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Biomedical subjects

Y S Kuo

Publications and source records attributed to Y S Kuo.

At least 19 recordsLinked to original sources

Arecoline cytotoxicity on human oral mucosal fibroblasts related to cellular thiol and esterase activities.

Betel quid (BQ) chewing is associated with an increased risk of oral submucous fibrosis (OSF) and oral cancer in India and many south-east Asian countries. Recently, we have shown that arecoline is cytotoxic to cultured human oral mucosal fibroblasts. This study investigated protective effects of various agents against the cytotoxicity of arecoline and its mechanisms. Arecoline, at concentrations of 0.2 and 0.4 mM, decreased the cell numbers by 38% and 63%, respectively. At a concentration of 2 mM, N-acetyl-L-cysteine [a glutathione (GSH) synthesis precursor] could prevent arecoline-induced cytotoxicity. The decrease in cell numbers was reduced to 17% relative to control. Extracellular addition of esterase at a concentration of 0.1 U/ml could almost completely protect the oral mucosal fibroblast (OMF) from arecoline-induced cytotoxicity. Arecoline is a muscarinic receptor agonist. However, atropine, a muscarinic receptor antagonist was unable to protect the cells from arecoline cytotoxicity at a concentration of 10 microM. Pretreatment of OMF with 50 microM buthionine sulfoximine (a cellular GSH synthesis inhibitor) or 0.5 mM diethylmaleate (a cellular GSH depleting agent) potentiated the cytotoxic effects of arecoline. These results indicate that cytotoxicity of arecoline on OMF is associated with cellular GSH levels and esterase activities. Factors that induce the GSH synthesis or esterase activity of oral mucosal cells can be used for future chemoprevention of BQ chewing-related lesions.

Acetylcysteine

Diagnosis of oral cancer by light-induced autofluorescence spectroscopy using double excitation wavelengths.

A cancer diagnostic algorithm, light-induced autofluorescence spectroscopy using double excitations wavelengths, was employed for distinguishing between cancerous and normal oral mucosa. For emission spectra at the shorter excitation wavelengths (280, 290, and 300 nm), the ratio between the area under 325-335 nm and the area under 465-475 nm was calculated. In the same way, for emission spectra at the longer excitation wavelengths (320, 330, and 340 nm), the ratio between the area under 375-385 nm and the area under 465-475 nm was calculated. Receiver operating characteristic curves were used to evaluate the performance of algorithms using single and the double (by combining shorter and longer) excitation wavelengths. The results showed that better performance, up to sensitivity 81.25%, specificity 93.75%, and positive predictive value 92.86%, could be achieved by using the double excitation wavelengths. The present study can be useful as a basis for further investigation on in vivo autofluorescence measurement and analysis using double excitation wavelength.

Algorithms

Expression of p53 protein correlates with decreased survival in patients with areca quid chewing and smoking-associated oral squamous cell carcinomas in Taiwan.

Expression of p53 protein was examined in oral squamous cell carcinoma (SCC) from patients who were areca quid (AQ) chewers and/or tobacco smokers, using anti-p53 antibodies with an immunoperoxidase technique. Positive p53 stain was observed in 47 of 81 (58%) cases of oral SCC. p53 overexpression was found to be higher in patients without AQ chewing and smoking habits than in patients with these two habits (80% vs 52%, P=0.076). No significant correlation was found between p53 expression and the patients' age, sex, cancer location, clinical staging, primary tumor TNM status, or histological differentiation of SCC. The Kaplan-Meier analysis showed that the prognosis for patients with p53-negative tumors was significantly better than that for patients with p53-positive tumors (P<0.05). A significant correlation was also observed between positive lymph node status and poor prognosis (P<0.05). These results suggest that p53 may serve as an adjuvant marker of poor survival in patients with oral SCCs in Taiwan.

Adult

Infrequent p53 mutations in patients with areca quid chewing-associated oral squamous cell carcinomas in Taiwan.

Mutations in the conserved regions (exons 5-9) of the p53 gene were investigated in 37 untreated human primary oral squamous cell carcinomas (SCCs) using polymerase chain reaction-single strand conformation polymorphism and DNA sequencing analyses. P53 mutations were detected in 2 of 37 (5.4%) oral SCC cases. One tumor sample (case 23) showed a mis-sense point mutation at codon 177, changing CCC to CTC, which resulted in a substitution of proline to leucine in the p53 protein. The other tumor (case 33) had a point mutation at codon 266, changing GGA to AGA and causing a substitution of glycine to arginine in the p53 protein. These two patients with p53 mutations did not have an areca quid chewing habit. These results suggest that mutations in the p53 gene may not play a role in the pathogenesis of human oral SCCs in Taiwan. Recently, we have shown that positive p53 staining was observed in 47 of 81 (58%) cases of oral SCC. The discrepancies between positive p53 protein staining and the low prevalence of p53 mutation in oral SCCs indicate that other mechanism(s) are involved in p53 overexpression.

Adult

Loss of heterozygosity of APC and MCC genes in oral squamous cell carcinomas in Taiwan.

Loss of heterozygosity (LOH) at adenomatous polyposis coli (APC) and mutated in colon cancer (MCC) genes was investigated in 37 untreated human primary oral squamous cell carcinomas (SCCs) using the polymerase chain reaction. LOH was observed in 14 of 26 (53.8%) heterozygous (informative) patients at APC and 9 of 13 (69.2%) heterozygous patients at MCC> Homozygous deletion of MCC was detected in one patient. Of the 37 patients, 29 were informative at APC or MCC or both; LOH at APC and/or MCC was detected in 68.9% (20/29) of the cases. Ten cases were informative for both genes; LOH at both loci was found in only three of these cases. LOH at the APC and/or MCC was found in both early and advanced stages of oral SCCs. No significant correlation was observed between LOH at the APC and/or MCC locus and the patients' tobacco/betel quid consumption, tumour location, TNM status, or histological differentiation. These results suggest that LOH at the APC and/or MCC may be an early event and may play a role in the pathogenesis of human oral SCCs in Taiwan.

Carcinoma, Squamous Cell

Genetic polymorphisms of CYP2E1, GSTM1, and GSTT1; environmental factors and risk of oral cancer.

Both genetic and environmental factors are involved in the development of cancer; some phase I and II enzymes involved in the metabolism of carcinogens are polymorphic in genotypes. This case-control study focused on the interactions between oral cancer risk factors and genetic polymorphisms of cytochrome P-450 (CYP) 2E1 and glutathione S-transferase (GST) M1 and GSTT1. A total of 41 male oral cancer cases was recruited from National Taiwan University Hospital, and 123 healthy controls frequency-matched on ethnicity, sex, and age were recruited from residents living in Taipei City and Taipei County. History of cigarette smoking, alcohol drinking, and betel quid chewing was obtained through a standardized questionnaire interview, and genotypes of CYP2E1, GSTM1, and GSTT1 were determined by PCR. Cigarette smoking, alcohol drinking, and betel quid chewing were significantly associated with the risk of oral cancer in a dose-response relationship. All betel quid chewers smoked cigarettes in both the case and control groups. In the multiple logistic regression analysis, those who had null genotypes of GSTM1 and/or GSTT1 had an increased oral cancer risk compared with those who had non-null genotypes of both GSTM1 and GSTT1, showing a multivariate-adjusted odds ratio (OR) of 4.6 with a 95% confidence interval (CI) of 0.9-23.7 (P = 0.08). The CYP2E1 c1/c2 and c2/c2 genotypes were associated with a significantly increased oral cancer risk compared with the c1/c1 genotype among those who did not chew betel quid (OR, 4.7; 95% CI, 1.1-20.2), but not among betel quid chewers. Habitual alcohol drinking was associated with a significantly increased oral cancer risk, showing an OR of 3.0 (95% CI, 1.1-8.8). These results implied that there are gene-gene and gene-environment interactions in the development of oral cancer.

Alcohol Drinking

Cytotoxic and cytostatic effects of arecoline on oral mucosal fibroblasts.

Betel quid (BQ) chewing shows strong correlation to the incidence of oral submucous fibrosis and oral cancer in Taiwan. Arecoline, the main areca alkaloid, is considered to be one of the etiologic factors in BQ. To elucidate the role(s) of arecoline in the pathogenesis of BQ chewing related oral mucosal lesions, we used oral mucosal fibroblasts to study the effects of serum concentration, cell density, and incubation time on the cytotoxic response to arecoline. At a concentration less than 0.2 mM, arecoline was not cytotoxic to oral mucosal cells after 1, 3, and 6 days of incubation. After 3 days of incubation, the cytotoxic and cytostatic effects of arecoline became evident when the cells were exposed to higher concentrations of arecoline (0.2 mM) and serum (10% FCS). Exposure of cells (1 x 10(4) cells/well) to 0.2 mM of arecoline in 0.5% FCS for 3 and 6 days led to a 20% and 23% decrease, respectively, in the cell number, whereas exposure of cells (1 x 10(4) cells/well) to 0.2 mM arecoline in 10% FCS led to a 38% and 53% decrease, respectively, in cell number. At a higher cell density (5 x 10(4) and 1 x 10(5) cells/well), 0.2 mM arecoline led to less cytotoxicity (38% and 21% of decreasing in cell number, respectively) after 6 days of incubation. Our results indicated that arecoline was not mitogenic to oral mucosal fibroblasts, and that the cytotoxic and cytostatic effects of arecoline on oral mucosal fibroblasts could be modulated by the changes in the cell density, serum concentrations, and incubation time.

Arecoline

Acute pulmonary oedema following administration of vasopressin for control of massive GI tract haemorrhage in a major burn patient.

A 35-year-old male sustained a full-skin thickness chemical burn involving 60 per cent of TBSA when hydrochloric acid was applied to his face, trunk and extremities by his girlfriend. Debridements and skin graftings were performed smoothly and he was doing well until day 23 after injury, when massive GI tract bleeding caused a drop in blood pressure. Vasopressin was given intravenously to control the bleeding, which stopped, and the blood pressure returned to normal after transfusion. After the vasopressin infusion was tapered off acute pulmonary oedema developed abruptly, which required treatment by intubation and PEEP using a respirator. The lung condition had returned to normal by the following day. A second episode of massive GI tract bleeding recurred 10 days later, again vasopressin was given through a catheter into the inferior mesenteric artery. Again pulmonary oedema developed 38 h after the vasopressin use, the oedema disappeared within 2 days when the vasopressin infusion tapered off. It should be kept in mind that acute pulmonary oedema may develop when high doses of vasopressin are used in the treatment of Curling's ulcer or other GI tract bleeding.

Acute Disease

Verruciform xanthoma. Case report and literature review.

Verruciform xanthoma is a relatively uncommon lesion. Half of the reported cases occurred in the gingiva or alveolar ridge. In most cases, the clinical impressions are papilloma or verrucous carcinoma, which demonstrates the importance of the clinical and pathological recognition of this lesion. The cause of pathogenesis is still unknown since the first report in 1971. There are some cases reported in conjunction with leukoplakia, carcinoma in situ, pemphigus, and discoid lupus erythematosus (DLE), which merits close evaluation of this disease. This article reports two cases of verruciform xanthoma and reviews the evidence of its pathogenesis from the available literature.

Adult

Comparison of calcium phosphate cement mixture and pure calcium hydroxide as direct pulp-capping agents.

Calcium phosphate cement (CPC) and pure calcium hydroxide were used as direct pulp-capping agents on the deliberately exposed pulp tissue of 60 teeth in five monkeys. Their effects on the pulp tissue of individual teeth were observed and histologically compared after 12, 20 and 24 weeks. The results showed that both materials produced similar responses with regard to their biocompatibility and induction of hard tissue barrier formation. Vasodilatation, chronic inflammation and calcification nidi scattered within the pulp tissue of the 12-week group were observed. Twenty weeks after application of capping materials, a crude reparative dentinal bridge with inclusion of soft tissue or bulky capping agents appeared. A more mature, hard tissue barrier with a better degree of mineralization and formation of dentinal tubules was demonstrated in the 24-week group. The above findings associated with the abilities of self-setting and fair compressive strength suggest that CPC appears superior to pure calcium hydroxide and may have potential for clinical application, although many issues remain to be further investigated.

Animals

Light-induced fluorescence spectroscopy: a potential diagnostic tool for oral neoplasia.

For the early detection of oral neoplasia, light-induced fluorescence spectroscopy was used to measure the fluorescence emission of malignant (squamous cell carcinoma & verrucous carcinoma) and premalignant (epithelial dysplasia, hyperkeratosis & lichen planus) oral tissues as well as normal oral mucosa ex vivo to assess the ability of this technique to distinguish neoplastic from normal oral tissues. The emission spectra of histologically normal and neoplastic oral tissues were obtained under excitation wavelengths varied from 270 nm to 400 nm at 10-nm intervals. At 300-nm excitation, the most intensely fluorescent peak occurred at 330-nm and 470 nm emission. At 330-nm emission, the spectrum of the malignant oral tissue was significantly stronger than that of the normal oral mucosal tissue after area normalization. However, at 470-nm emission, the spectrum of the malignant oral tissue was significantly weaker than that of the normal oral mucosal tissue. A diagnostic algorithm based on the ratio of relative intensities of 330 nm to 470 nm emission within the +/-5 nm peak area of each sample was calculated and paired. The histogram of ratios showed that histologically neoplastic oral tissues could be distinguished from normal oral mucosal tissues using the 300 nm excitation wavelength. The average ratio of malignant or premalignant oral samples was significantly greater than that of the normal oral mucosal samples (p < 0.001). This ex vivo study indicated that fluorescence spectroscopy may be useful in differentiating malignant or premalignant oral tissue from normal oral mucosa.

Areca

Pregnancy following oocyte donation and tubal embryo transfer in patients with premature ovarian failure: report of two cases.

Two pregnancies in patients with premature ovarian failure utilizing donated oocytes, in-vitro fertilization (IVF) and tubal embryo transfer (TET), are reported. The recipients received cyclic hormone replacement therapy for six months to prepare the endometrium for implantation. An evaluation cycle was tested to document that the hormone milieu established by the hormone replacement protocol was similar to that of a natural ovulatory cycle. During the oocyte donation cycle, the recipient received incremental estrogen replacement treatment of flexible length during the follicular phase of the donor's stimulated cycle to synchronize the recipient's endometrium to the donor's embryo. Concurrently, the donor underwent controlled ovarian hyperstimulation and transvaginal ultrasound-guided oocyte retrieval. After fertilization of the donated oocytes with sperm from the recipient's husband and cleavage of the fertilized oocytes into the 2- to 4-cell stage, laparoscopic embryo transfer into the recipient's fallopian tube was performed. Case 1 received 4 embryos by the TET procedure. Pregnancy was confirmed by visualization of a gestational sac in the uterine cavity 3 weeks after TET, but miscarriage occurred at the tenth gestational week. In Case 2, the pregnancy was established after TET of 2 embryos. Estrogen and progesterone supplements were maintained until day 100 after TET. The patient delivered a healthy male baby, weighing 2,520 g at 38 weeks of gestation.

Adult