multicellular aspect of hemostasis and thrombosis.

Adenosine Diphosphate↗
PubMed1993

Drug resistance of Mycobacterium tuberculosis in Karachi, Pakistan.

We determined the primary and secondary resistance of isolates of M. tuberculosis to the standard antituberculous drugs in Karachi (Pakistan). Primary resistance to one or more anti-tuberculous drugs was found in 17% of 123 isolates of M. tuberculosis (obtained from patients with no history of previous treatment for tuberculosis). Secondary resistance was found in 36% of 33 isolates (obtained from individuals who had received anti-tuberculous treatment in the past). The drug to which organisms were most commonly resistant was isoniazid (11% primary resistance, 30% secondary resistance). Fifteen per cent of isolates obtained from previously-studied patients showed secondary resistance to rifampicin. We discuss the importance of these findings for tuberculosis treatment and control.

Antitubercular Agents↗
PubMed1993

Fructosamine: an alternative assessment of past glycaemic control in developing countries.

Fructosamine assay determines glycaemic control in diabetic patients by measuring glycosylated plasma protein. This study was done to assess the value of fructosamine as an alternative test to HbA1c as a measure of glycaemia. Sixty patients (both insulin dependent diabetes mellitus and non insulin dependent diabetes mellitus) were selected from the diabetic clinic and fasting blood samples were collected for estimation of glucose, HbA1c and fructosamine levels. The results were compared by correlation analysis and major discrepancies/discordance was detected by dividing the results into 3 clinical categories and detecting the cases in which the values fell in opposite clinical categories. Fructosamine correlated well with HbA1c (r = 0.41, p < 0.01) and with fasting blood glucose (r = 0.45 p < 0.01). Major discordance was detected in the results of only 7 patients which can partly be attributed to different periods over which HbA1c and fructosamine reflect average glycaemia. Fructosamine measures glycaemia over the past 2-3 weeks and HbA1c over 8 weeks. As fructosamine assay is relatively inexpensive, reliable and simple to perform; it can be used as an alternative to HbA1c and is particularly suited for developing countries.

Blood Glucose↗
PubMed1993

Diabetic ketoacidosis in a hospital based population in Pakistan.

Sixty-two consecutive episodes of diabetic ketoacidosis (DKA) were studied at Aga Khan University Hospital, Karachi. Forty-four (71%) were type I and 18 (29%) type II diabetics. Mean age was 28.1 years and mean duration of diabetes 4.1 years. Infections were the most common precipitating factor accounting for 28 episodes (45.2%). Twenty-two patients (35.5%) had hyperosmolality (serum osmolality > 320 mosmol/L). Mean serum Na+ was 131.7 mmol/L and K+ 4.6 mmol/L. Twenty-three (37.1%) were hyperkalemic at presentation with seven patients (11.3%) being comatosed and 35 (56.5%) alert. Mean random blood glucose (RBG) was 624 mg/dl, mean pN 7.09, osmolality 316 mosmol/L and the neurological status correlated statistically significantly with mean RBG, pH and osmolality. A leukemoid response was seen in 83.9% episodes. Mortality rate was 8.0% in patients with DKA managed in this hospital.

Adolescent↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗