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Biomedical subjects

Y C Wang

Publications and source records attributed to Y C Wang.

At least 91 records · Page 5Linked to original sources

Alpha-1-antichymotrypsin polymorphism in schizophrenia: frequency, age at onset and cognitive function.

A common polymorphism in the alpha1-antichymotrypsin (ACT) gene is associated with Alzheimer's disease. ACT is also a trophic factor in the hippocampal neurons. In order to examine if the ACT gene plays a role in the pathogenesis of schizophrenic disorders, patients (n = 175) and control subjects (n = 114) were genotyped for ACT. We also investigated the relationship between genotypes and patients' cognitive function as evaluated by the Clinical Dementia Rating Scale and the Mini-Mental State Examination. The results demonstrated no association between schizophrenia and/or cognitive deficit in schizophrenia and ACT polymorphism. The data suggest that the ACT gene is not of major importance for the genesis of schizophrenia. Further studies measuring ACT expression as messenger RNA or serum ACT level may help to exclude the role of ACT in the pathogenesis of schizophrenia.

Adult↗

Influence of polymorphism at p53, CYP1A1 and GSTM1 loci on p53 mutation and association of p53 mutation with prognosis in lung cancer.

BACKGROUND: We previously found that the majority (9/11) of p53 tumor suppressor gene mutations in 60 lung cancer patients in Taiwan were small intragenic deletions and nonsense mutations. To gain insights into the possible etiologic factors involved in these mutations and the prognostic significance of p53 gene mutations in lung cancer in Taiwan, we investigated the influence of polymorphism at p53, cytochrome p450 1A1 (CYP1A1) and glutathione S-transferase M1 (GSTM1) loci on p53 gene mutation, and the association of p53 gene mutation with prognosis in these lung cancer patients. METHODS: The polymorphism of these genes was determined by polymerase chain reaction followed by restriction enzyme digestion. The Pearson chi 2 test was used to compare allelic distributions between lung cancer patients and controls. The log-rank test was used to assess the significance of the survival differences between patients with and without p53 mutations. RESULTS: There was no significant difference with respect to the genotype distribution of p53, CYP1A1 and GSTM1 polymorphisms between patients with and without p53 mutations, although a tendency toward increasing frequency of the wild-type homozygote genotype of p53 polymorphism was noted in lung cancer patients containing p53 mutations. We further analyzed the association of p53 mutation with prognoses in lung cancer patients for whom postoperative survival data were available. The estimated median survival times for patients with and without p53 mutation were 25 and 28 months, respectively. There was no significant correlation between p53 mutation and survival. CONCLUSIONS: Our data suggest that p53 gene mutation may not be associated with polymorphisms of p53, CYP1A1 and GSTM1 genes, and it may have no significant effect on the prognosis of lung cancer patients in Taiwan.

Chromosome Mapping↗

[Studies of beef performance traits in Piemontese x Nanyang crossbred using microsatellites as genetic markers].

Five microsatellites, IDVGA-2, IDVGA-27, IDVGA-46, IDVGA-55 and TGLA-44 were associated to beef performance traits of 100 heads of Nanyang cattle, Piemontese and their hybrid cattle using general linear model (GLM) with statistical analysis system (SAS). For microsatellite IDVGA-27, allele 136 had a positive relation with heart girth, height at hip cross and chest depth (body measurements) and loin width (muscularity evaluation); however, allele 142 showed a significant negative correlation with above performance traits. For IDVGA-46, the individuals with allele 205 had a good muscular development at loin width, on the contrary, the allele 211, which was not found in Piemontese cattle, had a negative correlation with shoulder development. Allele 203 (IDVGA-55) had a positive association with body measurement parameters including wither height, body length, height at hip cross and rump width.

Animals↗

[Effects of inhibition of PKC alpha on breast cancer cell phenotype and expressions of cyclin E and CDK2].

Human breast cancer cell line Bcap-37 was stably transfected with the plasmid expressing antisense PKC alpha RNA, and cells, in which PKC alpha was inhibited due to antisense PKC alpha RNA, were isolated. Changes in serum-dependent growth in cell culture, cell clonogenicity in soft agar and growth in nude mice were tested, and the expressions of cyclin E and CDK2 were analyzed. After PKC alpha was inhibited, the cells showed that serum-dependent growth and anchorage-dependent growth enhanced, tumorigenicity in nude mice decreased. The results suggest that less aggressive breast cancer phenotypes may be induced by inhibition of PKC alpha. Levels of cyclin E and CDK2 mRNA in cells with antisense PKC alpha RNA were lower than those in control cell. These indicate that signal transduction system with PKC alpha is closely related to cell cycle control system with cyclin/CDK in the functions.

Animals↗

p53 codon 72 polymorphism in Taiwanese lung cancer patients: association with lung cancer susceptibility and prognosis.

An association between the BstUI (Pro/Pro) genotype of the p53 codon 72 polymorphism and lung cancer has been reported previously (X. Jin et al., Carcinogenesis (Lond.), 16: 2205-2208, 1995). However, the genotype distribution of p53 codon 72 polymorphism as well as the association of this polymorphism with lung cancer risk and prognosis remain undefined in the Taiwanese population. Therefore, we investigated the genotype distribution of p53 codon 72 polymorphism in 194 lung cancer patients and 152 noncancer controls. The genotype frequencies in Taiwanese noncancer controls were 0.56 (Arg) and 0.44 (Pro). Chi2 analysis indicated significant differences in genotype distribution of p53 from other reports in Swedish (P < 0.001), Spanish (P < 0.001), Caucasians in the United States (P = 0.002), and African-Americans (P = 0.027). In addition, our data suggest that the Pro allele of the p53 codon 72 polymorphism increased the risk of lung cancer among female Taiwanese. The female patients with genotype Pro/Pro showed a significantly increased odds ratio (3.14; confidence interval, 1.48-6.64; P = 0.003) of having lung adenocarcinoma, compared with normal controls with the other genotypes. Patients with the Pro/Pro genotype had an odds ratio of 2.63 (confidence interval, 1.22-5.68; P = 0.01) higher than those with the other genotypes to be diagnosed with lung cancer at the early ages. We further investigated the association of p53 codon 72 polymorphism with prognosis in 133 lung cancer patients. Patients with the Pro/Pro genotype tended to have poorer prognosis than those with the Arg/Pro genotype (P = 0.05, by the log-rank test). Our data suggested that p53 codon 72 polymorphism may play a role in cancer susceptibility and prognosis in specific classes of lung cancer patients in Taiwan.

Adenocarcinoma↗

The effect of trigeminal neurotomy on the alteration of local cerebral blood flow of normotensive and hypertensive rats in acute cold stress.

The cold season is reported to have the highest incidence of stroke in a year. Cold is usually detected by cold receptors in the face. The present studies were designed to test whether the trigeminal nerve plays a role in the regulation of local cerebral blood flow (LCBF) in animals exposed to a cold environment. Since hypertension affects the incidence of strokes, both Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were used. Each species was divided into four groups: trigeminal neurotomy (TNx) or control group at room temperature (20 degrees C) or cold environment (5 degrees C), respectively. LCBF in 14 brain structures was measured using the [14C] iodoantipyrine technique and tissue dissecting methods. Our results show that TNx did not alter physiological parameters and LCBFs in WKY and SHR kept either at 20 degrees C or at 5 degrees C for 30 min. However, a transient exposure (30 minutes) to cold caused concomitantly a significant decrease in core body temperature of both WKY and SHR groups (p<0.05, Student's paired t-test) and a significant decrease in LCBFs at the temporal cortex (TC), hypothalamus (HYP) and midbrain (MID) of WKY and TC of SHR (P<0.05, MANOVA). TNx did not alter LCBFs significantly following transient cold exposure in WKY and SHR. Our findings indicate that in the cold environment, the lowered LCBFs in some areas of the brain may relate to the decreased metabolic rate caused by decreased body temperature, and may partly contribute to the higher prevalence of stroke in winter. Our findings also suggest that trigeminal nerve do not exert tonic control of LCBFs and the cold afferents in trigeminal nerve are not important in modulation of the LCBFs.

Animals↗

High frequency of deletion mutations in p53 gene from squamous cell lung cancer patients in Taiwan.

Lung cancer is the leading and second-leading cause of cancer deaths among women and men in Taiwan, respectively. However, the molecular mechanisms involved in lung tumorigenesis in Taiwan remain poorly defined. A study that analyzed the mutation spectrum of the p53 tumor suppressor gene in 35 female lung cancer patients in Hong Kong showed that a high proportion of the mutations observed were deletions, suggesting the possible involvement of a distinct mutagenic factor(s) in Chinese female lung cancer patients (Y. Takagi et al., Cancer Res., 55: 5354-5357, 1995). Therefore, to gain insight into the role of the p53 tumor suppressor gene and possible etiological factors in lung tumorigenesis in Taiwan, we investigated the mutation spectra of exons 4-11 in the p53 tumor suppressor gene of 60 lung cancer patients in Taiwan. These data were also correlated with clinical pathological characteristics of patients. Lung tumors were surgically resected, genomic DNA was isolated, and their mutation spectra were examined using PCR/single-strand conformational polymorphism analysis and direct sequencing. The frequency of p53 gene mutation was 18% (11 of 60). However, distinct patterns of p53 gene mutation were observed. Seven of 11 mutations detected (64%) were deletions of 1-12 bp at G:C bp or at bp in the immediate vicinity of repetitive sequences and/or tandem repeat sequences. In addition, two patients (2 of 11, 18%) exhibited nonsense mutations. In contrast to the frequent occurrence of missense mutations in the p53 gene reported in the literature, the majority (82%) of the mutations in lung cancer patients in Taiwan were nonmissense mutations, ie., deletions and nonsense mutations. Immunohistochemical staining indicated that p53 mutations including non-in-frame deletions and nonsense mutations all resulted in no expression of p53 protein. Notably, mutations occurred more frequently in patients suffering from squamous cell carcinoma (SQ). Nine of 31 SQ patients (29%) exhibited deletions or nonsense mutations, suggesting that deletions and nonsense mutations in the p53 gene are involved in the formation of SQ in Taiwan. In addition, mutations occurred more frequently in patients with stage III or IV lung cancer. However, mutations were not correlated with patients' smoking habits. Our data suggest that p53 gene mutation involved in the formation of SQ and distinct environmental factor(s) and/or genetic factor(s) that induced specific short deletions in repeat sequences may be involved in lung tumorigenesis in Taiwan.

Aged↗

Absence of expression of the Wiskott-Aldrich syndrome protein in peripheral blood cells of Wiskott-Aldrich syndrome patients.

Wiskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency that is usually associated with thrombocytopenia and eczema. The very variable phenotype of WAS results from defects in the WAS protein (WASP), the function of which is not well understood. In many cases causative mutations have now been identified in the WAS gene. Attempts have been made to correlate the nature of the mutations with the severity of the disease. In this study we investigated mutations in 13 patients with WAS and analyzed the expression of WASP in patient blood samples by immunoblot analysis. We found that despite extensive variation in the nature of the mutations in patients with severe WAS symptoms, none express the protein. However, in 1 patient with a mild clinical phenotype WASP expression was detected. Such an analysis could be used as an initial screening procedure for the diagnosis of WAS prior to genotypic analysis.

Base Sequence↗

Giant ossified cavernous hemangioma of an extremity associated with an equinovarus deformity.

A 39-year-old woman suffered from swelling and tenderness of the right leg for 31 years. Imaging studies showed a large soft tissue lesion on the right side extending from the proximal portion of the thigh to the ankle. She underwent several operations due to the leg mass and associated equinovarus deformity of the right ankle. The pathologic findings were those of an ossified cavernous hemangioma. This appears to be one of the largest hemangiomas to be reported. It revealed the three types of calcification characteristic of hemangiomas. Equinovarus deformity of the ankle caused by contracture of the calf in this case was probably related to repeated bleeding.

Adult↗

Ticlopidine-associated aplastic anemia. A case report and review of literature.

Serious hematologic complications associated with ticlopidine have been reported, including aplastic anemia. We report here an additional case of fatal aplastic anemia due to ticlopidine. A 66-year-old male patient developed fever and pancytopenia 2 months after ticlopidine was started. Despite the administration of granulocyte colony-stimulating factor (G-CSF) and broad-spectrum antibiotics, as well as aggressive red cell and platelet transfusions, the patient died 16 days after admission due to septic shock. Eighteen other cases of ticlopidine-induced aplastic anemia published in the English literature are also reviewed and presented here. Eight of the total 19 patients (including the one reported here) have died, mostly due to infection. Of the seven who received supportive treatment only, four had spontaneous recovery. Nine cases were treated with G-CSF or granulocyte-macrophage colony-stimulating factor (GM-CSF), and response was observed in only four of them. Several other cases were treated with high-dose corticosteroids or androgens; however, it was not possible to evaluate the efficacy of these treatments because of the limited number of cases. In the absence of satisfactory treatment for ticlopidine-induced aplastic anemia at present, it may be reasonable to try antilymphocyte globulin or cyclosporine. Also, great efforts should be made in the prevention and management of infection accompanying this disease.

Adrenal Cortex Hormones↗

Analysis of K-ras gene mutations in lung carcinomas: correlation with gender, histological subtypes, and clinical outcome.

PURPOSE: Lung cancer is respectively the leading and second-leading cause of cancer deaths among women and men in Taiwan. The commonest pathological type of lung carcinoma found in Taiwan is adenocarcinoma. and it has been documented that K-ras oncogene mutation occurs in a subset of lung adenocarcinoma. We therefore investigated the mutation spectrum and clinicopathological significance of K-ras oncogene mutations in lung cancer patients in Taiwan. METHODS: The lung tumors were surgically resected from 84 lung cancer patients. DNA was isolated and the mutation spectrum was examined by direct sequencing. These data were also correlated with the clinicopathological characteristics of patients. RESULTS: K-ras gene mutations were detected in 5 cases among the 84 patients investigated (6.0%). The majority of mutations occurred in exon 1 (80%, 4 of 5) and were located mainly in codons 12 and 13. Two patients had G x C --> T x A transversions and 2 patients had G x C --> A x T transitions. Notably, 1 patient had a G x C base-pair deletion from the contiguous G x C base pairs located between codons 68 and 69. All mutations occurred in male patients who were smokers. The incidences of K-ras gene mutation among male and female patients with adenocarcinoma were 13% and 0% respectively. Patients with K-ras gene mutation survived for shorter periods than those without mutations (P = 0.08, by the log-rank test). CONCLUSIONS: The incidence of K-ras gene mutations for male and female patients with adenocarcinoma was 13% and 0% respectively. Thus, the role of K-ras in the development of lung adenocarcinoma among Chinese men who are predominantly smokers is not significantly different from that in other populations worldwide. However, K-ras mutations may not be associated with adenocarcinoma among women in Taiwan, who are virtually all nonsmokers.

Adenocarcinoma↗

Purification of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) and analyses of the structural proteins.

The Kaposis's sarcoma-associated herpesvirus (KSHV) infected BCBL-1 cell line, adapted to and grown in medium containing 10% horse serum, was induced to lytic replication with 12-O-tetradecanoylphorbol-13-acetate (TPA) for virus production. Supernatants from induced cells were filtered through a 0.45-microm filter and virions were concentrated by polyethylene glycol extraction and high speed centrifugation. The virus was purified by a glycerol gradient zonal centrifugation step followed by isopycnic separation using positive density negative viscosity gradients. Two visible bands were detected after the final centrifugation step: an upper band that contained a homogenous population of purified virions and a lower band that contained aggregates of purified virus and other cellular debris. Fractionation of purified virion preparations by SDS-PAGE revealed 32 bands with estimated molecular weights between 19 and 280 K in silver stained gels. The glycoprotein bands in purified virus were identified with biotinylated lectins and horseradish peroxidase-labeled streptavidin. Two lectins were used to identify the KSHV glycoproteins: concanavalin A and Ricinus communis agglutinin I. Eight distinct glycoproteins were detected with these lectins. In addition, antisera from KS patients were used to detect immunoreactive proteins in purified virions. An apparent immunodominant band of Mr 94,000 (94 K) was recognized by patients' antisera. Other proteins detected with some of the KS antisera tested corresponded to molecular weights of 57 K, 70 K, 180 K, 200 K and 240 K. The 94 K band was identified as gp94 by Endo F digestion.

Cell Line↗

Search for mutations near the alternatively spliced 8-amino-acid exon in the GABAA receptor gamma 2 subunit gene and lack of allelic association with alcoholism among four aboriginal groups and Han Chinese in Taiwan.

The alternatively spliced 8-amino-acid exon for the GABAA receptor gamma2 subunit gene (GABRC2) has been postulated to mediate behavioral actions of alcohol. A rapid search for splice-junction mutations near the 8-amino-acid exon using restriction enzymes which normally recognize sequences near or in the exon gave negative results among 217 alcoholics in four aboriginal groups (Ami, Atayal, Bunun and Paiwan) and Han Chinese in Taiwan. The role of the GABRC2 gene in alcoholism was further assessed by a comparison of allelic frequencies revealed by a NciI RFLP between case and control groups. No significant association of alcohol dependence with GABRC2 alleles was observed. These results suggest that the GABRC2 gene probably does not play an essential role in predisposition to alcoholism in the sample population.

Alcoholism↗

The use of antibodies to the polypyrimidine tract binding protein (PTB) to analyze the protein components that assemble on alternatively spliced pre-mRNAs that use distant branch points.

We are using the rat beta-tropomyosin (beta-TM) gene as a model system to study the mechanism of alternative splicing. Previous studies demonstrated that the use of the muscle-specific exon is associated with the use of distant branch points located 147-153 nt upstream of the 3' splice site. In addition, at least one protein, the polypyrimidine tract binding protein (PTB), specifically interacts with critical cis-acting sequences upstream of exon 7 that are involved in blocking the use of this alternative exon in nonmuscle cells. In order to further study the role of PTB, monoclonal antibodies to PTB were prepared. Anti-PTB antibodies did not inhibit the binding of PTB to RNA because they were able to supershift RNA-PTB complexes. To determine if additional proteins interact with sequences within the pre-mRNA, 35S-met-labeled nuclear extracts from HeLa cells were mixed with RNAs and the RNA-protein complexes were recovered by immunoprecipitation using antibodies to PTB. When RNAs containing intron 6 were added to an 35S-met-labeled nuclear extract, precipitation with PTB antibodies showed a novel set of proteins. By contrast, addition of RNAs containing introns 5 or 7 gave the same results as no RNA, indicating that these RNAs are unable to form stable complexes with PTB. These results are in agreement with our previous studies demonstrating that PTB interacts with sequences within intron 6, but not with sequences within introns 5 and 7. When 35S-met-labeled HeLa nuclear extracts were mixed with biotinylated RNA containing intron 6 and the RNA-protein complexes were recovered using streptavidin-agarose beads, an identical pattern of proteins was observed when compared with the immunoprecipitation assay. Analysis of the proteins that assembled on introns 5, 6, or 7 using biotinylated RNA revealed a unique set of proteins that interact with each of these sequences. The composition of proteins interacting with sequences associated with the use of the 3' splice site of intron 6 included proteins of 30, 40, 55, 60, 65, 70, 80, and 100 kDa. Microsequencing identified two of the proteins to be Sam68 and the Far Upstream Element Binding Protein (FBP) from the c-myc gene. In addition, a comparison of the proteins that assemble on introns from the alpha- and beta-TM genes that utilize distant branch points revealed common as well as unique proteins that assemble on these introns. These studies identify a set of proteins, in addition to PTB, that are likely involved in the use of distant branch sites associated with the use of alternatively spliced introns.

Alternative Splicing↗

Intraosseous schwannoma of the fourth lumbar vertebra: case report.

OBJECTIVE AND IMPORTANCE: Intraosseous schwannomas (neurilemomas) are rare neoplasms. In one large series, schwannomas accounted for less than 0.2% of all primary bone tumors. These schwannomas most commonly arise in the mandible and have also been observed, very rarely, in the vertebra. We present a patient with an unusual intraosseous schwannoma in the lumbar vertebra. CLINICAL PRESENTATION: A 58-year-old man who was admitted to Cathay General Hospital had complained of numbness and pain in his lower extremities for approximately 1 year. At the time of admission, a neurological examination revealed mild motor weakness and sensory numbness bilaterally in his lower legs. Magnetic resonance images showed a neoplastic lesion occupying the entire L4 body and the superior part of the L5 body, with marked perivertebral protrusion and compression of the thecal sac and bilateral neuroforamina. INTERVENTION: The patient underwent a computed tomography-guided needle biopsy and a two-stage operation. During the initial surgical procedure, the tumor mass was totally removed via an anterolateral approach. Fixation and fusion of the third to fifth lumbar vertebral bodies was accomplished using a full-thickness iliac bone graft with an anterior locking plate and screws. During the second operation, posterior fusion of L2, L3, L4, L5, and S1 with Luque wires and a Hartshill rectangle rod was performed to increase the spinal stability. CONCLUSION: Intraosseous schwannomas are rare neoplasms that are not commonly observed in the lumbar vertebral bodies. Schwannomas in the lumbar spine commonly originate from the nerve passing through the neural foramina. We report a rare case of L4 intraosseous schwannoma, the magnetic resonance imaging, computed tomographic, and histological findings, and the surgical procedures.

Biopsy, Needle↗

Tuberculum sellae meningiomas: clinical manifestation, radiologic diagnosis, surgery and visual outcome.

BACKGROUND: Most patients with tuberculum sellae meningioma (TSM) present with visual symptoms mimicking a pituitary macroadenoma. Accurate preoperative differentiation is important because TSM requires a craniotomy, whereas the transsphenoidal route is preferred for removal of most pituitary macroadenomas. METHODS: From 1989 to 1994, five patients with TSM were treated at Taichung Veterans General Hospital. All were female, ranging in age from 20 to 60 years. This paper is a retrospective review of clinical features, diagnostic methods, treatment and postoperative visual recovery. RESULTS: The most common symptom, with a duration of one month to two years, was asymmetrical visual loss. Abnormal endocrine levels were found in one patient (prolactin: 47.91 ng/ml). Another patient was misdiagnosed as having a pituitary adenoma by coronal view computed tomography (CT) and underwent a transsphenoidal operation. Later, an accurate diagnosis was made using magnetic resonance imaging (MRI). She then underwent another operation--unilateral subfrontal craniotomy with total removal of the tumor. The other patients were preoperatively diagnosed as having meningioma by MRI. They also underwent unilateral subfrontal craniotomy with total removal of tumor. All patients showed good visual improvement after their operation. The extent of visual improvement was closely related to the duration of preoperative visual loss. There was no tumor recurrence after a follow-up period of six months to five years (mean, two years and six months). CONCLUSIONS: It should be emphasized that the diagnosis of TSM must first be based on clinical symptoms and signs, or "chiasma-syndrome". It can be accurately diagnosed preoperatively by sagittal view MRI. Early diagnosis will increase the chances of a good postoperative visual outcome.

Adult↗