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Biomedical subjects

T S Wang

Publications and source records attributed to T S Wang.

At least 37 records · Page 2Linked to original sources
PubMed1999

The birhombic transposition flap for soft tissue reconstruction.

BACKGROUND: Soft tissue reconstruction requires a thorough understanding of both anatomy and tissue movement. Flaps and grafts should be considered when simpler closure methods result in excessive tension or distortion of surrounding structures. OBJECTIVE: We describe our experience with the birhombic transposition flap. METHODS: The birhombic flap was used to repair 19 surgical defects after excision of skin cancer. RESULTS: The average defect size was 3.0 x 2.4 cm with the 19 wounds located on the nose (6), forearm (5), hand (4), forehead/temple (3), and preauricular cheek (1). No cases of excessive tension, infection, or flap necrosis occurred. CONCLUSION: Conceptualization of a larger defect into multiple smaller defects may be useful to facilitate closure of each smaller defect in an easier fashion. Our series demonstrates the usefulness of this concept with the birhombic transposition flap repair.

Humans↗
PubMed1999

Isolated extragenital bowenoid papulosis of the neck.

We report a case of extragenital bowenoid papulosis (BP) in a healthy immunocompetent 42-year-old man. The lesions occurred on the anterolateral aspects of the neck and were not associated with genital, oral, or periungual lesions. Lesional skin tested positive with the Digene hybrid capture system cocktail assay that identifies infection with a mixture of high to intermediate oncogenic human papillomavirus (HPV) types, including types 16, 18, 31, 33, 35, 45, 51, 52, and 56. This cocktail assay identifies infection with HPV types typically associated with high-grade squamous intraepithelial lesions and invasive carcinoma. This case represents the sixth case of isolated cutaneous BP occurring a significant distance from the genital region.

Adult↗
PubMed1999

Mutator phenotype induced by aberrant replication.

We have identified thermosensitive mutants of five Schizosaccharomyces pombe replication proteins that have a mutator phenotype at their semipermissive temperatures. Allele-specific mutants of DNA polymerase delta (poldelta) and mutants of Polalpha, two Poldelta subunits, and ligase exhibited increased rates of deletion of sequences flanked by short direct repeats. Deletion of rad2(+), which encodes a nuclease involved in processing Okazaki fragments, caused an increased rate of duplication of sequences flanked by short direct repeats. The deletion mutation rates of all the thermosensitive replication mutators decreased in a rad2Delta background, suggesting that deletion formation requires Rad2 function. The duplication mutation rate of rad2Delta was also reduced in a thermosensitive polymerase background, but not in a ligase mutator background, which suggests that formation of duplication mutations requires normal DNA polymerization. Thus, although the deletion and duplication mutator phenotypes are distinct, their mutational mechanisms are interdependent. The deletion and duplication replication mutators all exhibited decreased viability in combination with deletion of a checkpoint Rad protein, Rad26. Interestingly, deletion of Cds1, a protein kinase functioning in a checkpoint Rad-mediated reversible S-phase arrest pathway, decreased the viability and exacerbated the mutation rate only in the thermosensitive deletion replication mutators but had no effect on rad2Delta. These findings suggest that aberrant replication caused by allele-specific mutations of these replication proteins can accumulate potentially mutagenic DNA structures. The checkpoint Rad-mediated pathways monitor and signal the aberrant replication in both the deletion and duplication mutators, while Cds1 mediates recovery from aberrant replication and prevents formation of deletion mutations specifically in the thermosensitive deletion replication mutators.

Alleles↗
PubMed1999

Tinospora tuberculata suppresses nitric oxide synthesis in mouse macrophages.

We have obtained evidence that co-incubation of thioglycollate-elicited peritoneal macrophages with an aqueous extract of Tinospora tuberculata inhibits lipopolysaccharide-stimulated excessive production of nitric oxide (NO) in vitro. This effect is concentration-dependent and appears to involve suppression of both inducible nitric oxide synthase (iNOS) activity and NADPH-diaphorase activity, thus altering NO production. As NO is one of the critical mediators in various disorders and iNOS inhibitors may have therapeutic potential, these results may explain some aspects of the multifunctional properties of Tinospora tuberculata, which has been used in various folk remedies in southeast Asia and China.

Animals↗
PubMed1999

Semiautomated typing of human papillomaviruses by restriction fragment length polymorphism analysis of fluorescence-labeled PCR fragments.

A simplified version of a PCR-based reductional restriction fragment length polymorphism (rRFLP) approach for typing of human papillomaviruses (HPVs) is described previously [Wang et al., 1997]. It is achieved by the use of a biotin-labeled primer in PCR which, on restriction digestion and staining, is associated with only a single restriction fragment. In this report, we describe a further development of the rRFLP approach with the use of a fluorescence-labeled primer in PCR and fragment detection by laser scanning in an automatic sequencer. HPV typing is achieved by computer-assisted matching of the fluorescence-labeled rRFLP patterns with a database of rRFLP patterns of all known anogenital HPV types. On analysis of the typing of 133 HPV-positive cases using this procedure, 20 different HPV types were detected in exfoliated cervical cells in PAP smear samples derived from Taiwanese women. The results indicate the existence of a heterogeneous population of HPV types in Taiwan. Although most cases were associated with the more common HPV types, a significant fraction (about 20%) of the HPV types detected was related to the less common genotypes, which are often not included in commercial kits available for HPV typing. The results indicate the importance of covering as many HPV types as possible in clinical HPV genotyping protocols.

Cervix Uteri↗
PubMed1999

[Purity analysis of cephalosporins with capillary zone electrophoresis].

A capillary zone electrophoresis method is proposed for the purity determination of nine cephalosporin drugs. A background electrolyte comprising of either 20 mmol/L pH 9.20 borate buffer or 20 mmol/L pH 6.86 phosphate buffer was used for most drugs studied except for cefaloridine which formed neutral molecules at these pH values. For it 50 mmol/L pH 2.05 phosphate buffer was used instead. Internal normalization method was employed for quantitation. The method is simple, rapid and versatile. Analysis was completed within 8 min. The merits and limitations of the method were also discussed.

Cefazolin↗
PubMed1998

Mutant PCNA alleles are associated with cdc phenotypes and sensitivity to DNA damage in fission yeast.

Twenty-eight site-directed mutations were introduced into the fission yeast gene (pcn1+) that encodes proliferating cell nuclear antigen (PCNA) and their in vivo effects analyzed in a strain with a null pcn1 background. Mutants defective in enhancing processivity of DNA polymerase delta have previously been identified. In this study, we assessed all of the mutants for their sensitivities to temperature, hydroxyurea, UV irradiation and methyl methanesulfonate (MMS), and specific mutants were also tested for sensitivity to gamma irradiation. One cold-sensitive allele, pcn1-3, was characterized in detail. This mutant had a recessive cold-sensitive cdc phenotype and showed sensitivity to hydroxyurea, UV, and gamma irradiation. At the non-permissive temperature pcn1-3 protein was able to form homotrimers in solution and showed increased stimulation of both synthetic activity and processivity of DNA polymerase delta relative to the wild-type Pcn1+ protein. Epistasis analyses indicated that pcn1-3 is defective in the repair pathway involving rad2+ but not defective in the classical nucleotide excision repair pathway involving rad13+. Furthermore, pcn1-3 is either synthetically or conditionally lethal in null checkpoint rad backgrounds and displays a mitotic catastrophe phenotype in these backgrounds. A model for how pcn1-3 defects may affect DNA repair and replication is presented.

Alleles↗
PubMed1998

In vivo biodistribution of a radiotracer for imaging serotonin-1A receptor sites with PET:[11C]LY274601.

LY274601 [R-(+)8-thiomethyl-2-(di-n-propyl-amino)tetralin], a full agonist of the 5-HT1A receptor with high affinity and selectivity, was labeled with 11C and 3H, and its in vivo behavior was studied to evaluate [11C]LY274601 as a PET radiotracer for imaging 5-HT1A receptor sites in living brain. Following intravenous tail injection into mice, [11C]LY274601 showed high blood-brain barrier permeability and accumulated in regions known to have high densities of 5-HT1A receptor sites such as the brain stem including the raphe nuclei. The binding of the radiotracer in target tissues is blocked by pre-injection of the 5-HT1A receptor selective ligand 8-OH-DPAT (1 mg/kg, s.c.), suggesting that the binding is specific to 5-HT1A receptor sites. Using ex vivo autoradiography, the target tissues such as hippocampus CA1-4 fields, piriform cortex, dorsal raphe nucleus and lateral septum were visualized as hot spots. These tissues were observed to have binding 2-2.7 times greater than the cerebellum. The distribution of the radiotracer agrees well with the distribution of 5-HT1A receptors revealed by in vitro autoradiography with [3H]8-OH-DPAT. However, the radiotracer was metabolized quickly and cleared from target tissues with a half life of approximately 15 min. [11C]LY274601 showed high non-specific binding in regions with low number of 5-HT1A receptor sites such as cerebellum.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1998

A simple method of preparation for [123I]-(S)-(-)-IBZM.

Sterile, apyrogenic [123I]IBZM was prepared in a sealed, capped 'V' vial, followed by SEP-PAK C-18 cartridge purification, and then was placed under sealed vial condensation. The quantity of BZM present in the final product ranged from 3.3-5.9 micrograms, as measured by a UV spectrophotometer at 254 and 308 nm. Animal biodistribution studies revealed that the [123I]IBZM prepared by this method which contained 5.9 micrograms of BZM, compared to the standard preparation method containing 0 microgram of BZM, resulted in identical brain uptakes at 15, 30, 60, and 120 min post-injection. The in vitro and in vivo studies demonstrated that a small amount of BZM presence in the final product did not affect the radiochemical purity, nor the D2 receptor binding capacity in the rat brain of [123I]IBZM. The preparation time can be shortened to 1.5 h compared with at least 2-4 h needed for the standard method of preparation. This factor may be important in routine clinical application.

Animals↗
PubMed1998

Two pimarane diterpenoids from Ephemerantha lonchophylla and their evaluation as modulators of the multidrug resistance phenotype.

Two new pimarane diterpenoids, lonchophylloids A (1) and B (2), were isolated from the stems of Ephemerantha lonchophylla. The structures of 1 and 2 were established predominantly through the application of extensive 1H-and 13C-NMR, 1D- and 2D-homonuclear and heteronuclear correlation NMR experiments, and X-ray diffraction methods. Consistent with structure--activity predictions, both compounds were capable of sensitizing cells that expressed the multidrug resistance phenotype to the toxicity of the anticancer drug doxorubicin.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Mutational effect of fission yeast polalpha on cell cycle events.

Polalpha is the principal DNA polymerase for initiation of DNA replication and also functions in postinitiation DNA synthesis. In this study, we investigated the cell cycle responses induced by mutations in polalpha+. Germinating spores carrying either a deletion of polalpha+ (polalphaDelta) or a structurally intact but catalytically dead polalpha mutation proceed to inappropriate mitosis with no DNA synthesis. This suggests that the catalytic function, and not the physical presence of Polalpha, is required to generate the signal that prevents the cells from entering mitosis prematurely. Cells with a polalphats allele arrest the cell cycle near the hydroxyurea arrest point, but, surprisingly, polalphats in cdc20 (polepsilon mutant) background arrested with a cdc phenoytpe, not a polalphats-like phenotype. At 25 degrees C, replication perturbation caused by polalphats alleles induces Cds1 kinase activity and requires the checkpoint Rads, Cds1, and Rqh1, but not Chk1, to maintain cell viability. At 36 degrees C, replication disruption caused by polalphats alleles induces the phosphorylation of Chk1; however, mutant cells arrest with heterogeneous cell sizes with a population of the cells entering aberrant mitosis. Together, our results indicate that the initiation DNA structure synthesized by Polalpha is required to bring about the S phase to mitosis checkpoint, whereas replication defects of different severity caused by polalphats mutations induce differential downstream kinase responses.

Amino Acid Sequence↗
PubMed1998

Complete spontaneous regression of pulmonary metastatic melanoma.

BACKGROUND: Complete spontaneous regression of melanoma metastatic to the lungs is a rare event. OBJECTIVE: To report a case of biopsy-proven melanoma metastatic to the lung with complete spontaneous regression. METHODS: Multidisciplinary case report. RESULTS: A 35-year-old white female was diagnosed with metastatic melanoma to the lung. A pleural biopsy confirmed the diagnosis. Partial spontaneous regression was noted by a staging computed tomography scan prior to enrollment in an investigational protocol. Complete spontaneous regression occurred over 5 months without any form of conventional or alternative therapy, and the patient remains disease-free 3 years after diagnosis. CONCLUSIONS: Our case represents the seventh case of complete spontaneous regression of melanoma metastatic to the lung, and the only case with histologic confirmation of both the primary and pulmonary metastatic lesions. The patient was pregnant twice between the time of her initial diagnosis of primary melanoma and pulmonary metastatic disease.

Adult↗
PubMed1998

Cytotoxicities of alkaloids from processed and unprocessed seeds of Strychnos nux-vomica.

AIM: To examine the cytotoxicities of 6 crude Strychnos alkaloid fractions from the seeds of Strychnos nux-vomica unprocessed or processed with various traditional processing methods and 13 pure Strychnos alkaloids from the fractions. METHODS: Using cell culture, their inhibitory effects on Vero cell growth-inhibition assay, and host cell DNA synthesis by [3H]thymidine ([3H]TdR) uptake assay. RESULTS: The IC50 of processed seeds were 155% and 212% of unprocessed ones in cell growth-inhibition assay and in [3H]TdR uptake assay, respectively. The IC50 of 13 compounds were 0.45-0.80 mmol.L-1 and 0.50-12 mmol.L-1, respectively. The processing method with sand bath exhibited a wide safety margin compared with other traditional processing methods or no processing. The isomers of Strychnos alkaloids and their N-oxides showed much lower cytotoxicities among these alkaloids. Isobrucine N-oxide showed the lowest cytotoxicity. The contents of isomers and N-oxides of Strychnos alkaloids were the highest in the sand processing. CONCLUSION: Processing of nux vomica plays a critical role in its toxicity.

Alkaloids↗
PubMed1997

DNA polymerase delta isolated from Schizosaccharomyces pombe contains five subunits.

DNA polymerase delta (pol delta) plays an essential role in DNA replication, repair, and recombination. We have purified pol delta from Schizosaccharomyces pombe more than 10(3)-fold and demonstrated that the polymerase activity of purified S. pombe pol delta is completely dependent on proliferating cell nuclear antigen and replication factor C. SDS/PAGE analysis of the purified fraction indicated that the pol delta complex consists of five subunits that migrate with apparent molecular masses of 125, 55, 54, 42, and 22 kDa. Western blot analysis indicated that the 125, 55, and 54 kDa proteins are the large catalytic subunit (Pol3), Cdc1, and Cdc27, respectively. The identity of the other two subunits, p42 and p22, was determined following proteolytic digestion and sequence analysis of the resulting peptides. The peptide sequences derived from the p22 subunit indicated that this subunit is identical to Cdm1, previously identified as a multicopy suppressor of the temperature-sensitive cdc1-P13 mutant, whereas peptide sequences derived from the p42 subunit were identical to a previously uncharacterized ORF located on S. pombe chromosome 1.

Amino Acid Sequence↗
PubMed1997

Glutathione peroxidase and catalase modulate the genotoxicity of arsenite.

The X-ray hypersensitive Chinese hamster ovary (CHO) cells, xrs-5, are also more sensitive to sodium arsenite in terms of cell growth and micronucleus induction than CHO-K1 cells. Since reactive oxygen species are suggested to be involved in arsenic toxicity, we have measured antioxidant mechanisms in xrs-5 as well as CHO-K1 cells. There were no apparent differences in the activities of superoxide dismutase, glutathione S-transferase, glutathione reductase, and the levels of glutathione between xrs-5 and CHO-K1 cells. However, the activities of glutathione peroxidase and catalase were 5.4- and 5.8-fold lower, respectively, in xrs-5 cells. The addition of catalase or glutathione peroxidase to cultures reduced the arsenite-induced micronuclei in xrs-5 cells. Whereas, simultaneous treatment with mercaptosuccinate, an inhibitor of glutathione peroxidase, and 3-aminotriazole, an inhibitor of catalase, synergistically increased the arsenite-induced micronuclei. These results suggest that both catalase and glutathione peroxidase are involved in defense against arsenite genotoxicity. The xrs-6 cells, another line of x-ray hypersensitive CHO cells, which had 1.6-fold higher catalase activity and 2.5-fold higher glutathione peroxidase activity than xrs-5 cells, were also more sensitive than CHO-K1 cells but were less sensitive than xrs-5 cells to cell growth inhibition of arsenite. Moreover, a 1.6-fold increase of glutathione peroxidase activity by selenite adaptation effectively removed the arsenite-induced micronuclei in CHO-K1 cells. These results suggest that glutathione peroxidase is more important than catalase in defending against arsenite toxicity. Our results also suggest that increasing the intracellular antioxidant level may have preventive or therapeutic effects in arsenic poisoning.

Amitrole↗
PubMed1997

Mucinous carcinoma of the skin.

Primary mucinous carcinoma of the skin is a rare adnexal neoplasm with sweat gland differentiation. We describe a case of primary mucinous carcinoma of the skin and characterize its clinical and histologic features. Mucinous carcinoma can occur in noncutaneous visceral sites and may metastasize to the skin. Thus it is important to exclude the possibility of a noncutaneous visceral primary tumor before diagnosing primary mucinous carcinoma of the skin.

Adenocarcinoma, Mucinous↗
PubMed1997

A novel mutant allele of Schizosaccharomyces pombe rad26 defective in monitoring S-phase progression to prevent premature mitosis.

A semipermissive growth condition was defined for a Schizosaccharomyces pombe strain carrying a thermosensitive allele of DNA polymerase delta (pol delta ts03). Under this condition, DNA polymerase delta is semidisabled and causes a delay in S-phase progression. Using a genetic strategy, we have isolated a panel of mutants that enter premature mitosis when DNA replication is incomplete but which are not defective for arrest in G2/M following DNA damage. We characterized the aya14 mutant, which enters premature mitosis when S phase is arrested by genetic or chemical means. However, this mutant is sensitive to neither UV nor gamma irradiation. Two genomic clones, rad26+ and cds1+, were found to suppress the hydroxyurea sensitivity of the aya14 mutant. Genetic analysis indicates that aya14 is a novel allele of the cell cycle checkpoint gene rad26+, which we have named rad26.a14. cds1+ is a suppressor which suppresses the S-phase feedback control defect of rad26.a14 when S phase is inhibited by either hydroxyurea or cdc22, but it does not suppress the defect when S phase is arrested by a mutant DNA polymerase. Analyses of rad26.a14 in a variety of cdc mutant backgrounds indicate that strains containing rad26.a14 bypass S-phase arrest but not G1 or late S/G2 arrest. A model of how Rad26 monitors S-phase progression to maintain the dependency of cell cycle events and coordinates with other rad/hus checkpoint gene products in responding to radiation damage is proposed.

Alleles↗