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Biomedical subjects

T Tran

Publications and source records attributed to T Tran.

At least 19 recordsLinked to original sources

Meta-analysis: the efficacy of over-the-counter gastro-oesophageal reflux disease therapies.

BACKGROUND: Over-the-counter histamine-2 receptor antagonists, antacids and alginate/antacids are commonly used for gastro-oesophageal reflux disease. AIM: To conduct a systematic review and meta-analysis of related treatment trials. METHODS: We performed a systematic search and abstraction of randomized, placebo-controlled trials conducted during 1972-2005. Study quality was measured by the Jadad score (0-5). Results were pooled using random effects model. RESULTS: Ten trials (n = 3442, placebo = 2940; Jadad score 3.5) showed a higher response with histamine-2 receptor antagonists in regard to complete relief of heartburn, symptomatic improvement, and episodes requiring rescue antacids. The absolute benefit increase was 10-12% and relative benefit increase was 19-41%. Four trials (n = 578, placebo = 577; Jadad score 3.5) showed a trend in favour of antacids in symptomatic improvement (absolute benefit increase 8%, 95% CI: 0-16%; relative benefit increase 0.11) and requirement of rescue antacids (OR 0.70, 95% CI: 0.59-0.84). Four trials (n = 146, placebo = 138; Jadad score 3.8) found alginate/antacid combination superior to placebo in symptomatic improvement (absolute benefit increase 26%, 95% CI: 12%-41%, relative benefit increase 0.60). CONCLUSIONS: Over-the-counter medications are effective in treating symptomatic gastro-oesophageal reflux disease. Compared with the placebo response, which ranged between 37% and 64%, the relative benefit increase was up to 41% with histamine-2 receptor antagonists, 60% with alginate/antacid combinations, and 11% with antacids.

Antacids↗

Genomic DNA pooling for whole-genome association scans in complex disease: empirical demonstration of efficacy in rheumatoid arthritis.

A pragmatic approach that balances the benefit of a whole-genome association (WGA) experiment against the cost of individual genotyping is to use pooled genomic DNA samples. We aimed to determine the feasibility of this approach in a WGA scan in rheumatoid arthritis (RA) using the validated human leucocyte antigen (HLA) and PTPN22 associations as test loci. A total of 203 269 single-nucleotide polymorphisms (SNPs) on the Affymetrix 100K GeneChip and Illumina Infinium microarrays were examined. A new approach to the estimation of allele frequencies from Affymetrix hybridization intensities was developed involving weighting for quality signals from the probe quartets. SNPs were ranked by z-scores, combined from United Kingdom and New Zealand case-control cohorts. Within a 1.7 Mb HLA region, 33 of the 257 SNPs and at PTPN22, 21 of the 45 SNPs, were ranked within the top 100 associated SNPs genome wide. Within PTPN22, individual genotyping of SNP rs1343125 within MAGI3 confirmed association and provided some evidence for association independent of the PTPN22 620W variant (P=0.03). Our results emphasize the feasibility of using genomic DNA pooling for the detection of association with complex disease susceptibility alleles. The results also underscore the importance of the HLA and PTPN22 loci in RA aetiology.

Arthritis, Rheumatoid↗

The invariant surface glycoprotein ISG75 gene family consists of two main groups in the Trypanozoon subgenus.

In Trypanosoma brucei brucei, an invariant surface glycoprotein of molecular weight 75 kDa (ISG75) is uniformly distributed over the surface of a trypanosome and is specific for bloodstream-form parasites. For the other taxa of the Trypanozoon subgenus no data about this surface molecule are available. Therefore, we investigated the ISG75 in the genomes of several pathogenic Trypanozoon by Southern blot, PCR and RT-PCR and sequence analysis. This study reveals that (i) all members of the Trypanozoon subgenus, i.e. T. b. brucei, T. b. gambiense, T. b. rhodesiense, T. evansi and T. equiperdum, harbour ISG75 as multiple gene copies with at least 4-16 copies per genome; (ii) ISG75 gDNA and cDNA sequences are distributed in 2 groups that share at least 75% and 77% identity respectively; (iii) sequences from both groups are transcribed in all species and subspecies of the Trypanozoon subgenus; (iv) the main differences between group I and group II are located in the variable region at the amino-terminus of the putative proteins; (v) however, all the sequences in both groups have some well-conserved features, such as the cysteine residues, an amino-terminal cleavable signal peptide, a single alpha-helix transmembrane domain and a cytoplasmic domain at the carboxy-terminus.

Amino Acid Sequence↗

MicroRNA enrichment among short 'ultraconserved' sequences in insects.

MicroRNAs are short (approximately 22 nt) regulatory RNA molecules that play key roles in metazoan development and have been implicated in human disease. First discovered in Caenorhabditis elegans, over 2500 microRNAs have been isolated in metazoans and plants; it has been estimated that there may be more than a thousand microRNA genes in the human genome alone. Motivated by the experimental observation of strong conservation of the microRNA let-7 among nearly all metazoans, we developed a novel methodology to characterize the class of such strongly conserved sequences: we identified a non-redundant set of all sequences 20 to 29 bases in length that are shared among three insects: fly, bee and mosquito. Among the few hundred sequences greater than 20 bases in length are close to 40% of the 78 confirmed fly microRNAs, along with other non-coding RNAs and coding sequence.

Animals↗

Airway smooth muscle phenotype and function: interactions with current asthma therapies.

Asthma incidence has climbed markedly in the past two decades despite an increased use of medications that suppress airway inflammation and repress contraction of smooth muscle that encircles the airways. Asthmatics exhibit episodes of airway inflammation that potentiates reversible airway smooth muscle spasm. A hallmark diagnostic symptom of asthma is airway hyperresponsiveness to inhaled non-allergic stimuli, such as methacholine, that directly induce airway smooth muscle contraction. Inhaled gluccocorticoids are used for first-line prevention of airway inflammation, and are frequently combined with inhaled beta2-adrenoceptor agonists that can effectively relax airway smooth muscle and restore airway conductance. Leukotriene receptor antagonists and anti-cholinergics can also be used in many patients to ensure optimal control of symptoms. With increasing disease duration irreversible airway restriction develops from inflammation-driven fibro-proliferative airway remodeling that includes increased deposition of extracellular matrix, the accumulation of airway smooth muscle, and increased numbers of myofibroblasts. Mature airway smooth muscle cells are phenotypically plastic, enabling them to subserve contractile, proliferative, migratory and secretory functional responses that contribute to airway remodeling and persistent hyperresponsiveness. This review assesses current understanding of acute and chronic effects of common anti-asthma medications on the diverse phenotype and functional characteristics of airway smooth muscle cells. Furthermore, we describe the significance of these effects in the treatment of asthma symptoms and pathogenesis.

Adrenergic beta-Agonists↗

A fast, high spatial resolution optical tomographic scanner for measurement of absorption in gel dosimetry.

A fast tomographic optical density measurement system has been constructed and evaluated for application in Fricke 3D gel dosimetry. Although the potential for full three-dimensional radiation dosimetry with Fricke gel dosimeters has been extensively reported, its application has been limited due to a lack of fast optical density measurement systems. In this work, the emphasis of the design has been to achieve a short scan time through the use of precision optics and minimal moving parts. The system has been demonstrated in the laboratory to be able to achieve better than 1mm resolution and a scanning time per tomographic slice of 2.4 seconds. Full volumetric sampling of a 10 cm diameter by 7cm long cylinder can be achieved in 3 minutes. When applied with a Fricke based gel dosimeter a linear response between reconstructed CT number and absolute dose was better than 3%.

Absorption↗

A comparative study of biphasic calcium phosphate ceramics for human mesenchymal stem-cell-induced bone formation.

For the repair of bone defects, a tissue engineering approach would be to combine cells capable of osteogenic (i.e. bone-forming) activity with an appropriate scaffolding material to stimulate bone regeneration and repair. Human mesenchymal stem cells (hMSCs), when combined with hydroxyapatite/beta-tricalcium phosphate (HA/TCP) ceramic scaffolds of the composition 60% HA/40% TCP (in weight %), have been shown to induce bone formation in large, long bone defects. However, full repair or function of the long bone could be limited due to the poor remodeling of the HA/TCP material. We conducted a study designed to determine the optimum ratio of HA to TCP that promoted hMSC induced bone formation yet be fully degradable. In a mouse ectopic model, by altering the composition of HA/TCP to 20% HA/80% TCP, hMSC bone induction occurred at the fastest rate in vivo over the other formulations of the more stable 100% HA, HA/TCP (76/24, 63/37, 56/44), and the fully degradable, 100% TCP. In vitro studies also demonstrated that 20/80 HA/TCP stimulated the osteogenic differentiation of hMSCs as determined by the expression of osteocalcin.

Animals↗

Human coronavirus OC43 causes influenza-like illness in residents and staff of aged-care facilities in Melbourne, Australia.

Three outbreaks of respiratory illness associated with human coronavirus HCoV-OC43 infection occurred in geographically unrelated aged-care facilities in Melbourne, Australia during August and September 2002. On clinical and epidemiological grounds the outbreaks were first thought to be caused by influenza virus. HCoV-OC43 was detected by RT-PCR in 16 out of 27 (59%) specimens and was the only virus detected at the time of sampling. Common clinical manifestations were cough (74%), rhinorrhoea (59%) and sore throat (53%). Attack rates and symptoms were similar in residents and staff across the facilities. HCoV-OC43 was also detected in surveillance and diagnostic respiratory samples in the same months. These outbreaks establish this virus as a cause of morbidity in aged-care facilities and add to increasing evidence of the significance of coronavirus infections.

Age Factors↗

[Diagnosis of premenstrual disorders].

BACKGROUND AND OBJECTIVE: There is no valid method in the German literature for assessing premenstrual disorders. This study was undertaken to translate into German, validate and test the reliability of the "Premenstrual Syndrome Tension Observer/Self-Rating Scale" and the "Visual Analogue Scale for Premenstrual Disorders". PATIENTS AND METHODS: 55 patients diagnosed with premenstrual dysphoric disorder took part in the study. After fullfilling the inclusion criteria, sociodemographic and medical data were studied. The self-assessment by PMTS-SR and VAS-PmD was done two days premenstrual and nine days postmenstrual by all 55 patients. The objective assessment (done by a clinical interview and the PMTS-O as the reference standard) was obtained afterwards without knowing the self-assessment. RESULTS: The average age of the tested women was 35 years. The average increase of 85 % in premenstrual symptoms (PMTS-O and PMTS-SR scale) indicates a group with severe premenstrual disorders. The correlation coefficient between PMTS-O and PMTS-SR scale, pre- and postmenstrually, was 0.83 and 0.84, respectively (p < 0.0001 for both). The correlation coefficient between PMTS-O and VAS-PmD, pre- and postmenstrually, was 0.5 and 0.69, respectively (p < 0.0001 for both). This was calculated at 0.64 and 0.67, respectively (p < 0.0001 for both) between PMTS-SR and VAS-PmD. Reliability analysis for PMTS-O was, pre- and postmenstrually, 0.71 and 0.29, respectively, for PMTS-SR 0.77 and 0.78, respectively, and for VAS-PmD it was 0.79 and 0.87, respectively. CONCLUSIONS: The German version of the PMTS-O and the PMTS-SR scale are "application friendly" as well as proven to be a valid and reliable method for supporting the diagnosis, course of disease and research aspects concerning premenstrual disorders. Initially VAS-PmD should be used in combination with PMTS-O and PMTS-SR scale.

Adult↗

Changing epidemiology of genital herpes simplex virus infection in Melbourne, Australia, between 1980 and 2003.

OBJECTIVE: To investigate changes in the proportions of patients infected with genital herpes simplex virus (HSV) types 1 and 2 from 1980 to 2003 in Melbourne, Australia. METHODS: A total of 25 372 patients were studied retrospectively. The proportions of HSV-1 and HSV-2 detected in these individuals were analysed by age, sex, and genital site. RESULTS: In 1980 only 15.8% of HSV positive genital specimens were HSV-1 compared to 34.9% in 2003. In 2003 HSV-1 was detected in 77% of patients aged less than 20 years. Females were more likely to be infected with HSV-1, although the rate of increased detection was more pronounced in males. Except for females over the age of 40, the trend for the increase in HSV-1 was detected in all age groups. No specific genital site in either sex was associated with the increase. CONCLUSIONS: The proportion of genital HSV-1 has increased in Australian patients, although HSV-2 is still the most common cause of genital infection. Confirmation of HSV type is necessary for optimal patient management.

Adolescent↗

Discontinuation of levetiracetam because of behavioral side effects: a case-control study.

BACKGROUND: Levetiracetam (LEV) is a recently approved anticonvulsant with proven efficacy and safety in the treatment of partial seizures. LEV may cause behavioral abnormalities that can be severe and require discontinuation of this drug. Risk factors for discontinuing LEV have not been established. OBJECTIVE: To determine incidence of behavioral abnormalities severe enough to require discontinuation of LEV and identify risk factors for such behavioral abnormalities. METHODS: All patients treated with LEV at MINCEP between January 2000 and February 2002 constituted the study population (n = 553). Patients who had discontinued LEV for behavioral reasons were selected as index cases. Case controls were patients starting LEV immediately after the index case. Potential risk factors for LEV discontinuation included age, gender, cognitive function, history of psychiatric diagnosis, epilepsy syndrome, number of antiepileptic drugs, titration rate, maximum dose of LEV, and LEV level at maximum dose. RESULTS: Thirty-eight patients (6.9%) discontinued LEV because of behavioral abnormalities. Variables associated with LEV discontinuation included faster titration rate to maximal dose, history of a psychiatric disorder, and diagnosis of symptomatic generalized epilepsy. Patients who discontinued LEV owing to behavioral reasons had significantly lower maximum LEV doses than controls. CONCLUSIONS: This study identified variables associated with discontinuation of LEV due to behavioral abnormalities. Slower titration of LEV should be considered in those patients at higher risk of discontinuing LEV for behavioral reasons.

Adolescent↗

Optimized clinical-scale culture conditions for ex vivo selective depletion of host-reactive donor lymphocytes: a strategy for GvHD prophylaxis in allogeneic PBSC transplantation.

BACKGROUND: Ex vivo selective depletion (SD) is a strategy to prevent GvHD, in which host-reactive donor lymphocytes are selectively eliminated from a PBSC allograft while conserving useful donor immune function. Prior to testing this strategy in patients, our goal was to develop a clinical-scale SD process, which involves co-culture of donor lymphocytes and irradiated recipient cells, followed by the addition of an immunotoxin (IT) directed against the alpha-chain of the IL-2 receptor (CD25), expressed on activated donor T cells. METHODS: Stimulator cells were generated from immunomagnetically selected and expanded recipient T lymphocytes. Donor PBMCs from G-CSF-mobilized peripheral blood were co-cultured for 72 h with irradiated stimulator cells. Alloreactive T cells were targeted for elimination by the addition of the anti-CD25 IT, RFT5-SMPT-dgA, and the IT enhancer, NH(4)Cl. RESULTS: Stimulator-cell selection/expansion yielded > 2 x 10(10) highly enriched CD3(+) cells (98.9 +/- 2.2%). After SD, cell recovery was 68.5 +/- 23.3% and viability was 84.6 +/- 6.4%. This permitted a potential T-cell dose >/= 1 x 10(8) CD3(+) cells kg(-1) to transplant recipients. Although SD donor lymphocytes retained little proliferative capacity against the original stimulator cells (2.6 +/- 0.6%), responses were conserved against third party cells (107.6 +/- 18.6%), the bacterial superantigen staphylococcus enterotoxin B (108.2 +/- 4.2%), and CMV Ag (72.1 +/- 3.8%). DISCUSSION: We have demonstrated that ex vivo SD is feasible in clinical-scale culture conditions. The ability of this strategy to prevent GvHD is the subject of an ongoing clinical trial, in which the SD lymphocyte product is transplanted in conjunction with a T cell-depleted PBSC allograft.

CD3 Complex↗

Isolation and characterization of the human stearoyl-CoA desaturase gene promoter: requirement of a conserved CCAAT cis-element.

Stearoyl-CoA desaturase is the rate-limiting enzyme in the production of mono-unsaturated fatty acids. We have recently cloned and characterized the human Scd cDNA and SCD (the stearoyl-CoA desaturase structural gene) on chromosome 10, as well as the non-transcribed pseudogene on chromosome 17. In order to further define SCD regulation and function, we have isolated and characterized the promoter of the structural gene. Screening of chromosome-10-specific libraries resulted in the isolation of 4.1 kb of SCD sequence upstream of the translation start site. Binding sites for transcription factors critical for mouse Scd1 and Scd2 promoter activity, such as sterol-regulated-element-binding protein and nuclear factor Y, were present in the human SCD promoter (Scd is the mouse stearoyl-CoA desaturase gene). Deletion analysis in HaCaT keratinocytes identified a critical region for promoter activity between nts 496-609 upstream of the translation start site. Site-directed mutagenesis of binding sites in this region identified the CCAAT box as the critical cis-element for SCD promoter activity. An electrophoretic mobility-shift assay confirmed that this element binds nuclear proteins from HaCaT keratinocytes. The polyunsaturated-fatty-acid (PUFA) response element, previously identified in the promoters of mouse Scd1 and Scd2, was found to be conserved in the human SCD promoter, and contained the critical CCAAT cis-element. A minimal promoter construct including this region was responsive to fatty acids, with oleate and linoleate decreasing transcription and stearate increasing it. These studies indicate that CCAAT-box-binding proteins activate SCD transcription in cultured keratinocytes and that fatty acids modulate transcription, most likely through the conserved PUFA response element.

Amino Acid Sequence↗

Breast cancer after mantle irradiation for Hodgkin's disease: correlation of clinical, pathologic, and molecular features including loss of heterozygosity at BRCA1 and BRCA2.

PURPOSE: Hodgkin's disease patients who receive mantle irradiation have an age-dependent increased risk of developing breast cancer. To determine if genetic factors predispose these patients to develop breast cancer, we evaluated breast cancer specimens for loss of heterozygosity (LOH) at regions where BRCA1 and BRCA2, two breast cancer tumor suppressor genes, are located. We also evaluated whether breast cancers in patients who were previously treated with radiation have a more aggressive phenotype, and whether the clinical course differed from a sporadic group of breast cancer patients. METHODS AND MATERIALS: All females with Hodgkin's disease who were subsequently diagnosed with breast cancer and for whom tissue blocks were available were included. Using a case-control design, case patients (previously treated with radiation therapy) were matched with sporadic control breast cancer patients for age, breast cancer stage, and date of breast cancer diagnosis. After microdissection of tumor and normal tissue from paraffin-embedded tissue blocks, DNA was extracted and samples were examined for LOH at chromosomal segments encompassing BRCA1 and BRCA2. Breast cancer specimens were also evaluated in a blinded fashion for tumor grade and immunoreactivity to estrogen and progesterone receptors, p53, her2-neu, and topoisomerase II alpha. Comparisons were made between the case and control populations using chi2 analysis, and a paired Student's t test. Survival differences were evaluated using a log-rank test. RESULTS: From January 1960 to December 1983, 917 patients were diagnosed with Hodgkin's disease. Twelve patients were subsequently diagnosed with breast cancer and tissue blocks were available on 10 cases. No statistical difference was observed between the case and control populations for LOH at BRCA1 or BRCA2. In the Hodgkin's disease group, LOH was observed in 30% of tumors at BRCA1 and 10% of tumors at BRCA2 vs. 10% and 0% of tumors in the control group at BRCA1 and BRCA2, respectively. Breast tumors from patients who received radiation therapy for Hodgkin's disease displayed greater nuclear pleomorphism (p < 0.02), and an increase in topoisomerase II alpha expression (p < 0.05) vs. the control population. Five of 10 patients were pregnant at the time of their Hodgkin's treatment, and those patients had a shorter time interval to the development of breast cancer compared with the patients who were not pregnant (12.4 years compared with 18.6 years). There was no significant difference in disease-free survival; however, overall survival was inferior in the population previously treated with radiation therapy for Hodgkin's disease (p = 0.01). 80% of patients with a previous Hodgkin's diagnosis died of breast cancer or treatment related effects vs. 30% in the control group. CONCLUSION: We were unable to find statistical evidence for LOH at BRCA1 and BRCA2 in breast cancers from patients previously irradiated for Hodgkin's disease. Breast cancer diagnosed after mantle irradiation may be more biologically aggressive based on the greater nuclear pleomorphism and increase in topoisomerase II alpha staining. This did not translate into a statistical difference in breast cancer disease-free survival; however, overall survival was significantly inferior in the Hodgkin's disease patients.

Adolescent↗

Quantitative brain magnetic resonance imaging in girls with attention-deficit/hyperactivity disorder.

BACKGROUND: Anatomic studies of boys with attention-deficit/hyperactivity disorder (ADHD) have detected decreased volumes in total and frontal brain, basal ganglia, and cerebellar vermis. We tested these findings in a sample of girls with ADHD. METHODS: Anatomic brain magnetic resonance images from 50 girls with ADHD, of severity comparable with that in previously studied boys, and 50 healthy female control subjects, aged 5 to 15 years, were obtained with a 1.5-T scanner with contiguous 2-mm coronal slices and 1.5-mm axial slices. We measured volumes of total cerebrum, frontal lobes, caudate nucleus, globus pallidus, cerebellum, and cerebellar vermis. Behavioral measures included structured psychiatric interviews, parent and teacher ratings, and the Wechsler vocabulary and block design subtests. RESULTS: Total brain volume was smaller in girls with ADHD than in control subjects (effect size, 0.40; P =.05). As in our previous study in boys with ADHD, girls with ADHD had significantly smaller volumes in the posterior-inferior cerebellar vermis (lobules VIII-X; effect size, 0.54; P =.04), even when adjusted for total cerebral volume and vocabulary score. Patients and controls did not differ in asymmetry in any region. Morphometric differences correlated significantly with several ratings of ADHD severity and were not predicted by past or present stimulant drug exposure. CONCLUSIONS: These results confirm previous findings for boys in the posterior-inferior lobules of the cerebellar vermis. The influence of the cerebellar vermis on prefrontal and striatal circuitry should be explored.

Adolescent↗

Linkage of body mass index to chromosome 20 in Utah pedigrees.

Several linkage studies have hinted at the existence of an obesity predisposition locus on chromosome 20, but none of these studies has produced conclusive results. Therefore, we analyzed 48 genetic markers on chromosome 20 for linkage to severe obesity (BMI> or =35) in 103 extended Utah pedigrees (1,711 individuals), all of which had strong aggregation of severe obesity. A simple dominant model produced a maximum multipoint heterogeneity LOD score of 3.5 at D20S438 (55.1 cM). Two additional analyses were performed. First, a one-gene, two-mutation model (with one dominant mutation and one recessive mutation) increased the LOD score to 4.2. Second, a two-locus model (with one locus dominant and one recessive) generated a multipoint LOD score of 4.9. We conclude that one or more severe obesity predisposing genes lie within an interval of approx. 10 cM on chromosome 20. This study generated significant LOD scores which confirm suggestive linkage reports from previous studies. In addition, our analyses suggest that the predisposing gene(s) is localized very near the chromosome 20 centromere.

Body Mass Index↗

Progesterone modulation of D5 receptor expression in hypothalamic ANP neurons, the role of estrogen.

Aberrant responses to dopamine consequent to a reduction of D1-like receptors in critical regions of the brain have been implicated in schizophrenia. Whereas estrogen may protect against the onset and incidence of psychosis in the illness, the neurobiological effects of the ovarian steroid remain unclear. Recently we have shown that estrogen augments the expression of D5 receptors, a member of the D1-like receptor family, in central neurons and enhances the functions of the host cells. Employing rat hypothalamic neuron cultures, we report here that another important ovarian steroid, progesterone, also augments dopamine D5 receptor expression in hypothalamic atrial natriuretic factor (ANP) neurons. However, unlike the effect of estrogen, progesterone acts indirectly through potentiating estrogen-mediated changes that include enhancement of D5 receptor expression, immunoreactive (ir)-ANP release and pro-ANP mRNA abundance. We conclude that whilst progesterone has little effect by itself, the steroid works in synergism with estrogen to augment the function of ANP neurons. The possibility that progesterone may further enhance the protective effect of estrogen against the incidence of psychosis in schizophrenia now needs to be considered.

Animals↗