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Biomedical subjects

S Alam

Publications and source records attributed to S Alam.

At least 19 recordsLinked to original sources

Inhibition of vascular smooth muscle cell proliferation by the calcium antagonist clentiazem: role of protein kinase C.

The proliferation of vascular smooth muscle cells has been implicated as a causative factor in atherogenesis. Calcium channel blockers have been shown to retard the progression of atherosclerosis. To elucidate the mechanism by which these drugs mediate such actions, we studied the effects of a new calcium antagonist, clentiazem, on the in vitro proliferation of vascular smooth muscle cells. PDGF-induced prolifertion of these cells is markedly inhibited by clentiazem. The probable involvement of protein kinase C (PKC) in this cellular response is suggested. Clentiazem appear to cause inhibition of PKC translocation that is induced by phorbol esters and PDGF-BB and the phosphorylation of the 80 kDa protein substrate of PKC in vascular smooth muscle cells. Moreover, treatment with clentiazem leads to a marked decrease in the number of specific phorbol ester binding sites. Analysis of the membrane bound isoenzymes of protein kinase C revealed that the inhibition was specific to delta enzymes. Arterial cholesterol ester hydrolysis is not significantly altered by clentiazem. Our results suggest that clentiazem may inhibit cell proliferation by regulating cytosolic PKC and preventing its membrane translocation and activation.

Adenosine Monophosphate

Induction and persistence of a cytotoxic T lymphocyte (CTL) response against a herpes simplex virus-specific CTL epitope expressed in a cellular protein.

CD8+ cytotoxic T-lymphocytes recognize small epitope peptides in association with MHC class I molecules expressed on the cell surface. In this study, we have determined whether an 8 amino acid viral CTL epitope, when expressed in a cellular protein, can be appropriately processed, presented, and recognized by the corresponding epitope-specific CTL and whether it is capable of inducing a CTL response in vivo. An H-2Kb-restricted CTL epitope from herpes simplex virus type 1 (HSV-1) glycoprotein B (gB epitope, residues 498-505) was cloned into the mouse dihydrofolate reductase protein (DHFR) at amino acid position 87. The recombinant DHFRs were expressed in vaccinia virus recombinants. To distinguish the recombinant DHFR proteins from the endogenous DHFR, an antibody epitope, recognized by monoclonal antibody PAb 901 and derived from simian virus 40 (SV40) T antigen was tagged to the C-termini of recombinant DHFR proteins. In vivo expression of recombinant DHFR was demonstrated by immunoprecipitation with the monoclonal antibody PAb 901. The H-2b cells infected with recombinant vaccinia virus expressing the recombinant DHFR were specifically lysed by gB epitope-specific CTL. Furthermore, the recombinant DHFR was functional in inducing a long lasting HSV gB epitope-specific CTL response upon immunization of C57BL/6 (B6) mice. These results indicate that a viral epitope expressed in a cellular protein can be efficiently processed, presented, and recognized by epitope-specific CTL and show that cellular proteins expressing CTL epitopes can be used for induction of CD8+ T lymphocyte responses.

Animals

Antinociceptive effects of epidural and intravenous ketamine to somatic and visceral stimuli in rats.

PURPOSE: To evaluate the antinociceptive effect of epidural and intravenous ketamine on somatic and visceral stimuli and to address the emergency reaction. METHODS: Rats were randomly allocated into nine groups (n = 6); five groups with chronically implanted epidural catheters received saline or 0.5, 1, 2 and 4 mg. kg-1 ketamine epidurally, four groups received saline, or 1, 5 and 10 mg. kg-1 ketamine i.v. To assess somatic and visceral antinociceptive effects, tail flick (TF) test and colorectal distension (CD) test were carried out, respectively. Emergence reactions were graded. Maximal possible effects (% MPE) were calculated. RESULTS: Epidural ketamine increased % MPE in both tests in a dose-dependent fashion for 30 min (vs saline group, P < 0.05). Epidural ketamine 0.5 mg. kg-1 produced an increase in % MPE in the CD test (P < 0.05) but failed in the TF test. Intravenous ketamine, 10 mg. kg-1, produced 100 +/- 0 (mean +/- SE) % MPE in the CD test but 36 +/- 15% MPE in the TF test. Dose response curves indicated greater visceral antinociception than somatic. All rats showed emergence reactions following intravenous ketamine 10 and 5 mg. kg-1. CONCLUSION: Both epidural and intravenous ketamine produce greater antinociceptive effects to visceral than to somatic stimulation, and that epidural ketamine has a low incidence of emergence reactions.

Analgesics, Non-Narcotic

Anaesthetic management for caesarean section in a patient with Kawasaki disease.

Kawasaki disease (KD) or mucocutaneous lymph node syndrome is an acute febrile illness affecting mainly children under four years of age. The most important clinical feature of this disease is coronary arteritis associated with aneurysms and thrombotic occlusions, which may lead to ischaemic heart disease or sudden death. It has now been more than 20 yr since its first description, and a number of survivors of childhood KD have reached child-bearing age. Despite the possible fatal outcome of this disease in adult patients with coronary artery manifestations, no information is available regarding the obstetrical anaesthetic management of patients with a history of KD. The purpose of this report is to describe the successful use of epidural anaesthesia in a patient with a history of KD undergoing Caesarean section and to discuss the anaesthetic considerations that should be given to adult survivors of childhood KD.

Adult

Cloning of cDNAs encoding a cell-cycle-regulatory GTP-binding low-M(r) (GBLM) protein, Ran/TC4, from micronucleated Tetrahymena thermophila and amicronucleated Tetrahymena pyriformis.

Using PCR we have isolated two novel, closely related cDNA clones coding for a GTP-binding low-M(r) protein from Tetrahymena cells. The two clones from T. thermophila and T. pyriformis have open reading frames encoding proteins of 225 amino acids (aa) with a calculated M(r) of 25,648, and of 223 aa with a calculated M(r) of 25,421, respectively. The two gene products were very homologous to Ran/TC4 which are involved in chromatin condensation and control of the cell cycle: they possess much higher similarities to human, chicken, Schizosaccharomyces pombe and Dictyostelium discoideum Ran/TC4 homologues than those to other GTP-binding low-M(r) proteins, such as Ras and Rho. Thus, the two clones isolated from Tetrahymena were designated as Tt-ran and Tp-ran, respectively. Tt-ran and Tp-ran share 83% identity at nucleotide level, and about 92% identity and 94% homology at aa level. Tt- and Tp-Ran, as well as other Ran/TC4, contain the four consensus regions involved in GTP/GDP-binding and GTPase activities. However, at the C-terminal end, although all the known Ran/TC4 terminate in a consensus D-L motif, Tt-Ran and Tp-Ran do not have the unique aa sequence of other Ran/TC4, but have a F-N motif. Tt-ran and Tp-ran were actively transcribed in vivo as a 1.0-kb mRNA.

Amino Acid Sequence

The role of anticoagulation in the development of pericardial effusion and late tamponade after cardiac surgery.

This study aimed at elucidating the role of anticoagulation in the genesis of late pericardial effusion and tamponade after cardiac surgery. Using serial 2-D echocardiography, 141 patients undergoing surgery for coronary artery bypass (56), valvular (69) or congenital (16) [corrected] heart disease were studied postoperatively. Group 1 (74 patients) received full anticoagulation (warfarin 73; heparin 1) and group 2 (67 patients) received either antithrombotic agents (aspirin plus dipyridamole), or no treatment. Fifty percent (70/141) of patients developed effusion. There was no significant difference between the two groups in the incidence of either effusion in general (43/74; 58% vs 27/67; 40%, respectively) or small or medium sized effusion. However, a large effusion was significantly more common in group 1 than in group 2 (32% vs 4%, P < 0.005). Twelve patients (12/141; 8.5%) developed late tamponade, 7 to 33 (15 +/- 7.3 mean +/- SD) days after surgery. All had a large effusion demonstrated by echo, drained by pericardiocentesis, and none died. All 12 patients with tamponade belonged to group 1 (P < 0.001). Excess anticoagulation was detected at least once in 41 of the 74 group 1 patients (55%). When compared to properly anticoagulated patients, excessively anticoagulated patients had a similar overall incidence of effusion and a similar incidence of small or moderate effusion, but a higher incidence of large effusion (18% vs 44%, [corrected] P < 0.05) and tamponade (3% vs 27%, P < 0.025). We conclude that, unlike small or medium-sized effusions, large pericardial effusions and tamponade are more likely to occur among anticoagulated patients, especially if they are excessively anticoagulated.

Adult

Hemobilia due to gallbladder contusion following blunt trauma--sonography and CT scanning for early detection: case report.

Gallbladder injury following blunt trauma is rare and early diagnosis is difficult when it is associated with other injuries. Clinical symptoms and signs alone are not necessarily helpful in diagnosing such cases. However, modern diagnostic imaging procedures such as ultrasonography and CT scanning are valuable for investigating possible gallbladder injuries. Patients with blunt trauma should be carefully examined by US and CT for early detection and treatment of gallbladder injuries.

Cholecystography

Deleterious cardiac effects of captopril during acute myocardial ischaemia in the dog.

OBJECTIVE: The aim was to evaluate the effects of the angiotensin converting enzyme inhibitor captopril on acute myocardial ischaemia. METHODS: Seventeen anaesthetised open chest dogs were randomised to 3 minute angioplasty balloon occlusions of the left circumflex coronary artery before and after intravenous infusion of captopril (n = 8) or placebo (n = 9). RESULTS: There was apparent worsening of ischaemia during balloon inflation after captopril infusion, when compared with control inflation, as suggested by further ST segment elevation of 1.8 (SD 1.8) mm, p less than 0.03, and by further lowering of regional myocardial pH [-0.05(0.05), p = 0.06], and peak positive and peak negative dP/dt [-439(337)mm Hg.s-1, p less than 0.008; -470(316) mm Hg.s-1, p less than 0.004, respectively]. The increase in ischaemia occurred despite reduced double product after captopril administration. Regional myocardial blood flow in the ischaemic artery distribution was lower during post captopril balloon occlusion [-0.1(0.06) ml.min-1.g-1, p less than 0.005] than during control balloon inflation, while coronary vascular resistance increased by 161(172)% (range 45 to 497%, p less than 0.04). There were no significant differences in ST segments, pH, haemodynamic variables, or blood flow during balloon inflations before and after saline infusion. CONCLUSIONS: Despite lower myocardial metabolic demands, acute intravenous administration of captopril was associated with increased ischaemia during transient coronary artery occlusion.

Acute Disease

Hemodynamic assessment of chronic venous insufficiency.

To study the pathogenesis of chronic venous insufficiency (CVI), photoplethysmography and strain-gauge plethysmography were simultaneously performed in 84 patients. Of the 128 limbs studied, 24 were normal, 64 had primary varicose veins and 40 had post-thrombotic syndrome. Venography was also performed in all patients. The results of this study indicate that reflux in the superficial veins is the main pathophysiology involved in the development of CVI, though incompetence of the perforators and deep veins plays some role. In post-thrombotic syndrome, however, CVI is mainly a sequel of deep venous incompetence, the condition being complicated by incompetent perforators and superficial venous reflux.

Chronic Disease

Wartime determinants of arteriographically confirmed coronary artery disease in Beirut.

This study investigates the association of wartime stress variables and coronary artery disease as determined by coronary angiography in Lebanon in 1986, a country with an ongoing civil war for ever a decade. A total of 127 patients who underwent coronary angiography at the American University of Beirut Medical Center were individually matched on age and sex with visitor controls free from any evidence of clinical coronary artery disease. Arteriographic cases (greater than or equal to 70% maximal stenosis) were compared with two control groups: arteriographic controls (entirely normal coronaries) and visitor controls. Findings suggest that there is a relation between exposure to both acute and chronic war events and coronary artery disease in this patient population. The reporting of exposure to acute war events was significantly higher in cases compared with both visitor controls (odds ratio (OR) = 2.4, 95% confidence interval (CI) 1.17-4.90) and arteriographic controls (OR = 2.8, 95% CI 0.93-8.47). Crossing the "green-lines" that separate two belligerent sides, considered as an attribute of war-related chronic stress, was more frequent in cases compared with visitor controls (OR = 3.25, 95% CI 1.54-6.89) and arteriographic controls (OR = 5.38, 95% CI 1.65-17.6). The relation observed between wartime stress and coronary artery disease could not be explained by possible overreporting of stressful events in patients with suspected coronary artery disease or by an increase in clinical awareness for the disease for those under continuous stress. Adjusting for the effect of the well-established coronary artery disease risk factors did not alter the above findings.

Adult

Receptor-mediated uptake and 'retroendocytosis' of high-density lipoproteins by cholesterol-loaded human monocyte-derived macrophages: possible role in enhancing reverse cholesterol transport.

Human monocyte-derived macrophages (MDM) are cholesterol-loaded, and the rates of uptake, degradation and resecretion of high-density lipoproteins are measured and compared to the rates in control cells. Results show the binding activity of these lipoproteins is upregulated in cholesterol-loaded cells; the bound and internalized lipoproteins are not degraded to any appreciable extent but primarily resecreted as a larger particle. The enhancement of binding activity for high-density lipoproteins is arrested when cycloheximide is added to the medium, suggesting that protein synthesis is involved. Preliminary evidence also indicates that HDL3 (without apoE) after internalisation is converted intracellularly to a larger apoE-containing HDL2-like particles. Thus, MDM appears to possess specific receptors for HDL3 without apoE that may function to facilitate HDL-mediated removal of excess cholesterol from cells.

Biological Transport

Kidney-preserving radical tumor resection in advanced neuroblastoma.

The possibility of kidney-preserving radical tumor resection in advanced neuroblastoma was evaluated. Eighteen patients with stage III and IV adrenal neuroblastoma underwent delayed primary surgery after chemotherapy consisting of high doses of cyclophosphamide (1,250 mg/m2). Radical tumor resection with nephrectomy was performed in 13 patients (group A) and kidney-preserving radical tumor resection was performed in six patients (group B). Macroscopic findings were evaluated in all patients; angiographic and microscopic findings were evaluated in group A patients and tumor recurrence in group B patients. Macroscopically, the tumors were observed within the tumor capsule (C1) in five, outside the tumor capsule but not beyond the midline (C2) in seven, and beyond the midline (C3) in six. In group A, under microscopic examination, the tumor invasion into the renal parenchyma was observed in only three patients among C2 and C3 cases. Tumor vessels from the capsular and/or perforating arteries plus from the intrarenal arteries could be visualized in all patients, three of whom had tumor invasion into the renal parenchyma. In group B, no tumor recurrence around the kidney occurred, and two patients have survived for greater than 2 years. The kidney-preserving radical tumor resection is recommended in surgical treatment of advanced neuroblastoma following preoperative chemotherapy, and is predictable preoperatively by angiography.

Adrenal Gland Neoplasms

Wartime determinants of arteriographically confirmed coronary artery disease in Beirut.

This study investigates the association of wartime stress variables and coronary artery disease as determined by coronary angiography in Lebanon in 1986, a country with an ongoing civil war for over a decade. A total of 127 patients who underwent coronary angiography at the American University of Beirut Medical Center were individually matched on age and sex with visitor controls free from any evidence of clinical coronary artery disease. Arteriographic cases (greater than or equal to 70% maximal stenosis) were compared with two control groups: arteriographic controls (entirely normal coronaries) and visitor controls. Findings suggest that there is a relation between exposure to both acute and chronic war events and coronary artery disease in this patient population. The reporting of exposure to acute war events was significantly higher in cases compared with both visitor controls (odds ratio (OR) = 2.4, 95% confidence interval (Cl) 1.17-4.90) and arteriographic controls (OR = 2.8, 95% Cl 0.93-8.47). Crossing the "green-lines" that separate two belligerent sides, considered as an attribute of war-related chronic stress, was more frequent in cases compared with visitor controls (OR = 3.25, 95% Cl 1.54-6.89) and arteriographic controls (OR = 5.38, 95% Cl 1.65-17.6). The relation observed between wartime stress and coronary artery disease could not be explained by possible overreporting of stressful events in patients with suspected coronary artery disease or by an increase in clinical awareness for the disease for those under continuous stress. Adjusting for the effect of the well-established coronary artery disease risk factors did not alter the above findings.

Adult