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Biomedical subjects

T Wu

Publications and source records attributed to T Wu.

At least 37 records · Page 2Linked to original sources

Real-time monitoring of acute liver-allograft rejection using the Banff schema.

BACKGROUND: The Banff schema is the internationally accepted standard for grading acute liver-allograft rejection, but it has not been prospectively tested. METHODS: Complete Banff grading was prospectively applied to 2,038 liver-allograft biopsies from 901 adult tacrolimus-treated primary hepatic allograft recipients between August 1995 and September 2001. Histopathologic data was melded with demographic, clinical, and laboratory data into a database on an ongoing basis using locally developed software. RESULTS: Acute rejection developed in 575 of 901 (64%) patients and the worst grade was mild in 422 of 575 (73%). At least one episode of moderate or severe acute rejection developed in 153 of 901 (17%) patients and most episodes, irrespective of severity, occurred within the first year after transplantation. Patients with moderate or severe acute rejection showed higher alanine aminotransferase (P =0.007) and aspartate aminotransferase ( P=0.07) levels and were more likely to develop perivenular fibrosis on follow-up biopsies (P =0.001) and graft failure from acute or chronic rejection ( P=0.004) than those with mild rejection. Regardless of severity, 80% of patients with acute rejection did not develop significant fibrosis in follow-up biopsies, and graft failure from acute or chronic rejection occurred in only 11 of 901 (1%) allografts. CONCLUSIONS: Most acute-rejection episodes are mild and do not lead to clinically significant architectural sequelae. When tested prospectively under real-life and -time conditions, the Banff schema can be used to identify those few patients who are potentially at risk for more significant problems. Creation, capture, and integration of non-free text, or "digital," pathology data can be used to prospectively conduct outcomes-based research in transplantation.

Acute Disease↗

Iodised salt for preventing iodine deficiency disorders.

BACKGROUND: Iodine deficiency is the main cause for potentially preventable mental retardation in childhood, as well as causing goitre and hypothyroidism in people of all ages. It is still prevalent in large parts of the world. OBJECTIVES: To assess the effects of iodised salt in comparison with other forms of iodine supplementation or placebo in the prevention of iodine deficiency disorders. SEARCH STRATEGY: We searched the Cochrane Library, Medline, the Register of Chinese trials developed by the Chinese Cochrane Centre, and the Chinese Med Database. We performed handsearching of a number of journals (Chinese Journal of Control of Endemic Diseases, Chinese Journal of Epidemiology, Chinese Journal of Preventive Medicine, and Studies of Trace Elements and Health up to February 2001), and searched reference lists, databases of ongoing trials and the Internet. Date of latest search: November 2001. SELECTION CRITERIA: We included prospective controlled studies of iodised salt versus other forms of iodine supplementation or placebo in people living in areas of iodine deficiency. Studies reported mainly goitre rates and urinary iodine excretion as outcome measures. DATA COLLECTION AND ANALYSIS: The initial data selection and quality assessment of trials was done independently by two reviewers. Subsequently, after the scope of the review was slightly widened from including only randomised controlled trials to including non-randomised prospective comparative studies, a third reviewer repeated the trials selection and quality assessment. As the studies identified were not sufficiently similar and not of sufficient quality, we did not do a meta-analysis but summarised the data in a narrative format. MAIN RESULTS: We found six prospective controlled trials relating to our question. Four of these were described as randomised controlled trials, one was a prospective controlled trial that did not specify allocation to comparison groups, and one was a repeated cross-sectional study comparing different interventions. Comparison interventions included non-iodised salt, iodised water, iodised oil, and salt iodisation with potassium iodide versus potassium iodate. Numbers of participants in the trials ranged from 35 to 334; over 20,000 people were included in the cross-sectional study. Three studies were in children only, two investigated both groups of children and adults and one investigated pregnant women. There was a tendency towards goitre reduction with iodised salt, although this was not significant in all studies. There was also an improved iodine status in most studies (except in small children in one of the studies), although urinary iodine excretion did not always reach the levels recommended by the WHO. None of the studies observed any adverse effects of iodised salt. REVIEWER'S CONCLUSIONS: The results suggest that iodised salt is an effective means of improving iodine status. No conclusions can be made about improvements in other, more patient-oriented outcomes, such as physical and mental development in children and mortality. None of the studies specifically investigated development of iodine-induced hyperthyroidism, which can be easily overlooked if just assessed on the basis of symptoms. High quality controlled studies investigating relevant long term outcome measures are needed to address questions of dosage and best means of iodine supplementation in different population groups and settings.

Cross-Sectional Studies↗

Change in demographic picture and increase of drug resistance in pulmonarytuberculosis in a 10-year interval in Taiwan.

BACKGROUND: This study was designed to compare the change in demographics, medical characteristics and drug resistance of patients with active pulmonary tuberculosis (TB) between two time periods within a 10-year interval. PATIENTS AND METHODS: We retrospectively reviewed the clinical records and chest radiographs of 1,826 patients with active pulmonary TB for two time periods from 1992-1996 (n = 884) and 1982-1986 (n = 942). RESULTS: The mean age was significantly higher and there were significantly more female patients in the 1992-1996 period than in the 1982-1986 period. In the 1992-1996 period, there were significantly fewer patients with the main complaints of cough, fever and body weight loss at the time of diagnosis but significantly more patients who had diabetes mellitus, obstructive airway disease, cancer other than lung cancer or who were on corticosteroid therapy. During the 1992-1996 period, single drug resistance against isoniazid (INH), rifampin (RIF) and streptomycin increased by 0.5%, 3% and 0.7%, respectively. Multiple drug resistance against both INH and RIF increased by 2% in the 1992-1996 period. A history of pulmonary TB and extensive pulmonary involvement were two significant factors for drug resistance against INH, RIF or ethambutol (EMB). CONCLUSION: In the 1992-1996 period, the mean age of patients and number of female patients significantly increased. There were more patients with diabetes mellitus, obstructive airway diseases, cancer other than lung cancer and prior steroid therapy but fewer patients presenting with classic clinical symptoms of TB. In consideration of the high prevalence and increasing rate of single and multiple drug resistance, we recommend an initial four-drug regimen (INH, RIF, EMB, pyrazinamide) for the treatment of pulmonary TB in Taiwan.

Adolescent↗

Intra- and interindividual variability of motor responses to repetitive transcranial magnetic stimulation.

OBJECTIVES: Repetitive transcranial magnetic stimulation (rTMS) can modify cortical excitability and is widely used for clinical and research purposes. We sought to determine the intra- and interindividual variability of its effects on motor cortex excitability, and whether repeated paired-pulses yield less variability than repeated single-pulses. METHODS: We investigated rTMS over the left motor cortex of 6 healthy subjects and recorded motor evoked potentials (MEPs) from the right abductor digiti minimi muscle. Eighty single suprathreshold stimuli or conditioning-test pairs of stimuli were delivered at 2Hz frequency. The pairs consisted of a subthreshold pulse followed by a suprathreshold pulse after 2, 5 or 10ms. In each subject we studied all types of rTMS 5 times on separate days. Single suprathreshold pulses at 0.17Hz preceded rTMS for baseline determination. RESULTS: The day-to-day variability of MEPs during either type of rTMS was small compared to the subject-to-subject variability. MEPs increased during all types of rTMS except for interstimulus interval (ISI) 2ms. Paired-pulses yielded less variability than single-pulse rTMS. CONCLUSIONS: Motor responses to rTMS show a high interindividual, but a low intraindividual variability. Repeated paired-pulses yield less variability than repeated single-pulses.

Adult↗

Rapamycin and T cell costimulatory blockade as post-transplant treatment promote fully MHC-mismatched allogeneic bone marrow engraftment under irradiation-free conditioning therapy.

Hematopoietic macrochimerism, established by bone marrow transplantation, can be used as an approach for treating autoimmune disease and inducing transplant tolerance. In this study, we investigated whether a stable, high level of fully MHC-mismatched hematopoietic macrochimerism can be induced by using irradiation-free protocols, and whether rapamycin and T cell costimulatory blockades (anti-CD40L monoclonal antibody (mAb) and CTLA4Ig) as post-transplant treatment promote bone marrow engraftment. Donor-specific blood transfusion (DST), anti-lymphocyte serum (ALS), busulfan, and cyclophosphamide were given pretransplantation. Balb/c (H-2(d)) bone marrow cells, at a dose of 4 x 10(7), were infused into each C57BL/6 mouse (H-2(b)). Rapamycin, anti-CD40L mAb, and CTLA4Ig were then administered, either alone or in combination. Without ALS or busulfan and cyclophosphamide, macrochimerism can only rarely be induced. Donor-specific transfusion (DST) enhances induction of hematopoietic macrochimerism. Rapamycin, anti-CD40L mAb and CTLA4Ig, alone or in combination, induce a stable and high level of hematopoietic macrochimerism. In the chimeric mice, donor-derived cells were detected in all lymphohematopoietic tissues and donor-specific tolerance was induced in vitro. We conclude that a stable and high level of fully MHC-mismatched hematopoietic macrochimerism can be induced in mice after transplanting a single modest dose of bone marrow cells without irradiation. Rapamycin and T cell costimulatory blockade as post-transplant treatment promote bone marrow engraftment.

Animals↗

[Developing authoring tools for web-based multi-media orthopedics education modules].

In the framework of the EC-Project VOEU ("Virtual Orthopaedic European University"), authoring tools have been developed to support the implementation of online interactive courses for multimedia orthopaedic educational modules. Based on the pedagogical concept of case-based, problem-oriented learning, different user-interaction scenarios and Learning Objects (LOs) were analyzed and developed. Each LO acts as an interactive dialogue presenting one kind of question with certain rules and interactions. The multimedia course content entailing anamnesis, diagnosis and therapy is managed in a database and can be adaptively generated as certain LO with the help of Active Server Pages (ASPs). As an example, an interactive course on Developmental Dislocation of Hip has been implemented.

Computer-Assisted Instruction↗

[Empirical studies of the reliability of surgical navigation systems].

A number of studies demonstrate the clinical relevance of systems for computer assisted surgery (CAS systems). As however studies on human error in medicine indicate, reliability of the results strongly depends on aspects of usability and error tolerance of the system. This paper presents studies which aim to assess these aspects of reliability of CAS systems. In a clinical study, interaction with a CAS system by 16 expert and novice surgeons was observed and assessed. From 133 recorded incidents 41% were rated to have significant impact on the clinical result or to inhibit successful completion of the task, which indicates a low degree of error tolerance of the system. These findings are supported by the results obtained from questionnaire, were learnability and error tolerance were judged to be not sufficient.

Attitude of Health Personnel↗

In vivo persistence of retrovirally transduced murine long-term repopulating cells is not limited by expression of foreign gene products in the fully or minimally myeloablated setting.

Many nonmalignant hematologic disorders could potentially be treated by genetic correction of as few as 5-10% of target lineage cells. However, immune system clearance of cells expressing gene products perceived as foreign could be limiting. There is evidence that tolerance to foreign proteins can result when myeloablative conditioning is used, but this limits the overall applicability of such techniques. Therefore, we sought to evaluate the engraftment of hematopoietic stem cells carrying a foreign transgene after low-dose irradiation by comparing in vivo survival of murine long-term repopulating cells (LTRC) transduced with either a retroviral vector expressing the bacterial neomycin phosphotransferase gene (neo) or a vector containing neo gene sequences but modified to prevent protein expression (nonexpression). First, marrow cells from congenic donors were transduced with either vector and transplanted into recipients treated with standard dose irradiation of 800 rads. High-level engraftment and gene marking resulted, without differences in the marking levels or pattern of persistence of the cells between cells transduced with either vector. Low-dose irradiation at 100 rads was tested using higher cell doses. Marking levels as high as 10% overall were obtained, again with no differences between mice receiving cells transduced with the neo versus the nonexpression vectors. To investigate a potentially more immunogenic protein, marrow cells were transduced with a vector containing the green fluorescent protein (GFP) gene, and their persistence was studied in recipient mice receiving 100 rads. Stable GFP expression in 5-10% of circulating cells was observed long term. We conclude that even with very low dose conditioning, engraftment by genetically modified LTRC cells at clinically significant levels can be achieved without evidence for clearance of cells known to be expressing immunogenic proteins.

Animals↗

A novel photosensitizer, 2-butylamino-2-demethoxy-hypocrellin B (2-BA-2-DMHB) - its photodynamic effects on HeLa cells: efficacy and apoptosis.

A novel hypocrellin congener, 2-butylamino-2-demethoxy-hypocrellin B (2-BA-2-DMHB) was found to be an effective photosensitizer. Compared with its parent compound hypocrellin B (HB), its absorption bands extended toward longer wavelength and the extinction coefficients raised to some degree (lambda(max) (nm) (log(epsilon)): 463 (4.06), 583 (4.09), 621 (4.10) for 2-BA-2-DMHB and 466 (4.06), 548 (3.70), 580 (3.52) for HB). And it also had a much higher photopotentiation factor than HB (i.e., more than 250 versus 10 at a dose of 24 J cm(-2) of red light on HeLa cells). This might be correlated to the higher ability of superoxide anion generation and the higher cellular uptake of 2-BA-2-DMHB. Meanwhile, the examinations of Hoechst 33342-labeled nuclei, DNA fragmentation on agarose gel and flow cytometry showed that 2-BA-2-DMHB induces apoptosis in photosensitized HeLa cells more quickly than HB, which might be correlated to the higher cellular uptake of 2-BA-2-DMHB and the difference of their cellular localization. The study suggested that 2-BA-2-DMHB was a well-suited candidate for a new generation of photodynamic therapy photosensitizer.

Apoptosis↗

Electroresistance and electronic phase separation in mixed-valent manganites.

The sensitivity of transport in colossal magnetoresistance (CMR) manganites to external electric and magnetic fields is examined using field effect configurations with La(0.7)Ca(0.3)MnO(3) (LCMO), Na(0.7)Sr(0.3)MnO(3), La(0.7)Ba(0.3)MnO(3), and La(0.5)Ca(0.5)MnO(3) (0.5-doped LCMO) channels, and ferroelectric PbZr(0.2)Ti(0.8)O(3) (PZT) or dielectric (SrTiO(3)) gates. A large electroresistance (ER) of approximately 76% at 4 x 10(5) V/cm is found in LCMO with PZT-ferroelectric gate, but the magnitude of the effect is much smaller (a few percent) in the other three channels. The ER and CMR effects are remarkably complimentary. The size and systematics of the effect strongly favor a percolative phase separation picture.

Journal Article↗

Immunotherapy with nondepleting anti-CD4 monoclonal antibodies but not CD28 antagonists protects islet graft in spontaneously diabetic nod mice from autoimmune destruction and allogeneic and xenogeneic graft rejection.

BACKGROUND: T-cell activation and the subsequent induction of effector functions require not only the recognition of antigen peptides bound to MHC molecules by T-cell receptor (TCR) for antigen but also a costimulatory signal provided by antigen presenting cells. CD4 T-cell activation and function require the CD4 molecule as a coreceptor of TCR. The CD28/B7 pathway is a major costimulatory signal for T-cell activation and differentiation. METHODS: The effect of targeting CD4 by nondepleting anti-CD4 monoclonal antibodies (mAbs) versus blocking CD28/B7 by CTLA4Ig, anti-CD80 mAbs, and anti-CD86 mAbs on the prevention of recurrence of autoimmune diabetes after MHC-matched nonobese diabetes-resistant (NOR) islet transplantation in nonobese diabetic (NOD) mice were compared. Whether nondepleting anti-CD4 mAbs prolong allogeneic islet graft survival and xenogeneic pig islet graft survival in diabetic NOD mice were studied. Furthermore, the effect of nondepleting anti-CD4 mAbs combined with CTLA4Ig on allogeneic islet graft survival in NOD mice was investigated. RESULTS: Recurrence of autoimmune diabetes can be prevented by nondepleting anti-CD4 mAbs. Blocking the CD28/B7 costimulatory pathway by CTLA4Ig or by anti-CD80 mAbs and anti-CD86 mAbs cannot prevent recurrence of autoimmune diabetes after islet transplantation. Short-term treatment with nondepleting anti-CD4 mAbs significantly prolongs allogeneic islet graft survival and xenogeneic pig islet graft survival in diabetic NOD mice. But nondepleting anti-CD4 mAbs combined with CTLA4Ig decreased allogeneic islet graft survival. CONCLUSIONS: Nondepleting anti-CD4 mAbs but not CD28 antagonists protect islet grafts in diabetic NOD mice from autoimmune destruction and allogeneic and xenogeneic graft rejection. The efficacy of nondepleting anti-CD4 mAbs is compromised when it combines with CTLA4Ig.

Abatacept↗

Need for alternative trial designs and evaluation strategies for therapeutic studies of invasive mycoses.

Studies of invasive fungal infections have been and remain difficult to implement. Randomized clinical trials of fungal infections are especially slow and expensive to perform because it is difficult to identify eligible patients in a timely fashion, to prove the presence of the fungal infection in an unequivocal fashion, and to evaluate outcome in a convincing fashion. Because of these challenges, licensing decisions for antifungal agents have to date depended heavily on historical control comparisons and secondary advantages of the new agent. Although the availability of newer and potentially more effective agents makes these approaches less desirable, the fundamental difficulties of trials of invasive fungal infections have not changed. Therefore, there is a need for alternative trial designs and evaluation strategies for therapeutic studies of invasive mycoses, and this article summarizes the possible strategies in this area.

Antifungal Agents↗

Application of furanyl carbamate cycloadditions toward the synthesis of hexahydroindolinone alkaloids.

A convenient synthesis of various substituted hexahydroindolinones has been achieved by an intramolecular Diels--Alder cycloaddition reaction (IMDAF) of furanyl carbamates bearing tethered alkenyl groups. The initially formed [4 + 2]-cycloadduct undergoes nitrogen-assisted ring opening followed by deprotonation of the resulting zwitterion to give the rearranged ketone. The stereochemical outcome of the IMDAF cycloaddition has the sidearm of the tethered alkenyl group oriented syn with respect to the oxygen bridge. A synthetic route to (+/-)-mesembrane and (+/-)-crinane was accomplished using this methodology. It was possible to carry out a stereoselective reduction of the initially formed hexahydroindolinone ring to produce the cis-3a-aryl-hydroindole skeleton. A related [4 + 2]-cycloaddition/rearrangement sequence was also used for a formal synthesis of the Chinese ornamental orchid (+/-)-dendrobine. The tricyclic alkaloid core was formed stereoselectivity from the thermolysis of N-[(2-methyl-2-cyclopentenyl)methyl]-N-(4-isopropyl-furan-2-yl)carbamic acid tert-butyl ester. Kende's advanced intermediate 33 was prepared in seven additional steps by standard transformations, thereby completing a formal synthesis of (+/-)-dendrobine.

Alkaloids↗

Confocal microscopic study of glial-vascular relationships in the retinas of pigmented rats.

Astroglia are interposed between the cerebral vasculature and neurons, where they may mediate the transfer of substances from the circulation to neurons and couple changes in neuronal activity to changes in cerebral blood flow. The retina is a particularly advantageous model system for studying glial-vascular interactions in situ. Confocal microscopy and three-dimensional image reconstruction were used to study the anatomical relationships between glia and the surface vasculature in retinas acutely isolated from adult pigmented rats. Retinas were immunostained using antibodies directed against the basal lamina surrounding the vasculature as well as antibodies directed against glial fibrillary acidic protein. Surface vessels of all calibers were contacted by the processes of astrocytes. The vitreal surfaces of the large retinal vessels were covered by a meshwork of immunoreactive astrocyte processes of a variety of shapes, whereas the scleral surfaces of the vessels were supported by thick bundles of astrocyte processes. In addition, glial cells were filled intracellularly with the gap junction-permeable tracers Lucifer yellow and Neurobiotin. Intracellular fills clearly demonstrated the presence of astrocytes with somata that were closely apposed to the large retinal vessels. Tracer-filled astrocytes displayed a variety and complexity of shapes that was not apparent in immunostained material. Gap junctional coupling was stronger between astrocytes adjacent to the same artery than between periarterial astrocytes and astrocytes located away from arteries. Significantly fewer Müller cells were labeled when Neurobiotin was injected into astrocytes associated with arteries than when Neurobiotin was injected into astrocytes that were distant from arteries.

Animals↗

Assessment of thermal tissue ablation with MR elastography.

An important part of thermal ablation therapy is the assessment of the spatial extent of tissue coagulation. In this work, the mechanical properties of thermally-ablated tissue were quantitatively evaluated using magnetic resonance elastography (MRE). This study shows that the mechanical properties of focused ultrasound ablated tissue are significantly different from normal tissue, and the difference can be imaged and measured using MRE. Repeated experiments revealed a reproducible pattern of tissue mechanical property change during thermal ablation in ex vivo bovine muscle. This pattern may reflect changes in intrinsic tissue structure and could be used to evaluate tissue coagulation during thermal ablation therapy. Magn Reson Med 45:80-87, 2001.

Animals↗