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Biomedical subjects

Y S Ho

Publications and source records attributed to Y S Ho.

At least 109 records · Page 6Linked to original sources

Transgenic mice overexpressing glutathione peroxidase are resistant to myocardial ischemia reperfusion injury.

To test the authors' hypothesis that cellular antioxidant enzymes constitute a cellular defense against acute stress, myocardial ischemia reperfusion injury in transgenic mice overexpressing the cellular glutathione peroxidase (GSHPx-1) was studied. Transgenic mice were generated using the entire mouse GSHPx-1 gene including approximately 2.0 kb 5'flanking sequence. A 400% increase of GSHPx activity was found in the hearts of transgenic mice compared with non-transgenic controls. Isolated perfused hearts were prepared from two groups of mice: transgenic overexpressed; non-transgenic controls. Hearts were perfused by Langendorff mode, and after 10 min of stabilization subjected to 30 min of ischemia followed by 20 min of reperfusion. In addition, a group of hearts were perfused for 50 min without subjecting them to ischemia and reperfusion to demonstrate the stability of heart preparation. Transgenic mouse hearts demonstrated significantly improved recovery of contractile force and the rate of contraction, compared to non-transgenic control mouse hearts. The infarct size was also lower in transgenic mouse hearts compared to those of non-transgenic controls. In concert, following ischemia, release of creatine kinase from the transgenic hearts was significantly lower than the control group. The results of this study indicate that increased GSHPx-1 expression renders the heart more resistant to myocardial ischemia reperfusion injury.

Analysis of Variance↗

Effect of selenium on 1,2-dimethylhydrazine-induced intestinal cancer in rats.

PURPOSE: This study was designed to determine the cancer prevention and therapeutic effects of selenium on rats treated with 1,2-dimethylhydrazine (DMH). METHODS: One hundred sixty Spraque-Dawley male rats were divided into seven groups and received 20 mg/kg/week DMH, subcutaneously for 20 weeks. Two different dosages of selenium (8 and 4 ppm) were administered to the rats through drinking water during DMH treatment (B and C groups) or one month before and during DMH treatment (D and E groups). The rats of Groups A (control group), B, C, D, and E were killed immediately after the last DMH injection. The incidence of intestinal cancer in each group was compared. Eight ppm selenium was also administered to rats after DMH treatment (Group F), and survival times were observed and compared with Group G (treated with DMH only). RESULTS: Rats of Groups B and D received 8 ppm selenium and had a significantly decreased incidence of intestinal cancer (from 65.8 percent (Group A) to 33.3 percent (Group B) and 27.8 percent (Group D); P = 0.0225 and 0.0038). Rats receiving 4 ppm selenium had a relatively decreased incidence of intestinal cancer (from 65.8 percent (Group A) to 44.4 percent (Group C) and 47.1 percent (Group E) but P > 0.05). Survival time of Groups F and G showed no difference. CONCLUSIONS: Eight ppm selenium provided via drinking water has a significant intestinal cancer prevention effect in the presence of a high dose of DMH (20 mg/kg x 20 weeks), and the cancer therapeutic effect of selenium is doubtful in this animal model.

1,2-Dimethylhydrazine↗

Newly established MST-1 tumour cell line and tumour-infiltrating lymphocyte culture from a patient with soft tissue melanoma (clear cell sarcoma) and their potential applications to patient immunotherapy.

The establishment and characterisation of paired autologous tumour cell line (MST-1) and tumour-infiltrating lymphocyte (TIL) culture from a tumour mass of a 14-year-old Taiwanese girl with soft tissue melanoma are described. MST-1 cells grown in vitro were heterogeneous in morphology, ranging from floating round cells, loosely attached round/oval or elongated cells with prominent pseudopod-like processes, to well-attached spindle and elongated dendritic cells without obvious pseudopods. Immunostaining revealed that major melanoma-associated antigens, such as S100 protein, HMB-45, melanotransferrin, chondroitin sulphate proteoglycan, and the gangliosides GD2 and GD3, were consistently expressed by the tumour tissue, severe combined immunodeficiency (SCID) mouse xenograft and derived cell lines. Flow cytometric analysis of the tumour DNA content showed an index of 1.8 relative to normal peripheral blood lymphocyte DNA. Chromosome analysis revealed all cells at a hypotetraploid level with several clonal chromosome aberrations, including deletions at 10p and 12q, an addition at 12q, translocations t(1;14) and t(5;6). Electron microscopy showed melanosome structures. This observation and the expression of the major melanoma-associated antigens were all indicative of the melanocytic origin of MST-1 tumour. Interleukin-2 (IL-2) expanded TILs had the predominant CD8+ phenotype and the capacity to lyse cells of the cultured autologous tumour. The availability of the soft tissue melanoma cell line, the SCID mouse xenograft tumour system as well as autologous TILs described herein would provide useful materials for identifying T-cell-defined antigens as well as a model system for devising individualised cancer biotherapeutic strategies. This cell line can also be used for further studies aimed at uncovering the histogenesis of this rare cancer.

Adolescent↗

Primary cardiac chondrosarcoma.

A case of primary cardiac chondrosarcoma in a 41-year-old woman who presented with cardiac tamponade and cardiac intracavitary obstruction is described. The tumor originated from the right atrium and invaded the adjacent right ventricular wall and interatrial septum. Primary cardiac chondrosarcoma is extremely rare, and its clinical, computed tomographic, echocardiographic, and magnetic resonance imaging findings are described.

Adult↗

Clinical presentations and treatment for 74 occult thyroid carcinoma. Comparison with nonoccult thyroid carcinoma in Taiwan.

There is limited clinical information of Chinese patients with occult well-differentiated thyroid cancer (OTC). The purposes of this study were to elucidate the clinical presentations and results of treatment in the patients with OTC in Taiwan. The data of 568 patients with pathologically verified papillary and follicular thyroid carcinomas who received primary treatment in Chang Gung Memorial Hospital were retrospectively reviewed. Seventy-four of 568 patients with well-differentiated thyroid carcinoma were OTC; those included 71 papillary thyroid carcinomas and three follicular carcinomas. Among the 74 OTC patients, five cases (6.8%) presented with distant metastases, but 41 cases (10.1%) were found with distant metastases in 416 nonoccult thyroid cancer (NOTC) (p = 0.509). In the five OTC with distant metastases, there were three papillary carcinomas and two follicular carcinomas. Only one case (1.4%) died of distant metastasis of the occult papillary thyroid carcinoma versus 20 cases out of the total 568 (4.1%) well-differentiated thyroid carcinomas. After statistical analysis, there were no differences between the survival rates of OTC and NOTC patients. In the present study, 1 month postoperative serum thyroglobulin level could be used as prognostic factor in both OTC and NOTC patients. Only 54.17% of OTC patients were diagnosed as thyroid cancer by thyroid ultrasonography with the fine needle aspiration cytology. In conclusion, most OTC had relatively benign clinical courses, but distant metastases may result in mortality still observed. Therefore, OTC should be treated as NOTC, since relatively high rate of distant metastases were found in the patients with OTC.

Adenocarcinoma, Follicular↗

Antioxidant enzyme expression in rat lungs during hyperoxia.

To understand the molecular mechanisms that upregulate the activities of pulmonary antioxidant enzymes in adult rats during exposure to 85% oxygen, the relative contents of corresponding mRNA in normal and hyperoxic lungs were determined. Hyperoxic exposure drastically induced the expression of lung manganese-containing superoxide dismutase (MnSOD) mRNA. Maximal induction of MnSOD mRNA occurred at days 3 and 5 of exposure to hyperoxia, reaching a 600 and a 340% increase over the levels of air-exposed rats, respectively. In addition, hyperoxia induced lung mRNA for glucose-6-phosphate dehydrogenase, glutathione peroxidase, glyceraldehyde-3-phosphate dehydrogenase, alpha-tubulin, and gamma-actin to different extends at various days of exposure. Hyperoxia had little or no effect on the levels of mRNA for copper/zinc-containing superoxide dismutase (CuZnSOD), catalase, heat shock protein (HSP70), and creatine kinase. Nuclear run-on experiments showed that the transcriptional rate of the MnSOD gene is enhanced in hyperoxic rat lungs by approximately 400% at day 3 of exposure compared with that of controls. The specific activities of CuZnSOD and MnSOD in these lung samples per unit of lung protein or DNA were also determined. The activity of CuZnSOD in hyperoxic lungs was found to be unchanged compared with controls, except a 20% decrease at day 7 of exposure when standardized against protein content of lung homogenate. Changes of CuZnSOD activity were more dramatic in hyperoxic lungs (a 40% increase at days 3, 5, 7, and 14 of exposure) when enzyme activity was normalized using lung DNA content. Surprisingly, no proportional increase of lung MnSOD enzyme activity was observed at days 3 and 5 of oxygen exposure. The increase of MnSOD activity per unit of lung protein also did not parallel the increase in MnSOD protein content at days 5, 7, and 14 of exposure. These data suggest that, in addition to transcriptional activation, translational and/or posttranslational regulation of the MnSOD gene expression may play a critical role in controlling lung MnSOD activity on hyperoxic exposure.

Animals↗

Effects of hypoxia on expression of superoxide dismutases in cultured ATII cells and lung fibroblasts.

This study investigated whether hypoxia affected the expression of mitochondrial manganese-containing superoxide dismutase (Mn-SOD) and the cytosolic copper and zinc-containing superoxide dismutase (Cu,Zn-SOD) in alveolar type II epithelial (ATII) cells and lung fibroblasts. Cells were exposed in vitro to air (controls) or to 2.5% oxygen (hypoxia) for 24 h. Mn-SOD and Cu,Zn-SOD mRNA expression was measured by quantitative reverse transcriptase-polymerase chain reaction. Both Mn-SOD and Cu,Zn-SOD mRNA expression in ATII cells decreased significantly after 1 day in hypoxic conditions. The decrease in Mn-SOD mRNA (-69%) was greater than that in Cu,Zn-SOD mRNA (-48%). ATII cell surfactant protein A transcript expression remained constant. Mn-SOD (-52%) and Cu,Zn-SOD (-54%) mRNA expression decreased similarly in lung fibroblasts cultured during hypoxia. The half-life of the Mn-SOD mRNA measured in lung fibroblasts exposed to air or hypoxia for 24 h decreased significantly from 5.8 +/- 0.1 to 3.8 +/- 0.7 h (-34%). The half-life for the Cu,Zn-SOD decreased significantly from 4.0 +/- 0.3 to 2.4 +/- 0.1 h (-40%). Neither Mn-SOD nor Cu,Zn-SOD protein expression in ATII cells changed significantly during hypoxia. Hypoxia decreases expression of Mn-SOD and Cu,Zn-SOD mRNA in ATII cells and lung fibroblasts in part by decreasing stability of the mRNA transcripts.

Animals↗

Nasopharyngeal Castleman's disease.

A 19-year-old male was admitted to our clinic because of nasal obstruction and intermittent postnasal drip of 3 to 4 years' duration. Physical examination revealed a wide-based, smooth-surfaced nasopharyngeal tumor which was suspected to be a nasopharyngeal angiofibroma after examination of computed tomographic scans and an angiogram. However, after the tumor was removed by surgical excision via a transpalatal approach, the pathologic examination revealed Castleman's disease of the hyaline-vascular type. There was neither evidence of recurrence nor nasal problems at 4 years' follow-up. To our knowledge, Castleman's disease, or angiofollicular lymph node hyperplasia, may present as a local or generalized tumor-like condition, usually in the chest or abdomen, and may involve both the lymph nodes and non-nodal tissues. A review of previous articles reveals that there has not been any report of Castleman's disease found in the nasopharynx. This rare disorder is presented and discussed.

Adult↗

Prognostic evaluation of DNA flow cytometric and histopathologic parameters of colorectal cancer.

BACKGROUND: The clinical value of DNA flow cytometry of colorectal cancer is unclear. The purpose of this retrospective study was to evaluate the relationship between tumor flow cytometry, histopathologic parameters, and survival. METHODS: Flow cytometry was performed on paraffin embedded specimens from 653 patients who had surgery from 1980 to 1983. RESULTS: Aneuploidy was associated with distal tumor, perineural invasion, desmoplastic reaction, and failure to secrete mucin. TNM Stage I tumors were more frequently diploid than were more advanced tumors (71% vs. 41%). An abnormal DNA content had a marginal impact on survival as evaluated by univariate analysis (69% vs. 61% 10-year survival rate, P = 0.06). Multivariate analysis revealed that significant predictors of outcome were lymph node metastasis (95% confidence interval of relative risks of death from recurrent disease, 1.50-2.92), rectal cancer (1.22-2.19), absence of lymphocytic infiltration (1.20-2.17), invasion through bowel wall (1.17-3.13), lymphatic vessel invasion outside bowel wall (1.05-2.69), perineural invasion (1.15-3.19), and male gender (1.00-1.79). CONCLUSIONS: These findings suggest that ploidy is associated with some histopathologic parameters, but flow cytometry does not correlate with long term survival of patients with colorectal carcinoma.

Adult↗

Preferential promutagenic lesions at exons 7-8 of human p53 genomic DNA induced by the direct-acting hepatocarcinogens N-nitroso-2-acetylaminofluorene and N-acetoxy-2-acetylaminofluorene.

DNA polymerase fingerprint analysis (DPFA) was employed for identifying DNA-carcinogen adduct formation in the human p53 and lac gene sequence. Two 'hot regions' at codons 223-250 and 257-283 of the p53 gene were easily attacked by nitroso-2-acetylaminofluorene or acetoxy-2-acetylaminofluorene. However, the promutational lesions in lac gene were rather randomly distributed. The chemical treated plasmid (pUC 19) which contains lac gene were transfected into Escherichia coli JM109 cells and the induced lac gene mutants were selected with X-Gal plate as indicated by the appearance of white colonies. No mutational hot regions were found in the lac gene.

2-Acetylaminofluorene↗

Isolation and molecular cloning of human sorcin a calcium-binding protein in vincristine-resistant HOB1 lymphoma cells.

A vincristine-resistant lymphoma cell line (HOB1/VCR1.0) that is resistant to 1.0 microM of vincristine has been established from a human immunoblastic B lymphoma cell line, HOB1. HOB1/VCR1.0 cells demonstrated the typical multidrug resistant phenotypes. Using two-dimensional gel electrophoresis, we discovered one protein with a molecular mass of 22 kDa and pI 5.7 that was overexpressed in HOB1/VCR1.0 cells. This protein was purified to the degree of apparent homogeneity by preparative isoelectric focusing and sodium dodecylsulfate-polyacrylamide gel electrophoresis. The identification of this protein with sorcin was revealed by comparing the internal amino acid sequence of three Lys-C digested peptides from the purified protein with the sequence previously determined for hamster sorcin. The complete primary structure of the human sorcin was deduced from nucleotide sequence analysis of its cDNA clones. It is composed of 198 amino acid residues with a calculated molecular weight of 21,676, and its sequence is highly similar to that of hamster sorcin (95%). Direct-binding assay with calcium showed that human sorcin is a calcium-binding protein with four 'E-F hand' structures typical of calcium-binding sites. Like the sorcin of hamster, two of the calcium-binding sites of human sorcin contain putative recognition sites for cAMP-dependent protein kinase. Southern and Northern blot analyses showed that the human sorcin gene was greatly amplified and overexpressed in resistant HOB1/VCR1.0 cells but not detected in the parental HOB1 cells. The overproduction of this protein in resistant cells implies that sorcin plays a role in expression of the resistant phenotype.

Amino Acid Sequence↗

Overexpression of cellular activity and protein level of protein kinase FA/GSK-3 alpha correlates with human thyroid tumor cell dedifferentiation.

Computer analysis of protein phosphorylation sites sequence revealed that transcriptional factors and viral oncoproteins are prime targets for regulation of proline-directed protein phosphorylation, suggesting an association of the proline-directed protein kinase (PDPK) family with neoplastic transformation and tumorigenesis. In this report, an immunoprecipitate activity assay of protein kinase FA/glycogen synthase kinase-3 alpha (kinase FA/GSK-3 alpha) (a member of the PDPK family) has been optimized for human thyroid tissue and used to demonstrate for the first time significantly increased (P < 0.001) activity in thyroid carcinoma (24.2 +/- 2.8 units/mg of protein) (n = 7), thyroid adenoma (14.5 +/- 2.2 units/mg of protein) (n = 6), and thyroid hyperplasia (8.0 +/- 2.4 units/mg of protein) (n = 5) when compared to five normal controls (4.1 +/- 1.8 units/mg of protein). Immunoblotting analysis further revealed that increased activity of kinase FA/GSK-3 alpha in thyroid tumor cells is due to overexpression of the protein synthesis of the enzyme. Taken together, the results provide initial evidence that overexpression of protein level and cellular activity of kinase FA/GSK-3 alpha is involved in human thyroid tumor cell dedifferentiation, supporting an association of PDPK with neoplastic transformation and tumorigenesis. Since kinase FA/GSK-3 alpha may function as a possible regulator of transcription factors/protooncogenes, kinase FA/GSK-3 alpha may therefore play an important role in thyroid cell carcinogenesis, especially in its differentiation.

Adenoma↗

Association of protein kinase FA/GSK-3alpha (a proline-directed kinase and a regulator of protooncogenes) with human cervical carcinoma dedifferentiation/progression.

Computer analysis of protein phosphorylation-sites sequence revealed that most transcriptional factors and viral oncoproteins are prime targets for regulation of proline-directed protein phosphorylation, suggesting an association of proline-directed protein kinase (PDPK) family with neoplastic transformation and tumorigenesis. In this report, an immunoprecipitate activity assay of protein kinase FA/glycogen synthase kinase-3alpha (kinase FA/GSK-3alpha) (a particular member of PDPK family) has been optimized for human cervical tissue and used to demonstrate for the first time significantly increased (P < 0.001) activity in poorly differentiated cervical carcinoma (82.8 +/- 6.6 U/mg of protein), moderately differentiated carcinoma (36.2 +/- 3.4 U/mg of protein), and well-differentiated carcinoma (18.3 +/- 2.4 U/mg of protein) from 36 human cervical carcinoma samples when compared to 12 normal controls (4.9 +/- 0.6 U/mg of protein). Immunoblotting analysis further revealed that increased activity of kinase FA/GSK-3alpha in cervical carcinoma is due to overexpression of protein synthesis of the kinase. Taken together, the results provide initial evidence that overexpression of protein synthesis and cellular activity of kinase FA/GSK-3alpha may be involved in human cervical carcinoma dedifferentiation/progression, supporting an association of proline-directed protein kinase with neoplastic transformation and tumorigenesis. Since protein kinase FA/GSK-3alpha may function as a possible regulator of transcription factors/proto-oncogenes, the results further suggest that kinase FA/GSK-3alpha may play a potential role in human cervical carcinogenesis, especially in its dedifferentiation and progression.

Amino Acid Sequence↗

p53 gene mutational spectra in hepatocellular carcinomas induced by 2-acetylaminofluorene and N-nitroso-2-acetylaminofluorene in rats.

In this study, the mutation frequencies of the p53 gene in rat hepatocellular carcinomas (HCCs) induced by N-nitroso-2-acetylaminofluorene (NO-AAF) and 2-acetylaminofluorene (AAF) were 19.23% (20 of 104) and 31.1% (33 of 106), respectively. Four noteworthy features of the mutation spectrums of the p53 gene in HCCs induced by both NO-AAF and AAF were observed: (i) There was preferential clustering of mutations at exons 5-8 in both the NO-AAF or AAF groups. (ii) Nearly all the mutations (98%) induced by NO-AAF and AAF were point mutations. (iii) A high frequency of the p53 mutations were transition mutations, and the ratios of transition to transversion in the NO-AAF and the AAF group were 13:6 and 21:12, respectively. Almost all the mutations were G-->A transitions and guanosine was the major target base. (iv) The frequency and base location of p53 mutations were significantly associated with cancer cell differentiation. In poorly differentiated HCCs (58 individual tumor samples), mutations were detected in 24 of 58 samples (41.1%) and clustered mostly in exons 7 and 8 (19 of 24 samples), whereas in well-differentiated HCCs (105 individual tumor samples), the incidence of mutations was low (one of 10 in the AAF group, 17 of 95 in the NO-AAF group), and the mutations were located in exon 5 (11 of 18). The biological significance of these different mutational spectra among p53 genes deserves further investigation.

2-Acetylaminofluorene↗

Combination chemotherapy with carmustine and cisplatin before, during, and after radiotherapy for adult malignant gliomas.

Twenty-two patients, aged 16 to 67, who had malignant gliomas after surgical resection were treated with carmustine and cisplatin intravenous infusion before, during, and after radiotherapy. All patients had subtotal or total resection, or biopsy as the initial procedure. Twenty-one patients who had at least 2 cycles of chemotherapy and finished the whole course of radiotherapy were considered to be evaluable for responses. Among them, 5 had glioblastoma multiforme, 16 had anaplastic astrocytoma. The median time to tumor progression was 35 weeks (range 12-130 weeks) and median survival time was 66 weeks (range 10-156 weeks). Early progression occurred more frequently in patients with biopsy only and subtotal resection, and in patients with glioblastoma than in those with anaplastic astrocytoma. This combined modality treatment program was associated with reversible hematologic toxicity which was severe in 2 patients, and with ototoxicity in 1 patient, nephrotoxicity in 2 patients. Combination of carmustine and cisplatin with cranial irradiation for malignant gliomas is moderately toxic and appears to offer no obvious survival advantage compared with radiation therapy plus BCNU alone.

Adolescent↗

Oxidative modification of DNA bases in rat liver and lung during chemical carcinogenesis and aging.

The extent of DNA modification in cancerous rat live and lung tissues was investigated and compared to their respective normal tissues. Liver tumors were induced by 2-fluorenylacetamide (2-FAA) or N-nitroso-N-2-fluorenylacetamide (N-NO-2-FAA), and lung tumors were induced by sodium nitrite plus trimethylamine. In the DNA samples isolated from these tissues, two pyrimidine-derived and four purine-derived modified DNA bases were identified and quantified by gas chromatography/mass spectrometry with selected-ion monitoring. These compounds were characterized as 5-hydroxyuracil (5-OHUra), thymine glycol (TG), 4,6-diamino-5-formamidopyrimidine (FapyAde), 2,6-diamino-4-hydroxy-5- formamidopyrimidine (FapyGua), 8-hydroxyadenine (8-OHAde), and 8-hydroxyguanine (8-OHGua). Elevated amounts of modified DNA bases were found in most cancerous tissues when compared to the controls. Chemicals used for tumor induction were responsible for inducing DNA lesions that could be promutagenic in vivo and could lead to various types of mutations. When endogenous oxidative damage to DNA during aging was examined, a roughly 2-fold increase of thymine glycol, 8-OHAde and 8-OHGua was found in aged (12 months) rat liver tissues compared to young tissues (1 month). The same results were also found in lung tissues, except that the amount of thymine glycol exhibited more than a 10-fold increase in aged tissues when compared to young tissues. The association of the modified bases with the processes of aging and carcinogenesis deserves further investigation.

2-Acetylaminofluorene↗

Adriamycin-inducible proteins associated with drug sensitivity in resistant immunoblastic B lymphoma cells.

We have previously established an immunoblastic B lymphoma cell line, designated HOB1. This cell line is hypersensitive to a wide spectrum of chemotherapeutic agents. Two co-regulated polypeptides around 64 kDa (termed p64) were induced 10-30-fold in response to adriamycin and some other drugs at the IC50 (the concentration inhibiting cell growth by 50%). These inducible proteins are localized as monomeric forms in the cytosolic fraction, with isoelectric points of pH = 6.2 (major protein) and pH = 7.0 (minor protein). An adriamycin-resistant cell line was established from HOB1 cells. The p64 inducibility was dramatically reduced in resistant HOB1 cells or unrelated cell lines which show phenotypic resistance to adriamycin toxicity. The loss of p64 inducibility in resistant cells is not due to a failure of cells to take up adriamycin since drug accumulation kinetics remained the same as in the parental cells.

Antibodies, Neoplasm↗