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Biomedical subjects

S Alam

Publications and source records attributed to S Alam.

At least 19 recordsLinked to original sources
PubMed2000

The 460Trp polymorphism of the human alpha-adducin gene is not associated with isolated systolic hypertension in elderly Australian Caucasians.

The study was undertaken to determine whether polymorphic variants of the alpha-adducin gene are associated with isolated systolic hypertension (ISH) in elderly Australian Caucasians. Participants were classified with ISH (n = 87, systolic blood pressure (SBP) > or =160 mm Hg and diastolic blood pressure (DBP) < or =90 mm Hg) or normotension (n = 124, SBP <140 mm Hg and DBP <90 mm Hg with no family history of hypertension). To collect demographic data, a structured questionnaire was used. DNA was extracted using standard techniques from 211 subjects (age range 61-89, mean age 73 +/- 6.6 years, male: female ratio 1.1:1). Genotypes (gly/gly, trp/gly and trp/trp) were assigned in triplicate by polymerase chain reaction (PCR) followed by electrophoresis, using a laser scanning electrophoresis unit. The validity of the method was confirmed by sequencing. Frequencies of allele distribution in ISH or control groups were determined by Chi-square tests and a stepwise logistic regression model, which controlled for potential confounders, was used to examine any independent association between alpha-adducin genotypes or alleles with ISH and normotensive controls. Mean BP (+/- s.d.) was: 170/79.8 +/- 14.9/8.3 mm Hg and 122.1/ 73.4 +/- 8. 8/7.6 mm Hg in the ISH and normotension groups respectively. The unadjusted allele and genotypes frequencies were not significantly different in the ISH patients groups compared with normotensive controls (chi2 = 1.59, P = 0.45 and chi2 = 1.23, P = 0.28 respectively). In this elderly cohort, after adjustment for potential confounders, no statistically significant association was found between alpha-adducin genotype and SBP (P = 0.65 for homozygotes, P = 0.59, for heterozygotes), DBP (P = 0.49 homozygotes, for heterozygotes P = 0.45) pulse pressure (P = 0.87 homozygotes, for heterozygotes P = 0.95) diagnosis of ISH (P = 0.72 for homozygotes, P = 0.68 for heterozygotes). However age and renal disease predicted the diagnosis of ISH (P = 0.001, P = 0.459, respectively), a large pulse pressure (P < 0.0001, P = 0.033, respectively) and a higher SBP (P < 0.0001, P = 0.025, respectively) in this large cohort of elderly Australian Caucasian volunteers. Journal of Human Hypertension (2000) 14, 199-203.

Aged↗
PubMed2000

Evidence for activation of the alternate complement pathway in patients with juvenile rheumatoid arthritis.

OBJECTIVE: Complement activation has been shown to occur in patients with juvenile rheumatoid arthritis (JRA). Since the two pathways of complement are activated by different stimuli (the alternate pathway by microbial products and IgA, and the classical pathway by immune complexes), we decided to study the relative contribution of the two pathways of complement activation in patients with JRA. METHODS: In 56 patients with JRA, plasma levels of C3 and C4 were measured by turbidimetric assays, and those of C4d, factor Bb and sC5-9 complex by solid-phase enzyme immunoassays. Levels beyond the mean +/- 2 S.D. of normal were considered abnormal. RESULTS: Plasma C3 and C4 levels were decreased in one patient each. The C4d values were increased in 17 patients, whereas levels of factor Bb were elevated in 42 patients and levels of sC5-9 complex were elevated in 51 patients. The values of factor Bb and sC5-9 had a linear correlation (r = 0.75), but there was no significant correlation between C4d and sC5-9 levels (r = 0.36). CONCLUSION: Complement activation in JRA is initiated predominantly by the alternate pathway and culminates in the formation of terminal membrane attack complex.

Adolescent↗
PubMed2000

Direct coronary vasomotor effects of sevoflurane and desflurane in in situ canine hearts.

BACKGROUND: An extracorporeal system was used to investigate the direct coronary vasomotor effects of sevoflurane and desflurane in vivo. The role of the adenosine triphosphate-sensitive potassium channels (KATP channels) in these effects was evaluated. METHODS: Twenty-one open-chest, anesthetized (fentanyl-midazolam) dogs were studied. The left anterior descending coronary artery was perfused at controlled pressure (80 mmHg) with normal arterial blood or arterial blood equilibrated with either sevoflurane or desflurane. Series 1 (n = 16) was divided into two groups of equal size on the basis of whether sevoflurane (1.2, 2.4, and 4.8%) or desflurane (3.6, 7.2, and 14.4%) was studied. The concentrations for the anesthetics corresponded to 0.5, 1.0, and 2.0 minimum alveolar concentration (MAC), respectively. Coronary blood flow (CBF) was measured with an ultrasonic, transit-time transducer. Local coronary venous samples were obtained and used to evaluate changes in myocardial oxygen extraction (EO2). In series 2 (n = 5), changes in CBF by 1 MAC sevoflurane and desflurane were assessed before and during intracoronary infusion of the KATP channel inhibitor glibenclamide (100 microg/min). RESULTS: Intracoronary sevoflurane and desflurane caused concentration-dependent increases in CBF (and decreases in EO2) that were comparable. Glibenclamide blunted significantly the anesthetic-induced increases in CBF. CONCLUSIONS: Sevoflurane and desflurane have comparable coronary vasodilative effects in in situ canine hearts. The KATP channels play a prominent role in these effects. When compared with data obtained previously in the same model, the coronary vasodilative effects of sevoflurane and desflurane are similar to those of enflurane and halothane but considerably smaller than that of isoflurane.

ATP-Binding Cassette Transporters↗
PubMed1999

A meta-analysis of randomised controlled trials (RCT) among healthy normotensive and essential hypertensive elderly patients to determine the effect of high salt (NaCl) diet of blood pressure.

To examine the effect of chronic NaCl ingestion on blood pressure (BP) in the elderly, a meta-analysis was undertaken of 11 randomised controlled trials of which five included patients > or =60 years of age only and six included patients with a mean age close to 60 years. The following databases were used: Medline, Embase, Current Contents, The Cochrane Library, the AMI and IPA databases. Mean erect systolic and diastolic blood pressures (SBP/DBP) on chronic (> or =9 weeks) high and low NaCl diets were recorded, the pooled mean effect, the pooled standard error and 95% confidence intervals (Cl) were calculated and linear regression was used to evaluate the potential association between NaCl intake and BP. When all trials were pooled, a chronic high NaCl diet significantly increased mean SBP and DBP by 5.58 mm Hg (95%Cl 4.31-6.85) and 3.5 mm Hg (95%Cl 2.62-4.38) respectively. There was a significant association between the level of NaCl intake and SBP (P = 0.05, r2 = 0.37) but not DBP (P = 0.76, r2 = 0.01). When trials were pooled separately, a chronic high NaCl diet increased SBP by 5.46 mm Hg (95%Cl 3.56-7.36) and DBP by 2.63 mm Hg (95%Cl 1.18-4.08) in trials including patients > or =60 years of age only, and increased SBP by 3.27 mm Hg (95%Cl 1.23-5.31) and DBP by 2.69 mm Hg (95%Cl 1.44-3.94) in trials including patients with a mean age close to 60 years. These data suggest that a chronic high NaCl diet in elderly patients with essential hypertension is associated with an increase in SBP and DBP, the association is significant for both SBP and DBP but more marked for SBP than DBP, the effect is more pronounced the older the patient and NaCl dose strongly predicts SBP in older patients.

Aged↗
PubMed1999

Evaluation of the potential interaction between NaCl and prostaglandin inhibition in elderly individuals with isolated systolic hypertension.

OBJECTIVE: To evaluate whether prostaglandin inhibition with the non-steroidal anti-inflammatory drug (NSAID), indomethacin (I) interacts synergistically with different doses of salt (NaCl) in elevating systolic blood pressure (SBP). DESIGN AND METHODS: This randomized, placebo-controlled, double-blind, crossover study examined the interaction between NaCl and the prostaglandin inhibitor, I in 31 healthy elderly individuals with a mean age (+/- SD) of 68.7+/-5.7 years (range 61-85 years). Participants aged more than 60 years on a 140 mmol/day NaCl dose for 6 weeks were chosen with normal blood pressure [24-h SBP <148 mm Hg, diastolic blood pressure (DBP) <85 mm Hg on the Takeda Ambulatory Blood Pressure Monitor (TABPM); n = 15] and isolated systolic hypertension (ISH), [24-h SBP >148 mm Hg, 24-h DBP <85 mm Hg on TABPM; n = 16]. Exclusion criteria included uncontrolled hypertension (SBP >220 mm Hg and/or DBP >110 mm Hg), cardiac disease, creatinine clearance <60 ml/min, dementia and recent cerebrovascular accident or secondary hypertension. A 2x2 Latin square design was structured using four treatment groups [low salt (NaCl = 90 mmol/day) + I placebo, high salt (NaCl = 240 mmol/day) + I placebo, low salt + I (25 mg three times daily) and high salt + I] for 2 weeks each, balanced and interspersed with 2 week washout periods to minimize carryover effects. Twenty-four hour SBP, DBP and heart rate were measured and summarized using a moving interval averaging technique. The mean change in 24-h SBP, DBP, heart rate, urinary Na+, K+, protein and creatinine, creatinine clearance and serum electrolytes were compared across treatments in the total cohort and in ISH and control groups separately using ANCOVA (SAS). RESULTS: In the total cohort, compared with low NaCl, chronic high NaCl increased mean SBP (5.76 mm Hg; P = 0.0002) and DBP (3.36 mm Hg; P = 0.002). Indomethacin significantly increased mean SBP (2.66 mm Hg, P = 0.015) but not DBP (0.31 mm Hg, P = 0.419). High salt and I were additive (SBPT, DBPT) but there was no interaction (P = 0.795 and P = 0.739, respectively). Additionally, chronic high NaCl increased serum Na (P = 0.0001) and 24-h urinary Na (P = 0.0001) as expected. Indomethacin significantly decreased mean heart rate (P = 0.018). The effects of NaCl and I on SBP, DBP and heart rate were not modified by age, alcohol intake, serum K+, body mass index or treatment order. In the ISH group, NaCl dose significantly elevated SBP (9.87 mm Hg; P = 0.0001) and DBP (5.26 mm Hg, P = 0.006) but did not significantly alter blood pressure in the normotensive group. Indomethacin significantly elevated SBP (P = 0.03) in normotensive individuals but had no effect on blood pressure in the ISH group. CONCLUSIONS: Chronic high salt diet elevated blood pressure more than I in the total cohort of elderly individuals. No interaction was demonstrated and their effects were additive. In the ISH group, chronic high salt diet significantly increased SBP and DBP while I failed to alter blood pressure. In the normotensive group, I, but not salt, elevated SBP. Patients with ISH are sensitive to the pressor effect of NaCl but resistant to the pressor effect of prostaglandin inhibition in contrast to elderly normotensive control individuals where the reverse was found.

Aged↗
PubMed1999

PCR-Based methods for genotyping viridans group streptococci.

Standard repetitive extragenic palindromic (REP)-PCR, enterobacterial repetitive intergenic consensus-PCR, and Salmonella enteritidis repetitive element-PCR methods for bacterial strain typing were performed with DNA extracted by boiling members of each of the currently recognized species of human viridans group streptococci. Each of the methods was reproducible. The unique isolates (n = 72) from 15 species of viridans group streptococci were readily distinguishable, with no two isolates showing greater than 90% per cent similarity. The majority of strains exhibited much less than 90% similarity. Isolates identical by REP-PCR were also identical by the other two methods. These PCR-based typing methods, although they do not permit determination of the species of the isolates, are simple to perform and are suitable for clinical and ecological investigations of viridans group streptococci.

Genotype↗
PubMed1999

The Gal3p-Gal80p-Gal4p transcription switch of yeast: Gal3p destabilizes the Gal80p-Gal4p complex in response to galactose and ATP.

The Gal3, Gal80, and Gal4 proteins of Saccharomyces cerevisiae comprise a signal transducer that governs the galactose-inducible Gal4p-mediated transcription activation of GAL regulon genes. In the absence of galactose, Gal80p binds to Gal4p and prohibits Gal4p from activating transcription, whereas in the presence of galactose, Gal3p binds to Gal80p and relieves its inhibition of Gal4p. We have found that immunoprecipitation of full-length Gal4p from yeast extracts coprecipitates less Gal80p in the presence than in the absence of Gal3p, galactose, and ATP. We have also found that retention of Gal80p by GSTG4AD (amino acids [aa] 768 to 881) is markedly reduced in the presence compared to the absence of Gal3p, galactose, and ATP. Consistent with these in vitro results, an in vivo two-hybrid genetic interaction between Gal80p and Gal4p (aa 768 to 881) was shown to be weaker in the presence than in the absence of Gal3p and galactose. These compiled results indicate that the binding of Gal3p to Gal80p results in destabilization of a Gal80p-Gal4p complex. The destabilization was markedly higher for complexes consisting of G4AD (aa 768 to 881) than for full-length Gal4p, suggesting that Gal80p relocated to a second site on full-length Gal4p. Congruent with the idea of a second site, we discovered a two-hybrid genetic interaction involving Gal80p and the region of Gal4p encompassing aa 225 to 797, a region of Gal4p linearly remote from the previously recognized Gal80p binding peptide within Gal4p aa 768 to 881.

Adenosine Triphosphate↗
PubMed1999

Nitric oxide does not modulate whole body oxygen consumption in anesthetized dogs.

The effects of the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) and the NO donor sodium nitroprusside (SNP) on whole body O2 consumption (VO2) were assessed in 16 dogs anesthetized with fentanyl or isoflurane. Cardiac output (CO) and mean arterial pressure (MAP) were measured with standard methods and were used to calculate VO2 and systemic vascular resistance (SVR). Data were obtained in each dog under the following conditions: 1) Control 1, 2) SNP (30 microg. kg-1. min-1 iv) 3) Control 2, 4) L-NAME (10 mg/kg iv), and 5) SNP and adenosine (30 and 600 microg. kg-1. min-1 iv, respectively) after L-NAME. SNP reduced MAP by 29 +/- 3% and SVR by 47 +/- 3%, while it increased CO by 39 +/- 9%. L-NAME had opposite effects; it increased MAP and SVR by 24 +/- 4% and 103 +/- 11%, respectively, and it decreased CO by 37 +/- 3%. Neither agent changed VO2 from the baseline value of 4.3 +/- 0.2 ml. min-1. kg-1, since the changes in CO were offset by changes in the arteriovenous O2 difference. Both SNP and adenosine returned CO to pre-L-NAME values, but VO2 was unaffected. We conclude that 1) basally released endogenous NO had a tonic systemic vasodilator effect, but it had no influence on VO2; 2) SNP did not alter VO2 before or after inhibition of endogenous NO production; 3) the inability of L-NAME to increase VO2 was not because CO, i.e., O2 supply, was reduced below the critical level.

Anesthesia↗
PubMed1999

Clinical scoring system: a valuable tool for decision making in cases of acute appendicitis.

OBJECTIVE: Decision making in cases of acute appendicitis poses a clinical challenge specially in developing countries where advanced radiological investigations do not appear cost effective and so clinical parameters remain the mainstay of diagnosis. The aim of our study was to devise a scoring system from our local database and test its accuracy in the preoperative diagnosis of acute appendicitis. METHODS: Clinical data from 401 patients having undergone appendectomy were collected to identify predictive factors that distinguished those with appendicitis from those who had a negative appendectomy. Ten such factors were identified and using Bayesian probability a weight was assigned to each and the results summated to get an overall score. A cut-off point was identified to separate patients for surgery and those for observation. The scoring system was then retrospectively applied to a second population of 99 patients in order to compare suggested actions (derived from the scoring system) to those actually taken by surgeons. The sensitivity, specificity and accuracy for the level of decision was then calculated. RESULTS: Of the 99 patients, the method suggested immediate surgery for 65 patients, 63 of whom had acute appendicitis (3.1% diagnostic error rate). Of the 33 patients in whom the score suggested active observation, 18 had appendicitis. The accuracy of our scoring system was 82%. The method had a sensitivity of 78%, specificity 89% and a positive predictive value of 97%. The negative appendectomy rate determined by our study was 7% and the perforation rate 13%. CONCLUSION: Scoring system developed from a local database can work effectively in routine practice as an adjunct to surgical decision making in questionable cases of appendicitis.

Acute Disease↗
PubMed1998

Immortalization by gene transfection.

Cultured cell lines that maintain specific differentiated phenotypes have been indispensable tools in cell biology. Progress in understanding the function of differentiated cells in vivo can be facilitated by creating cell lines via immortalizing gene transduction, if they retain the essential differentiated features of the same cells in vivo. Rodent cells immortalize spontaneously with a frequency of 10(-5) to 10(-6). Thus, it is easy to isolate immortal cells from rodent cell populations even without the transfer of immortalizing genes. Immortalizing genes can be used to increase this frequency to approximately 100%. In contrast, the spontaneous immortalization of human cells is a very rare event; the frequency is thought to be < 10(-12). Immortalizing genes can also be used to increase this frequency. Several genes that promise efficient immortalization of cultured cells have been identified. Immortalizing genes include simian virus 40 large T antigen, papillomaviruses E6 and E7, adenovirus E1A, Epstein-Barr virus, human T-cell leukemia virus, herpesvirus saimiri, oncogenes, and mutant p53 gene. Equally important, innovative means of gene delivery have been developed as well. These immortalizing genes, together with gene transfer methodologies, have provided the means to generate cell lines from cell types that are not abundant or are difficult to obtain in pure form in primary culture, are in short supply as human cells, and/or have brief lifetimes in culture. This chapter focuses primarily on the immortalization method by gene transfection. The chapter is not meant to be comprehensive, but rather to provide an account of the power and usefulness of immortalization methodology.

Animals↗
PubMed1998

Pleural perforation of an aspergilloma cavity occurring in a patient with interstitial lung disease.

An aspergilloma is a fungus ball resulting from colonization of pre-existing pulmonary cavities, which usually represents a non-invasive form of aspergillosis. Spontaneous rupture of the cavity containing the fungi into the pleural space is an unusual complication that has been reported occasionally in patients with leukemia and invasive aspergillosis. We report on this unusual complication occurring in a patient with underlying interstitial lung disease, in whom the aspergilloma cavity abruptly ruptured into the pleural space with subsequent hydropneumothorax and pleural spillage of the fungi.

Aspergillosis↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗