Biomedical subjects

J Wu

Publications and source records attributed to J Wu.

At least 73 records · Page 4Linked to original sources

PubMed2004

Pulmonary vascular morphology in a fetal rabbit model for congenital diaphragmatic hernia.

BACKGROUND/PURPOSE: Although the pulmonary vascular abnormalities in congenital diaphragmatic hernia (CDH) are described from a morphologic point of view, the treatment of pulmonary hypertension (PH) remains one of the main unsolved problems in clinical daily practice. For this reason, detailed studies in well-validated animal models could still be of significance in our understanding of the pathogenesis of CDH. METHODS: In does of 23 days' gestational age (GA), 39 fetuses underwent creation of diaphragmatic hernia (DH) and 15 fetuses a sham thoracotomy (SHAM). Thirty-nine nonoperated littermates served as internal controls (CTR). Fetuses were harvested by cesarean section on days 25, 27, 29, and 30 of gestation. Lung specimens were obtained and formalin fixed for further vascular morphometry studies. RESULTS: Lung vessels from DH fetuses started to show significantly smaller internal diameter (ID), external diameter (ED), larger arterial wall thickness (WT), and, in particular, a proportionally higher medial thickness (%MT) and adventitial thickness (%AT) from day 27 onward when compared with control fetuses. SHAM fetuses, which were harvested at term, showed no differences with CTR. CONCLUSIONS: This is the first report documenting changes over time in the vascular system in a rabbit fetal model of surgically induced DH. These changes mimic pathologic findings observed in human fetuses and are also concordant with earlier observations in the surgical ovine model and the toxic nitrofen rat model.

Animals↗

PubMed2004

Synaptically stimulated induction of group I metabotropic glutamate receptor-dependent long-term depression and depotentiation is inhibited by prior activation of metabotropic glutamate receptors and protein kinase C.

We have investigated metaplasticity of the group I metabotropic glutamate receptor (mGluR)-dependent long-term depression (LTD) and depotentiation (DP) induced by physiological synaptic stimulation in the medial perforant path of the dentate gyrus in vitro. Group I mGluR-LTD/DP was inhibited by prior preconditioning brief high frequency stimulation (HFS) if the preconditioning HFS induced long-term potentiation (LTP) or if the induction of LTP was inhibited by an NMDA receptor antagonist. The inhibitory effect of the preconditioning HFS on LTD/DP was dependent upon activation of mGluRs, as it was blocked by the presence of the mGluR antagonist (S)-alpha-methyl-4-carboxyphenylglycine during the preconditioning stimulation. The inhibitory effect of the preconditioning HFS involved stimulation of PKC, as the presence of the PKC inhibitor bisindolylmaleimide (BIS) during the preconditioning stimulation prevented the inhibitory effect of such preconditioning stimulation. Activation of PKC was also necessary for the induction of mGluR-LTD itself, as the PKC inhibitor BIS prevented the induction of the mGluR-LTD. We suggest that the physiological stimulation of mGluRs by the preconditioning stimulation produces a PKC-dependent inactivation of subsequent group I mGluR functioning and thereby an inhibition of induction of group I mGluR-dependent LTD/DP induction.

Animals↗

PubMed2004

Febuxostat (TMX-67), a novel, non-purine, selective inhibitor of xanthine oxidase, is safe and decreases serum urate in healthy volunteers.

In order to evaluate the safety, pharmacological properties, and urate-lowering efficacy of febuxostat, a non-purine, selective inhibitor of xanthine oxidase, a Phase 1, 2-week, multiple-dose, placebo-controlled, dose-escalation study was conducted in 154 healthy adults of both sexes. Daily febuxostat doses in the range 10 mg to 120 mg resulted in proportional mean serum urate reductions ranging from 25% to 70% and in proportional increases in maximum febuxostat plasma concentrations and area under plasma concentration versus time curves. Accompanying the hypouricemic effect were increases in serum xanthine concentrations, decreases in urinary uric acid excretion, and increases in urinary xanthine and hypoxanthine excretion, confirming inhibition of xanthine oxidase activity by febuxostat. Hepatic conjugation and oxidative metabolism were the major pathways of elimination of febuxostat from the body, and renal elimination did not appear to play a significant role. Although not uncommon, adverse events were mild and self-limited, and no deaths or serious adverse events were observed. Febuxostat is a safe and potent hypouricemic agent in healthy humans.

Adult↗

PubMed2004

Prognostic scoring systems in patients with follicular thyroid cancer: a comparison of different staging systems in predicting the patient outcome.

BACKGROUND: The use of prognostic scoring systems is important for predicting the survival of individuals with thyroid carcinoma. Relatively few studies have addressed this issue for patients with follicular thyroid cancer. The goal of this retrospective study was to establish the best and most pertinent prognostic scoring system to predict survival in patients with follicular thyroid cancer. METHODS: We selected 86 patients with follicular thyroid cancer treated at University of California, San Francisco (UCSF) hospitals from January 1954 to April 1998. The mean follow-up time was 11.5 years. There were 60 women (70%) and 26 men (30%), with a mean age if 48.6 years. Prognostic scoring systems included tumor, node, metastases (TNM), European Organization for Research and Treatment of Cancer (EORTC), Age, Grade, Extent, Size (AGES), Age, Metastases, Extent, Size (AMES), and the Metastases, Age, Completeness of resection, Invasion, Size (MACIS). Survival time was calculated using the Kaplan-Meier method. Using Cox proportional hazards analysis, the relative importance of each scoring method was determined by calculating the proportion of variation in survival time explained (PVE). RESULTS: Kaplan-Meier analysis indicated that all scoring systems were significant predictors of survival time (p < 0.0001). The PVE associated with each system was (from highest to lowest) 0.48 for MACIS, 0.46 for AGES, 0.44 for EORTC, 0.40 for AMES, and 0.33 for TNM. These results indicate that the MACIS scoring system accounted for a great proportion of explained variance in survival and is a more precise predictor of survival compared to the other scoring systems. CONCLUSIONS: TNM, EORTC, AGES, AMES, and MACIS, all provided useful prognostic information about the survival in our 86 patients with follicular thyroid cancers. The MACIS classification, however, was the most accurate predictor using PVE as a method of evaluation. Future scoring systems considering additional prognostic factors, may obtain a higher PVE.

Adenocarcinoma, Follicular↗

PubMed2004

Lung function changes in coke oven workers during 12 years of follow up.

AIMS: To investigate the effect of exposure to coke oven emissions on the lung function of coke oven workers. METHODS: The study population, followed from 1978 and 1990, was 580 male workers with at least two sets of lung function measurements (FVC, FEV1, FEV1/FVC, and FEF25-75%). An annual rate of change (time slope) for age and height adjusted lung function index was estimated for each subject. This "time slope" was then treated as the response variable in a weighted multiple regression analysis with selected predictors. RESULTS: For all 580 subjects, each year of working in the "operation" group (the most exposed) was found to increase the FVC decline by around 0.7 ml/year (95% CI 0.1 to 1.3 ml/year). After the exclusion of 111 subjects without detailed work history, the above finding was confirmed and each year of exposure in "operation" was also found to increase the FEV1 decline by around 0.8 ml/year (95% CI 0.1 to 1.4 ml/year). CONCLUSIONS: These findings are consistent with the results of previous cross-sectional studies. Work duration in the most exposed position in the coke ovens was associated with increased annual decline for FVC and FEV1. The estimated effect of one year of work exposure in "operation" is equivalent, in terms of the reduction in lung function, to an estimated 2.1 pack-years of smoking for FVC and 1.2 pack-years of smoking for FEV1.

Adult↗

PubMed2004