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Biomedical subjects

A Ismail

Publications and source records attributed to A Ismail.

At least 55 records · Page 3Linked to original sources
PubMed1999

T-cell response in human leishmaniasis.

In the present communication we provide evidence for the existence of a Th1/Th2 dichotomy in the T-cell response to Leishmania antigens in human leishmaniasis. Our data suggest that the pattern of IL-4 and IFN-gamma response is polarised in these patients. Lymphocytes from individuals recovered from cutaneous leishmaniasis (CL) responded by IFN-gamma production following stimulation with Leishmania antigens whereas cells from patients recovered from visceral leishmaniasis (VL) showed a mixed pattern of IFN-gamma and IL-4 responses. The cells producing these cytokines were predominantly CD4+. Furthermore, IL-10 plays an important role in the development of post kala azar dermal leishmaniasis (PKDL) from VL. The balance between the parasitic-specific T-cell response plays an important regulatory role in determining the outcome of Leishmania infections in humans.

Antigens, Protozoan↗
PubMed1999

Leishmania-specific T cells expressing interferon-gamma (IFN-gamma) and IL-10 upon activation are expanded in individuals cured of visceral leishmaniasis.

Peripheral blood mononuclear cells (PBMC) from patients who have recovered from visceral leishmaniasis often respond to Leishmania antigens in vitro by production of both IL-4, IFN-gamma and IL-10. In order to establish the cellular sources of these cytokines, we activated cells from individuals with a history of visceral leishmaniasis with Leishmania antigen for 6 days in culture, and identified cytokine production at the single-cell level by flow cytometry. The cytokines were only found in CD3+ cells and among these mainly within the CD4+ subset. The percentage of cytokine-producing cells was compared in Leishmania-activated PBMC cultures from the previous patients and from individuals living in a village where leishmaniasis does not occur. The percentage of IL-10- and IFN-gamma-containing cells was significantly higher in the previous patients than in the controls, indicating that Leishmania-specific T cells producing IL-10 and/or IFN-gamma had been expanded as a result of the infection. The cytokine-producing cells in the previous patients could be divided into three types: (i) cells producing IFN-gamma only; (ii) cells producing IL-4 only; and (iii) cells producing IFN-gamma and IL-10 simultaneously. The first and second group of cells can be described as Th1- and Th2-type cells, respectively. The third group could be a regulatory subset of T cells important for maintaining a balance between Th1- and Th2-type cells in these individuals.

Animals↗
PubMed1999

Predictors of large esophageal varices in patients with cirrhosis.

OBJECTIVE: Recent guidelines recommend that all cirrhotics undergo screening upper endoscopy to identify those patients at risk for bleeding from varices. However, this practice may not be cost effective as large esophageal varices are seen only in 9-36% of these patients. The aim of this study was to determine whether clinical variables were predictive of the presence of large esophageal varices. METHODS: This is a retrospective analysis of cirrhotics who had a screening upper endoscopy during an evaluation for liver transplantation at three different centers and who had not previously bled from varices. A multivariate model was derived on the combined cohort using logistic regression. Three hundred forty-six patients were eligible for the study. RESULTS: The prevalence of large esophageal varices was 20%. On multivariate analysis, splenomegaly detected by computed tomographic scan (odds ratio: 4.3; 95% confidence interval: 1.6-11.5) or by physical examination (odds ratio: 2.0; 95% confidence interval: 1.1-3.8), and low platelet count were independent predictors of large esophageal varices. On the basis of these variables, cirrhotics were stratified into high- and low-risk groups for the presence of large esophageal varices. Patients with a platelet count of > or = 88,000/mm3 (median value) and no splenomegaly by physical examination had a risk of large esophageal varices of 7.2%. Those with splenomegaly or platelet count < 88,000/mm3 had a risk of large esophageal varices of 28% (p < 0.0001). CONCLUSIONS: Our data show that clinical predictors could be used to stratify cirrhotic patients for the risk of large esophageal varices and such stratification could be used to improve the cost effectiveness of screening endoscopy.

Adrenergic beta-Antagonists↗
PubMed1999

Kala-azar in a high transmission focus: an ethnic and geographic dimension.

In 1994-1996, we studied a group of 58 game wardens stationed in an area known to be highly endemic for visceral leishmaniasis (kala-azar) for evidence of infection with Leishmania donovani. Leishmania DNA was detected by the polymerase chain reaction in the peripheral blood of cases of active kala-azar, former patients with visceral leishmaniasis, patients, and asymptomatic subjects. Using the cloned antigen rk39, antibodies were detected in 44.2% of the game wardens while leishmanin skin test result was positive in 77% of our sample. It was shown that certain tribes from northern Sudan were more likely to develop subclinical infections, while those of the Baria tribe from southern Sudan and those of the Nuba tribe from western Sudan were more likely to develop visceral leishmaniasis. Whether this is due to genetic factors or previous exposure to Leishmania parasites remains to be elucidated.

Animals↗
PubMed1999

Detrimental subtype-specific endothelin-1 (ET-1) signaling in myocardial cells: the ET(A) mediated proliferation and ET(B)receptor down-regulation.

Many physiological and pathological processes in the cardiac tissue have been shown to be associated with a release of endothelin (ET) peptides and with induction of specific ET-receptors and G-protein-coupled ion channels. However, the exact mechanism regulating ET-receptors in the myocardium is controversial. The response to ET-1, the most important member of the ET family, is rapidly attenuated by down-regulation of ET-receptors. The internalization of ET-1 bound to two subclasses of specific receptors (ET(A) and ET(B)) that are abundant in the myocardium has been hypothesized to activate and/or inhibit a variety of intracellular signal transducing systems. The [125I]ET-1, BQ-3020 and selective ET-antagonists were used to study the subtype-selective component of regulation of ET-1 receptors in myocardial membranes. We determined the characteristics of [125I]ET-1 binding and [3H]thymidine incorporation in whole cell saturation studies and measured Ca2+ channel induction and the total number of inactive Ca2+ channels in photoaffinity studies with [3H]azidopine. Here we demonstrate four important components of the complex ET-1 response in human, porcine and rat myocardium, leading to aberrant responses of cells. After ET-1 induction, adaptive subtype-ETB selective down-regulation predominated in human embryonic fibroblasts, in porcine membrane vesicles and in microsomal membranes of renal hypertensive rats, with preferential high affinity ET-1 binding to ETA receptors and with the resultant ETA mediated proliferative and mitogenic activation of human fibroblasts. The ET-1 induction was also accompanied by profound inactivation of Ca2+ channels in myocardial membranes.

Animals↗
PubMed1998

Increased osteoclast-like cells formation in long-term bone marrow cultures from patients with a spinal cord injury.

Patients with a spinal cord section loose a significant amount of bone. After paraplegia, bone loss occurs below the lesional level and is the more dramatic in iliac bones and in the metaphyseal area of long bones. A peak of urinary calcium and hydroxyprolinuria is observed approximately 6 weeks after their lesion. To further understand the mechanisms underlying the bone damage, we used long-term bone marrow cultures to compare osteoclast-like (OCL-like) cell formation above and below the lesional level. Seven paraplegic, one quadriparetic, one quadriplegic patients and five normal subjects were investigated. Six weeks after their spinal cord section, the number of OCL-like cells formed in iliac bone marrow cultures was significantly greater than those formed in sternal bone marrow cultures for all paraplegic patients tested. No significant differences were seen between iliac and sternal bone marrow cultures for the quadriparetic, the quadriplegic patient, or for the five normal subjects. Conditioned media (CM) from iliac marrow of paraplegic patients increased OCL-like cell formation in normal bone marrow cultures. IL-1, TNF-alpha, IL-6, and PGE2 were measured in the CM after 3 weeks of culture. IL-6 was found to be significantly higher in iliac CM compared with sternal CM in six out of seven paraplegic patients. In two patients, addition of an anti-IL-6 monoclonal antibody to the marrow cultures significantly decreased the number of OCL-like cells formed at 3 weeks. We conclude that paraplegia caused by a cord section locally induces an increase in the capacity of progenitors to form OCL-like cells in long-term bone marrow cultures. A locally increased IL-6 production in the marrow below the lesional level could be partly responsible for this observation.

Bone Marrow Cells↗
PubMed1998

Optimization of the enzymatic synthesis of butyl glucoside using response surface methodology

Enzymatic synthesis of butyl glucoside by beta-glucosidase from bitter almonds was optimized using response surface methodology (RSM). Empirical models were developed to describe relationships between the operating variables (temperature, water/butanol volume ratio, glucose concentration, enzyme concentration) and responses (butyl glucoside concentration, conversion yield). Statistical analysis indicated that the four factors had significant effects on the butyl glucoside synthesis. Optimal concentration (41.6 g/L) was reached when the operating conditions were temperature (44.7 degreesC), water/butanol volume ratio (17.6%), glucose concentration (199.2 g/L), and enzyme concentration (2.5 g/L). Good agreement between predicted and measured data at the predicted optimal conditions confirmed the usefulness of the model. Synthesis at a laboratory pilot scale was successful.

Journal Article↗
PubMed1998

High levels of plasma IL-10 and expression of IL-10 by keratinocytes during visceral leishmaniasis predict subsequent development of post-kala-azar dermal leishmaniasis.

Some patients develop post-kala-azar dermal leishmaniasis (PKDL) after they have been treated for the systemic infection kala-azar (visceral leishmaniasis). It has been an enigma why the parasites cause skin symptoms after the patients have been successfully treated for the systemic disease. We report here that PKDL development can be predicted before treatment of visceral leishmaniasis, and that IL-10 is involved in the pathogenesis. Before treatment of visceral leishmaniasis, Leishmania parasites were present in skin which appeared normal on all patients. However, IL-10 was detected in the keratinocytes and/or sweat glands of all patients who later developed PKDL (group 1) and not in any of the patients who did not develop PKDL (group 2). Furthermore, the levels of IL-10 in plasma as well as in peripheral blood mononuclear cell culture supernatants were higher in group 1 than in group 2.

Adolescent↗
PubMed1998

Humoral and cellular immune responses to synthetic peptides of the Leishmania donovani kinetoplastid membrane protein-11.

Native kinetoplastid membrane protein-11 (KMP-11), purified from crude extracts of Leishmania donovani parasites, activates T cells from individuals who have recovered from visceral leishmaniasis. In this work we used three 38-mer peptides spanning the amino acid sequence of the L. donovani KMP-11 as solid-phase ligands in enzyme-linked immunosorbent assays (ELISAs) and as stimulating antigens in lymphoproliferative assays in order to evaluate humoral and cellular immune responses to well-defined sequences of the protein. Antibody reactivity against the three peptides was measured in plasma from 63 Sudanese visceral leishmaniasis patients (VL) and the percentage of patients with anti-KMP-11 antibodies in ELISA were 37% (KMP-11-1), 30% (KMP-11-2) and 58% (KMP-11-3). The fraction of VL patients with measurable antibody reactivity in one or more of the three ELISAs was 79%. Cross-reactivity to the KMP-11 peptides was detected in plasma from Sudanese patients suffering from Leishmania major infections and in plasma from Sudanese and Danish patients infected with Plasmodium falciparum. In lymphoproliferative assays, 10 of 17 PBMC isolates from donors previously infected with L. donovani showed a response to one or more of the three KMP-11 peptides.

Adolescent↗
PubMed1998

Susceptibility pattern of Streptococcus pneumoniae among pre-school children in Kota Bharu, Malaysia.

Streptococcus pneumoniae (S. pneumoniae) is the most common bacterial cause of pneumonia, meningitis, and otitis media, with the highest incidence among young children and the elderly. S. pneumoniae was once routinely susceptible to penicillin, but since the mid-1980s the incidence of resistance to penicillin and other antimicrobial agents has been increasing all over the world. To optimize empirical regimens and initial therapy for S. pneumoniae infections, clinical healthcare providers must be informed about the prevalence and pattern of drug resistance among the isolates in their communities. No such data are available for the Malaysian population. Therefore, this study was designed to determine the antibiotic susceptibility pattern of S. pneumoniae among colonized pre-school children in Kota Bharu, Malaysia. Pharyngeal swabs were collected from children 1 month to 6 years of age. S. pneumoniae isolates were identified according to the standard and tested for penicillin resistance with a 1-microgram oxacillin disk by the Kirby-Bauer disk diffusion methods. Of 355 nasopharyngeal specimens obtained from kindergarten students, in-patients and pediatric clinics over a period of 1 year, S. pneumoniae was isolated from 36 (10 per cent). All isolates, except one, were susceptible to penicillin. The resistant isolates was susceptible to erythromycin, chloramphenicol and cephalosporins.

Child, Preschool↗
PubMed1998

The Leishmania promastigote surface antigen-2 (PSA-2) is specifically recognised by Th1 cells in humans with naturally acquired immunity to L. major.

The promastigote surface antigen-2 (PSA-2) is a Leishmania parasite antigen, which can induce Th1-mediated protection against murine leishmaniasis when used as a vaccine. To evaluate PSA-2 as a human vaccine candidate the specific T-cell response to PSA-2 was characterised in individuals immune to cutaneous leishmaniasis. Peripheral blood mononuclear cells from Sudanese individuals with a past history of self-healing cutaneous leishmaniasis proliferated vigorously in response to PSA-2 isolated from Leishmania major, whereas the antigen did not activate cells from presumably unexposed Danes. Peripheral blood mononuclear cells from individuals with previous L. major infection had varying proliferative responses to PSA-2 derived from L. donovani promastigotes. Peripheral blood mononuclear cells activated by PSA-2 from L. major produced high amounts of interferon-gamma and tumour necrosis factor-beta, and little interleukin-4, thereby showing a Th1 cytokine pattern. Parallel cultures showed clear Th1 and Th2 response patterns to purified protein derivative of tuberculin or tetanus toxoid, respectively. Flow cytometric analysis revealed that PSA-2 induced blastogenesis in the CD3 positive population and that these cells were the major source of interferon-gamma. The results show that Th1-like cells recognising PSA-2 are expanded during infection by L. major and that they maintain their Th1-like cytokine profile upon reactivation in vitro. Since immunity to cutaneous leishmaniasis is mediated by antigen-specific Th1-like cells, PSA-2 might be considered a vaccine candidate for human leishmaniasis.

Animals↗
PubMed1998

Modulation of fluorouracil cytotoxicity by interferon-alpha and -gamma.

Because interferons (IFN)-alpha and -gamma individually have increased fluorouracil (FUra) cytotoxicity in several in vitro models, we studied the effects of FUra combined with IFN-alpha + gamma in HT29 colon cancer cells. A 96-hr exposure to IFN-alpha (500 units/ml) plus IFN-gamma (10 units/ml) and a 72-hr exposure to 0. 25-1 microM FUra (hr 24-96) inhibited cell growth and colony formation in an additive or more-than-additive fashion. When cells were exposed to IFN-alpha + gamma and FUra, free FdUMP levels became detectable, whereas [3H]FUra-RNA incorporation decreased. Exposure to IFN-alpha + gamma, FUra, or the combination decreased dTTP pools to 58%, 43%, and 17% of control, respectively. A marked increase in the dATP to dTTP ratio was seen with FUra with or without IFN-alpha + gamma. Thymidylate synthase catalytic activity was reduced to 28% and 24% of control with FUra with or without IFN-alpha + gamma, suggesting that the enhanced dTTP depletion must be due to another mechanism. FUra-mediated thymidylate synthase inhibition was accompanied by a 124-fold increase in total deoxyuridylate immunoreactivity and a 31-fold increase in dUTP pools, but the addition of IFN-alpha + gamma attenuated the accumulation. Treatment with IFN-alpha + gamma and FUra individually interfered with nascent DNA chain elongation, whereas the three-drug combination produced the most striking effects. IFN-alpha + gamma plus FUra produced the greatest amount of single-strand breaks in nascent DNA and dramatically decreased net DNA synthesis. IFN-alpha + gamma with or without FUra produced double-strand breaks in parental DNA. These results suggest that dTTP depletion, dATP/dTTP imbalance, pronounced inhibition of DNA synthesis, and damage to nascent and parental DNA contribute to the enhanced cytotoxicity with the triple combination.

DNA Fragmentation↗
PubMed1997

Recurrent colonic volvulus in children.

Recurrent intestinal obstruction caused by colonic volvulus is a rare cause of intestinal obstruction in children. Because the condition is self rectifying at times, the diagnosis can be missed or delayed. The authors present two patients, one with sigmoid volvulus and the other with sigmoid and cecal volvulus, and discuss the diagnosis and management of this condition in children. In view of the recurring nature of this condition, the authors believe that nonoperative treatment of this condition in children has no place beyond the emergency situation and that the definitive treatment should always be surgical.

Child↗
PubMed1997

Trans (elaidic) fatty acids adversely affect the lipoprotein profile relative to specific saturated fatty acids in humans.

Although dietary trans fatty acids can affect plasma lipoproteins negatively in humans, no direct comparison with specific saturated fatty acids has been reported, even though trans fatty acids were designed to replace saturates in foods and food processing. In this study, dietary trans 18:1 [elaidic acid at 5.5% energy (en)] was specifically exchanged for cis 18:1, 16:0 or 12:0 + 14:0 in 27 male and female subjects consuming moderate fat (31% en), low cholesterol (<225 mg/d) whole food diets during 4-wk diet periods in a crossover design. The trans-rich fat significantly elevated total cholesterol and LDL cholesterol relative to the 16:0-rich and 18:1-rich fats and uniquely depressed HDL cholesterol relative to all of the fats tested. Trans fatty acids also elevated lipoprotein (a) [Lp(a)] values relative to all dietary treatments. Furthermore, identical effects on lipoproteins were elicited by 16:0 and cis 18:1 in these subjects. The current results suggest that elaidic acid, one of the principal trans isomers produced during industrial hydrogenation of edible oils, adversely affects plasma lipoproteins. Thus, the negative effect of elaidic acid on the lipoprotein profile of humans appears to be unmatched by any other natural fatty acid(s).

Adult↗
PubMed1997

Beta particle attenuation characteristics of CaSO4.

The beta particle mass attenuation coefficient for CaSO4 in a Teflon matrix has been estimated by two methods: an experiment using collimated sources and a collimated gas flow proportional counter and simulations using the EGS4 Monte Carlo code. The attenuation coefficient has been cast in the general form of mu/rho = aE(-b), where E is the maximum beta particle energy and a and b are fitting parameters. The a and b parameters are given as a function of the atomic number of the material.

Beta Particles↗
PubMed1997

Restorative treatments received by children covered by a universal, publicly financed, dental insurance plan.

OBJECTIVES: This study sought to identify risk markers associated with the provision of new restorations in children and to investigate whether the carious status of a tooth surface is associated with the restorative decisions of dentists. METHODS: A total of 911 schoolchildren in grades one, two, and three were randomly selected from the island of Montreal, Quebec, Canada. Dental examinations were carried out in 1990, 1991, and 1992. Tooth surfaces of first permanent molars were classified as sound, noncavitated, and cavitated. The carious status of a tooth was matched with restorative decisions reported to the insurance board. RESULTS: The presence of a carious cavity was a strong risk marker for placement of new restorations (odds rations > or = 4.11). After one year, less than 2 percent of sound tooth surfaces of first permanent molars were restored and about 21 percent of noncavitated tooth surfaces were restored. When new class I restorations placed in maxillary first permanent molars within 3-6 months after the baseline examination were evaluated, we found that between 73 percent and 86 percent of these new restorations were placed in sound or noncavitated tooth surfaces. A similar trend also was observed in mandibular first permanent molars. Poor agreement between epidemiologic diagnosis and restorative decisions was found. The restorative profile of dentists was a significant risk marker for placement of new restorations. CONCLUSION: The majority of new restorations in first permanent molars were placed in sound and noncavitated tooth surfaces because of the ubiquitous prevalence of these tooth surfaces and the validity problems of current caries diagnosis methods.

Child↗
PubMed1997

Longevity of antibody responses to a Salmonella typhi-specific outer membrane protein: interpretation of a dot enzyme immunosorbent assay in an area of high typhoid fever endemicity.

The objective of this study was to investigate the longevity of positive dot enzyme immunosorbent assay (dot EIA) results for IgM and IgG to a Salmonella typhi outer membrane protein in Malaysian children with enteric fever. The patients were children one month to 12 years of age with clinical evidence of typhoid fever, positive blood or stool cultures for S. typhi, and/or a positive Widal test result who were admitted over a two-year period to General Hospital (Kota Bharu, Malaysia). These patients received standard inpatient treatment for enteric fever including chloramphenicol therapy for 14 days. Dot EIA tests were performed as part of clinical and laboratory assessments on admission, at two weeks, and then at 3, 6, 9, 12, 15, 18, and 21 months postdischarge. Assessment of the longevity of positive dot EIA IgM and IgG titers was done by Kaplan-Meier analysis. In 94 evaluable patients, 28% were dot EIA IgM positive but IgG negative on admission, 50% were both IgM and IgG positive, and 22% were IgM negative and IgG positive. Mean persistence of IgM dot EIA positivity was 2.6 months (95% confidence interval = 2.0-3.1 months) and that of IgG was 5.4 months (4.5-6.3 months). There were no significant differences between the three subgroups. Thus, positive IgM and IgG results determined by dot EIA within four and seven months, respectively, following documented or suspected enteric fever in a child from an endemic area should be interpreted with caution. In other clinical situations, the dot EIA remains a rapid and reliable aid to diagnosis.

Anti-Bacterial Agents↗