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Biomedical subjects

J T Wu

Publications and source records attributed to J T Wu.

At least 37 records · Page 2Linked to original sources
PubMed2001

The processing of coreference for reduced expressions in discourse integration.

Three reading-time experiments in Chinese are reported that test contrasting views of how pronominal coreference is achieved. On the one hand, studies of reading time and eye tracking suggest that reduced expressions, such as the pronoun he, serve as critical links to integrate separate utterances into a coherent model of discourse. On the other hand, probe-word recognition studies indicate that full anaphoric expressions, such as a repeated name, are more readily interpreted than reduced expressions due to their rich lexical information, which provides effective cues to match the representation of the appropriate referent in memory. The results indicate that the ease of integrating the critical referent into a model of discourse is a function of the congruence of lexical, semantic, and discourse features conveyed by a syntactically prominent reduced expression within linguistic input. This pattern supports the view that a reduced expression is interpreted on-line and indeed plays a critical role in promoting discourse coherence by facilitating the semantic integration of separate utterances.

Adult↗
PubMed2001

Tissue remodeling of rat pulmonary artery in hypoxic breathing. I. Changes of morphology, zero-stress state, and gene expression.

The remodeling of the pulmonary arterial tissue in response to a step change of the oxygen concentration in the gas in which a rat lives was recorded as function of time and function of O2 concentration. Three steps of changing from 20.9% to 17.2%, 13.6%, and 10% O2 were imposed. Earlier work in our laboratory has shown that pulmonary arterial tissue remodeling is significant in the first 24 h after a step change of oxygen tension. Hence we made measurements in this period. Furthermore, data were obtained for tissue remodeling of circumferential and axial lengths of the pulmonary arteries. We recorded the activities of gene expressions in the lung tissues by microarray, determined the dose response curves of gene expression in the homogenized whole lungs with respect to four levels of O2 concentration, and obtained the time courses of gene expression in the lung parenchyma in 30 days after a step decrease of O2 concentration from 20.9% to 10%. We would like to suggest that the correlation of gene expression with physiological function parameters, i.e., time, O2 tension, blood pressure, opening angle, wall thicknesses, etc., is the way to narrow down the search for specific genes for specific physiological functions.

Animals↗
PubMed2001

Tissue remodeling of rat pulmonary artery in hypoxic breathing. II. Course of change of mechanical properties.

When cells and the matrix of a tissue remodel, the mechanical properties of the tissue do change. The mechanical properties are expressed by constitutive equations. In this article the remodeling of the constitutive equation of the pulmonary artery is studied. The remodeling was induced in a rat breathing a gas whose oxygen concentration was suddenly decreased as a step function of time and maintained constant (17.2%, 13.6%, or 10%) afterwards. Since the mathematical form of the constitutive equation has been identified in earlier papers, we need to determine only the elastic constants that change in the process of tissue remodeling. We consider arteries subjected to blood pressure and longitudinal stretch, and limit ourselves to two-dimensional problems involving only circumferential and longitudinal stress and strain. In the neighborhood of an in vivo state, the perturbations of stresses and strains are related by linear, anisotropic, tensor equations involving three elastic constants: the incremental Young's modulus in the circumferential direction Ythetaz, that in the longitudinal direction Yzz, and the cross modulus Ythetaz. Over a 24 h period, changes of Ythetatheta between 164 and 187 kN/m2, Yzz between 64 and 92 kN/m2, and Ythetaz between 61 and 88 kN/m2 are statistically insignificant.

Animals↗
PubMed2001

Transient vs. prolonged histone hyperacetylation: effects on colon cancer cell growth, differentiation, and apoptosis.

The role of histone hyperacetylation in regard to growth, differentiation, and apoptosis in colon cancer cells was assessed in an in vitro model system. HT-29 cells were grown in +/-10% fetal bovine serum with either 5 mM sodium butyrate or 0.3 microM trichostatin A [single dose (T) or 3 doses 8 h apart (TR)] for 24 h. Serum-starved HT-29 cells were further treated with epidermal growth factor or insulin-like growth factor I for an additional 24 h. Apoptosis was quantified with propidium iodide and characterized by electron microscopy. Northern blot analyses were performed with cDNA probes specific for intestinal alkaline phosphatase, Na-K-2Cl cotransporter, the cell cycle inhibitor p21, and the actin control. Flow cytometric analysis revealed a time-dependent growth suppression along with early induction of p21 mRNA in the butyrate, T, and TR groups. Histone hyperacetylation, assessed by acid-urea-triton gel electrophoresis, was transient in the T group but persisted for up to 24 h in the butyrate and TR groups. Induction of apoptosis, growth factor unresponsiveness, and differentiation occurred in the butyrate- and TR-treated cells but not those treated with a single dose of trichostatin A. Thus transient hyperacetylation of histones is sufficient to induce p21 expression and produce cellular growth arrest, but prolonged histone hyperacetylation is required for induction of the programs of differentiation, apoptosis, and growth factor unresponsiveness.

Acetylation↗
PubMed2001

Seroprevalence of Neospora caninum in beef cattle in northern Alberta.

Blood samples were collected from 1806 pregnancy-tested cows from 174 herds at a northern Alberta auction mart in the fall of 1998. One hundred sixty-two (9.0%) of these samples were positive for antibodies to N. caninum. Thirty-five of 260 samples (13.5%) collected from the same region in the 1980s were also serologically positive for N. caninum.

Alberta↗
PubMed2001

Reproductive performance of a cow-calf herd following a Neospora caninum-associated abortion epidemic.

This study examines the long-term impact of a Neospora caninum-associated abortion outbreak in a large cow-calf herd in northern Alberta. Blood samples were collected 4 times from all bred females and heifer calves born during the spring before the outbreak: (1) at the time of the outbreak, (2) the following spring, (3) the subsequent fall, and, finally, (4) the second spring after the outbreak. The samples were analyzed using a commercially available enzyme-linked immunosorbent assay for N. caninum. Calves born immediately following the outbreak were also monitored. Individual calving or abortion records were available from all cows for 2 calving seasons. All cows and heifers were pregnancy tested after the 2 subsequent breeding seasons. At the time of the abortion outbreak in 1997, 81% of all bred females and 87% of the heifer calves were serologically positive. In spring 1998, 49% of the cows and 47% of the heifer calves remained positive. In fall 1998, 48% of the remaining cows and heifers were serologically positive. After the first breeding season following the outbreak (1998), 13.5% of the heifers and 22.2% of the cows were open (not pregnant). Animals that were serologically positive in the spring were more likely to be open in the fall (odds ratio, 2.0; 95% confidence interval, 1.1 to 3.7). No subsequent associations with increased risk of abortion, stillbirth, or nonpregnancy were identified.

Abortion, Veterinary↗
PubMed2000

Dynamic optimization of a linear-quadratic model with incomplete repair and volume-dependent sensitivity and repopulation.

PURPOSE: The linear-quadratic model typically assumes that tumor sensitivity and repopulation are constant over the time course of radiotherapy. However, evidence suggests that the growth fraction increases and the cell-loss factor decreases as the tumor shrinks. We investigate whether this evolution in tumor geometry, as well as the irregular time intervals between fractions in conventional hyperfractionation schemes, can be exploited by fractionation schedules that employ time-varying fraction sizes. METHODS: We construct a mathematical model of a spherical tumor with a hypoxic core and a viable rim, which is most appropriate for a prevascular tumor, and is only a caricature of a vascularized tumor. This model is embedded into the traditional linear-quadratic model by assuming instantaneous reoxygenation. Dynamic programming is used to numerically compute the fractionation regimen that maximizes the tumor-control probability (TCP) subject to constraints on the biologically effective dose of the early and late tissues. RESULTS: In several numerical examples that employ five or 10 fractions per week on a 1-cm or 5-cm diameter tumor, optimally varying the fraction sizes increases the TCP significantly. The optimal regimen incorporates large Friday (afternoon, if 10 fractions per week) fractions that are escalated throughout the course of treatment, and larger afternoon fractions than morning fractions. CONCLUSION: Numerical results suggest that a significant increase in tumor cure can be achieved by allowing the fraction sizes to vary throughout the course of treatment. Several strategies deserve further investigation: using larger fractions before overnight and weekend breaks, and escalating the dose (particularly on Friday afternoons) throughout the course of treatment.

Algorithms↗
PubMed2000

Direct plasma sample injection in multiple-component LC-MS-MS assays for high-throughput pharmacokinetic screening.

The simultaneous dosing of numerous compounds followed by multiple-component analysis using LC-MS-MS (the N-in-1 approach) has significantly improved the throughput of the drug-screening process. However, plasma samples still need to be extracted before LC-MS-MS analysis, which frequently limits the throughput of the assay. In this work, a high-throughput on-line extraction technique has been developed for multiple-component LC-MS-MS assays using a high-flow column-switching technique. In N-in-1 LC-MS-MS assays, high sensitivity is required since the dose level is generally reduced to minimize drug-drug interactions. In addition, good chromatographic separation is essential to minimize interference and suppression effects. The direct plasma sample injection method developed in this work has successfully met the two requirements for multiple-component LC-MS-MS assays in high-throughput pharmacokinetic screening. Plasma samples containing a large number of potential drug candidates were directly injected onto an extraction column operated under a flow rate sufficiently high to exhibit a turbulent-flow profile. The extracted analytes were then eluted onto an analytical column via column switching for LC-MS-MS analysis. The use of turbulent flow resulted in a faster and more rugged extraction with reduced carryover compared with results obtained under laminar-flow conditions. Meanwhile, the use of a column-switching method maintained the chromatographic resolving power and high sensitivity of the LC-MS-MS assay. Separation efficiency, dynamic range, accuracy, and precision comparable with those of solid-phase extraction have been achieved with the turbulent-flow column-switching technique. As a result, this technique has been successfully and routinely used for high-throughput pharmacokinetic screening.

Animals↗
PubMed2000

Heritability of prostate-specific antigen and relationship with zonal prostate volumes in aging twins.

Both benign prostatic hyperplasia and prostate-specific antigen (PSA) have been shown to increase with age and with prostate volume in men, but the influence of heredity on these relationships is not completely understood. This study has two aims: 1) to investigate the inter-relationships of age, PSA, and various zonal measurements in the prostate; and 2) to assess the impact of heritable influences on total PSA. Eighty-four monozygotic twin pairs and 83 dizygotic twin pairs were studied, and serum total PSA, free PSA, and PSA-alpha1-antichymotrypsin were measured. Their prostate volumes [total (TV), transition zone (TZ), and peripheral zone) were quantitated using transrectal ultrasound. Total PSA is significantly correlated with all zonal prostate measurements (TZ, peripheral zone, TV, and TZ/TV) and with age. When linear regression was applied, only age and TZ were retained in the final model. The proportion of variability in total PSA explained by these two factors, however, is below 24%. In contrast, estimates of heritability show that approximately 45% of the variability in total PSA can be explained by inherited factors. Whereas age and TZ are linearly related to total PSA, their influence is much less than that of familial and genetic factors. It is uncertain whether these factors predispose also to prostate cancer or if they are independent of those, whether they confound the accuracy of using total serum PSA level as a diagnostic tool.

Adult↗
PubMed2000

Quantification of HER2 oncoprotein in fine-needle aspirates of the breast.

Measurements of either HER2 gene overexpression or its gene-coded protein (p185) are clinically useful for predicting prognosis in breast cancer. The measurements are also useful for identifying metastatic breast cancer patients who may benefit from Herceptin treatment. Since fine needle aspiration (FNA) of the breast has become an increasingly popular technique for obtaining tissue specimens, we have developed a sensitive method to quantify p185 in the aspirate. For this procedure, p185 from the cell pellet of FNA is extracted with a buffer containing Triton X-100, and the p185 is measured with an enzyme immunoassay. Most of the malignant breast tumors (N=7) in this study were associated with elevated p185 concentrations (6/7, 319+/-222 U/mg), compared to the p185 concentrations in normal breast tissue (42.8+/-35 U/mg, N=47) or benign lesions (43.1+/-20.2 U/mg, N=22). Quantification of p185 in FNA may improve the assessment of breast cancer patients, revealing whether they are at high risk and may benefit from Herceptin treatment.

Biopsy, Needle↗
PubMed2000

Elevated serum chromogranin A is detectable in patients with carcinomas at advanced disease stages.

Chromogranin A (CgA), a marker of neuroendocrine cells and an indicator for neuroendocrine differentiation, is associated with a poor prognosis when detected in tumor tissue, based on immunohistochemical techniques. We sought to determine whether it is possible to detect elevated serum CgA in patients with commonly occurring carcinomas of non-neuroendocrine origin. CgA was measured in both random and serial serum specimens, using a serum CgA assay developed in our laboratory. Elevated levels of serum CgA were detected in patients with carcinoma of the prostate, breast, ovary, pancreas, and colon. Serum CgA levels in patients with all types of carcinoma appeared to parallel the changes of serum dominant tumor markers and were found in sera containing highly elevated tumor markers. Based on these preliminary findings, perhaps we should monitor CgA, in addition to the routinely used tumor markers, during the treatment of patients with carcinomas to determine if CgA is useful as a prognostic marker in carcinomas other than prostatic cancer.

Biomarkers, Tumor↗
PubMed1999

Culture-negative ulcerative keratitis after laser in situ keratomileusis.

A 40-year old man, highly myopic in both eyes, had laser in situ keratomileusis (LASIK) in the left eye in November 1996. Corneal melting and ulceration and fine striae-like interface infiltrates were noticed 1 day postoperatively. There was no response to intensive topical antibiotics in the form of hourly ofloxacin 3% (Tarivid), and satellite lesions developed on day 4. Corneal scrapings for gram stain and culture were done twice. No bacterial or fungal organisms were identified. Intensive topical fortified vancomycin (50 mg/mL) was added, and the lesions resolved gradually over the ensuing 2 weeks. Eighteen months after LASIK, refraction was -1.50 - 0.75 x 105 in the left eye, and uncorrected visual acuity was 20/70, correctable to 20/25 with spectacles.

Adult↗
PubMed1999

Management of severe flap wrinkling or dislodgment after laser in situ keratomileusis.

PURPOSE: To review the management and results of cases with severe flap wrinkling or dislodgment after laser in situ keratomileusis (LASIK). SETTING: University Eye Center, Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, The Chinese University of Hong Kong. METHODS: Four patients with severe flap wrinkling or dislodgment after LASIK are described. Surgical repositioning of the flap was performed in all cases. Flap status, refractive changes, and final uncorrected and best corrected visual acuities were used to evaluate the outcome of flap repositioning. RESULTS: Flap repositioning required suturing in 2 patients, 1 of whom developed severe epithelial ingrowth with melting of the corneal flap and stromal bed and eventually required flap removal. The stromal inflammation resolved, and the corneal surface re-epithelialized after flap excision. In 2 other patients, wedge-shaped tissue excision (1.0 x 1.5 mm) from the superior portion of the corneal flap was necessary to allow better flap realignment. In 1 of these patients, the corneal flap was eventually converted to a free cap to correct residual wrinkling. At a mean follow-up of 15 months, the postoperative uncorrected visual acuity ranged from 20/20 to 20/60, and the best spectacle-corrected visual acuity (BSCVA) was 20/30 or better in all patients. In 1 patient, BSCVA decreased by 1 line. CONCLUSIONS: Flap dislodgment and wrinkling are serious postoperative complications of LASIK. Early recognition of these complications and prompt surgical management are crucial to achieve a successful surgical and visual outcome.

Adult↗
PubMed1999

Epicutaneous administration of hapten through patch application augments TH2 responses which can downregulate the elicitation of murine contact hypersensitivity.

BACKGROUND AND OBJECTIVE: Allergic contact dermatitis and its animal model, contact hypersensitivity (CHS), have long been documented as type 1 T-cell-predominant immune responses. Although type 1/type 2 T-cell deviation has been repeatedly demonstrated to play an important role in many human diseases and their animal models, the potential of tilting type 1/type 2 T-cell differentiation of CHS by modulating the manner of administration and dosage of hapten remains unexplored. This study examined the effect of these two factors on type 1/type 2 balance of CHS. METHODS: ELISA methods for detection of isotypes of hapten-specific antibodies and cytokine profiles of in vitro reactivation culture as well as ear-swelling assay were used to indicate type 1 or type 2 T-cell immune responses. RESULTS: In this paper, it was demonstrated that dosage of hapten has no effect on the type 1/ type 2 T-cell balance of CHS, whereas epicutaneous administration of hapten through patch application could tilt the type 1/type 2 balance to decrease type 1 and to augment type 2 T-cell responses. Patch application-induced modulation is still effective in ever-sensitized mice and the augmented type 2 T-cell responses are persistent and increase progressively in strength after repeated immunizations. Moreover, it was demonstrated that the augmented type 2 T-cell response can downregulate the elicitation of CHS. The major mediating cells of the enhanced type 2 T-cell responses were determined to be CD4+ T cells (TH2 cells). CONCLUSIONS: These data show that epicutaneous administration of hapten through patch application augments TH2 response which can downregulate the elicitation of murine CHS. This exploration may contribute to the understanding of regulatory mechanisms involved in contact allergy.

Adoptive Transfer↗
PubMed1999

Short-chain fatty acids and thyroid hormone interact in regulating enterocyte gene transcription.

BACKGROUND: Enterocyte differentiation is known to be regulated by a variety of extracellular compounds, among which are triiodothyronine (T3) and the short-chain fatty acids (SCFAs). Because several SCFAs are known to induce histone hyperacetylation, and T3 action has been recently linked to chromatin structure, we sought to investigate the interplay between SCFAs and T3 in regard to the enterocyte differentiation marker, intestinal alkaline phosphatase (IAP). METHODS: Caco-2 cells were transiently transfected with a reporter construct containing 2.4 kb of the human IAP gene 5' flanking region (IAP2.4CAT). Cotransfections were carried out with and without thyroid hormone receptor-1 (TR beta-1) or histone deacetylase-1 (HDAC-1) expression plasmids. Cells were treated with 5 mmol/L SCFAs (propionic, butyric, valeric, or caproic acids as propionate, butyrate, valerate, or caproate, respectively), with and without 10 nmol/L T3. Reporter gene activity was measured and the level of histone acetylation assessed by means of acid-urea-triton (AUT) gel assays. RESULTS: TR beta-1 cotransfection caused a marked decrease in IAP reporter gene activity, which is consistent with the well-known phenomenon of ligand independent repression (LIR), whereas T3 treatment reversed the LIR and caused further reporter gene activation. Treatment with SCFAs similarly resulted in a complete blockage of LIR, and, in fact, turned the TR beta-1 into a transcriptional activator, even in the absence of T3. Concomitant treatment with T3 and butyric acid produced an additive effect on IAP transactivation. In contrast, cotransfection with HDAC-1 attenuated the effects of SCFAs on IAP gene activation. AUT gel studies demonstrated histone hyperacetylation in response to SCFA treatment. CONCLUSION: One or more DNA cis-elements in the human IAP gene mediate ligand independent repression by the TR beta-1, an effect that can be entirely reversed by those SCFAs that induce histone hyperacetylation. In addition T3 and SCFAs can act in concert to induce IAP gene transcription, demonstrating an important link between triiodothyronine and histone hyperacetylation in regard to enterocyte-specific gene expression.

Alkaline Phosphatase↗
PubMed1999

CT of adrenal myelolipoma: report of 7 cases.

Seven cases of adrenal myelolipoma are reported. The series consisted of 1 male and 6 females, ranging in age from 30 to 76 years. In 5 cases the tumor originated from the right adrenal, in 1 case from the left adrenal and the remaining patients had bilateral tumors. Symptoms related to the mass were present in 4 cases but in contrast to other reports no hematuria was found in this series. All the tumors laid behind the angles formed by the lateral and medial limbs of adrenals. Fat density dominated in 6 tumors and soft tissue density dominated in 2. Calcification spots were revealed in 3 tumors. In two predominantly soft tissue density tumors the complete peripheral rims were revealed, while in the remaining 6 tumors the peripheral rims were considered incomplete based on the CT images. In 3 cases large amounts of fat were found surrounding the normal contralateral adrenal. The cause is still open to further investigation. Spiral CT with thin collimation provided detailed morphological information for adrenal myelolipoma.

Adrenal Gland Neoplasms↗
PubMed1999

Different patterns of serum chromogranin A in patients with prostate cancer with and without undergoing hormonal therapy.

Elevated serum chromogranin A (CgA) levels have been detected in patients with prostate cancer who have developed resistance to hormonal therapy. We would like to reexamine these cases by using serial specimens to determine whether such elevated levels are also detectable in prostate cancer patients not undergoing hormonal therapy. Serum CgA was measured in both random and serial specimens from prostate cancer patients with and without undergoing hormonal therapy. We found that serum CgA levels became elevated much earlier than did the levels of serum PSA in approximately one-third of prostate cancer patients developing resistance to hormonal therapy. On the other hand, serum CgA levels became elevated at later, more advanced stages of the disease in patients not undergoing hormonal therapy. Elevated serum CgA levels were usually detected in specimens containing highly elevated PSA. The early rise of serum CgA levels provides an early signal allowing a change of therapy to be made before the disease progresses to a fatal stage. Drugs targeting neuroendocrine cells should be considered for prostate cancer patients with elevated serum CgA levels.

Antineoplastic Agents, Hormonal↗