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T Haque

Publications and source records attributed to T Haque.

At least 19 recordsLinked to original sources

An immunohistochemical analysis of the temporal and spatial expression of growth factors FGF 1, 2 and 18, IGF 1 and 2, and TGFbeta1 during distraction osteogenesis.

Distraction osteogenesis (DO) is a well established surgical technique that generates new bone by gradual distraction of two bony segments. In this study, we investigated the temporal and spatial profile of FGF 1, 2 and 18, IGF 1 and 2, and TGFbeta1 during distraction osteogenesis using immunohistochemistry. An osteotomy was performed on the right tibia of 13 white male New Zealand rabbits. After a delay of 7 days, distraction was started at a rate of 0.25 mm/12 hrs for 3 weeks which was followed by a 3 week period of consolidation. Immunohistochemical analysis was performed on a weekly interval to determine the expression of the growth factors. Staining of all growth factors was apparent at various levels in the centre and callus region in fibroblasts and chondrocyte cells. FGF2 however, showed continued high expression in osteoblasts. Within two weeks after the end of distraction all growth factors showed a reduction in expression except for FGF18 which maintained high levels of expression (up to 100% staining) throughout the distraction and consolidation phases. The study suggests that in comparison to the other investigated growth factors, FGF18 may play in important role throughout the entire process of distraction osteogenesis.

Animals↗

A review of FGF18: Its expression, signaling pathways and possible functions during embryogenesis and post-natal development.

FGF18 is a novel growth factor first reported in 1998. Current evidence suggests that FGF18 may play a prominent role in chondrogenesis and osteogenesis during skeletal development and growth. However, its function extends to many other biological processes. Although there remains much to be discovered and investigated on the functions and mechanisms of FGF18, it may play a role as a useful therapeutic target for various applications. The following review summarizes the current knowledge on FGF18 with special emphasis on its skeletal functions and highlights its potential areas for future research.

Animals↗

In-vitro analysis of APA microcapsules for oral delivery of live bacterial cells.

Oral administration of microcapsules containing live bacterial cells has potential as an alternative therapy for several diseases. This article evaluates the suitability of the alginate-poly-L-lysine-alginate (APA) microcapsules for oral delivery of live bacterial cells, in-vitro, using a dynamic simulated human gastro-intestinal (GI) model. Results showed that the APA microcapsules were morphologically stable in the simulated stomach conditions, but did not retain their structural integrity after a 3-day exposure in simulated human GI media. The microbial populations of the tested bacterial cells and the activities of the tested enzymes in the simulated human GI suspension were not substantially altered by the presence of the APA microcapsules, suggesting that there were no significant adverse effects of oral administration of the APA microcapsules on the flora of the human gastrointestinal tract. When the APA microcapsules containing Lactobacillus plantarum 80 (LP80) were challenged in the simulated gastric medium (pH = 2.0), 80.0% of the encapsulated cells remained viable after a 5-min incubation; however, the viability decreased considerably (8.3%) after 15 min and dropped to 2.6% after 30 min and lower than 0.2% after 60 min, indicating the limitations of the currently obtainable APA membrane for oral delivery of live bacteria. Further in-vivo studies are required before conclusions can be made concerning the inadequacy of APA microcapsules for oral delivery of live bacterial cells.

Administration, Oral↗

Investigation of a new microcapsule membrane combining alginate, chitosan, polyethylene glycol and poly-L-lysine for cell transplantation applications.

Microencapsulation of living cells may serve as an alternative therapy for patients requiring organ transplants. One of the limiting factors in the progress of such therapy is attaining a biocompatible and mechanically stable polymer. The current study investigates the potential of a novel membrane combining alginate, chitosan, polyethylene glycol (PEG) and poly-L-lysine (PLL) with the objective of proposing a membrane suitable for cell entrapment that may overcome some of the shortcomings of the widely studied alginate-poly-L-lysine-alginate (APA) capsules. The novel microcapsule was formulated using a 1.5% alginate solution coated with 0.05% chitosan, 0.1% PEG and 0.05% poly-L-lysine with a final layer of 0.1% alginate. Microcapsules having a diameter of 450 +/- 30 microm were prepared. Upon citrate treatment, the membrane remained intact and retained its spherical structure. The membrane was able to support liver cell proliferation and the encapsulated cells were capable of secreting proteins. The study demonstrated that the new membrane can be used for cell entrapment. However, further investigations are needed to assess its potential for long term transplantation and usage in the development of bioartificial organs.

Albumins↗

Complete regression of posttransplant lymphoproliferative disease using partially HLA-matched Epstein Barr virus-specific cytotoxic T cells.

BACKGROUND: Adoptive immunotherapy with autologous and donor-derived cytotoxic T lymphocytes (CTL) has recently been used to treat Epstein Barr virus (EBV)-positive posttransplant lymphoproliferative disease (PTLD). METHODS AND RESULTS: We report complete regression of EBV-positive PTLD in an 18-month-old small bowel and liver transplant recipient after one infusion of partially human leukocyte antigen (HLA)-matched EBV-specific CTL grown ex vivo from an EBV seropositive unrelated blood donor. No infusion-related toxicity or evidence of graft-versus-host disease was observed. The tumor showed signs of regression within 1 week and EBV load in peripheral blood dropped to undetectable levels. Limiting dilution analyses (LDA) detected no EBV-specific CTL precursor (CTLp) cells before the infusion, and high numbers of CTLp at 4 hr and 24 hr post-CTL infusion. There was a reversal of the CD4/8 ratio in peripheral blood and an increase in HLA-DR positive CD8 cells. The patient has been in complete remission for 24 months. CONCLUSION: If this success is repeated in more PTLD patients, then stored CTL could be used for antiviral and antitumor therapies in immunocompromised patients.

HLA-DR Antigens↗

Selective inhibition of bacterial dihydroorotate dehydrogenases by thiadiazolidinediones.

Dihydroorotate dehydrogenase is a critical enzyme of de novo pyrimidine biosynthesis in prokaryotic and eukaryotic cells. Differences in the primary structure of the enzymes from Gram-positive and -negative bacteria and from mammals indicate significant structural divergence among these enzymes. We have identified a class of small molecules, the thiadiazolidinediones, that inhibit prototypical enzymes from Gram-positive and -negative bacteria, but are inactive against the human enzyme. The most potent compound in our collection functioned as a time-dependent irreversible inactivator of the bacterial enzymes with k(inact)/K(i) values of 48 and 500 M(-1) sec(-1) for the enzymes from Escherichia coli and Enterococcus faecalis, respectively. The data presented here indicate that it is possible to inhibit prokaryotic dihydroorotate dehydrogenases selectively while sparing the mammalian enzyme. Thus, this enzyme may represent a valuable target for the development of novel antibiotic compounds.

Anti-Bacterial Agents↗

Myocardial viability detected by dobutamine echocardiography in patients with chronic coronary artery disease, and long-term outcome after coronary angioplasty.

Viable but dysfunctional myocardium detected by dobutamine echocardiography (DE) predicts early improvement in regional left ventricular (LV) function after percutaneous transluminal coronary angioplasty (PTCA). Whether DE can predict the long-term (>2 years) outcome after PTCA is still unclear. Thus, 50 patients (age 60.4+/-9.5 years) with chronic coronary artery disease and regional LV dysfunction who underwent DE 1 week before PTCA to assess myocardial viability were followed for 4.0+/-0.8 years. Regional LV function and LV ejection fraction (LVEF) were evaluated by 2-dimensional echocardiography in patients who remained event-free (cardiac death or myocardial infarction or unstable angina pectoris) after PTCA. At late follow-up (>2 years after PTCA), 29 patients showed regional LV function improvement, 15 showed no improvement, 3 showed worsening and 3 patients had cardiac events (1 nonfatal myocardial infarction and 2 unstable angina pectoris). LVEF improved (0.53+/-0.09 to 0.60+/-0.09, p<0.001) in patients with improved regional LV function, but deteriorated (0.38+/-0.03 to 0.30+/-0.03) in the 3 patients with worsened regional LV function. Of the 29 patients with improvement, 27 (93%) had viable myocardium, whereas only 3 (20%) of the 15 with no improvement had viable myocardium and all 6 of those with poor outcomes (3 with cardiac events and 3 with worsening) had viable myocardium (chi2 = 28.9, p<0.001). Patients with viable myocardium and a poor outcome had a lower mean LVEF before PTCA, and at 1 week and 3 months after PTCA (p = 0.004, <0.001, and =0.001, respectively), and a higher restenosis rate (p = 0.007) than patients with viable myocardium and without a poor outcome. It is concluded that viable myocardium detected by DE may predict long-term improvement in regional and global LV function after PTCA. However, patients with viable myocardium and persistent low LVEF are at risk for cardiac events or worsening of LV function.

Aged↗

Epstein-Barr virus (EBV) associated B-cell lymphoproliferative disease following HLA identical sibling marrow transplantation for aplastic anaemia in a patient with an EBV seronegative donor.

BACKGROUND: B-cell lymphoproliferative disorders (BLPD*) caused by Epstein-Barr virus (EBV) occurring after allogeneic bone marrow transplantation (BMT) are usually of donor origin. Treatment such as discontinuation of immunosuppression may be successful in some cases, but infusion of donor T cells results in successful eradication of EBV BLPD in most cases. METHODS AND RESULTS: We report a case of EBV positive aggressive BLPD after HLA matched sibling BMT for aplastic anaemia. The tumour completely regressed after withdrawal of cyclosporin and donor lymphocyte infusion. However, although the tumor was of donor origin, the donor serum was negative for antibodies to EBV antigens and no EBV-specific cytotoxicity was detected in donor peripheral blood mononuclear cells. The recipient was seropositive for EBV before BMT. CONCLUSIONS: We speculate that a 'second primary' EBV infection occurred involving donor cells in the recipient during BMT immunosuppression, with subsequent outgrowth of donor-derived BLPD. EBV infection may have been by an endogenous EBV isolate, from external sources, or from third party transfusions.

Adult↗

Reconstitution of EBV-specific T cell immunity in solid organ transplant recipients.

EBV-specific autologous CTL were grown in vitro from three adults (two liver transplant recipients and one patient on hemodialysis awaiting kidney retransplant). All CTL lines were TCR alphabeta, CD8 positive cells, EBV specific, and MHC class I restricted. The CTL lines were expanded in vitro and infused in three escalating doses (5 x 10(7), 1 x 10(8), and 2 x 10(8) at monthly intervals. Weekly blood samples were collected following each infusion. EBV-specific CTL precursor cells in peripheral blood were quantitated by limiting dilution analysis, and their effect on EBV load in vivo was assessed by semiquantitative PCR. In all three patients, the numbers of CTL precursor cells increased during the weeks following the infusions and were highest after the third infusion. This level gradually declined but remained above the preinfusion levels for up to 3 mo. EBV genome copy number, on the other hand, dropped following the first infusion and became undetectable thereafter. The EBV DNA level remained lower than the pretransplant level in all patients for up to 3 mo after the last infusion. Our study shows that it is feasible to generate and expand EBV-specific CTL from pretransplant blood samples of solid organ transplant recipients, that these CTL can be stored and infused posttransplant, and that they remain cytotoxic and EBV specific in vivo. The aim of this study is to use these CTL for prevention and treatment of lymphoproliferative disease in solid organ transplant recipients.

Adult↗

Echocardiography and fatty acid single photon emission tomography in predicting reversibility of regional left ventricular dysfunction after coronary angioplasty.

AIMS: The present study was performed to evaluate whether echocardiographic assessment of end-diastolic wall thickness and myocardial fatty acid metabolic single-photon emission tomographic imaging with 123I-beta-methyl-iodophenyl pentadecanoic acid could be used to predict the reversibility of dysfunctional left ventricular segments after coronary artery revascularization. METHODS AND RESULTS: Twenty-eight patients with wall motion abnormalities related to stenosed coronary arteries underwent resting two-dimensional echocardiography and 123I-beta-methyl-iodophenyl pentadecanoic acid single photon emission tomography before coronary angioplasty. A dysfunctional segment was considered viable by the presence of either preserved wall thickness (> or = 75% of the thickness of a normal segment) or preserved fatty acid uptake (> or = 50% of that in normal region). Echocardiography was repeated after successful angioplasty. Functional recovery was observed in 32 (74%) of 43 hypokinetic and nine (100%) of nine akinetic segments with preserved wall thickness and in 11 (79%) of 14 thinned akinetic segments with preserved fatty acid uptake. In contrast, no functional recovery was observed in any of the 13 thinned segments with < 50% fatty acid uptake (eight akinetic and five dyskinetic). Using combined evaluation of both methods, positive and negative predictive values for post-revascularization functional outcome were 79% and 100%, respectively, in all dysfunctional segments; and 87% and 100%, respectively, in akinetic/dyskinetic segments. CONCLUSIONS: The present study showed that echocardiographic findings of preserved wall thickness and single-photon emission tomography evaluated preserved fatty acid uptake in thinned segments are reliable predictors of post-revascularization functional recovery and the concordant absence of both accurately predict negative outcome.

Adult↗

Non-correlation of in vivo and in vitro parameters of Epstein-Barr virus persistence suggests heterogeneity of B cell infection.

Following primary infection Epstein-Barr virus (EBV) establishes a persistent infection which is maintained for the life-time of the host. EBV can be found in a small number of circulating B cells, but the nature of the virus-cell interaction has not been fully established. Several assay systems are used to quantify persistent EBV infection, including PCR amplification of EBV DNA and spontaneous outgrowth of lymphoblastoid cell lines in culture. More recently, outgrowth of EBV-positive B cell tumours in severe combined immunodeficient (SCID) mice inoculated with peripheral blood mononuclear cells (PBMC) from normal EBV-seropositive donors has also been used to study B cell infection in vivo. In the present study we have compared the results of these two biological assay systems with PCR detection of EBV DNA and a regression assay as a measure of host T cell immunity to EBV. PBMC from ten normal EBV-seropositive donors were studied and although each test gave consistent results on repeat assays, no correlation was found between any of the assays tested. This result suggests that each assay measures a separate aspect of EBV persistence in B cells, and indicates a previously unrecognized degree of heterogeneity in the B cell population in which EBV resides.

Animals↗

A prospective study in heart and lung transplant recipients correlating persistent Epstein-Barr virus infection with clinical events.

BACKGROUND: A 2-year prospective study was set up with 30 cardiothoracic transplant recipients to study Epstein-Barr virus (EBV) infection and immunity and their correlation with clinical events. METHODS: Regression assays were used to measure EBV-specific cytotoxic T lymphocyte (CTL) function. Tissue culture, immunoblotting, and polymerase chain reaction were used for EBV detection and isolate variation studies. RESULTS: CTL activity was significantly lower in pretransplant seropositive patients than in healthy controls (P<0.001). CTL response was undetectable in all patients during the first 6 months after transplantation, but returned at levels significantly lower than pretransplant and control levels during the second posttransplant year (P<0.001). Return of CTL function was directly correlated with time of last treated rejection episode (P<0.003) and duration of high plasma levels of cyclosporine (over 400 ng/ml; P<0.003). Significantly higher levels of EBV were detected in peripheral blood during the first 6 months than in pretransplant or control samples (P<0.05). Excretion of EBV in throat washings was significantly lower during the first 3 months when all patients were receiving acyclovir than in pretransplant and control samples (P=0.02). An increase in virus shedding was noted 3-6 months after transplantation, which was significantly higher than in pretransplant patients and controls (P<0.05). Comparison of recipients' and donors' virus isolates in 11 cases showed that seropositive recipients retained their original EBV isolate and did not acquire the donor virus. CONCLUSIONS: Immunosuppression decreased EBV-specific host immune function, which in turn favored increased EBV load in peripheral blood and increased excretion in the oropharynx. The transfer of donor virus to the seropositive recipients was not observed.

Adolescent↗

An assessment of dobutamine echocardiography and end-diastolic wall thickness for predicting post-revascularization functional recovery in patients with chronic coronary artery disease.

AIMS: This study investigated the functional outcome of wall-thinned, akinetic myocardium after revascularization and evaluated the accuracy of dobutamine echocardiography in predicting post-revascularization functional recovery with the assessment of end-diastolic wall thickness in chronic ischaemic patients. METHODS AND RESULTS: Fifty-three patients underwent dobutamine echocardiography before coronary revascularization. End-diastolic wall thickness was also evaluated before and after revascularization. The sensitivity and specificity of dobutamine echocardiography to predict postrevascularization functional recovery were 69% and 100% in 58 akinetic/dyskinetic segments, and 86% and 57% in 96 hypokinetic segments. Of 19 akinetic/dyskinetic segments with a preserved end-diastolic wall thickness, 17 (89%) showed functional recovery after revascularization, and dobutamine detected 14 (83%) of these 17 segments. Of 39 akinetic/dyskinetic segments with a thinned end-diastolic wall thickness, 15 (38%) achieved functional recovery, whereas dobutamine echocardiography detected recovery in only eight (53%). Further, of these 15 viable, Wall-thinned segments, 12 (80%) showed an increased end-diastolic wall thickness after revascularization (mean +/- SD were from 5.6 +/- 0.7 mm at baseline to 7.4 +/- 1.3 mm and 9.7 +/- 1.4 mm after 1 week and after 3 months, respectively), and only 5 (42%) of these responded to dobutamine. CONCLUSION: Dobutamine echocardiography showed a lessened sensitivity to predict post-revascularization functional recovery in akinetic/dyskinetic segments with a thinned end-diastolic wall thickness that subsequently increased in size.

Adult↗

PCR amplification is more sensitive than tissue culture methods for Epstein-Barr virus detection in clinical material.

In this study we have compared the use of PCR and conventional tissue culture methods to detect Epstein-Barr virus (EBV) in peripheral blood mononuclear cells and throat wash samples. The study population included 29 healthy adult and 20 immunocompromised EBV-seropositive donors. The results show significantly higher EBV detection rates by PCR than the tissue culture methods in throat wash samples from both donor groups (P < 0.01 in healthy donors and P < 0.009 in the immunocompromised donors) and in peripheral blood from the immunocompromised but not from the healthy donors (P < 0.008). Furthermore, when EBV DNA detection rates in throat wash cell pellet and supernatant fluid were compared, a higher positive result was obtained with the cell pellets which reached statistical significance in the immunocompromised group (P < 0.02). No correlation was found between positivity in throat wash and peripheral blood from the same donors.

Adult↗

Seroepidemiological study of Epstein-Barr virus infection in Bangladesh.

A seroepidemiological study was carried out on 502 sera to determine the prevalence of EBV infection in a group of Bangladeshi people (age range: 15 days-90 years). All sera were tested for IgG antibody to the EBV viral capsid antigen (VCA) by a commercially available enzyme linked immunosorbent assay (ELISA) and the negative sera were checked subsequently by indirect immunofluorescence (IF) methods. The prevalence of EBV infection in the study group was 81.27%. 42.37% of infants had antibodies to EBV by the age of 1 year. A significant rise in the percentage of seropositives between 0-1- and 1-2-year-old children was demonstrated, indicating a high rate of primary infection at these ages. The prevalence of IgG antibody to VCA was 87.93% in the 2-10 years age group and was sustained at over 85% thereafter. Higher ELISA values were more common both in the 0-2- and > 25-year age groups, the latter being statistically significant (P < 0.025). Similar higher values were also observed in females as compared to males (P = 0.05). Eighteen out of 109 negative sera and two equivocal sera by ELISA were found to be positive by indirect IF, indicating a negative predictive value of 82% for ELISA. The concordance between the two methods was 97% with ELISA proving to be less sensitive than indirect IF. It is concluded that the prevalence of EBV infection in Bangladeshi population is similar to that observed in other developing countries and that ELISA can be used for seroepidemiological surveys; however, the sera negative by ELISA should be checked routinely by indirect IF.

Adolescent↗

Transmission of donor Epstein-Barr virus (EBV) in transplanted organs causes lymphoproliferative disease in EBV-seronegative recipients.

Epstein-Barr virus (EBV) is associated with post-transplant lymphoproliferative disease (PTLD). To determine whether the donor EBV isolate is transmitted to the recipient via the allograft and causes PTLD, EBV isolates from four cases of PTLD in cadaveric heart and/or lung transplant recipients were compared with the donor isolates by PCR and DNA sequence analysis. Two recipients who were EBV seronegative at transplantation acquired an EBV isolate indistinguishable from that of the donor and developed PTLD. In contrast, in two patients who were seropositive before transplantation, the donor isolate differed from that present in PTLD of the recipient. The results suggest that the acquisition of donor EBV is a risk factor for PTLD development in a previously seronegative transplant recipient.

Adolescent↗