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Biomedical subjects

Y C Yang

Publications and source records attributed to Y C Yang.

At least 37 records · Page 2Linked to original sources

Influence of residual stress on bonding strength and fracture of plasma-sprayed hydroxyapatite coatings on Ti-6Al-4V substrate.

Six hydroxyapatite coatings (HACs) were plasma sprayed on Ti-6Al-4V substrates by varying the substrate temperatures and the cooling conditions. This study is aimed not only to measure the residual stress of HACs under various conditions, but also to assess the influence of residual stress in HACs on their bonding strength. The residual stress and bonding strength were measured by XRD "sin2 psi" technique and standard adhesion test (ASTM C-633), respectively. The result of the study clearly established the relationship between bonding strength and residual stress. The arguments leading to the above conclusion were discussed in detail. Fractographic analysis indicated that fracture of the system occurred mainly inside the hydroxyapatite coating under lower residual stress; as residual stress increased, fracture tended to occur more easily along the crucial HA-Ti alloy substrate interface. A mechanism was presented for the relationships between residual stress, fracture behaviour and bonding strength for the plasma-sprayed hydroxyapatite coatings on Ti-6Al-4V substrate.

Alloys↗

Frequent gain of copy number on the long arm of chromosome 3 in human cervical adenocarcinoma.

We analyzed genomic aberrations in 20 cervical adenocarcinomas by comparative genomic hybridization (CGH). Most tissue samples (85%) showed DNA copy number changes; gains were more common than losses. The most consistent region of chromosomal gain was mapped to chromosome arm 3q, found in 70% of the cases, with a minimal common region of 3q28-ter. Other recurrent amplifications of genetic material were detected on 17q (45%), 1p (30%), 1q (25%), and 11q (20%). High-level copy number increases were found in chromosomal regions 3q27-ter and 9pter-13. DNA losses were seldom observed, occurring primarily in underrepresented regions of chromosome arms 4q, 13q, and 18q. The presence of high-risk human papilloma virus genomes in the cervical adenocarcinoma samples was detected in 90% of the cases. However, there was no correlation between human papilloma virus type and the pattern of genomic changes. This study is the first report of CGH analysis in human cervical adenocarcinoma. Among the major genomic alterations, our results demonstrate the importance of DNA copy increases of chromosome arm 3q in the development of cervical adenocarcinoma and identify other amplified chromosomal regions that are also associated with cervical carcinogenesis.

Adenocarcinoma↗

Determinants of visual outcome after pars plana vitrectomy for posteriorly dislocated lens fragments in phacoemulsification.

PURPOSE: To evaluate the visual outcome of patients with posteriorly dislocated lens fragments after phacoemulsification managed with pars plana vitrectomy (PPV) and identify risk factors for poor visual outcome. SETTING: Vitreo-Retinal Service, St. Paul Eye Unit, Liverpool, United Kingdom. METHODS: The medical records of all patients who had PPV for posteriorly dislocated lens fragments after phacoemulsification between March 1993 and August 1998 were retrospectively reviewed. Demographics, preexisting eye conditions, details of the previous cataract surgery, findings at presentation, details of the vitreoretinal procedure, final visual acuity, and complications observed during the follow-up were evaluated. Univariate and multiple regression analyses were used to determine the significance of these clinical variables as determinants of poor visual outcome (visual acuity 6/12 or worse). RESULTS: Of the 106 patients identified, 89 had a full set of data and were included in the study. In 79 patients (89%), PPV was performed from 1 to 357 days (median 15 days) after cataract extraction. In 10 patients (11%), PPV was done on the same day as the cataract surgery. Sixty-two patients (69%) had a final visual acuity of 6/12 or better. Preexisting eye disease (P <.01), PPV delayed for more than 4 weeks (P <.03), occurrence of retinal detachment after vitrectomy (P <.01), and the use of ultrasound (US) fragmentation (P <.01) were statistically significantly correlated with a poor visual outcome. CONCLUSIONS: Posterior dislocated lens fragments after phacoemulsification were safely retrieved using PPV. It appears that intervening early (within 4 weeks) and avoiding the use of US fragmentation are associated with a better visual outcome and reduced rate of postoperative complications.

Aged↗

Metabolic activation of the tumorigenic pyrrolizidine alkaloid, riddelliine, leading to DNA adduct formation in vivo.

Riddelliine is a representative naturally occurring genotoxic pyrrolizidine alkaloid. We have studied the mechanism by which riddelliine induces hepatocellular tumors in vivo. Metabolism of riddelliine by liver microsomes of F344 female rats generated riddelliine N-oxide and dehydroretronecine (DHR) as major metabolites. Metabolism was enhanced when liver microsomes from phenobarbital-treated rats were used. Metabolism in the presence of calf thymus DNA resulted in eight DNA adducts that were identical to those obtained from the reaction of DHR with calf thymus DNA. Two of these adducts were identified as DHR-modified 7-deoxyguanosin-N(2)-yl epimers (DHR-3'-dGMP); the other six were DHR-derived DNA adducts, but their structures were not characterized. A similar DNA adduct profile was detected in the livers of female F344 rats fed riddelliine, and a dose-response relationship was obtained for the level of the total (eight) DHR-derived DNA adducts and the level of the DHR-3'-dGMP adducts. These results suggest that riddelliine induces liver tumors in rats through a genotoxic mechanism and the eight DHR-derived DNA adducts are likely to contribute to liver tumor development.

Animals↗

Tumour necrosis factor-alpha-induced apoptosis in cord blood T lymphocytes: involvement of both tumour necrosis factor receptor types 1 and 2.

Cord blood T cells are much more likely to be induced to apoptosis in vitro than adult T cells. Nevertheless, the expression of Fas is markedly lower on cord blood lymphocytes than on peripheral blood lymphocytes. In the current investigation, we determined the capacity of tumour necrosis factor-alpha (TNF-alpha) to induce apoptosis in human naïve T cells in cord blood, and assessed the roles of two distinct TNF receptors (TNFRs) in mediating death signals. After activation, cord blood T cells were sensitive to TNF-alpha-induced apoptosis, and interleukin 2 (IL-2) could prevent this apoptotic response. Both TNFR1 (p55) and TNFR2 (p75) expressed on activated cord blood T cells were able to transmit apoptotic signals. Moreover, a synergistic effect was observed by a combination of TNFR1- and TNFR2-signals. Additionally, CD4(+) T cells showed higher sensitivity to TNFR-mediated apoptosis than CD8(+) T cells. These data suggest that TNF-alpha probably is a mediator of apoptosis in cord blood T cells in vivo and may contribute to the low incidence of graft-versus-host disease in cord blood transplantation.

Antigens, CD↗

Histologic and immunophenotypic classification of cervical carcinomas by expression of the p53 homologue p63: a study of 250 cases.

Recent studies of the p53 homologue p63 indicate that this gene is preferentially expressed in basal and immature cervical squamous epithelium. This study correlated p63 expression with morphologic phenotype and human papillomavirus (HPV) type in a wide range of cervical neoplasms. Two hundred fifty cases of cervical carcinoma, including squamous cell carcinoma (SCCA; n = 178), adenocarcinoma (ADCA; n = 28), adenosquamous carcinoma (ASCA; n = 8), neuroendocrine carcinoma (NECA; n = 15), and other variant or mixed types (n = 21) were studied. Ninety-seven percent of SCCA, 0% of ADCA, and 0% of SCUC showed strong (>75% v <30%) positivity for p63 (P<.001). p63 sharply distinguished SCCA (p63+) from ADCA (p63-), Large-cell, poorly differentiated carcinomas were distinguished as putative glandular (glassy cell) or squamous (lymphoepithelial-like or spindle cell) types based on p63 staining. Eight (73%) of 11 neuroendocrine tumors tested were chromogranin positive; all showed no or low (<30%) levels of p63 immunostaining. Absence of p63 was also associated with a subset of nonneuroendocrine undifferentiated carcinomas. Transitions from squamous to columnar or undifferentiated morphology coincided with loss of p63 expression. A strong association between HPV 16 and p63 positivity was identified because of the colocalization of both within tumors of squamous phenotype. p63 is a powerful marker for squamous differentiation and, when diffusely expressed, excludes a glandular or neuroendocrine differentiation. p63 may be useful for differentiating pure squamous or glandular from adenosquamous carcinomas, tracking shifts in differentiation within tumors, supporting (by its absence) the diagnosis of neuroendocrine carcinomas, and clarifying the spectrum of poorly differentiated carcinomas lacking either squamous or neuroendocrine differentiation.

Adenocarcinoma↗

Microsatellite alterations in exfoliated cervical epithelia deoxyribonucleic acid as a marker for high-grade dysplasia.

OBJECTIVE: The purpose of this study was to evaluate the feasibility of the use of deoxyribonucleic acid microsatellite alterations in cervical epithelia in the prediction of high-grade dysplasia and to compare it with a strategy based on human papillomavirus testing. STUDY DESIGN: Our prospective study subjects were from a cohort of 498 women with minimally abnormal Papanicolaou test results including atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion who had documented repeated Papanicolaou and human papillomavirus tests. Of these, 52 eligible patients having conizations or hysterectomies as their histologic outcomes were subjected to tests of loss of heterozygosity on a panel of 5 microsatellites (D3S1110, THRB, D3S1228, D6S291, D3S1289) within the deoxyribonucleic acid of exfoliated cervical epithelia. These genetic alterations were analyzed through fluorescence polymerase chain reaction by comparison of allele ratios of exfoliated cells with those of normal control tissue. Predictive values for high-grade cervical dysplasia and cancer between this deoxyribonucleic acid marker and human papillomavirus status were compared. RESULTS: With the use of loss of heterozygosity in at least one locus for predicting high-grade cervical neoplastic lesion, the sensitivity, specificity, positive predictive value, and negative predictive value were 96.7%, 59.1%, 76.3%, and 92.9%, which were superior to those of the human papillomavirus test (80%, 59.1%, 72.7%, and 92.9%). As a triage for atypical squamous cells of undetermined significance, its sensitivity and negative predictive value were up to 100%. CONCLUSION: The promising results on determining microsatellite alteration in dysplastic lesions might imply that it is possible to detect the earliest changes by potential molecular markers with exfoliated cervical epithelial cells.

Adolescent↗

Significantly increased cortisol secretion in normal adrenocortical cells transfected with K-ras mutants derived from human functional adrenocortical tumors.

Our previous study showed that the mutation hotspots of the K-ras proto-oncogene in human functional adrenocortical tumors are in codons 15, 16, 18, and 31, thus differing from the sites in other tumors. In addition, analyzing the K-Ras protein by a recombinant DNA technique showed that the activity of endogenic GTPase and the GTPase-activating protein (GAP)-binding ability were significantly decreased in patients with these tumors. The aim of this study was to understand whether those K-ras mutants, which were found only in human adrenocortical tumors, play an important role in these tumors. Thus, the mutant K-ras cDNA was constructed with mammalian expression vectors and transfected into normal adrenocortical cells. The amount of cortisol secreted by the transfected cells was 20 to 30 times that of normal cells. Furthermore, Northern blot analysis revealed that the expression of the three steroidogenesis-related genes P450(scc) (cholesterol side-chain cleavage enzyme), P450(C17) (17alpha-hydroxylase/17, 20-lyase), and P450(C21) (steroid 21-hydroxylase) gene increased in the transfected cells. The K-ras oncogene significantly increases cortisol secretion by normal adrenocortical cells.

Adrenal Cortex↗

Sex differences of body fat distribution and cardiovascular dysmetabolic factors in old age.

BACKGROUND: The relationship between sexual differences of body fat distribution and cardiovascular dysmetabolic factors in old people is controversial. OBJECTIVES: To use centrality index-derived body fat distribution to clarify its relationship with glucose tolerance status, blood pressure and lipid profile. DESIGN: Cross-sectional survey in a tertiary-care medical centre in Tainan, Taiwan. SUBJECTS: 114 men and 101 women, aged > or = 60 years. METHODS: We measured total % body fat and body fat distribution (reflected as centrality index) by dual energy x-ray absorptiometry, and plasma glucose, glycosylated haemoglobin, blood pressure, total cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol and atherogenic index (total cholesterol/HDL cholesterol). RESULTS: Centrality index showed better linear correlation with cardiovascular dysmetabolic factors than body mass index, total % body fat and waist-to-hip ratio, except in systolic blood pressure. Women had higher total % body fat, but the % abdominal fat and centrality index were both higher in men. Subjects with diabetes mellitus had the highest centrality index compared with those with impaired or normal glucose tolerance. After adjustment for age and total % body fat, men still had higher diastolic blood pressure, triglyceride levels and atherogenic indices, but lower HDL cholesterol levels than women. However, when further adjusted for centrality index, the sex differences in cardiovascular dysmetabolic factors were statistically insignificant. CONCLUSIONS: Centrality index is a useful method for assessing body fat distribution in older people. Body fat distribution is an important factor in sex differences of cardiovascular dysmetabolic factors in old people.

Aged↗

The presence of three isoflavonoid compounds in Psoralea corylifolia.

The optimization of a high-performance liquid chromatographic method to determine three isoflavonoids (daidzein, genistein, and biochanin A) in the fruit of Psoralea corylifolia is developed and validated. Dried psoralea fruit powder is extracted with aqueous methanol followed by the hydrolysis of the analytes' conjugated glycosides with hydrochloric acid. The HPLC assay is performed on a reverse-phase C18 column with gradient elution using acetonitrile and 10% acetic acid as the mobile phase at a flow rate of 0.8 mL/min. Flavone is used as the internal standard and the substances are detected at 260 nm. Calibrations are linear (correlation coefficient > or = 0.995) for all three analytes. The limits of detection are 0.01 microg/mL for daidzein and genistein and 0.1 microg/mL for biochanin A. The overall intra- and interassay precision range from 2.5% to 4.9% and from 0.5% to 4.7%, respectively. The method proved to be sensitive, specific, accurate, and precise for the determination of daidzein, genistein, and biochanin A in Psoralea corylifolia.

Calibration↗

Effect of p53 polymorphism on the susceptibility of cervical cancer.

Using PCR amplification followed by confirmation with BstU I restriction enzyme digestion, the p53 Pro sequence was determined in tissues from 88 normal cervices, in 184 cervical swabs with mildly abnormal Pap smear, in 50 squamous cell cervical carcinoma specimens, and in 30 cervical adenocarcinoma samples. The frequencies for homozygous proline (Pro-72), homozygous arginine (Arg-72), and heterozygous proline/arginine (Pro/Arg-72) were 23% (n = 20), 28% (n = 25), and 49% (n = 43), respectively, in normal cervices; 24% (n = 45), 28% (n = 51), and 48% (n = 88), respectively, in samples with mild dyskaryotic changes in Pap smears; 26% (n = 13), 28% (n = 14), and 46% (n = 23), respectively, in squamous cell carcinomas, and 33.3% (n = 26), 46.2% (n = 36), and 20.5% (n = 16), respectively, in adenocarcinomas. In the present study, we have found that p53 polymorphism may have a role in the development of adenocarcinoma but not squamous cell carcinoma. The arginine-encoding allele may thus be an important factor affecting host susceptibility to the development of adenocarcinoma.

Adenocarcinoma↗

The differential inhibitory effects of genistein on the growth of cervical cancer cells in vitro.

The biological effect of genistein on cervical cancer was studied on two cervical cancer cell lines with different cellular characteristics. Here we report that genistein exhibits inhibitory effects on the growth of HeLa and ME-180 cells. The IC50 was 35 microM and 60 microM for HeLa and ME-180 cells, respectively. ME-180 cells showed obvious G2/M arrest with genistein treatment while most of the HeLa cells were accumulated in S phase. The underlying molecular mechanism was further elucidated by apoptosis analysis and expression levels of cell cycle regulatory proteins. Treatment of the cell lines with genistein also resulted in suppression of invasion through a surrogate membrane in a dose-dependent manner, particularly the HeLa cells. While the underlying mechanism needs to be further studied, the higher suppressive effect on invasion of HeLa cells, an adenocarcinoma cell line, are noteworthy. This in vitro observation may have clinical implication to improve the treatment of cervical adenocarcinoma.

Adenocarcinoma↗

Possible cofactor in cervical carcinogenesis: proliferation index of the transformation zone in cervicitis.

BACKGROUND: Most cervical cancers arise from the transformation zone. Human papillomavirus (HPV) has been identified as playing a central role in cervical carcinogenesis. However, the lengthy period from initial HPV infection through the precancerous stage to cancer lesions implicates that the cofactors involved in the process might be random events. Our study was designed to study the relationship between the cell mitotic index and tissue inflammation of the uterine cervix. The results may help to explain the role of chronic inflammation as a possible cofactor of cervical carcinogenesis. METHODS: Using Ki-67 immunostaining, the proliferation index (PI) was determined in 30 cervices removed in hysterectomies for non-cervical diseases. The chronic cervical inflammation was graded according to quantification of inflammatory cells in adjacent stromal tissue. The relationships of these two parameters within the exocervix, the transformation zone (T-zone) and the endocervix were analyzed and their differences were compared. RESULT: A significant correlation between the microscopic inflammation scale and the PI was found in the T-zone of the cervix (p = 0.034). The PI of the T-zone, exocervix and endocervix were significantly different (p < 0.001) with scores of 66.1 (SD 26.3), 41.6 (SD 23.3) and 7.1 (SD 5.0), respectively. CONCLUSION: The results, based on modern cellular evidence, explain, at least partially the observation that cervical cancer occurs predominantly in the T-zone and suggest that implementation of antibiotic treatment in selected human papillomavirus-infected patients might decrease the development of cervical cancer.

Cell Division↗

p29, a novel GCIP-interacting protein, localizes in the nucleus.

GCIP, a newly identified cyclin D-interacting protein, was found to reduce the phosphorylation of retinoblastoma protein and inhibit E2F1-mediated transcriptional activity. To explore more GCIP interacting proteins, the yeast two-hybrid screening using GCIP as a bait protein was performed. One novel gene, p29, was demonstrated to associate with GCIP in the yeast two-hybrid method and in vitro GST pull-down assay. Multiple tissue Northern blot analysis showed that p29 was abundantly expressed in the heart, skeletal muscle, and kidney relative to other tissues. The transient expression of HA-tagged p29 in HeLa cells localized in the nucleus. Taken together, we have isolated a novel protein, p29, which may be involved in the functional regulation of GCIP.

Amino Acid Sequence↗

MRG1 expression in fibroblasts is regulated by Sp1/Sp3 and an Ets transcription factor.

MRG1 (melanocyte-specific gene 1 (MSG1)-related gene), a ubiquitously expressed transcription factor that interacts with p300/CBP, TATA-binding protein and Lhx2, is the founding member of a new family of transcription factors. Initial characterization of this newly discovered transcription factor has underscored its potential involvement in many important cellular processes through transcriptional modulation. We previously demonstrated that MRG1 can be induced by various biological stimuli (Sun, H. B., Zhu, Y. X., Yin, T., Sledge, G., and Yang, Y. C. (1998) Proc. Natl. Acad. Sci. U. S. A. 95, 13555-13560). As a first step in understanding its role in different biological processes, we investigated mechanisms that regulate transcription of the mouse MRG1 gene in fibroblasts. Transient transfection of Rat1 fibroblast cells with sequential 5'-deletions of mouse MRG1 promoter-luciferase fusion constructs indicated that the -104 to +121 region contains the full promoter activity. Deletion and site-directed mutations within this region revealed that the Ets-1 site at -97 to -94 and the Sp1 site at -51 to -46 are critical for MRG1 expression in fibroblasts. Gel mobility shift and supershift assays performed with Rat1 nuclear extracts identified nucleoprotein complexes binding to the Ets-1 site and the Sp1 site. In Drosophila SL2 cells, which lack the Sp and Ets family of transcription factors, expression of Sp1, Sp3, and Ets-1 or Elf-1 functionally stimulated MRG1 promoter activity in a synergistic manner. These results suggest that multiple transcription factors acting in synergy are responsible for MRG1 expression and the responsiveness of cells to different biological stimuli.

Animals↗

Involvement of the ubiquitin-proteasome pathway in the degradation of nontyrosine kinase-type cytokine receptors of IL-9, IL-2, and erythropoietin.

The ubiquitin-dependent proteasome-mediated (Ub-Pr) degradation pathway has been shown to regulate a large variety of substrates, including nuclear, cytosolic, and membrane proteins. In mammalian systems, polyubiquitin modification has been identified in a number of cell surface receptors for more than a decade; however, its biological significance has remained unclear until recently. For growth factor receptors with intrinsic tyrosine kinase domains, polyubiquitination is believed to trigger the internalization and subsequent degradation via the lysosomal pathway. In this study we provide the first evidence that non-tyrosine kinase-type cytokine surface receptors, IL-9R alpha-chain, IL-2 receptor ss-chain, and erythropoietin receptor, can be polyubiquitinated and degraded by proteasomes. The Ub-Pr pathway regulates both the basal level turnover and the ligand-induced degradation of the receptors. A previously identified putative molecular chaperon, valosin-containing protein, undergoes tyrosine phosphorylation in a cytokine-dependent manner and associates with the receptor complexes following receptor engagement, suggesting that valosin-containing protein may target the ubiquitinated receptors to the proteasome for degradation.

Adenosine Triphosphatases↗

Noncompetitive inhibition of the glycine receptor-mediated current by melatonin in cultured neurons.

The effect of melatonin on the glycine receptor-mediated response was studied in cultured chick spinal cord neurons using the whole-cell voltage-clamp recording technique. Melatonin rapidly and reversibly inhibited the glycine-induced current in a dose-dependent fashion, with an EC(50) of 934 microM and a maximal inhibition of 100%. Furthermore, melatonin noncompetitively inhibited the glycine response by an agonist-independent mechanism that was distinct from that of an open-channel blocker.

Animals↗

14-3-3zeta interacts with the alpha-chain of human interleukin 9 receptor.

Interleukin 9 (IL-9) exerts its pleiotropic effects through the IL-9 receptor (IL-9R) complex, which consists of the IL-9R alpha-chain, which determines the cytokine specificity, and the IL-2 receptor gamma-chain. In the present study we used a modified yeast two-hybrid system to isolate cDNA species encoding proteins that interacted with the intracellular domain of the human IL-9R alpha-chain (hIL-9Ralpha). We have identified 14-3-3zeta as an hIL-9Ralpha-interacting protein. We also mapped residues 518-522 (Arg-Ser(519)-Trp-Thr(521)-Phe) in hIL-9Ralpha and helix I of 14-3-3zeta as being important for interaction. Moreover, peptide competition experi-ments suggested that interaction between hIL-9Ralpha and 14-3-3zeta requires the phosphorylation of Ser(519) or Thr(521). This is the first demonstration that 14-3-3 can interact with a non-tyrosine kinase receptor. The interaction between 14-3-3 and IL-9Ralpha but not IL-4Ralpha also suggests a potential role for 14-3-3 in determining cytokine specificity.

14-3-3 Proteins↗