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Biomedical subjects

T Wu

Publications and source records attributed to T Wu.

At least 73 records · Page 4Linked to original sources
PubMed2001

Posteroventral pallidotomy for advanced Parkinson's disease.

BACKGROUND: Provoked by the limitations and late complications of levodopa therapy, the advances in stereotactic surgery, and better understanding of the pathophysiology of the basal ganglia, the role of pallidotomy in the treatment of advanced Parkinson's disease (PD) has been revived. METHODS: We included 11 patients with advanced PD, who had a good response to levodopa but had late complications of motor fluctuation and severe dyskinesia. The internal globus pallidus was identified with computed tomography prior to posteroventral pallidotomy and it was reaffirmed by microelectrode recording during surgery. Clinical evaluations were carried out in both the "on" and "off" motor periods at baseline and at 1 week, 3 months, 6 months and 1 year postoperatively. Repeated measures ANOVA followed by multiple comparisons were used for statistical analysis. RESULTS: Dyskinesia improved bilaterally but only significantly in the contralateral limbs. This benefit was sustained up to 1 year. Parkinsonism, particularly contralateral tremor and rigidity, improved in the "off" motor period but not in the "on" motor period. The average Unified Parkinson's Disease Rating Scale motor score was reduced 36% at 3 months and 26% at 1 year in the "off" motor period. Both of the mean Hoehn and Yahr staging and Schwab and England activities of daily living score improved in "off" motor period. Improvement in parkinsonism, however, did not reach a significant level. Mild dysarthria and unstable gait were observed temporarily in 2 patients. Mild weakness in the contralateral limbs was found in 1 patient. CONCLUSIONS: Unilateral pallidotomy guided by microelectrode recording is helpful for severe levodopa-induced dyskinesia in advanced PD. Contralateral parkinsonian disabilities also improve in the "off" motor period.

Adult↗
PubMed2001

Preventive effects of ginsenosides on osteopenia of rats induced by ovariectomy.

AIM: To determine the effect of ginsenosides (GSL) on ovariectomized rats by analysis of cancellous bone histomorphometry. METHODS: Forty Sprague-Dawley female rats at age of 3 months were sham-operated (Sham, n = 8) and treated orally with vehicle, or ovariectomized (OVX, n = 32 which were divided into three group with n = 8 per group) and treated orally with either vehicle, 17alpha-ethynylestradiol (EE, 100 microg . kg-1 . d-1), or ginsenosides (GSL) at 100 or 300 mg . kg-1 . d-1 for 10 weeks. Double in vivo fluorochrome labeling was administrated. The undecalcified longitudinal proximal tibial metaphyseal sections were cut and stained with Goldner's Trichrome (4-micron thickness) or unstained (8-micron thickness) for the bone histomorphometric analysis. RESULTS: After 10 weeks post OVX the cancellous bone mass was lost markedly and showed high bone turnover indices (increased bone resorption and formation). EE decreased the resorptive surface and bone formation rate related to bone turnover and prevented bone loss. GSL at the two doses (100 and 300 mg . kg-1 . d-1) reduced the resorptive surfaces as did EE, but did not depress the mineral bone formation. High dose of GSL greatly increased bone mass and had a tendency to decrease bone turnover when compared with OVX group. CONCLUSION: GSL partially prevented OVX-induced cancellous bone loss by inhibiting osteoclast bone resorption and by a mild depression of bone turnover.

Animals↗
PubMed2001

[Plasma autoantibodies to heat shock proteins in idiopathic sensorineural hearing loss].

OBJECTIVE: To identify the specificity of autoantibodies to heat shock proteins in idiopathic sensorineural hearing loss (ISNHL) and to evaluate the existence of autoantibodies. METHOD: Plasma samples were obtained from patients with ISNHL (n = 41), systemic lupus erythematosus (n = 22), and normal controls (n = 30). Plasma autoantibodies to heat shock proteins (HSPs) were detected by Western blot using purified recombinant human HSP27, HSP60, HSP71 HSP90 alpha and HSP90 beta as antigen respectively. RESULT: In the ISNHL, the incidence of plasma autoantibodies to recombinant human HSP27, HSP60, HSP71, HSP90 alpha and HSP90 beta were 12.1%, 7.3%, 51.2%, 4.8% and 0% respectively. The incidence of autoantibody to HSP71 was significantly greater than that in systemic lupus erythematosus and in normal controls (P < 0.01). CONCLUSION: These results indicated that the autoantibody to HSP71 was main autoantibodies to HSPS in ISNHL and its presence might serve as a marker for an autoimmune etiology of these patients' hearing loss.

Adult↗
PubMed2001

[Transdermal delivery of cyclosporin A solubilized in mixed micelles through mice skin].

AIM: To investigate the transdermal delivery effects of cyclosporine A solubilized in mixed micelles composed of phospholipid and different surfactants. METHODS: When applied onto the excised abdominal skin of the mice occlusively, the enhancing effects of various mixed micelles on the penetration of cyclosporin A were assessed by an in vitro permeation technique. In vivo study was carried out by topical application of sodium cholate-phospholipid mixed micelles onto the mice skin and drug blood concentration was detected. RESULTS: In vitro, mixed micelles containing different surfactants displayed distinct permeability and corresponded to the following order: sodium cholate > sodium deoxycholate > Trition X-100 > Tween-20. In vivo, peak drug concentration was detected at 5 h and after that the concentration fell down slowly. CONCLUSION: Mixed micelles were shown to be efficient carrier for the transdermal delivery of the lipophilic polypeptide when kept in solution during the application process.

Administration, Cutaneous↗
PubMed2000

Periodontal disease and risk of cerebrovascular disease: the first national health and nutrition examination survey and its follow-up study.

BACKGROUND: Periodontal disease has been found to be a potential risk factor for coronary heart disease. However, its association with cerebrovascular accidents (CVAs) is much less studied. METHODS: This study examines the association between periodontal disease and CVA. The study cohort comprises 9962 adults aged 25 to 74 years who participated in the First National Health and Nutrition Examination Survey and its follow-up study. Baseline periodontal status was categorized into (1) no periodontal disease, (2) gingivitis, (3) periodontitis, and (4) edentulousness. All CVAs (International Classification of Diseases, Ninth Revision [ICD-9], codes 430-438) were ascertained by hospital records for nonfatal events and death certificates for fatal events. The first CVA, nonfatal or fatal, was used to define incidence. Relative risks were estimated by hazard ratios from the Cox proportional hazard model with adjustment for several demographic variables and well-established cardiovascular risk factors. Weights were used to generate risk estimates. RESULTS: Periodontitis is a significant risk factor for total CVA and, in particular, nonhemorrhagic stroke (ICD-9, 433-434 and 436-438). Compared with no periodontal disease, the relative risks (95% confidence intervals) for incident nonhemorrhagic stroke were 1.24 (0.74-2.08) for gingivitis, 2.11 (1.30-3.42) for periodontitis, and 1.41 (0.96-2.06) for edentulousness. For total CVA, the results were 1.02 (0.70-1.48) for gingivitis, 1.66 (1.15-2.39) for periodontitis, and 1.23 (0.91-1.66) for edentulousness. Increased relative risks for total CVA and nonhemorrhagic stroke associated with periodontitis were also seen in white men, white women, and African Americans. Similar results were found for fatal CVA. CONCLUSION: Periodontal disease is an important risk factor for total CVA and, in particular, nonhemorrhagic stroke.

Adult↗
PubMed2000

Alternative splicing of the rat sodium/bile acid transporter changes its cellular localization and transport properties.

Bile secretion involves the structural and functional interplay of hepatocytes and cholangiocytes, the cells lining the intrahepatic bile ducts. Hepatocytes actively secrete bile acids into the canalicular space and cholangiocytes then transport bile acids in a vectorial manner across their apical and basolateral plasma membranes. The initial step in the transepithelial transport of bile acids across rat cholangiocytes is apical uptake by a Na(+)-dependent bile acid transporter (ASBT). To date, the molecular basis of the obligate efflux mechanism for extrusion of bile acids across the cholangiocyte basolateral membrane remains unknown. We have identified an exon-2 skipped, alternatively spliced form of ASBT, designated t-ASBT, expressed in rat cholangiocytes, ileum, and kidney. Alternative splicing causes a frameshift that produces a 154-aa protein. Antipeptide antibodies detected the approximately 19 kDa t-ASBT polypeptide in rat cholangiocytes, ileum, and kidney. The t-ASBT was specifically localized to the basolateral domain of cholangiocytes. Transport studies in Xenopus oocytes revealed that t-ASBT can function as a bile acid efflux protein. Thus, alternative splicing changes the cellular targeting of ASBT, alters its functional properties, and provides a mechanism for rat cholangiocytes and other bile acid-transporting epithelia to extrude bile acids. Our work represents an example in which a single gene appears to encode via alternative splicing both uptake and obligate efflux carriers in a bile acid-transporting epithelial cell.

Alternative Splicing↗
PubMed2000

Many multipotential gene-marked progenitor or stem cell clones contribute to hematopoiesis in nonhuman primates.

Retroviral insertion site analysis was used to track the contribution of retrovirally transduced primitive progenitors to hematopoiesis after autologous transplantation in the rhesus macaque model. CD34-enriched mobilized peripheral blood cells were transduced with retroviral marking vectors containing the neo gene and were reinfused after total body irradiation. High-level gene transfer efficiency allowed insertion site analysis of individual myeloid and erythroid colony-forming units (CFU) and of highly purified B- and T-lymphoid populations in 2 animals. At multiple time points up to 1 year after transplantation, retroviral insertion sites were identified by performing inverse polymerase chain reaction and sequencing vector-containing CFU or more than 99% pure T- and B-cell populations. Forty-eight unique insertion sequences were detected in the first animal and also in the second animal, and multiple clones contributed to hematopoiesis at 2 or more time points. Multipotential clones contributing to myeloid and lymphoid lineages were identified. These results support the concept that hematopoiesis in large animals is polyclonal and that individual multipotential stem or progenitor cells can contribute to hematopoiesis for prolonged periods. Gene transfer to long-lived, multipotent clones is shown and is encouraging for human gene therapy applications.

Animals↗
PubMed2000

Lasting influence of repetitive transcranial magnetic stimulation on intracortical excitability in human subjects.

We studied the effects of a train of 30 pulses of repetitive transcranial magnetic stimulation (rTMS) at frequencies of 5 and 15 Hz and at an intensity of 120% of resting motor threshold on human motor cortex excitability. Intracortical inhibition (ICI) and intracortical facilitation (ICF) after rTMS were tested by a conditioning-test designed paired-pulse paradigm. After 15 Hz rTMS, ICI was significantly reduced for 3.2 min, ICF was enhanced for 1.5 min, muscle evoked potentials from single TMS were increased in the first 30 s only. After 5 Hz rTMS ICI was significantly reduced in the first 32 s. We conclude that high-frequency suprathreshold rTMS transiently suppresses the activity of the intracortical inhibitory circuitry and, with a different time course, increases the excitability of the excitatory circuitry.

Adult↗
PubMed2000

Antigen-specific cancer immunotherapy using a GM-CSF secreting allogeneic tumor cell-based vaccine.

Granulocyte-macrophage colony-stimulating factor (GM-CSF)-transduced autologous tumor cell-based vaccines are currently one of the major forms of cancer vaccines. However, the preparation of GM-CSF-transduced autologous tumor vaccines is time-consuming and technically challenging. In addition, the host antigen presenting cells, rather than the tumor vaccine cells themselves, present tumor-specific antigens and prime the host T cells. Therefore, we tested the efficacy of antigen-specific allogeneic tumor vaccines. We used human papillomavirus 16 (HPV-16) E7 protein as a model tumor antigen, which is associated with the development of most cervical carcinoma. B16, a C57BL/6 (H-2(b)) derived melanoma cell line, was genetically engineered to produce GM-CSF alone (B16GM), HPV-16 E7 alone (B16E7), or both (B16GME7). These vaccine cells were injected into BALB/c (H-2(d)) mice (10(6) cells/mouse). Two weeks later, mice were challenged with 10(5) live HPV-16 E7(+) BL-1 (H-2(d)) tumor cells and monitored for tumor progression twice weekly. To determine the effective cell population in the antitumor immunity elicited by B16GME7, we carried out in vivo antibody depletion experiments using CD4 and CD8 specific antibodies. In addition, as a measure of the immune responses produced by B16GME7, we performed an in vitro cytotoxic T lymphocyte assay using a standard chromium release method. We found that all of the mice vaccinated with B16GME7 remained tumor free 49 days post-BL-1 challenge. In contrast, mice vaccinated with B16GM and B16E7 did not show any tumor protection against a similar dose of BL-1 cells. Furthermore, the antitumor immunity produced by B16GME7 was dependent on both CD4 and CD8 T cells. In addition, E7-specific cytotoxic T lymphocyte activity could be readily demonstrated in mice immunized with B16GME7. These results suggest that allogeneic tumor cells transduced with GM-CSF and the tumor antigen, HPV-16 E7, cannot only generate an E7-specific cytotoxic T lymphocytes response in vitro, but can also elicit a potent antitumor immune response against an E7 expressing tumor in vivo.

Animals↗
PubMed2000

Point mutation associated with X-linked dominant Charcot-Marie-Tooth disease impairs the P2 promoter activity of human connexin-32 gene.

Many lines of evidence suggest that connexin-32 gap junction is involved in the exchange of information and metabolites in the peripheral nervous system. It has been shown that connexin-32 protein and mRNA are expressed in Schwann cells that function as myelinating cells of the peripheral nervous system. The physiological importance of connexin-32 gap junctions in regulating the normal function of myelinating Schwann cell is indicated by recent findings that X-linked dominant Charcot-Marie-Tooth disease, a hereditary peripheral neuropathy, is associated with the mutations of connexin-32 gene. Recently, we encountered a Taiwanese family affected with X-linked dominant Charcot-Marie-Tooth neuropathy. Therefore, we investigated the possible mutation in the coding and noncoding regions of the connexin-32 gene of affected members of this family. Our results suggest that a G-to-A transition at the position -215 (in relation to the transcription initiation site) of the nerve-specific P2 promoter region is associated with the pathogenesis of X-linked dominant Charcot-Marie-Tooth disease. Further experiments using the promoter assay indicate that G-to-A mutation at the position -215 greatly impairs the transcriptional activity of connexin-32 P2 promoter. These findings propose that a reduced expression of connexin-32 mRNA and protein in the myelin sheath could be responsible for the development of X-linked dominant Charcot-Marie-Tooth neuropathy.

Animals↗
PubMed2000

The effect of steroid sulfatase inhibition on learning and spatial memory.

Steroid sulfatase inhibitors can enhance the concentration of the neurosteroid DHEAS in rat brain. Previous studies have demonstrated that the steroid sulfatase inhibitor (p-O-sulfamoyl)-N-tetradecanoyl tyramine (DU-14) could reverse scopolamine induced amnesia in rats in a passive avoidance memory paradigm. The intent of this study was to determine whether chronic pretreatment with DU-14 could reverse scopolamine amnesia and/or enhance spacial memory in the place, probe and cued versions of the Morris water maze (MWM). Rats were divided into four groups and administered IP for 15 days either DU-14 (30.0 mg/Kg) or corn oil (1.0 ml/Kg) vehicle. On training days animals were administered either scopolamine (1.0 mg/Kg) or saline (1.0 ml/Kg). The groups administered DU-14 displayed a significant enhancement in learning and spacial memory in the place version of the MWM, when compared to respective vehicle-scopolamine and vehicle-saline groups. In the probe version, the DU-14-saline group remained in the target quadrant of the maze significantly longer than any of the other groups indicating enhanced retention. In the cued version of the MWM, treatment with DU-14 did not significantly change escape latency suggesting that the steroid sulfatase inhibitor did not alter motivation or locomotion. These results suggest that the chronic administration of steroid sulfatase inhibitors enhance learning and spatial memory in rats.

Amnesia↗
PubMed2000

Examination of the relation between periodontal health status and cardiovascular risk factors: serum total and high density lipoprotein cholesterol, C-reactive protein, and plasma fibrinogen.

Using data from the Third National Health and Nutrition Examination Survey (1988-1994), the authors examined the relation between periodontal health and cardiovascular risk factors: serum total and high density lipoprotein cholesterol, C-reactive protein, and plasma fibrinogen. A total of 10,146 participants were included in the analyses of cholesterol and C-reactive protein and 4,461 in the analyses of fibrinogen. Periodontal health indicators included the gingival bleeding index, calculus index, and periodontal disease status (defined by pocket depth and attachment loss). While cholesterol and fibrinogen were analyzed as continuous variables, C-reactive protein was dichotomized into two levels. The results show a significant relation between indicators of poor periodontal status and increased C-reactive protein and fibrinogen. The association between periodontal status and total cholesterol level is much weaker. No consistent association between periodontal status and high density lipoprotein cholesterol was detectable. Similar patterns of association were observed for participants aged 17-54 years and those 55 years and older. In conclusion, this study suggests that total cholesterol, C-reactive protein, and fibrinogen are possible intermediate factors that may link periodontal disease to elevated cardiovascular risk.

Adolescent↗
PubMed2000

MR imaging of shear waves generated by focused ultrasound.

This study has shown that magnetic resonance elastography (MRE) can detect shear waves excited by focused ultrasound (FUS) in both gel phantoms and ex vivo muscle. Good agreement was shown between the shear modulus measured from MRE images generated using FUS and that using previously reported MRE techniques. The shear wave displacement amplitude at the FUS focus was studied and found to be proportional with both FUS ultrasonic pulse intensity and the FUS modulation pulse period over the range tested.

Animals↗
PubMed2000

Prolonged high-level detection of retrovirally marked hematopoietic cells in nonhuman primates after transduction of CD34+ progenitors using clinically feasible methods.

Low-level retroviral transduction and engraftment of hematopoietic long-term repopulating cells in large animals and humans remain primary obstacles to the successful application of hematopoietic stem cell (HSC) gene transfer in humans. Recent studies have reported improved efficiency by including stromal cells (STR), or the fibronectin fragment CH-296 (FN), and various cytokines such as flt3 ligand (FLT) during ex vivo culture and transduction in nonhuman primates. In this work, we extend our studies using the rhesus competitive repopulation model to further explore optimal and clinically feasible peripheral blood (PB) progenitor cell transduction methods. First, we compared transduction in the presence of either preformed autologous STR or immobilized FN. Long-term clinically relevant gene marking levels in multiple hematopoietic lineages from both conditions were demonstrated in vivo by semiquantitative PCR, colony PCR, and genomic Southern blotting, suggesting that FN could replace STR in ex vivo transduction protocols. Second, we compared transduction on FN in the presence of IL-3, IL-6, stem cell factor (SCF), and FLT (our best cytokine combination in prior studies) with a combination of megakaryocyte growth and development factor (MGDF), SCF, and FLT. Gene marking levels were equivalent in these animals, with no significant effect on retroviral gene transfer efficiency assessed in vivo by the replacement of IL-3 and IL-6 with MGDF. Our results indicate that SCF/G-CSF-mobilized PB CD34+ cells are transduced with equivalent efficiency in the presence of either STR or FN, with stable long-term marking of multiple lineages at levels of 10-15% and transient marking as high as 54%. These results represent an advance in the field of HSC gene transfer using methods easily applied in the clinical setting.

Animals↗
PubMed2000

Introduction of a xenogeneic gene via hematopoietic stem cells leads to specific tolerance in a rhesus monkey model.

Host immune responses against foreign transgenes may be a major obstacle to successful gene therapy. To clarify the impact of an immune response to foreign transgene products on the survival of genetically modified cells, we studied the in vivo persistence of cells transduced with a vector expressing a foreign transgene compared to cells transduced with a nonexpressing vector in the clinically predictive rhesus macaque model. We constructed retroviral vectors containing the neomycin phosphotransferase gene (neo) sequences modified to prevent protein expression (nonexpressing vectors). Rhesus monkey lymphocytes or hematopoietic stem cells (HSCs) were transduced with nonexpressing and neo-expressing vectors followed by reinfusion, and their in vivo persistence was studied. While lymphocytes transduced with a nonexpressing vector could be detected for more than 1 year, lymphocytes transduced with a neo-expressing vector were no longer detectable within several weeks of infusion. However, five of six animals transplanted with HSCs transduced with nonexpression or neo-expression vectors, and progeny lymphocytes marked with either vector persisted for more than 2 years. Furthermore, in recipients of transduced HSCs, infusion of mature lymphocytes transduced with a second neo-expressing vector did not result in elimination of the transduced lymphocytes. Our data show that introduction of a xenogeneic gene via HSCs induces tolerance to the foreign gene products. HSC gene therapy is therefore suitable for clinical applications where long-term expression of a therapeutic or foreign gene is required.

Animals↗
PubMed2000

Photodynamic action of amino substituted hypocrellins: EPR studies on the photogenerations of active oxygen and free radical species.

A novel method has been employed to prepare 2-butylamino-2-demethoxy hypocrellin A (BADMHA) and 2-butylamino-2-demethoxy hypocrellin B (BADMHB). Both compounds exhibit stronger absorption at the phototherapeutic window (600-900 nm). The spin trapping and spin counteraction studies have shown that they are both efficient generators of the active oxygen (1O2, O2*-) in the aerobic condition. Under the anaerobic condition they generate non-oxygen free radical (semiquinone radical anion), and the active oxygen mechanism of photosensitization can be converted into non-oxygen free radical mechanism with the depletion of oxygen. The quantum yields of 1O2 generation of BADMHA and BADMHB are 0.46 and 0.44, respectively. Both are lower than those of their parent compounds HA and HB. But the productions of superoxide anion are enhanced significantly compared with HA and HB, indicating they are both favorable Type I phototherapeutic agents.

Cyclic N-Oxides↗