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Biomedical subjects

A Halim

Publications and source records attributed to A Halim.

At least 19 recordsLinked to original sources

The incidence of deep and lobar intracerebral hemorrhage in whites, blacks, and Hispanics.

BACKGROUND: Black and Hispanic Americans have a greater risk of primary intracerebral hemorrhage (ICH) than whites. Deep ICH is most often associated with hypertension, while lobar ICH is associated with cerebral amyloid angiopathy. The authors conducted a population-based incidence study to directly compare the incidence of deep vs lobar ICH in all three race-ethnic groups. METHODS: The authors used an active hospital and community surveillance program and autopsy reports to identify incident ICH cases among white, black, and Caribbean Hispanic adults in Northern Manhattan between July 1993 and June 1997. Incidence rates were adjusted for age and sex to the 1990 US Census. CIs for risk ratios (RR) were calculated with Byar's chi2 approximation of the Poisson distribution. RESULTS: The authors identified 155 cases of ICH for an annual incidence of 30.9/100,000 (26.7 to 35.0). Men had a higher risk of ICH than women (RR 1.5, 95% CI 1.2 to 1.8), driven entirely by the incidence of deep ICH (RR 1.8) rather than lobar ICH (RR 1.0). Compared with whites, RR for blacks was all ICH 3.8 (2.2 to 8.9), deep 4.8 (2.3 to 21.1), lobar 2.8 (1.2 to 14.4); RR for Hispanics was all 2.6 (1.4 to 6.1), deep 3.7 (1.7 to 16.5), lobar 1.4 (0.4 to 7.4). CONCLUSIONS: ICH is a heterogeneous disease with deep and lobar subtypes distinguishable on an epidemiologic basis. The different patterns of these two subtypes in our race-ethnically diverse population lend credence to the notion that ICH should no longer be treated as a single entity.

Adult↗

Presenting features in Pakistani patients suffering from the antineutrophil cytoplasmic antibody--classical subtype (c-ANCA) associated vasculitis.

OBJECTIVES: To study the clinicopathological features in c-ANCA positive patients suffering from vasculitis with a view to find out the most common mode of presentation. STUDY DESIGN: Retrospective. SETTINGS: Department of Immunology, AFIP, Rawalpindi, MH Rawalpindi, CMH Rawalpindi, Department of Rheumatology, PIMS, Islamabad, RGH Rawalpindi, FFH, Rawalpindi. SUBJECTS: Seventeen patients suffering from vasculitis and found to be positive for c-ANCA. MAIN OUTCOME MEASURES: Clinico-pathological features at presentation. RESULTS: There were 9 males in age range 11-60 years (mean age 32.5 years) and 8 females in age range 26-42 years (mean age 32.3 years). Common presenting features were a combination of cough, blocked nose and post nasal drip 14/17 (82%) followed by nose bleed and haematuria 11/17 (65%). Six patients were demonstrated to be suffering from Wegener's granulomatosis after biopsy. C-ANCA was detected by indirect immunofluorescence in the titre range of 8-640. The auto antibody levels related to disease activity. CONCLUSION: c-ANCA associated vasculitis is a rare (17 patients in five years) but aggressive form of vasculitis. It must be suspected in patients with persistent respiratory tract related symptoms associated with fever and joint pains which fail to respond to adequate treatment for infections. The c-ANCA estimations can be utilised as sensitive and specific diagnostic and prognostic marker in this form of vasculitis.

Adolescent↗

Environmental risk factors for Parkinson's disease in an urban multiethnic community.

Environmental risk factors were examined using univariate and multivariate unconditional logistic regression models in 89 nondemented patients with Parkinson's disease (PD) and 188 control subjects in a multiethnic urban community. Rural living, area farming, and drinking well water were associated with PD only in African-Americans. In Hispanics, area farming was protective, whereas drinking unfiltered water was a risk factor for PD. Consideration of ethnic and cultural origin may add to the epidemiologic study of PD.

Aged↗

Correlated plasma elastase and sera cytotoxicity in eclampsia. A possible role of endothelin-1 induced neutrophil activation in preeclampsia-eclampsia.

The activation of neutrophils was studied in preeclampsia (n = 10) and eclampsia (n = 20) compared to normotensive controls (n = 10) and nonpregnant essential hypertensives (n = 10). Plasma elastase levels were raised in preeclampsia (0.53 +/- 0.32 microgram/mL, P < .002) and eclampsia (1.26 +/- 0.8 microgram/mL, P < .001) respectively compared to normal pregnancies (0.032 +/- 0.009 microgram/mL). The plasma elastases were more elevated in eclamptic cases compared to essential hypertensive (0.53 +/- 0.27 microgram/mL; P = .01) patients. We analyzed the correlation among elastase values, systolic (SBP), mean blood pressures (MBP), endothelin-1 (ET-1) levels and sera cytotoxicity (as measured by fura-2 release from human umbilical venous endothelial cell culture) in eclamptic cases. SBP and MBP were significantly correlated with plasma elastase levels in preeclampsia (r = 0.67, 0.63, respectively; P < .03) and eclampsia (r = 0.49, 0.49, respectively; P < .02). ET-1 levels were correlated with SBP (P = .003) and MBP (P = .001) and corresponding elastase levels (r = 0.606, P < .003) in eclamptic patients. Doses of 10, 25, and 50 pmol/mL of ET-1 increased elastase release in human neutrophil cultures dose and time dependently. Cytotoxicity of eclamptic sera correlated (P < .001) to the corresponding plasma elastase values. Therefore, this study suggests that neutrophil activation and ET-1 induced neutrophil activation occurs in this disease.

Adult↗

Stretching of fetal membranes increases the concentration of interleukin-8 and collagenase activity.

OBJECTIVE: The aim of this study was to determine whether stretching of fetal membranes can increase interleukin-8 concentration and collagenase activity. STUDY DESIGN: Strips of whole fetal membranes, amnion, or muscles of the lower uterine segment were stretched for 2 or 4 hours. Interleukin-8 and collagenase activity were measured in homogenized control and stretched samples. Immunohistochemical staining for interleukin-8 was carried out. RESULTS: The interleukin-8 concentration increased significantly after the whole fetal membranes were stretched for 2 and 4 hours (p <0.0007 and 0.001, respectively). Also, stretching of amnion and muscles of the lower uterine segment for 2 and 4 hours increased the concentration of interleukin-8 significantly (p <0.0007 after 2 and 4 hours, respectively). Collagenase activity was significantly increased after stretching of amnion, amniochorion, and muscles of the lower uterine segment for 4 hours (p <0.0007, 0.006, and 0.0007, respectively). After stretching, samples were darkly stained for interleukin-8 compared with control nonstretched samples. CONCLUSION: Stretching of amnion, amniochorion, and muscles of the lower uterine segment increased interleukin-8 production and collagenase activity.

Amnion↗

Plasma P selectin (GMP-140) and glycocalicin are elevated in preeclampsia and eclampsia: their significances.

OBJECTIVE: We measured the concentrations of plasma P selectin (or GMP-140) and glycocalicin in preeclamptic and eclamptic women. Correlations between these two parameters and blood pressures, platelet counts, or plasma thrombin-antithrombin complex values were evaluated. STUDY DESIGN: By use of enzyme-linked immunosorbent assays we measured the plasma GMP-140 and glycocalicin levels in normal pregnancies (n = 10) and preeclamptic (n = 10) and eclamptic (n = 20) pregnancies. The glycocalicin index was calculated as follows: (glycocalicin x [250 x 10(6)/ml])/(Individual platelet counts). Correlations between plasma GMP-140, glycocalicin, glycocalicin index values, blood pressures, platelet counts, and plasma thrombin-antithrombin complex values were analyzed. RESULTS: Plasma GMP-140 levels were found to be significantly elevated in preeclamptic (p < 0.0005) and eclamptic cases (p < 0.0001) compared with normotensive controls. Plasma glycocalicin (p = 0.01, 0.007) and glycocalicin index (p = 0.005, 0.002) values were also markedly elevated in preeclamptic and eclamptic patients compared with normal pregnant patients. Significant correlations between platelet counts or plasma thrombin-antithrombin complex levels and their corresponding plasma GMP-140 and glycocalicin and glycocalicin index values have been found in preeclamptic and eclamptic cases. However, blood pressures had correlations with GMP-140, glycocalicin, and glycocalicin index values in eclamptic cases. CONCLUSIONS: We demonstrated an elevation of plasma GMP-140 and platelet glycocalicin in preeclampsia and eclampsia. This study also reflects the usefulness of glycocalicin as a marker of platelet activation or turnover and endothelial dysfunction in these diseases.

Adult↗

Biochemical changes in the cervical tissue of rabbit induced by interleukin-8, interleukin-1beta, dehydroepiandrosterone sulphate and prostaglandin E2: a comparative study.

The aim of this research was to study and compare the mechanism of action of interleukin (IL)-8, IL-1beta dehydroepiandrosterone sulphate (DHEA-S) and prostaglandin (PG)E2 on the cervix. Five equal groups of pregnant rabbits (n = 45) were tested by either placebo or tested drugs in the form of vaginal suppositories once daily for 3 days. The suppositories contained human recombinant IL-8 (100 ng), IL-1beta (200 ng), DHEA-S (10 mg) or PGE2 (1 mg). All rabbits were tested by one dose, two doses or three doses. Consistency, dilatation and water contents were estimated 24 h after the last dose of treatment. Leukocyte infiltration of the cervices was studied after staining the cervical tissue sections with antirabbit RT2 monoclonal antibodies. Relative collagen concentration was assessed after staining with Picrosirius Red. Collagenase, gelatinase and elastase activities were measured in 100 mg of homogenized cervical connective tissue. Water contents were significantly increased in all tested cervices. Neutrophil numbers were increased in IL-8 and IL-1beta groups after the second dose of treatment (P < 0.0005 and 0.001 respectively). In the PGE2 group, neutrophils were increased after the third dose of treatment, whereas in DHEA-S group no significant changes were observed. Collagen content was significantly decreased in IL-8, IL-1beta and PGE2 groups after the first dose of treatment (P < 0.004, and 0.005 and 0.03 respectively). In the DHEA-S group, the decrease in collagen content occurred after the third dose (P < 0.05). Collagenase activity was markedly increased in IL-8, IL-1, and DHEA-S groups after the second dose of treatment (P < 0.001, 0.003 and 0.007 respectively). No significant increase in collagenase activity was found in PGE2 group. Gelatinase activity was significantly increased in IL-8, IL-1beta, PGE2 and DHEA-S groups after the second dose of treatment (P < 0.008, 0.01, 0.003 and 0.05 respectively). Also, elastase activity was increased after the second dose of treatment in all groups (P < 0.001, 0.001, 0.001 and 0.006 respectively). Our data suggest that ripening of the cervix in rabbit can be initiated by different mechanisms. Cytokines play a vital role in cervical ripening, especially IL-8 and IL-1. IL-8 is one of the factors which could ripen the cervix in a manner similar to the physiological process at term.

Animals↗

Effects of urinary trypsin inhibitor on myometrial contraction in term and preterm deliveries.

The aim of this research was to study the concentration of urinary trypsin inhibitor in amniotic fluid (AF) and its effect on myometrial contraction in term and preterm deliveries. Urinary trypsin inhibitor was measured in AF of term and preterm labor. Immunohistochemical staining of amnion and myometrium was carried out. Isometric uterine contraction was studied to elucidate the effect of AF and urinary trypsin inhibitor on the contractile activity of term and preterm myometrium. The effect of urinary trypsin inhibitor on the production of prostaglandin E2 (PGE2) from myometrial cultures stimulated by IL-8, IL-1 and LPS was verified. Urinary trypsin inhibitor was significantly increased in AF of cases of preterm delivery (p < 0.0001). Amnion and myometrium of preterm deliveries were faintly stained for urinary trypsin inhibitor compared to term delivery. Amniotic fluid and urinary trypsin inhibitor could successfully inhibit-myometrial contraction. Also, urinary trypsin inhibitor could significantly inhibit the production of PGE2 in the myometrial cell cultures stimulated by IL-1 and LPS (p < 0.001 and 0.0005). IL-8 has no significant effect on PGE2 production from myometrial cell culture. Urinary trypsin inhibitor suppresses myometrial contraction in term and preterm deliveries. It may play a role in maintaining normal pregnancy and preventing preterm delivery.

Amnion↗

Immunohistological study in cases of HELLP syndrome (hemolysis, elevated liver enzymes and low platelets) and acute fatty liver of pregnancy.

We immunohistologically studied the hepatic tissue sections in cases with the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome; n = 2) and acute fatty liver of pregnancy (AFLP; n = 2) compared to necropsy controls. Unlike in the AFLP cases, a marked infiltration of neutrophils in liver tissues was found in both cases of the HELLP syndrome. Immunostaining with the antihuman (polyclonal) TNF-alpha, IL-1 beta, IL-8 and antihuman neutrophil elastase (monoclonal antibody) was performed in paraffin-embedded hepatic tissue sections. Liver tissues in HELLP syndrome patients were stained strongly with TNF-alpha and neutrophil elastase antibody. The strongest staining pattern was observed in the eclamptic case, whereas in the AFLP cases, as in the necropsy controls, a very weak staining for anti-TNF-alpha and elastase antibody was found. The liver sections of the HELLP syndrome cases were moderately stained with polyclonal IL-1 beta and IL-8 antibodies whereas AFLP and controls had a very faint staining. Significant correlations were found between the numbers of necrotic hepatocytes and elastase dots in the same microscopic fields (randomly selected) of liver sections from two cases of HELLP syndrome (r2 = 0.63; p < 0.0001), which might suggest a neutrophil-mediated tissue damage in such a disease. This study suggests that a cytokine- and neutrophil-mediated liver injury occurs in the HELLP syndrome but not in AFLP.

Adult↗

Biochemical changes in the cervical mucus after application of laminaria tent.

BACKGROUND: This research was aimed to study the biochemical changes in cervical mucus after application of laminaria tent. MATERIAL AND METHODS: Cervical mucus was collected before and after insertion of laminaria tent from 20 normal pregnant women in the first and second trimesters. Interleukin-1 beta, IL-8, collagenase activity, elastase activity, PGE2 and PGF2 alpha were measured in the collected samples. Laminaria tent was also inserted in one vaginal cervix of five non-pregnant rabbits and the clinical and histological changes were compared with five non-treated rabbits. Collagen contents were assessed histologically and Leukocyte number was counted. RESULTS: IL-1 beta and IL-8 and elastase activity were significantly increased after insertion of laminaria (p<0.0001 and 0.001 respectively). Collagenase activity was not significantly changed. Whereas concentration of PGE2 and PGF2 alpha in the mucus were markedly increased (p<0.0001 and 0.001 respectively). Collagen contents were significantly decreased in laminaria and opposite side cervices (p<0.0001). No significant changes in leukocyte count could be observed in treated and non treated cervices. CONCLUSIONS: Insertion of laminaria leads to increase concentration of IL-1 beta, IL-8, PGE2, PGF2 alpha and elastase activity. Mechanical stretching of the cervix and biochemical changes in cervical mucus may explain the mechanism of cervical ripening induced by laminaria.

Animals↗

Endothelin-1 evoked an increase and oscillations in cytosolic calcium concentration in adherent single human platelets and increased GMP-140 (P-selectin) in platelet suspension.

The effect of endothelin-1 (ET-1) on cytosolic calcium ion concentration ([Ca2+]i) in adherent single human blood platelet was determined by fluorescence digital imaging microscopy using Fura-2 as calcium probe. A dose dependent increase and oscillatory changes in [Ca2+]i in single platelets were evoked by ET-1 as with thrombin. Half and 1 microM of ET-1 increased (p < 0.01) the [Ca2+]i in single platelets from a resting level of 83 +/-3.4 nM to 120 +/- 13 nM and 240 +/- 20 nM respectively. The ET-1 induced increase in [Ca2+]i was suppressed by 1 mM EGTA, a calcium chelating agent in the medium. ET-1 increased the production of IP3 (quantitified by IP3 3H-radioreceptor assay kit) in platelets significantly (p < 0.05) in a dose dependent way. We measured the GMP-140 (P-selectin) level in the supernatant of human platelet suspensions incubated with thrombin and ET-1. Both thrombin and ET-1 increased the secretion of soluble GMP-140 in the supernatant of platelet suspensions. Therefore, we suggested that ET-1 increased [Ca2+]i in platelets by both calcium influx and IP3 mediated Ca2+ release resulting in activation and release of GMP-140.

Adult↗

Activated neutrophil by endothelin-1 caused tissue damage in human umbilical cord.

Immunostaining of human neutrophils incubated with endothelin-1 (ET-1) showed intense and spreading pattern of anti human granulocyte elastase within the cytosol. That reflected neutrophil activation followed by the release of granule contents by ET-1. In contrast, PBS (phosphate buffered saline) treated neutrophils showed localized and faintly stained granules. Intracellular calcium in fura-2 loaded neutrophils was measured at 340/380 nm. A dose and time dependent increase in intracellular calcium by ET-1 occurred in human single neutrophil. Elastase activity assay was done with chromogenic substrate S2484. ET-1 induces dose and time dependent increase in elastase activity in neutrophil suspensions like ionophore A23187. A similar time dependent increase in elastase activity was retained even after repeated wash and ET-1 treatment. That confirmed the viability of most of the neutrophils after each treatment. In umbilical cord preparations, ET-1 treated neutrophils could migrate from the venous lumen into the tissue matrix of the umbilical cords. Hematoxylin and eosin staining revealed a massive tissue destruction in ET-1 activated neutrophil treated cords when compared to sham control and untreated neutrophil injected cords. Immunostaining with monoclonal anti human elastase revealed an intense staining in former sections when compared to the others. We suggest that ET-1 activated neutrophil might play a major role in endothelial injury and tissue damage in conditions with high blood level of endothelin.

Calcium↗

Kunitz-type trypsin inhibitor prevents LPS-induced increase of cytosolic free Ca2+ in human neutrophils and HUVEC cells.

The protease inhibitor part of inter-alpha trypsin inhibitor is identical to urinary trypsin inhibitor (UTI). Preincubation of neutrophils and HUVEC cells with UTI inhibited increase of cytosolic free Ca2+ induced by LPS. Increase of cytosolic free Ca2+ induced by LPS in the presence of EGTA was also inhibited by UTI. In contrast, UTI did not inhibit increase of cytosolic free Ca2+ in cells stimulated by Ca2+ ionophore with or without EGTA. The effects of nine synthetic peptides of UTI on the concentration of cytosolic free Ca2+ in the neutrophils induced by LPS were examined. Preincubation with a peptide of UTI domain 2, NLPIVRGPCRAFIQL (83-97), was completely inhibited by the increase of cytosolic free Ca2+ in neutrophils. This region is identical to the trypsin inhibitor site of UTI. We propose that a function of UTI other than as a protease inhibitor is in regulation of intracellular Ca2+ and that this is due to its trypsin inhibitor region.

Amino Acid Sequence↗

Down-regulation of interleukin-8 gene expression in HL60 cell line by human Kunitz-type trypsin inhibitor.

Urinary trypsin inhibitor (UTI) is one of the Kunitz-type protease inhibitors in human. Little is known about its anti-inflammatory functions other than protease inhibition. We studied the effect of UTI on gene expression of interleukin-8 (IL-8), an inflammatory cytokine. UTI inhibited IL-8 gene expression induced by lipopolysaccharide (LPS) in HL60 cells. The IL-8 concentrations in the cells and medium after LPS stimulation increased time-dependently in the absence of UTI, but did not increase in the presence of UTI. On the other hand, UTI did not inhibit either the synthesis or the release of IL-8 induced by the calcium ionophore A23187. UTI inhibited increase of cytosolic Ca2+ stimulated by LPS but not by A23187. Our results suggest that the inhibition by UTI is due to its effect on the cell membrane involved in regulating Ca2+ influx.

Calcimycin↗

Regulatory effect of aminopeptidase inhibitor (bestatin) on the cervix during induction of ripening by interleukin-8.

Bestatin is an immunomodulatory peptide that stimulates the humoral and cell-mediated immune system. It also has an inhibitory effect on multiple aminopeptidases. Recently we found that aminopeptidase N inactivates interleukin-8 in vitro. Bestatin successfully suppresses the effect of aminopeptidase N on interleukin-8. During cervical maturation many biochemical changes occur including decrease in collagen concentration and increase in collagenase and elastase activities. Interleukin-8, which has a potent neutrophil chemotactic effect, was found to induce cervical ripening in rabbits. The combination of interleukin-8 with bestatin also induced cervical ripening by providing approximately regular levels of neutrophil numbers, collagenase, and elastase activities. We therefore suggest that this regulatory mechanism also takes place in vivo through the inhibitory effect of bestatin on aminopeptidase N.

Animals↗

Urinary trypsin inhibitor prevents uterine muscle contraction by inhibition of Ca++ influx.

OBJECTIVE: The aim of this research was to elucidate the mechanism of action of urinary trypsin inhibitor, a Kunitz-type protease inhibitor, in suppressing uterine muscle contraction. STUDY DESIGN: An isometric uterine contraction test was used to study this inhibitory effect of urinary trypsin inhibitor on the myometrium. Oxytocin, prostaglandin F2 alpha, and lipopolysaccharide were used to stimulate myometrial contraction. Prostaglandins F2 alpha and E2 were measured in the buffer solution. Influx of calcium into uterine smooth muscle cells was assessed by digital imaging microscopy. RESULTS: After incubation with urinary trypsin inhibitor or fetal urine, myometrial contractions stimulated by oxytocin, prostaglandin F2 alpha or lipopolysaccharide were suppressed completely. The concentrations of prostaglandins F2 alpha and E2 in the buffer solution during the isometric contraction test were significantly increased by lipopolysaccharide stimulation, but when urinary trypsin inhibitor was present in the buffer solution the concentrations of prostaglandins F2 alpha or E2 did not change significantly. Preincubation with urinary trypsin inhibitor also inhibited calcium influx, resulting in no detectable change in the intracellular free calcium concentration of smooth muscle cells. CONCLUSION: We proposed that urinary trypsin inhibitor from fetal urine inhibits uterine muscle contraction by regulation of intracellular Ca++.

Calcium↗

The effect of interleukin-1 in rabbit cervical ripening.

OBJECTIVE: In this research we studied the effect of interleukin-1 beta (IL-1 beta) on the cervix. STUDY DESIGN: Vaginal suppositories of a low dose of IL-1 beta (200 ng) were applied to non-pregnant and pregnant rabbits. Results were compared with a control group which were treated only by placebo. Water concentration, collagen content, collagenase and elastase activities were measured. Neutrophil numbers in the cervical connective tissue were counted. Also, interleukin-8 (IL-8) was measured in the supernatant of homogenized cervical tissue treated by IL-1 beta. RESULTS: Water contents of the tested cervices were increased (P < 0.006 and 0.03, respectively), whereas collagen content was markedly decreased (P < 0.0004 and 0.001, respectively). Collagenase activity was found to be increased in non-pregnant and pregnant cervices treated by IL-1 beta (P < 0.02 and 0.002, respectively). Also, elastase activity of these cervices were significantly increased compared to the control group (P < 0.0007 and 0.001, respectively). Neutrophil invasion was observed in the cervical connective tissues after application of IL-1 beta. IL-8 was significantly elevated (P < 0.0001) in the treated cervices. CONCLUSION: Interaction between IL-1 and IL-8 is suspected to be essential for cervical ripening.

Animals↗