Biomedical subjects

John Wang

Publications and source records attributed to John Wang.

13 recordsLinked to original sources

PubMed2026

GenProb-PCSM: A Simplified Weighted Germline Score for Prostate Cancer-Specific Mortality.

BACKGROUND: We previously developed a tier-based germline classification using the National Comprehensive Cancer Network (NCCN)-recommended DNA damage repair (DDR) genes and KLK3 I179T to predict prostate cancer (PCa)-specific mortality (PCSM). To provide an easier-to-use single inherited risk score while preserving gene-specific effects, we developed GenProb-PCSM. METHODS: We analyzed 14,644 men with incident PCa from the UK Biobank. The cohort was randomly divided into training (60%) and independent testing (40%) datasets. GenProb-PCSM was developed in the training cohort by integrating pathogenic variants in ten NCCN-recommended DDR genes and the KLK3 I179T variant using gene-specific weights derived from Fine-Gray competing-risk models. Performance was evaluated in the independent testing cohort by discrimination, calibration, and risk stratification. Secondary analyzes evaluated metastatic progression and the composite endpoint of metastatic progression and/or PCSM. RESULTS: Among 14,644 men with incident PCa, 1,581 died from PCa. GenProb-PCSM remained significantly associated with PCSM in the independent testing cohort (HR per SD, 1.18; 95% CI, 1.12-1.24; p < 0.001). Using predefined risk thresholds derived from the training cohort, patients in the intermediate- and high-risk groups had significantly increased risks of PCSM compared with the low-risk group (HR 1.49, 95% CI 1.22-1.84; and HR 4.04, 95% CI 2.58-6.33, respectively). GenProb-PCSM also predicted independent metastatic progression and the composite endpoint of metastatic progression and/or PCSM. CONCLUSIONS: GenProb-PCSM transforms complex germline findings into a single inherited risk score for PCSM and metastatic progression. Its simplicity and preservation of gene-specific effects may facilitate clinical implementation of germline prognostic assessment in PCa.

DNA damage repair genes↗

PubMed2007

An annotated cDNA library and microarray for large-scale gene-expression studies in the ant Solenopsis invicta.

Ants display a range of fascinating behaviors, a remarkable level of intra-species phenotypic plasticity and many other interesting characteristics. Here we present a new tool to study the molecular mechanisms underlying these traits: a tentatively annotated expressed sequence tag (EST) resource for the fire ant Solenopsis invicta. From a normalized cDNA library we obtained 21,715 ESTs, which represent 11,864 putatively different transcripts with very diverse molecular functions. All ESTs were used to construct a cDNA microarray.

Animals↗

PubMed2006

Does gum chewing ameliorate postoperative ileus? Results of a prospective, randomized, placebo-controlled trial.

BACKGROUND: A preliminary report has been interpreted to suggest that gum chewing reduces duration of postcolectomy ileus. STUDY DESIGN: We rigorously tested this hypothesis in a prospective, randomized, placebo-controlled study. Patients undergoing open colectomy (n = 66) were randomized to receive 1 of 3 postoperative regimens beginning on postoperative day 1: sips (control, n = 21); sips and accupressure wrist bracelet (placebo, n = 23); and sips and gum chewing (treatment, n = 22). Patients were unaware of which regimen constituted placebo or treatment; end points were assessed by blinded investigators. Power was set a priori at 85% to detect a 0.75-day difference in time to first postoperative passage of flatus between placebo and treatment groups. Groups were compared using the log-rank test. RESULTS: Groups were equivalent with respect to demographic and surgical characteristics. Median times to first postoperative passage of flatus were as follows: sips, 67 hours; bracelet and sips, 72 hours; gum and sips, 60 hours (p = 0.384). There were no significant differences in time to passage of first bowel movement, time until patients were ready for discharge, or time until actual discharge among the three groups. Inpatient and 30-day followup demonstrated no difference in frequency or distribution of postoperative complications. CONCLUSIONS: In contrast to findings of a preliminary study, our clinical trial suggests that gum chewing, although safe, does not reduce duration of postcolectomy ileus.

Adolescent↗

PubMed2006

Menstrual abnormalities in a woman with ACTH-dependent pituitary macroadenoma mimicking polycystic ovary syndrome.

OBJECTIVE: Here, we present a case of ACTH-dependent pituitary macroadenoma (Cushing's disease) resulting in secondary amenorrhea mimicking polycystic ovary syndrome (PCOS). CASE REPORT: A 20-year-old nulligravid woman had been suffering from oligomenorrhea, amenorrhea, and moderate hirsutism since the age of 18 years. She visited a gynecologic clinic where PCOS was impressed according to the clinical manifestation and ultrasound finding. The patient responded to medication in the 1st year, but gradually failed to induce menses. She was advised to visit the endocrinology department for secondary amenorrhea and endocrine survey. Physical examination revealed central obesity, supraclavicle fatpad, abdominal striae, and myopathy of four limbs. Endocrine studies revealed: serum prolactin 21 ng/mL (3.0-20 ng/mL), FSH 5.69 mIU/mL (3.4-10.0 mIU/mL), LH 1.01 mIU/mL (1.1-11.6 mIU/mL), E2 < 20 pg/mL (follicular phase 53-258 pg/mL), ACTH 110 pg/mL (0-46.0 pg/mL), cortisol 26.7 microg/dL at 8 a.m. (5.0-25 microg/dL), cortisol 21.3 microg/dL at 11 p.m. (half of normal morning value). Right pituitary macroadenoma was diagnosed through a series of dexamethasone tests and MRI. The patient received staging surgery including transsphenoidal adenomectomy and right frontotemporal craniotomy. As a result, the patient's physical condition gradually improved, and her menstrual cycle became regular with medication after the operation in the outpatient follow-up. CONCLUSION: PCOS is a common disease resulting in secondary amenorrhea. However, Cushing's syndrome resulting from pituitary macroadenoma should also be considered. Therefore, a careful history, observation, physical examination, and endocrine studies can differentiate between patients with PCOS and Cushing's disease.

ACTH-Secreting Pituitary Adenoma↗

PubMed2006

Investigations into the regulation and function of the SH2 domain-containing protein-tyrosine phosphatase, SHP-1.

Our laboratory is interested in identifying genes relevant to diseases. Our approach is to use spontaneous mouse mutants with immunological defects and decipher the molecular basis of the phenotypes. In the early 1990s, our attention was focused on the motheaten and viable motheaten mouse mutants. We used these mutant mice as a model system for elucidating the genetic and cellular events contributing to expression of normal hematopoietic and immune function. Our initial goal was to identify the gene responsible for the motheaten and viable motheaten phenotype. In 1993, we and others reported that both motheaten and viable motheaten mice have mutations in the SHP-1 gene. Currently, there are more than 600 publications involving SHP-1. In this review, rather than summarizing all these studies, we highlight work involving SHP-1 that were/are carried out in our and our collaborators' laboratories.

Animals↗

PubMed2005

Frequent FHIT gene loss of heterozygosity in human papillomavirus-infected non-smoking female lung cancer in Taiwan.

The fragile histidine triad (FHIT), located in chromosome region 3p14.2, had been reported to be a frequent allele with loss of heterozygosity (LOH) in smoking lung cancer and HPV-associated cervical cancer. Additionally, FHIT LOH may act as a tumor suppressor gene to involve in smoking-related lung tumorigenesis and HPV-related cervical tumorigenesis, respectively. In our previous report, a high prevalence of HPV 16/18 infection has been observed in non-smoking female lung cancer patients, and thus it was speculated that HPV 16/18 infection may increase the LOH frequency of FHIT in female cases to implicate in lung tumorigenesis. In this study, 157 lung cancer patients were enrolled and subjected to FHIT LOH analysis with three microsatellite markers. As expected, the frequency of FHIT LOH in males, smokers, and squamous cell carcinomas lung cancer patients was significantly higher than that of their corresponding counterpart (P=0.020 for gender, P<0.001 for smoking status, and P=0.038 for tumor type). Interestingly, a correlation between HPV 16 infection and FHIT LOH was observed in female lung cancer cases. To be more specifically, FHIT LOH frequency was remarkably increased from 18% (6 of 33) in HPV 16 non-infected female cases to 46% (11 of 24) in HPV 16 infected cases. The higher frequency of FHIT LOH observed in HPV 16-infected female lung tumors suggested that the involvement of HPV infection in lung tumorigenesis may, at least in part, be mediated through FHIT LOH.

Acid Anhydride Hydrolases↗

PubMed2005

Colorectal mesenchymal tumor: a clinicopathologic study of 25 cases.

BACKGROUND: It is important to distinguish gastrointestinal stromal tumors (GISTs) from other gastrointestinal mesenchymal tumors (GIMTs), because of the malignant potential of GISTs and the availability of molecular targeted therapy. GISTs represent the most common subgroup of GIMTs, and rarely occur in the colon and rectum. The first objective of our retrospective study was to reclassify colorectal mesenchymal tumors, from files collected over 20 years, to determine if, based on immunohistologic features, the lesions were truly GISTs. The second objective was to identify the relationship between clinicopathologic features and prognostic factors of GISTs in the colon and rectum. METHODS: We evaluated all cases of colorectal mesenchymal tumor identified from the database of the Department of Surgical Pathology at Taichung Veterans General Hospital for the period 1983-2001. For 25 patients, clinical data, and information about tumor characteristics, surgical procedures, and survival outcomes, were obtained and analyzed. Histopathologic evaluations, and appropriate immunohistochemical markers, were used to distinguish between various GIMT subtypes. The relationship between KIT expression and clinicopathologic features was investigated. RESULTS: The following variables were significantly associated with different CD117 results: symptomatic presentation, location, gross features, tumor size, mitotic count, cellularity, and type of surgery. Only 18 tumors were identified as GISTs. For these, the following variables were significantly associated (by univariate analysis) with increased lethality: tumor size (p = 0.049); mitotic count (p = 0.019); nuclear atypia (p = 0.019); and tumor necrosis (p = 0.045). However, only mitotic activity showed a significant difference in the survival analysis (p = 0.0304; log-rank test). CONCLUSION: Two clinicopathologically different categories were identified from our colorectal mesenchymal tumors: intramural GISTs and polypoid submucosal leiomyomas. Our study suggests that GIST is a better categorization than smooth muscle tumor because of the malignant potential. Prognosis is strictly related to the number of mitoses. However, tumor size, nuclear atypia and tumor necrosis are probably also significant predictive factors of lethality. Future studies with DNA analysis and larger patient numbers are essential to evaluate the prognostic significance of our findings.

Adult↗

PubMed2003

Global analysis of dauer gene expression in Caenorhabditis elegans.

The dauer is a developmental stage in C. elegans that exhibits increased longevity, stress resistance, nictation and altered metabolism compared with normal worms. We have used DNA microarrays to profile gene expression differences during the transition from the dauer state to the non-dauer state and after feeding of starved L1 animals, and have identified 1984 genes that show significant expression changes. This analysis includes genes that encode transcription factors and components of signaling pathways that could regulate the entry to and exit from the dauer state, and genes that encode components of metabolic pathways important for dauer survival and longevity. Homologs of C. elegans dauer-enriched genes may be involved in the disease process in parasitic nematodes.

Animals↗

PubMed2003

The use of recombinant activated factor VII to reverse warfarin-induced anticoagulation in patients with hemorrhages in the central nervous system: preliminary findings.

OBJECT: In this report the authors describe the use of the hemostatic agent recombinant activated factor VII (rFVIIa) in the perioperative treatment of hemorrhages in the central nervous system that are associated with warfarin therapy. METHODS: Two patients sustained hemorrhages within the spinal canal, and the other two had acute intracranial subdural hematomas. All patients had normal platelet counts, activated partial thromboplastin times, and fibrinogen levels, and all received fresh frozen plasma in conjunction with rFVIIa. The initial international normalized ratios (INRs) ranged from 1.9 to 5.6. Each dose of rFVIIa was 1200 microg, ranging from 16 to 22 microg/kg of body weight. Two patients received two perioperative doses of rFVIIa; the others required just one dose before surgery. The INR normalized within 2 hours of administration of rFVIIa in all patients. There were no thromboembolic complications, and surgical blood loss was less than 100 ml for all operations. CONCLUSIONS: This clinical experience indicates that rFVIIa may be safe and effective as the initial hemostatic agent for rapid reversal of orally administered anticoagulation medications in patients who require urgent neurosurgical intervention.

Acute Disease↗

PubMed2002

Transcriptional profile of aging in C. elegans.

BACKGROUND: Numerous gerontogene mutants leading to dramatic life extensions have been identified in the nematode Caenorhabditis elegans over the last 20 years. Analysis of these mutants has provided a basis for understanding the mechanisms driving the aging process(es). Several distinct mechanisms including an altered rate of aging, increased resistance to stress, decreased metabolic rate, or alterations in a program causing organismic aging and death have been proposed to underlie these mutants. RESULTS: Whole-genome analysis of gene expression during chronological aging of the worm provides a rich database of age-specific changes in gene expression and represents one way to distinguish among these models. Using a rigorous statistical model with multiple replicates, we find that a relatively small number of genes (only 164) show statistically significant changes in transcript levels as aging occurs (<1% of the genome). Expression of heat shock proteins decreases, while expression of certain transposases increases in older worms, and these findings are consistent with a higher mortality risk due to a failure in homeostenosis and destabilization of the genome in older animals. Finally, a specific subset of genes is coordinately altered both during chronological aging and in the transition from the reproductive form to the dauer, demonstrating a mechanistic overlap in aging between these two processes. CONCLUSIONS: We have performed a whole-genome analysis of changes in gene expression during aging in C. elegans that provides a molecular description of C. elegans senescence.

Aging↗

PubMed2002

Downstream targets of let-60 Ras in Caenorhabditis elegans.

In Caenorhabditis elegans, let-60 Ras controls many cellular processes, such as differentiation of vulval epithelial cells, function of chemosensory neurons, and meiotic progression in the germ line. Although much is known about the let-60 Ras signaling pathway, relatively little is understood about the target genes induced by let-60 Ras signaling that carry out terminal effector functions leading to morphological change. We have used DNA microarrays to identify 708 genes that change expression in response to activated let-60 Ras.

Animals↗

PubMed2002

A high-throughput, nonisotopic, competitive binding assay for kinases using nonselective inhibitor probes (ED-NSIP).

A novel competitive binding assay for protein kinase inhibitors has been developed for high-throughput screening (HTS). Unlike functional kinase assays, which are based on detection of substrate phosphorylation by the enzyme, this novel method directly measures the binding potency of compounds to the kinase ATP binding site through competition with a conjugated binding probe. The binding interaction is coupled to a signal amplification system based on complementation of beta-galactosidase enzyme fragments, a homogeneous, nonisotopic assay technology platform developed by DiscoveRx Corp. In the present study, staurosporine, a potent, nonselective kinase inhibitor, was chemically conjugated to a small fragment of beta-galactosidase (termed ED-SS). This was used as the binding probe to the kinase ATP binding pocket. The binding potencies of several inhibitors with diverse structures were assessed by displacement of ED-SS from the kinase. The assay format was specifically evaluated with GSK3alpha, an enzyme previously screened in a radioactive kinase assay (i.e., measurement of [(33)P]-gamma-ATP incorporation into the kinase peptide substrate). Under optimized assay conditions, nonconjugated staurosporine inhibited ED-SS binding in a concentration-dependent manner with an apparent potency (IC(50)) of 11 nM, which was similar to the IC(50) value determined in a radioactive assay. Furthermore, 9 kinase inhibitors with diverse structures, previously identified from chemical compound library screening, were screened using the competitive binding assay. The potencies in the binding assay were in very good agreement with those obtained previously in the isotopic functional activity assay. The binding assay was adapted for automated HTS using selected compound libraries in a 384-well microtiter plate format. The HTS assay was observed to be highly robust and reproducible (Z' factors > 0.7) with high interassay precision (R(2) > 0.96). Interference of compounds with the beta-galactosidase signal readout was negligible. In conclusion, the DiscoveRx competitive kinase binding assay, termed ED-NSIP trade mark, provides a novel method for screening kinase inhibitors. The format is homogeneous, robust, and amenable to automation. Because there is no requirement for substrate-specific antibodies, the assay is particularly applicable to Ser/Thr kinase assay, in which difficulties in identifying a suitable substrate and antibody preclude development of nonisotopic assays. Although the nonselective kinase inhibitor, staurosporine, was used here, chemically conjugating the ED fragment to other small molecule enzyme inhibitors is also feasible, suggesting that the format is generally applicable to other enzyme systems.

Adenosine Triphosphate↗

PubMed2002

Tidal volume and respiratory timing derived from a portable ventilation monitor.

STUDY OBJECTIVES: To determine the accuracy of a portable magnetometer designed to measure tidal volume (VT), inspiratory time (TI), and expiratory time (TE). PARTICIPANTS: Fourteen healthy subjects. DESIGN: Subjects breathed over a sixfold range of VTs while at rest (sitting and standing) and during treadmill exercise. We then compared VT, TI, and TE measured by magnetometry (VTmag, TImag, and TEmag) with VT, TI, and TE measured by spirometry (VTspiro, TIspiro, and TEspiro, respectively). SETTING: Pulmonary function and exercise physiology laboratories. MEASUREMENTS AND RESULTS: The sternal-umbilical distance and the anteroposterior displacements of the rib cage and abdomen were measured with two pairs of magnetometer coils. VT was calculated from the sum of these three signals, and was simultaneously measured using a spirometer or flow meter. A total of 1,111 breaths were analyzed for the resting condition, and 1,163 breaths were analyzed for the exercise condition. We found that VTmag was highly correlated with VTspiro at rest (R2 = 0.90) and during exercise (R2 = 0.79) for pooled data. The slope of this relationship approached the line of identity. The mean percentage differences between VTmag and VTspiro were 10.1 +/- 6.6% at rest and 13.5 +/- 8.6% with exercise. By Bland-Altman analysis, the mean differences between VTmag and VTspiro were 38 mL at rest with changes in posture, and 182 mL during exercise. TImag and TIspiro values and TEmag and TEspiro values also were highly correlated (R2 = 0.97 and R2 = 0.95, respectively) for pooled data. CONCLUSION: A portable magnetometer system can give useful measures of VT, TI, and TE over a wide range of VTs in sitting, standing, and exercising subjects.

Adult↗