Search PubMed⌕ Search

Biomedical subjects

T C Wu

Publications and source records attributed to T C Wu.

At least 127 records · Page 7Linked to original sources

Meiosis-induced double-strand break sites determined by yeast chromatin structure.

Double-strand DNA breaks (DSBs) occur at recombination hotspots during Saccharomyces cerevisiae meiosis and are thought to initiate exchange at these loci. Analysis of DSB sites in three regions of the yeast genome indicated that breaks occur at or near many potential transcription promoters and that DSBs initiate most, if not all, meiotic recombination. DSB sites displayed deoxyribonuclease I hypersensitivity in chromatin from mitotic and meiotic cells, and changes in chromatin structure produced parallel changes in the occurrence of DSBs. Thus, features of chromatin structure that are established before meiosis play a role in determining where meiotic recombination events initiate.

Chromatin↗

Low-grade squamous intraepithelial lesions: cytologic predictors of biopsy confirmation.

One hundred and seven smears demonstrating a low-grade squamous intraepithelial lesion (LSIL) were analyzed for features predicting subsequent biopsy confirmation. Twelve (29%) of 41 smears showing few LSIL cells were biopsy confirmed compared to 33 (60%) of 55 containing an intermediate number of LSIL cells and 9 (82%) of 11 displaying many LSIL cells (P < 0.002). Thirty-seven (47%) of 78 smears showing mainly condylomatous atypia (CA), 7 (54%) of 13 revealing predominantly cervical intraepithelial neoplasia 1 (CIN 1), and 10 (63%) of 16 displaying both CA and CIN 1 were histologically confirmed (N.S.). Biopsy confirmation was obtained in 35 (65%) of 54 women whose repeat smears obtained at colposcopy demonstrated SIL compared to four (15%) of 26 patients whose repeat smears were normal or contained atypical squamous cells of undetermined significance (P < 0.001). These results suggest that the number of diagnostic cells in an LSIL smear predicts biopsy confirmation and affirm the validity of combining CA and CIN 1 under the category of LSIL in the Bethesda System.

Adult↗

Expression of activin receptor II and IIB mRNA isoforms in mouse reproductive organs and oocytes.

Activins, the dimeric polypeptides of inhibin beta-subunits, exhibit paracrine effects on cell proliferation, differentiation, and various other cell functions. The complex biological response to activin appears to involve multiple receptors. In the present study, we examined the isoform mRNA expression of both activin receptor type II (ActR-II) and type IIB (ActR-IIB) genes in mouse reproductive organs, cumulus-oocyte complexes (COCs), and ovulated oocytes. Northern blot analyses of female and male reproductive organs with single-stranded ActR-II cDNA probes revealed that mouse ovaries expressed high levels of the 6.0 kilobase (kb) mRNA, whereas the 3.0 kb transcript was the major mRNA species found in the testis. Reverse transcriptase-polymerase chain reaction (RT-PCR) showed that both COCs and oocytes contained ActR-II mRNA. To examine the expression of ActR-IIB gene, primer selection was made outside the two alternative splicing sites in order to amplify the cDNAs of all four distinct receptor isoforms. The results of RT-PCR demonstrated that isoforms IIB2 and IIB4 were the major mRNA species expressed in both female and male gonads and extragonal reproductive tissues. The ovary expressed all four mRNA isoforms, whereas the testes expressed only three isoforms. whereas the testes expressed only three isoforms. Furthermore, COCs and oocytes contained only the ActR-IIB2 isoform. The differential expression of both activin receptor mRNA isoforms in the reproductive organs suggests that distinct alternative splicing mechanisms are involved in activin receptor gene expression in male and female gonads, and that each of the activin receptors may have its own biological function in reproduction.(ABSTRACT TRUNCATED AT 250 WORDS)

Activin Receptors↗

The expression of retinoid X receptor genes is regulated by all-trans- and 9-cis-retinoic acid in F9 teratocarcinoma cells.

Two classes of nuclear receptors for retinoic acid (RA) have been identified--retinoic acid receptor (RAR) and retinoid x receptor (RXR). Previously, we demonstrated that all-trans-retinoic acid (t-RA) differentially self-regulated the expression of RAR alpha, -beta, and -gamma transcripts. In the present study, we examined the effect of t-RA and 9-cis-RA (c-RA) on the expression of RXR genes in F9 cells by Northern blot analyses. The results showed that t-RA increased the levels of both the 5.6-kb RXR alpha and 3.8-kb RXR gamma mRNAs, decreased the amounts of 2.3-kb RXR gamma mRNA, but had no significant effect on the levels of RXR beta mRNA. Addition of a cyclic AMP analog along with t-RA further induced the differentiation of F9 cells to become parietal endodermal cells, but did not change the regulatory patterns of RXR mRNAs. The RNA synthesis inhibitor, actinomycin D, blocked the induction of 5.6-kb RXR alpha and 3.8-kb RXR gamma mRNA by t-RA, suggesting that the regulations at least in part were at the transcriptional levels. The protein synthesis inhibitor, cycloheximide, induced the expression of 5.6-kb RXR alpha mRNA and further enhanced the inductive effect of t-RA. In contrast, cycloheximide prevented the t-RA-regulated expression of both 3.8- and 2.3-kb RXR gamma mRNA, suggesting that ongoing protein synthesis was required for the regulation of RXR gamma gene. In addition, c-RA exerted effects similar to those of t-RA on RXR gene expression. A concentration of 10(-8) M was required for c-RA to regulate the expression of RXR genes, while 10(-9) M of t-RA was effective in regulating RXR genes. Addition of t-RA and c-RA simultaneously had neither synergistic nor additive effects in regulating RXR gene expression. These data suggest that RAR may play an important role in RA-regulated RXR gene expression.

Animals↗

Atypical oral presentation of herpes simplex virus infection in a patient after orthotopic liver transplantation.

An atypical oral presentation of herpes simplex virus infection in a 49-year-old woman after orthotopic liver transplantation is reported. Clinically, the differential diagnosis included chronic hyperplastic candidiasis, nodular leukoplakia of undetermined etiology, and malignant neoplasm. An excisional biopsy revealed herpesvirus infection, and immunoperoxidase staining confirmed herpes simplex virus infection. This report describes the clinical and histologic appearance of these lesions and the course and treatment of the patient.

Diagnosis, Differential↗

Myocarditis and cardiotropic viral infection associated with severe left ventricular dysfunction in late-stage infection with human immunodeficiency virus.

OBJECTIVES: The purpose of this study was to characterize the histologic and immunopathologic results of 37 endomyocardial biopsy samples from patients infected with human immunodeficiency virus type 1 (HIV-1) who were evaluated for unexplained global left ventricular dysfunction. BACKGROUND: Recent studies have identified a growing number of patients infected with HIV-1 who develop unexplained left ventricular dysfunction and congestive heart failure. Myocarditis has been confirmed at autopsy in small numbers of such patients, although a pathogenic opportunistic infectious agent can rarely be identified. METHODS: All patients had moderate to severe global left ventricular hypokinesia on two-dimensional echocardiography. Endomyocardial biopsy samples were evaluated by standard histologic studies, immunoperoxidase staining and in situ hybridization for cytomegalovirus and HIV-1 gene sequences. RESULTS: Twenty-eight patients presented with New York Heart Association functional class III or IV congestive heart failure. Four patients had myocarditis secondary to known etiologies (opportunistic infection n = 2; drug-induced hypersensitivity myocarditis n = 2). Of the remaining 33 samples, 17 (51%) showed histologic evidence of idiopathic active or borderline myocarditis. Immunohistologic findings revealed induced expression of major histocompatibility class I antigen on myocytes and increased numbers of infiltrating CD8+ T lymphocytes. Specific hybridization within myocytes was observed in 5 of 33 samples with the HIV-1 antisense riboprobe and in 16 of 33 samples with the cytomegalovirus immediate early (IE-2) antisense riboprobe. All but one patient with specific myocyte hybridization presented with congestive heart failure; all patients had myocarditis and CD4+ cell counts < 100/mm3. CONCLUSIONS: This study demonstrates that cardiotropic virus infection and myocarditis may be important in the pathogenesis of symptomatic HIV-associated cardiomyopathy.

AIDS-Related Opportunistic Infections↗

Immunology of the human papilloma virus in relation to cancer.

Human papillomaviruses (HPVs) have been associated with benign and malignant epithelial proliferations in either skin or mucosa. Two HPV oncogenic proteins, E6 and E7, are important in the induction and maintenance of cellular transformation and are co-expressed in the majority of HPV-containing carcinomas. Therefore, vaccines targeted to these proteins may provide an opportunity to prevent and treat HPV-associated malignancies. The encouraging results from recent experimental vaccination systems in animal models suggest that continued exploration in these systems might lead to trials on human subjects and might allow us to prevent HPV infection or control its potentially life-threatening consequences.

Animals↗

On the development of antifungal agents: perspective of the U.S. Food and Drug Administration.

As medical advances have prolonged the lives of patients with cancer, recipients of organ transplants, and patients with AIDS, there has been a marked increase in the number of fungal infections. Because of the known toxicity associated with amphotericin B, which has been the mainstay of therapy for systemic fungal infections, there has been a pressing need for regimens that are more effective and less toxic and that are more easily complied with by patients. This article provides a brief overview of the regulatory process of drug approval and discusses issues specific to the design of clinical trials for the treatment of systemic fungal diseases.

Antifungal Agents↗

[Chronic rheumatic cardiopathy in a patient with of hemophilia successfully treated with surgery].

A 52 year-old man, with rheumatic cardiopathy and hemophilia was admitted to the hospital for aortic valve replacement and mitral valve commisurotomy. He had a history of allergic reaction to cryoprecipitate, and to undergo to the cardiac surgery, the ideal level of factor VIII was estimated to be 100%. To reach this level he first received 2,500UI of the factor VIII:C increasing the factor VIII:C level from 20 to 58%. During the surgery he received an additional dose of 1,500UI of factor VIII plus 3,500,000UI of aprotinin (Trasylol), which was started at the beginning of the anaesthesia and maintained during the surgical procedure, increasing the factor VIII level to 220%. The patient was discharged 11 days after the surgery without any hemorrhagic complication.

Aortic Valve Stenosis↗

Allen score in clinical diagnosis of intracranial hemorrhage.

BACKGROUND: Allen score is a validated weighted linear score for clinical distinction between hemorrhagic and ischemic stroke. As the prevalence of hemorrhagic stroke differs between Caucasian and Chinese populations, and the predictive value of any diagnostic score depends greatly on the prevalence of disease being considered, we tried to verify prospectively this score among the Chinese living in Taiwan. METHODS: From 1 April to 31 August 1993, all patients with acute stroke syndrome, who visited the emergency room at Veterans General Hospital-Taichung, were studied prospectively. Clinical features were recorded thoroughly to calculate the Allen score. The diagnosis was all confirmed by computed tomography (CT) of the head. RESULTS: Totally 255 stroke cases were identified. The types of the stroke were cerebral infarction in 186 subjects (73%), cerebral hemorrhage in 64 subjects (25%), and subarachnoid hemorrhage in 5 subjects (2%). Seventy-five cases were excluded because of the lack of clinical details for calculation. Thus, 180 patients were included. When a cut-off of 4 or 24 was taken into account, the sensitivity of Allen score for diagnosing a hemorrhage was 67%, specificity 100%, accuracy 93%, positive predictive value 100%, and negative predictive value 91%. CONCLUSIONS: Although Allen score can be used for epidemiological studies of incidence and outcome in stroke as well as for a first bedside screening to decide the priority of patients for CT, it is not safe enough as a guide for anticoagulant or thrombolytic therapy. Its validity should be verified before use in a given population other than the Caucasian.

Cerebral Hemorrhage↗

Analysis of Epstein-Barr virus-encoded small RNA 1 expression in benign lymphoepithelial salivary gland lesions.

Salivary gland enlargement resulting from benign lymphoepithelial lesions may be seen in patients with Sjögren's syndrome (SS) and in the early stages of human immunodeficiency virus (HIV) infection. Although the pathogenesis of these lesions is thought to differ in SS and HIV infection, Epstein-Barr virus (EBV) has been suggested as a pathogenetic agent in both cases. We have assessed the presence of latent EBV infection in a series of 15 lymphoepithelial salivary gland lesions using RNA-RNA in situ hybridization with digoxigenin-labeled riboprobes complementary to the abundantly-expressed EBV-encoded small RNA 1 (EBER1). Two of four benign lymphoepithelial lesions (BLEL) from patients seropositive for HIV expressed EBER1 in lymphocyte nuclei in a fashion similar to that described previously in HIV-associated persistent generalized lymphadenopathy (PGL). By contrast, EBER1 was not expressed in any of four BLEL from patients with SS, or seven lymphoepithelial cysts (LEC) and BLEL from patients with neither HIV infection nor SS. These data suggest that latent EBV infection does not play a major pathogenetic role in the lymphoepithelial salivary gland lesions associated with SS or those seen in patients without systemic disease. In the case of HIV-associated salivary gland lesions, the data are consistent with earlier proposals that these BLEL result from the involvement of intraparotid lymph nodes by PGL.

Adult↗

Pancreatoblastoma: a case report.

Primary neoplasms of the pancreas are rare in children. One variant of these tumors is pancreatoblastoma, comprising 0.5% of epithelial tumors of the pancreas. It usually affects children at 1-8 years of age, with quite equal sex ratio. The tumor can be found at any site of pancreas, but it most commonly arises in the head of pancreas. Histopathologically, pancreatoblastoma is an encapsulated tumor with distinct organoid structures and sometimes squamoid corpuscles. Acinar cells with zymogen granules are occasionally found. The tumor has favorable prognosis. We present a 14-year-old female who was admitted due to prolonged jaundice for about 2 months. Physical examination revealed pale conjunctiva, yellowish skin color and hepatosplenomegaly. Abdominal sonography and CT scan showed dilated common bile duct and a tumor mass about 2 x 2 cm in dimension located a pancreatic head. She received surgical operation to relieve obstructive jaundice and later Whipple's operation for radical resection. Six months after operation, the patient received the examination of abdominal sonography, CT scan and gallium tumor scan but there was no evidence of local recurrence or distant metastasis. Now the patient is living well for more than one year. Because of its rare occurrence, we demonstrate this case and review the literature.

Adolescent↗

Dexamethasone increases the expression of retinoid X receptor genes in rat hepatoma cell lines.

BACKGROUND: Glucocorticoids and retinoic acid (RA) exert their effects through nuclear receptors; trans-acting factors that regulate the expression of target genes. Both glucocorticoids and retinoic acid have been shown to control hepatocyte phenotype to regulate expression of many liver specific genes such as alpha-fetoprotein and albumin. Two classes of receptors for retinoic acid have been identified, retinoic acid receptor and retinoic x receptor (RXR). RXRs, the receptors for 9-cis-RA (c-RA), are auxiliary factors that form heterodimers with retinoic acid receptors, vitamin D receptors, and thyroid hormone receptors and enhance the binding of the receptors to their cognate responsive elements. Thus, the level of RXR may be a crucial parameter to determine the effects of other hormones. EXPERIMENTAL DESIGN: The current study was designed to analyze the regulation of RXR gene expression by other hormones in hepatoma cells. The effects of c-RA, all-trans-RA, 3,3',5-Triiodo-L-Thyronine, estrogen, and dexamethasone on RXR genes were examined. The expression levels of RXR mRNAs were quantitated by northern hybridization. RESULTS: Dexamethasone, a crucial agent for hepatocyte differentiation, is the only hormone that up-regulates the levels of liver specific RXR alpha mRNA in three phenotypically different rat hepatoma cell lines. In addition, dexamethasone enhances the expression of RXR gamma mRNA in two cell lines but has no effect on RXR beta gene in any cell line. The regulation of RXR alpha gene is time- and dose-dependent and can be blocked by actinomycin D. However, cycloheximide has no effect on the dexamethasone induced RXR alpha gene expression. CONCLUSIONS: This study demonstrates that dexamethasone enhances the expression of RXR alpha gene probably by increasing the transcription of RXR gene and that glucocorticoids may enhance the differentiation effects of c-RA by increasing the levels of the RXRs in hepatoma cells.

Animals↗

A novel M(r) 32,000 nuclear phosphoprotein is selectively expressed in cells competent for self-renewal.

We investigated the association between expression of a novel M(r) 32,000 nuclear phosphoprotein (pp32) and cell proliferation in vivo using the well-characterized physiological model of androgen-dependent regeneration of prostate in orchiectomized rats, pp32 is expressed at high levels in neoplastic cell lines and in certain anatomically defined stem cell compartments of normal human tissues such as intestinal crypt epithelial cells. Immunohistochemistry and in situ hybridization were used to monitor pp32 expression in rat ventral prostatic epithelium following castration and androgen restoration. Castrated rats retained only 6% of prostate wet weight compared to intact controls but were capable of complete gland restoration upon androgen replacement. In intact controls, pp32 expression localized to small acini at the periphery of the gland and to rare basal cells in the central regions. Ten days following castration, there was a 3,5-fold enrichment in the frequency of pp32-positive cells with greater than 56% of remaining epithelial cells expressing pp32 protein. In situ hybridization showed that all remaining epithelial cells contained pp32 mRNA. Upon testosterone replacement, pp32 expression and localization returned to that of intact controls. In order to determine the association between pp32 expression and cell division, DNA synthesis was monitored by bromodeoxyuridine incorporation during prostate involution and regeneration. Bromodeoxyuridine incorporation peaked 3 days after androgen replacement and occurred diffusely throughout the gland. Thus, pp32-positive cells are anatomically distinguishable from the population of terminally differentiating cells undergoing rapid expansion. Preliminary immunohistochemical studies of human prostatic neoplasia demonstrated increased expression of pp32 in human prostatic adenocarcinoma and prostatic intraepithelial neoplasia compared to benign prostatic hypertrophy and normal human prostate. The highest degree of expression occurred in the higher Gleason grades and prostatic intraepithelial neoplasia. This work suggests that pp32 is a nuclear protein which has a selective but presently undefined role in cells competent for self-renewal.

Adenocarcinoma↗

Association of human papillomavirus with nasal neoplasia.

Since HPV-57b has been identified by two different techniques in benign, premalignant, and malignant lesions of the nasal cavity, but not in cases of chronic sinusitis, HPV-57 should be recognised as at least a co-factor in the aetiology of nasal neoplasia. Paraffin sections of 22 histologically confirmed nasal tumours were screened by in-situ hybridisation with riboprobes specific for HPV-57b. Virus was demonstrated in 6 of 7 fungiform papillomas, 6 of 8 inverted papillomas, 1 of 3 inverted papillomas with dysplasia, and 2 of 4 inverted papillomas with carcinoma. The presence of HPV-57b was confirmed with the polymerase chain reaction, which identified an additional 4 positive samples, bringing the total to 86% positive specimens. The results underscore the importance of HPVs in the aetiology of cancers at extragenital sites.

Adolescent↗

Isolation and characterization of a differentiation-dependent gene in the human colonic cell line HT29-18.

The human colonic epithelial cell line HT29, and its clonal derivatives HT29-18 and HT-29-18-C1, differentiate in vitro. Differential screening of a subtraction cDNA library enriched for sequences unique to HT29-18-C1, a highly differentiated subclone of HT29-18, resulted in the isolation of a differentiation-dependent cDNA clone, A4. A full-length clone encoding A4 was obtained and sequenced to its entirety. It is 945 bp in length and contains an open reading frame (ORF) of 456 bp. The amino acid sequence deduced from the ORF reveals a polypeptide of 152 amino acids with a predicted molecular mass of 17,000 Da, a size confirmed by coupled in vitro transcription and translation directed by the full-length A4 cDNA. This polypeptide contains four potential membrane-spanning domains and consensus sequences for N-linked glycosylation as well as phosphorylation sites for protein kinase C and casein kinase II. Comparison of A4 to published DNA and protein sequences revealed no significant homology. Genomic Southern blot analysis suggests that the gene is present in a single copy within the human genome and is conserved in the rat. Northern blot analysis of RNA obtained from various rat tissues shows that the expression of the A4 gene is tissue-selective and is enriched in colonic mucosa. In situ hybridization using human intestinal tissues indicates that the expression of A4 follows a gradient along the crypt-to-villus axis with the most abundant message occurring in the lower half of the crypt. Furthermore, nuclear run-on assays suggest that the induction of the A4 gene during differentiation of HT29-18 is regulated at a transcriptional level. A clone was isolated from a human genomic library and found to contain all five exons of A4. S1 nuclease analysis localized the start site of transcription to an adenosine residue 91 nucleotides upstream from the ATG translation initiation codon. Examination of the immediate sequence 5' to the mRNA start site reveals no TATA box and multiple known enhancer sequences. A4 is also noted to share certain features with the gene encoding the cystic fibrosis transmembrane conductance regulator protein. They include a similar vertical distribution of expression along the intestinal epithelium, enhanced transcription upon differentiation of HT29-18, and multiple shared putative regulatory sequences in the promoter regions. Further characterization of the mechanisms regulating expression of the A4 gene could contribute to the understanding of mammalian intestinal differentiation.

Adenocarcinoma↗