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Biomedical subjects

C Y Chou

Publications and source records attributed to C Y Chou.

At least 19 recordsLinked to original sources
PubMed1998

Involvement of PKC-alpha in regulatory volume decrease responses and activation of volume-sensitive chloride channels in human cervical cancer HT-3 cells.

1. The present study was carried out to identify the specific protein kinase C (PKC) isoform involved in regulatory volume decrease (RVD) responses, and to investigate the signal transduction pathways underlying the activation of volume-sensitive chloride channels in human cervical cancer HT-3 cells. The role of Ca2+ in RVD and in the activation of chloride currents was also studied. 2. The time course of RVDs was prolonged by microinjection of PKC-alpha antibody but not by PKC-beta or PKC-gamma antibody, and also by exposure to Ca2+-free medium, in particular when combined with microinjection of EDTA. Immunofluorescence staining showed that hypotonic superfusion evoked the translocation of PKC-alpha to the cell membrane, whereas PKC-beta or PKC-gamma remained unaffected. The translocation of PKC-alpha was observed a few minutes after hypotonic stress, reaching peak intensity at 30 min, and returned to the cytoplasm 60 min after hypotonic exposure. Western blot analyses showed an increased PKC-alpha level in terms of intensity and phosphorylation in the cell membrane, while neither PKC-beta nor PKC-gamma was activated upon hyposmotic challenge. 3. Whole-cell patch-clamp studies demonstrated that neomycin and PKC blockers such as staurosporine and H7 inhibited volume-sensitive chloride currents. The inhibitory effect of neomycin on chloride currents can be reversed by the PKC activator phorbol 12-myristate, 13-acetate (PMA). Moreover, the PKC inhibitor and PKC-alpha antibody, but not PKC-beta or PKC-gamma antibody, significantly attenuated the chloride currents. The activation of volume-sensitive chloride currents were insensitive to the changes of intracellular Ca2+ but required the presence of extracellular Ca2+. 4. Our results suggest the involvement of PKC-alpha and extracellular Ca2+ in RVD responses and the activation of volume-sensitive chloride channels in HT-3 cells.

Blotting, Western↗
PubMed1998

Differential osmosensing signalling pathways and G-protein involvement in human cervical cells with different tumour potential.

Previous studies show that the regulatory volume decrease (RVD) in human cervical cells with different tumour potential may be mediated by different ion channels. The signalling events involved in regulating these channel activities are not clear. To screen the possible mechanisms involved in cell volume regulation in these cells, we examine intracellular mechanisms and second messengers listed as follows: phospholipase C (PLC), phospholipase A2 (PLA2), tyrosine kinase (TK), protein kinase C (PKC), protein kinase A (PKA), and cAMP. The involvement of G-protein was also studied. Our results showed that PLC signalling with downstream activation of PKC was involved in the cell volume regulation of cervical cancer cells. On the other hand, different PKC isoforms that were not related to upstream PLC regulation were involved in the RVD of human papillomavirus (HPV)-immortalised and normal cervical epithelia. Furthermore, GTP-gamma S facilitated the process of RVD in cervical cancer cells, while pertussis toxin retarded this process. In contrast, neither GTP-gamma S nor pertussis toxin showed effect on the RVD responses of HPV-immortalised and normal cervical cells.

Cell Line, Transformed↗
PubMed1998

Polymorphisms of the apolipoprotein B 3' variable number of tandem repeats region associated with coronary artery disease in Taiwanese.

We studied the allelic frequency of the variable number of tandem repeats region 3' of the apolipoprotein B gene (apoB 3' VNTR) and its impact on coronary artery disease (CAD) in 150 patients with CAD and 153 normal controls in a Taiwan population. apoB 3' VNTR alleles were classified according to the number of repeats of a 15-bp hypervariable elements (HVE), the sequence of which was determined using the polymerase chain reaction and direct sequencing. Thirteen alleles comprising from 26 to 54 HVEs were identified. The CAD patients had greater heterozygosity (0.58 vs 0.42) and a higher frequency of long (> 36-HVE) apoB 3' VNTR alleles than the controls (18.7% vs 10.8%, p < 0.01). CAD patients with two HVE-36 alleles and no HVE-32 alleles (the two most common forms) had significantly higher concentrations of LDL-cholesterol, apolipoprotein B, and triglycerides, and significantly lower values of HDL-cholesterol and apolipoprotein AI than the control group (p < 0.01 for all comparisons). The length of the apoB 3' VNTR was not correlated with the plasma concentrations of any of the lipids. We conclude that long apoB 3' VNTR alleles occur more frequently in CAD patients, but that apoB 3'VNTR genotypic variation has little impact on the risk of dyslipidemia in Taiwanese.

Aged↗
PubMed1997

Electron microscopic studies of phenotypic modulation of smooth muscle cells in coronary arteries of patients with unstable angina pectoris and postangioplasty restenosis.

BACKGROUND: Proliferation and matrix protein secretion of coronary smooth muscle cells (SMCs) have been suggested as one of the mechanisms responsible for the development of postangioplasty restenosis and an alternative cause of unstable angina. Phenotypic modulation of SMCs may produce a pool of cells potentially responsive to growth stimulation that can synthesize abundant extracellular matrix. This study tested the hypothesis that phenotypic modulation of SMCs occurred during the evolution of postangioplasty restenosis and unstable angina. METHODS AND RESULTS: The SMCs of coronary atherectomy specimens from 24 patients were identified under electron microscope. Volume fractions of synthetic organelles (VFSOs) and other features related to phenotypic modulation of SMCs were measured. The results showed that the VFSO in SMCs from 5 patients with unstable angina (group 2) resembled those from 9 patients with postangioplasty restenosis (group 3; 0.42 +/- 0.13 versus 0.36 +/- 0.10; P = NS), and both were significantly higher than those from 6 patients with stable angina (group 1; 0.21 +/- 0.11). Four patients with restenosis lesions who underwent angioplasty > 6 months ago (group 4) also had a low VFSO in SMCs (0.19 +/- 0.05). This value was significantly less than those in groups 2 and 3 (P < .05) but similar to that in group 1. CONCLUSIONS: The coronary lesions from patients with unstable angina resembled those from patients with postangioplasty restenosis in terms of the phenotypic modulation and VFSO in SMCs. Our findings therefore suggest that after phenotypic modulation, the SMCs may become responsive to growth stimulation, with an ability to massively proliferate and synthesize abundant extracellular matrix. These processes may lead to plaque expansion and eventually to the development of unstable angina and restenosis.

Aged↗
PubMed1997

Uterine leiomyosarcoma has deregulated cell proliferation, but not increased microvessel density compared with uterine leiomyoma.

OBJECTIVE: To investigate the differences of biological aggressiveness in terms of proliferating cell nuclear antigen (PCNA) expression, cell proliferation, and microvessel density between uterine leiomyosarcoma and leiomyoma. STUDY DESIGN: All patients with uterine leiomyosarcoma undergoing surgery at National Cheng Kung University Hospital were eligible. Forty-four patients with uterine myoma were also studied as the benign counterpart. The paraffin-embedded slides were stained with hematoxylin and eosin to confirm the presence of tumor and to quantitate mitoses, PC 10 for measurement of PCNA expression, MIB 1 for measurement of cell proliferation, and factor VIII for quantitation of microvessel density. The immunohistochemical findings of the slides were correlated with clinocopathologic findings of the patients, and the data were analyzed by either chi2 or unpaired t test. RESULTS: Six patients with uterine leiomyosarcoma and 44 patients with uterine leiomyoma were studied. Statistically significant higher mean levels of PCNA and MIB 1 were observed in uterine leiomyosarcoma compared with those of uterine myoma (for PCNA expression, P = 0.0001; for MIB 1, 11.61 +/- 11.42% vs 0.45 +/- 0.21%, P < 0.0001). No significant difference of microvessel density was observed between these two groups (65.73 +/- 48.62 vs 41.97 +/- 28.20, P = 0.084). Among the six patients with leiomyosarcoma, two patients with a higher percentage of MIB 1-positive tumor cells died of recurrent disease. In contrast, two patients with lower MIB 1 counts were disease-free for 3 years or more. CONCLUSION: Deregulated cell growth in uterine leiomyosarcoma may account for the biological aggressiveness of this tumor. Furthermore, the percentage of MIB 1-positive tumor cells seems to be associated with the prognosis or extent of uterine leiomyosarcoma.

Adult↗
PubMed1997

Accuracy of three-dimensional ultrasonography in volume estimation of cervical carcinoma.

OBJECTIVE: To evaluate the accuracy of a three-dimensional (3D) ultrasound system in volume estimation of cervical carcinoma. STUDY DESIGN: Transvaginal 3D and two-dimensional (2D) scans on cervical carcinoma volumes were performed 1 day before surgery. The volume of cervical carcinoma measured from each surgical specimen was compared with the corresponding volume of the cervical tumor measured by a 3D ultrasound and with the conventional 2D ultrasound volume measurement calculated using the formula pi/6 x(R1 x R2 x R3), where R1, R2, and R3 were the maximal transverse, anteroposterior, and longitudinal length of tumor, respectively. Limits of agreement and 95% confidence intervals were calculated and systemic bias between the methods was analyzed. The Klotz test was also used to assess the statistical significance of the degree of dispersion. RESULTS: A total of 61 cases, 55 with exophytic tumors and 6 with endocervical tumors, were examined in this study. The limits of agreement between the volume measured from specimen and tumor volume determined by ultrasound were +6.68 to -6.10 mL for 3D measurements and +12.46 to -10.98 mL for 2D measurements. The Klotz test showed the discrepancy in the degree of dispersion between 3D and 2D ultrasound measurements was statistically significant (P = 0.01). CONCLUSION: The true volume of cervical carcinoma is measured more accurately by a 3D ultrasound system than 2D ultrasound.

Adult↗
PubMed1997

Enhanced deoxyribonucleic acid damage and repair but unchanged apoptosis in uterine leiomyomas treated with gonadotropin-releasing hormone agonist.

OBJECTIVE: Our purpose was to investigate the histopathologic changes in uterine leiomyomas in cell proliferation, proliferating cell nuclear antigen expression, angiogenesis, and apoptosis after treatment with gonadotropin-releasing hormone agonist. STUDY DESIGN: Fifteen consecutive patients who had undergone gonadotropin-releasing hormone agonist treatment before surgery and 44 patients who did not were studied. The volumes of myomas were determined ultrasonographically, and in patients receiving gonadotropin-releasing hormone agonist therapy measurements were done again after administration of the gonadotropin-releasing hormone agonist to evaluate the response to treatment. Paraffin sections were stained with hematoxylin and eosin, PC 10 for proliferating cell nuclear antigen expression, MIB 1 for measurement of cell proliferation, ApopTag for apoptosis, and factor VIII for quantitation of microvessel density. A deoxyribonucleic acid fragmentation test was also done on nine cases with available frozen tissues. RESULTS: Most of the leiomyomas showed substantial expression of proliferating cell nuclear antigen. Gonadotropin-releasing hormone agonist therapy further induced significant overexpression of proliferating cell nuclear antigen (p = 0.0004, chi 2 test). All three leiomyomas that failed to respond to therapy showed less proliferating cell nuclear antigen staining compared with the good responders. In contrast, data from MIB 1 immunostaining showed that < 0.3% of leiomyoma cells were proliferating. However, positive-staining cells were more frequently detected in the treatment group (0.075% +/- 0.091% vs 0.002% +/- 0.010%, p = 0.0002, Mann-Whitney U test). Apoptosis developed spontaneously in leiomyoma cells independent of gonadotropin-releasing hormone agonist therapy. No significant change in apoptosis but a significant increase in microvessel density was observed in the treatment group compared with the control group. CONCLUSION: Enhanced deoxyribonucleic acid damage or repair with cell growth arrest may be responsible for the action of gonadotropin-releasing hormone agonist in shrinking uterine leiomyomas. Moreover, the extent of proliferating cell nuclear antigen expression seems to be associated with the response to gonadotropin-releasing hormone agonist therapy.

Adult↗
PubMed1997

Volume-activated taurine transport is differentially activated in human cervical cancer HT-3 cells but not in human papillomavirus-immortalized Z183A and normal cervical epithelial cells.

1. Previous studies demonstrate that volume-sensitive chloride currents are distinctly activated in cervical cancer cells, but not in human papillomavirus (HPV)-immortalized and normal cervical cells. In the present study, the Na(+)-independent volume-activated transport of taurine in three cervical cell types was investigated. 2. Osmotic swelling of cervical cancer HT-3 cells suspended in Na(+)-free hypotonic medium led to increased membrane uptake of taurine. This taurine uptake was effectively blocked by various Cl- channel blockers with a similar potency in blocking volume-sensitive Cl- channels: 1,9-dideoxyforskolin > 5-nitro-2-(3-phenyl-propylamino)-benzoic acid (NPPB) > 4-acetamido-4'-isothiocyanastilbene-2,2'-disulphonic acid (SITS) > 4,4'-diisothio-cyanatostilbene-2,2-disulphonic acid (DIDS) > furosemide. The taurine influx was also abolished by pertussis toxin. In contrast, Na(+)-independent volume-activated taurine transport was not significantly activated in HPV-immortalized Z183A cells and in normal cervical cells. 3. Exposure of HT-3 cells to hypotonic medium also resulted in a marked increase in taurine efflux. The volume-activated taurine efflux was osmolarity dependent and the pattern of pharmacological inhibition by Cl- channel blockers was indistinguishable from that for taurine uptake. 4. These results suggest that volume-sensitive Cl- channels in HT-3 cells can mediate the transport of amino acids. In addition, the pertussis toxin-sensitive G-protein is linked with the activation of this transport mechanism.

Biological Transport, Active↗
PubMed1997

Cardiac angiomyolipoma: radiologic and pathologic correlation.

Primary tumors of the heart are rare. We report a case of large cardiac angiomyolipoma (hamartoma) that presented as a fat-containing tumor mass on imaging studies, diagnosed radiographically as teratoma. The patient was admitted through the emergency room at Tainan Municipal Hospital because of severe dyspnea. A chest radiograph revealed marked widening of the mediastinum. Echocardiography and computed tomographic scanning of the thorax showed a mass of mixed density with calcification. A teratoma with intrapericardial invasion was suspected. Sternotomy disclosed a large intrapericardial lobulated mass (34 x 30 x 12 cm, 3,150 g) arising from the right atrium, with severe adhesion to the origin of the inferior vena cava. Histopathologic examination demonstrated an angiomyolipoma of the heart. To our knowledge, this is the largest cardiac angiomyolipoma reported. We report this case to emphasize that a differential diagnosis of angiomyolipoma must be included in a patient with a fat-containing cardiac tumor.

Adult↗
PubMed1996

Establishment and characterization of a human-papillomavirus negative, p53-mutation negative human cervical cancer cell line.

A human cervical cancer cell line, CX, was established from a patient with squamous cell carcinoma of the uterine cervix. The CX cells were epithelial in morphology with relatively large vesicular nuclei, and prominent nucleoli. Cytoplasmic organelles were generally sparse but tonofilaments were relatively abundant. The cells grew as a compact sheet with close membrane approximation interconnected by desmosome-like junctions. CX cells contained cytokeratin, but not vimentin. Elevated levels of squamous cell carcinoma antigen and carcinoembryonic antigen were detected in the cell supernatants. Population doubling time was estimated to be about 20 h. CX cells were not able to grow in soft agar and not tumorigenic in nude mice. Chromosome analysis revealed that CX cells were heterogeneous and mainly had a female diploid karyotype. Unlike cervical cancer cell lines published previously, CX cells were demonstrated to be human papillomavirus-negative, p53 mutation-negative. Based on the distinct characteristics, CX cell line may prove to be a useful tool for the study of human cervical carcinogenesis.

Antigens, Neoplasm↗
PubMed1996

Volume-sensitive chloride channels in the primary culture cells of human cervical carcinoma.

Previous study shows volume-sensitive chloride currents are induced by hypotonicity in human cervical cancer cell lines, but not in normal cervical epithelium. To ascertain whether the preferential activation of these channels in cancer cell lines could be similarly and directly detected in cervical cancer tissues, we studied volume-sensitive chloride channels on the primary culture cells of invasive cervical carcinoma using the whole-cell patch-clamp technique. The process of regulatory volume decrease (RVD) was also studied using electronic cell sizing to measure cell volume. Results demonstrate that, in these cultured cells, RVD was mediated in part by chloride loss through the volume-sensitive Cl- channels. A small background current with a slope conductance of 0.32 +/- 0.07 nS/pF at +30 mV (n=60 cells from 10 different samples) was observed. Hypotonicity induced a fast activating and outward rectifying current which was reversed at about 0 mV, and the slope conductance at +30 mV was increased by 10-fold to 3.62 +/- 0.62 nS/pF. These effects were readily reversed by returning the cells to isotonic medium. Moreover, DIDS, NPPB, and 1,9-dideoxyforskolin, reversibly abolished the volume-sensitive Cl- currents. The EC50 required for the inhibitory effect of DIDS, NPPB and 1,9-dideoxyforskolin was 150, 120, and 50 microM, respectively. Volume-sensitive Cl- channels were ubiquitously expressed in cultured cells from 10 samples of different cancer stages, histopathologic types, and state of HPV DNA positivity. Interestingly, similar outward rectifying chloride currents were activated by intracellular 300 microM GTP gamma S. It is proposed that this Cl- conductance may play an important role leading to RVD in human cervical cancer.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1996

Intratumoral blood flow in uterine myoma correlated with a lower tumor size and volume, but not correlated with cell proliferation or angiogenesis.

OBJECTIVE: To investigate the correlation of intratumoral blood flow in uterine myoma with cell proliferation, angiogenesis, tumor size, and tumor volume. METHODS: Thirty-nine patients who had been scheduled for surgery because of symptomatic uterine myomas were evaluated by transvaginal sonography and color Doppler ultrasound before surgery. The largest dimension of each tumor and the volumes of myomas were determined ultrasonographically. Pulsatility index (PI) was determined by color Doppler ultrasound according to the maximum systolic, end-diastolic, and the mean flow velocities measured within the uterine nodules. After surgery, the paraffin-embedded slides containing representative leiomyoma tissues were stained with hematoxylin and eosin, proliferating cell nuclear antigen for measurement of cell proliferation, and factor VIII for quantitation of microvessel density. The ultrasonographic findings were correlated postoperatively with pathologic findings, and the data were analyzed by simple linear regression and Fisher r to z transformation. RESULTS: Simple regression analysis of the intratumoral PI values on the sizes of myomas showed a negative correlation (r = -0.47, P = .003; n = 39), whereas a less significant correlation between PI values and tumor volumes was observed (r = -0.42, P = .008). In contrast, no statistically significant correlation was observed between the intratumoral PI values and the values of the proliferating cell nuclear antigen index (r = 0.10, P = .547) or microvessel density counts (r = 0.18, P = .282). CONCLUSION: The intratumoral blood flow by transvaginal color Doppler ultrasound correlated with a reduced tumor size and tumor volume, but did not correlate with cell proliferation or angiogenesis.

Adult↗
PubMed1995

Volume-sensitive chloride channels associated with human cervical carcinogenesis.

Previous controversy has risen from the purported equivalence of the volume-sensitive chloride channels with P-glycoprotein. The aim of this study was to investigate the association between expression of volume-sensitive Cl- channels and the process of malignant transformation of cervical epithelial cells. We studied the activations of volume-sensitive and cAMP-mediated chloride currents in various human cervical squamous cells that were representative of different stages of cervical carcinogenesis, i.e., normal cervical epithelium, low-grade cervical intraepithelial neoplasia, carcinoma in situ, and invasive carcinoma using the whole-cell patch clamp technique. The volume-sensitive chloride channels, however, were significantly activated only in the four cervical cancer cell lines, primary culture cells of carcinoma in situ, and invasive cancer of the cervix. The expression of volume-sensitive chloride currents was independent of the state of human papillomavirus positivity. When these cells were exposed to hypotonic shock, the cells swelled, and outward rectified chloride currents were observed. These effects were readily reversed by returning the cells to isotonic medium. In addition, 4,4'-diisothiocyanatostilbene-2,2-disulfonic acid, 1,9-dideoxyforskolin, and verapamil reversibly abolished the volume-sensitive Cl- currents. In contrast, none of the cells from normal cervices and human papillomavirus-immortalized cell lines, the in vitro equivalent of low-grade cervical intraepithelial neoplasia, developed substantial chloride currents on exposure to hypotonicity. cAMP-mediated chloride currents were ubiquitously activated in all cervical squamous cells, regardless of the stages of carcinogenesis. This is the first report suggesting an in vivo association between the development of volume-sensitive chloride currents and human carcinogenesis.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1995

Intravaginal foreign body retained for a long duration.

An intravaginal foreign body of long duration can pose a diagnostic dilemma, since a number of diagnostic modalities may fail to detect its existence. We present the case of an 8-year-old girl who suffered from a bloody, malodorous vaginal discharge for over 4 years, during which time she had been evaluated by several gynecologists. A vaginal examination performed under analgesia revealed a pinpoint-sized opening 2 cm above the hymen. We inserted a cannula and injected radio-opaque contrast medium. An intravaginal filling defect was visible, which strongly suggested the presence of a foreign body. An incision through this scarred area was performed and two foreign bodies, one shaped like a plastic tube and the other a cap, were removed. We conclude that vaginography may provide an alternative diagnostic tool for this condition.

Child↗