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Biomedical subjects

R Ahmed

Publications and source records attributed to R Ahmed.

At least 73 records · Page 4Linked to original sources

Direct amplification of Entamoeba histolytica DNA from amoebic liver abscess pus using polymerase chain reaction.

An important and serious complication of intestinal infection with Entamoeba histolytica is the involvement of the liver (hepatic amoebiasis). Hepatic amoebiasis is usually diagnosed by the clinical picture (pain in the right upper quadrant and fever), ultrasound examination and positive serology. However, none of these tests are definitive and the picture overlaps with pyogenic liver abscess caused by bacteria. It is for this reason that the feasibility of using polymerase chain reaction (PCR) for the detection of E. histolytica DNA in liver abscess pus was investigated. A comparative study was done to verify the sensitivity of ten pairs of primers specific for detecting E. histolytica in stools. Samples of liver abscess pus from 22 serology-positive patients were collected under ultrasound guidance; and these were used directly in PCR assays without any prior pre-treatment of the samples. Of the ten pairs of previously published primers tested, two pairs of primers (PI + P2 and P11 + P12) were found to give 100% sensitivity. Based on these results, we recommend that PCR assay can be successfully used to confirm the diagnosis of amoebic liver abscess with the primers identified.

Animals↗

Costimulation in antiviral immunity: differential requirements for CD4(+) and CD8(+) T cell responses.

A key step toward improving vaccines is understanding the molecular interactions responsible for inducing antiviral T cell responses. An emerging theme from recent studies is that CD4(+) and CD8(+) T cell responses require distinct costimulatory pathways for activation. In addition, these costimulatory interactions can play a crucial role during the death phase of the T cell response and determine the number of effector T cells that survive to become memory T cells.

Animals↗

Long term response to gallstone treatment--problems and surprises.

OBJECTIVE: To re-evaluate after 5 years the results of a randomised trial of cholecystectomy and lithotripsy for the treatment of symptomatic gallstones. DESIGN: Late follow-up of a randomised controlled trial. SETTING: Teaching hospital, UK. SUBJECTS: 144 of the 179 patients originally randomised. INTERVENTIONS: Either elective open cholecystectomy under general anaesthesia or a maximum of 4 sessions of lithotripsy (up to 3000 shocks/session) on consecutive days with no anaesthesia or analgesia. RESULTS: Of the original 87 patients randomised to be treated by lithotripsy, 39 (45%) subsequently underwent cholecystectomy, most of them within 32 months of treatment ("crossover" group). Patients in both main groups had a pronounced reduction in the number of episodes of pain at 5 years and significant reductions in the mean severity scores both on VAS and the McGill rating. Those in the crossover group had the worst scores. Gastrointestinal symptoms improved in the two main groups, but again the crossover group did least well. Quality of life improved significantly over baseline in the two main groups, but was much poorer in the crossover group. CONCLUSIONS: Patients who had primary cholecystectomy were more likely to be free of pain than those treated by lithotripsy. Lithotripsy gave good symptomatic results in 55% of patients, and this was not dependent on clearance of stones. Patients who had a cholecystectomy after lithotripsy had the worst symptomatic results. It is difficult to identify patients who will not benefit from lithotripsy, but the presence of many coexisting symptoms may be an important predictor.

Adult↗

Fermentation of dietary starch in humans.

OBJECTIVE: Dietary starch that escapes digestion in the small intestine may be quantitatively more important than dietary fiber as a substrate for fermentation. The products of fermentation have important implications in the pathogenesis of colorectal cancer and other diseases of the large bowel, which are uncommon in Africans but have a high prevalence in Western populations. METHODS: Maize porridge is a staple of most blacks in South Africa. Stale maize porridge (high-resistant starch [HRS]) seems to induce greater fermentation in the large bowel than fresh maize porridge (low-resistant starch [LRS]). RESULTS: In the present study, healthy colostomy subjects fed stale maize porridge had significantly more production of short-chain fatty acids (SCFA) (mean SCFA, HRS = 182.6; mean SCFA, LRS = 116.1; p < 0.05) in their colostomy effluent together with a significant drop in stool pH (mean pH, HRS = 5.91; mean pH, LRS = 6.70; p < 0.001). The SCFA butyrate (mean, HRS = 35.1; mean, LRS = 17.6; p < 0.05) and acetate (mean, HRS = 93.9; mean, LRS = 65.8; p < 0.05) were significantly elevated on the stale maize porridge diet when compared with consumption of fresh maize porridge. SCFA propionate (mean, HRS = 43.1; mean, LRS = 24.8; p = 0.05), also increased with stale maize porridge, but was not statistically significant. CONCLUSION: A high-resistant starch diet and its resultant increase in fermentation products may be partly responsible for protecting the black population against colorectal cancers and other large bowel diseases.

Acetic Acid↗

Epidemiologic typing of Salmonella enterica serotype enteritidis in a Canada-wide outbreak of gastroenteritis due to contaminated cheese.

A major Canada-wide outbreak of gastroenteritis due to Salmonella enterica serotype Enteritidis phage type (PT) 8 occurred in 1998, and this was traced to contaminated cheese in a commercial lunch pack product. Phage typing and pulsed-field gel electrophoresis linked the clinical and cheese isolates of serotype Enteritidis but failed to differentiate outbreak from nonoutbreak PT 8 strains. Further differentiation was made by biotyping based on melibiose fermentation.

Bacterial Typing Techniques↗

Chimeric yellow fever/dengue virus as a candidate dengue vaccine: quantitation of the dengue virus-specific CD8 T-cell response.

We have constructed a chimeric yellow fever/dengue (YF/DEN) virus, which expresses the premembrane (prM) and envelope (E) genes from DEN type 2 (DEN-2) virus in a YF virus (YFV-17D) genetic background. Immunization of BALB/c mice with this chimeric virus induced a CD8 T-cell response specific for the DEN-2 virus prM and E proteins. This response protected YF/DEN virus-immunized mice against lethal dengue encephalitis. Control mice immunized with the parental YFV-17D were not protected against DEN-2 virus challenge, indicating that protection was mediated by the DEN-2 virus prM- and E-specific immune responses. YF/DEN vaccine-primed CD8 T cells expanded and were efficiently recruited into the central nervous systems of DEN-2 virus challenged mice. At 5 days after challenge, 3 to 4% of CD8 T cells in the spleen were specific for the prM and E proteins, and 34% of CD8 T cells in the central nervous system recognized these proteins. Depletion of either CD4 or CD8 T cells, or both, strongly reduced the protective efficacy of the YF/DEN virus, stressing the key role of the antiviral T-cell response.

Animals↗

In vitro responses of gallbladder muscle from patients with acalculous biliary pain.

BACKGROUND: Diagnosis and identification of patients with acalculous biliary pain, who would benefit from surgery, remains a significant clinical problem. The cholecystokinin (CCK) provocation test helps diagnosis, but lack of consistency limits its usefulness. AIM: To characterize the response of gallbladder muscle strips, from patients with acalculous biliary pain, to hormonal and muscarinic stimulation and to compare these with strips from gallstone patients and normal controls. PATIENTS: Eleven patients with acalculous biliary pain were studied, 5 had a positive CCK test. Eight gallbladders from gallstone patients and 6 from partial hepatectomies were used for comparison. METHODS: Muscle strips from the body and neck of the gallbladder were suspended in organ baths and dose-response curves were constructed for CCK-8 and carbachol. RESULTS: In the acalculous group the strips from the body were less sensitive to carbachol than those of the neck. CONCLUSION: Since we found no differences in the CCK responses for the groups, it casts doubt over the effectiveness of the CCK test to diagnose acalculous biliary pain. Since carbachol sensitivity was different, it might be that a similar test using muscarinic stimulation would help in the diagnosis of this difficult group of patients.

Adult↗

Learning approaches and academic performance of undergraduate medical students in Pakistan.

OBJECTIVE: To classify undergraduate medical students according to their learning approaches and to correlate the learning approaches with their academic achievements. MATERIALS AND METHODS: A questionnaire to appraise learning approaches of undergraduate medical students was administered and collected at the end of the regular certifying examinations. The responses were analysed through the principal component factor analysis. RESULTS: The results did not depict formation of demonstrable learning approaches during academic years. However, increased self-awareness about the approaches was indicated by the responses of final year students as compared to the third year students. The correlation of the learning approaches with the scores of the certifying examination and a mock test (consisting of specially developed integrated questions), through multivariate analysis depicted statistically insignificant results. CONCLUSION: There was a non-significant relationship between the learning approaches and academic performances and a weak statistical significance between achievement, orientation and performance in certifying examination. It is essential that along with changes in the instructional and assessment strategies awareness should be created in students about various learning approaches.

Adolescent↗

Retinoblastoma tells the story of our health care system.

OBJECTIVE: To review cases of retinoblastoma. SETTING: Department of Pathology Aga Khan University Hospital Karachi. METHOD: Twenty-three specimens from cases of retinoblastoma received over a period of eight years were routinely processes and stained with haematoxylin and Eosin stain. Other stains were used for tuberculoses and melanin. Immunochemistry was resorted to in undifferentiated tumors. RESULTS: Over 60% cases of retinoblastoma were diagnosed after 5 years and nine cases showed involvement of optinerve. CONCLUSION: Late diagnosis of retinoblastoma effects the stage of the tumors and the prognosis.

Child, Preschool↗

Impaired anti-viral T cell responses due to expression of the Ly49A inhibitory receptor.

Inhibitory receptors specific for alleles of MHC class I proteins play an important role in determining the reactivity and specificity of NK cells. To determine whether these receptors are also able to regulate T cell functions, we have studied anti-viral immune responses in mice transgenic for a class I-specific inhibitory receptor, Ly49A. Although nontransgenic mice express Ly49A primarily on NK cells and some T cells, the Ly49A transgenic mice express Ly49A on all lymphocytes, including T cells. We have assessed the activation, expansion, cytokine production, and cytotoxic activity of CD8 T cells in both transgenic and nontransgenic mice following infection with lymphocytic choriomeningitis virus. As expected, nontransgenic mice made a potent virus-specific CD8 T cell response following virus infection. However, as measured in cytolysis assays and by cytokine production, virus-specific CD8 T cell activity was reduced in Ly49A transgenic mice. This inhibition was largely, but not always exclusively, dependent upon the presence, either in vivo or in vitro, of the Ly49A ligand, H-2Dd. Strikingly Ly49A transgenic mice have reduced capacity to control infection with the virulent lymphocytic choriomeningitis virus variant clone 13. Overall, these studies demonstrate that expression of killer inhibitory receptors can modulate anti-viral T cell responses in vivo and in vitro.

Animals↗

Persistence of memory CD8 T cells in MHC class I-deficient mice.

An understanding of how T cell memory is maintained is crucial for the rational design of vaccines. Memory T cells were shown to persist indefinitely in major histocompatibility complex (MHC) class I-deficient mice and retained the ability to make rapid cytokine responses upon reencounter with antigen. In addition, memory CD8 T cells, unlike naïve cells, divided without MHC-T cell receptor interactions. This "homeostatic" proliferation is likely to be important in maintaining memory T cell numbers in the periphery. Thus, after naïve CD8 T cells differentiate into memory cells, they evolve an MHC class I-independent "life-style" and do not require further stimulation with specific or cross-reactive antigen for their maintenance.

Adoptive Transfer↗

4-1BB ligand, a member of the TNF family, is important for the generation of antiviral CD8 T cell responses.

4-1BB (CD137) is a costimulatory molecule expressed on activated T cells and interacts with 4-1BB ligand (4-1BBL) on APCs. To investigate the role of 4-1BB costimulation for the development of primary immune responses, 4-1BBL-deficient (4-1BBL-/-) mice were infected with lymphocytic choriomeningitis virus (LCMV). 4-1BBL-/- mice were able to generate CTL and eliminate acute LCMV infection with normal kinetics, but CD8 T cell expansion was 2- to 3-fold lower than in wild-type (+/+) mice. In the same mice, virus-specific CD4 Th and B cell responses were minimally affected, indicating that 4-1BB costimulation preferentially affects CD8 T cell responses. This result contrasts with our earlier work with CD40L-deficient (CD40L-/-) mice, in which the CD8 T cell response was unaffected and the CD4 T cell response was markedly impaired. When both 4-1BBL- and B7-dependent signals were absent, CD8 T cell expansion was further reduced, resulting in lower CTL activity and impairing their ability to clear LCMV. Altogether, these results indicate that T cells have distinct costimulatory requirements: optimal CD8 responses require 4-1BBL-dependent interactions, whereas CD4 responses are minimally affected by 4-1BB costimulation, but require CD40-CD40L and B7-dependent interactions.

4-1BB Ligand↗

Peptide vaccination using nonionic block copolymers induces protective anti-viral CTL responses.

High molecular weight nonionic block copolymers have been developed as vaccine adjuvants. We employed these adjuvants in water-in-oil emulsion and multiple emulsion formulations with a synthetic peptide-based antigen vaccine to test their ability to prime anti-viral CD8(+) T cell responses. Vaccines were made using the H-2(d)-restricted immunodominant peptide from lymphocytic choriomeningitis virus (LCMV), NP118-126, and administered to BALB/c ByJ (H-2(d)) mice. Peptide-containing emulsions were able to induce NP118-126 specific CTL and IFN-gamma secreting CD8(+) T cells in the vaccinated mice and these responses were maintained for at least 90 days post immunization. At all times, the responses induced by the copolymer formulations were equal to, or better than, formulations based on incomplete Freund's adjuvant (IFA). In addition, the responses induced by prophylactic vaccination using the multiple emulsion formulation resulted in accelerated viral clearance following infection with a strain of LCMV (clone 13) that causes a persistent infection in naïve adult mice. These results indicate that peptide vaccination using a formulation based on high molecular weight nonionic block copolymer in a simple water-in-oil or a multiple emulsion format can induce virus-specific CD8(+) T cell responses and confer protection sufficient enough to prevent the establishment of a persistent infection.

Adjuvants, Immunologic↗

CD40-CD40 ligand costimulation is required for generating antiviral CD4 T cell responses but is dispensable for CD8 T cell responses.

This study documents a striking dichotomy between CD4 and CD8 T cells in terms of their requirements for CD40-CD40 ligand (CD40L) costimulation. CD40L-deficient (-/-) mice made potent virus-specific CD8 T cell responses to dominant as well as subdominant epitopes following infection with lymphocytic choriomeningitis virus. In contrast, in the very same mice, virus-specific CD4 T cell responses were severely compromised. There were 10-fold fewer virus-specific CD4 T cells in CD40L-/- mice compared with those in CD40L+/+ mice, and this inhibition was seen for both Th1 (IFN-gamma, IL-2) and Th2 (IL-4) responses. An in vivo functional consequence of this Th cell defect was the inability of CD40L-/- mice to control a chronic lymphocytic choriomeningitis virus infection. This study highlights the importance of CD40-CD40L interactions in generating virus-specific CD4 T cell responses and in resolving chronic viral infection.

Animals↗

Stability constants of thiocyanato complexes of cobalt(II), nickel(II) and copper(II) in methanol.

A spectrophotometric study of cobalt(II), nickel(II) and copper(II) thiocyanato complexes was carried out in methanol at 25 degrees C and at a constant ionic strength of 1 M. Under the experimental conditions, two mononuclear complexes are identified with each of the three metal ions. Their stability constants are determined with a recent PC program SIRKO and the calculated values are: for cobalt, log beta 1 = 1.6, log beta 2 = 2.7; for nickel, log beta 1 = 1.8, log beta 2 = 3.0; and for copper, log beta 1 = 3.0, log beta 2 = 3.6.

Cobalt↗

Two roads diverged: interferon alpha/beta- and interleukin 12-mediated pathways in promoting T cell interferon gamma responses during viral infection.

Viral infections induce CD8 T cell expansion and interferon (IFN)-gamma production for defense, but the innate cytokines shaping these responses have not been identified. Although interleukin (IL)-12 has the potential to contribute, IL-12-dependent T cell IFN-gamma has not been detected during viral infections. Moreover, certain viruses fail to induce IL-12, and elicit high levels of IFN-alpha/beta to negatively regulate it. The endogenous factors promoting virus-induced T cell IFN-gamma production were defined in studies evaluating CD8 T cell responses during lymphocytic choriomeningitis virus infections of mice. Two divergent supporting pathways were characterized. Under normal conditions of infections, the CD8 T cell IFN-gamma response was dependent on endogenous IFN-alpha/beta effects, but was IL-12 independent. In contrast, in the absence of IFN-alpha/beta functions, an IL-12 response was revealed and substituted an alternative pathway to IFN-gamma. IFN-alpha/beta-mediated effects resulted in enhanced, but the alternative pathway also promoted, resistance to infection. These observations define uniquely important IFN-alpha/beta-controlled pathways shaping T cell responses during viral infections, and demonstrate plasticity of immune responses in accessing divergent innate mechanisms to achieve similar ultimate goals.

Animals↗