Search PubMed⌕ Search

Biomedical subjects

F J Hsieh

Publications and source records attributed to F J Hsieh.

At least 19 recordsLinked to original sources

Enhanced expression and stable transmission of transgenes flanked by inverted terminal repeats from adeno-associated virus in zebrafish.

Mosaic expression of transgenes in the F0 generation severely hinders the study of transient expression in transgenic fish. To avoid mosaicism, enhanced green fluorescent protein (EGFP) gene cassettes were constructed and introduced into one-celled zebrafish embryos. These EGFP gene cassettes were flanked by inverted terminal repeats (ITRs) from adeno-associated virus (AAV) and driven by zebrafish alpha-actin (palpha-actin-EGFP-ITR) or medaka beta-actin promoters (pbeta-actin-EGFP-ITR). EGFP was expressed specifically and uniformly in the skeletal muscle of 56% +/- 8% of the palpha-actin-EGFP-ITR-injected survivors and in the entire body of 1.3% +/- 0.8% of the pbeta-actin-EGFP-ITR-injected survivors. Uniform transient expression never occurred in zebrafish embryos injected with EGFP genes that were not flanked by AAV-ITRs. In the F0 generation, uniformly distributed EGFP could mimic the stable expression in transgenic lines early in development. We established five transgenic lines derived from palpha-actin-EGFP-ITR-injected embryos crossed with wild-type fish and 11 transgenic lines derived from pbeta-actin-EGFP-ITR-injected embryos crossed with wild-type fish. None of these transgenic lines failed to express the transgene, a result confirmed by polymerase chain reaction analysis. Stable mendelian transmission of the transgenes was achieved in both alpha-actin and beta-actin transgenic lines without changing the patterns of expression and integration. Progeny inheritance test and Southern blot analysis results strongly suggest that transgenes flanked by AAV-ITRs were integrated randomly into the genome at a single locus with a concatamerized multiplier. Thus, incorporating AAV-ITRs into transgenes results in uniform gene expression in the F0 generation and stable transmission of transgenes in zebrafish.

Actins↗

Cytosol vascular endothelial growth factor in endometrial carcinoma: correlation with disease-free survival.

OBJECTIVE: The aim of this study was to evaluate whether vascular endothelial growth factor (VEGF) could be a marker for disease-free survival in endometrial carcinoma patients. METHODS: Fifty-three patients with endometrial carcinoma undergoing surgery were enrolled. Clinical and pathologic items were recorded. Cytosol VEGF was quantified by enzyme immunoassay. The microvessel density (MVD) of the excised tumors was immunohistochemically assessed. The relationship among MVD, cytosol VEGF concentration of the tumor tissues, and clinicopathologic parameters was analyzed. The risk factors influencing clinical outcome were tested. RESULTS: Higher cytosol VEGF concentrations and MVD values were noted in tumors with advanced stage (more than stage I) (917 versus 125 pg/mg, P = 0.03; 94.1 +/- 37.8 versus 60.8 +/- 38.9, P = 0.008), lymphovascular emboli (917 versus 102 pg/mg, P = 0.001; 94.4 +/- 33.2 versus 62.4 +/- 40.7, P = 0.009), and lymph node metastasis (1032 versus 95 pg/mg, P < 0.001; 116.5 +/- 30.8 versus 56.7 +/- 33.3, P < 0.001). The cytosol VEGF and MVD showed a positive linear correlation (VEGF versus MVD, r = 0.41, P = 0.003). Grade 3 tumor and overexpressed cytosol VEGF (> 800 pg/mg) are independent risk factors for recurrence. There was a trend that patients with grade 1 or 2 tumors and normal-expressed VEGF had the highest probability of disease-free survival, and patients with grade 3 tumors and overexpressed cytosol VEGF had the poorest probability of disease-free survival. CONCLUSIONS: Cytosol VEGF had a good correlation with the disease progression and metastasis in endometrial carcinoma, and it might also be an independent prognostic factor for disease-free survival of endometrial carcinoma patients.

Adult↗

Interleukin-6 in cervical cancer: the relationship with vascular endothelial growth factor.

OBJECTIVE: Interleukin-6 (IL-6), a central proinflammatory cytokine, has been implicated in cervical cancer, though its role remains elusive. This study was an attempt to elucidate the role of IL-6 in the pathogenesis of cervical cancer, with particular emphasis on tumor angiogenesis. METHODS: Cytosolic IL-6, vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF) levels were determined via enzyme immunoassay in 60 FIGO stage IB-IIA cervical cancer patients. Immunohistochemical staining in tissue sections was performed to analyze the distributions of IL-6 and IL-6 receptors. Meanwhile, human papillomavirus (HPV) DNA was detected by polymerase chain reaction-based survey. In vitro studies of two cervical cancer cell lines, C33A and SiHa, for the interaction between IL-6 and VEGF were also performed. RESULTS: Consistently higher expression of IL-6 and VEGF was evident in cancerous tissues than in adjacent noncancer tissues in early-stage cervical cancer patients (P < 0.01). After recombinant human IL-6 was added, VEGF was induced in a time- and dose-dependent manner in cervical cancer cell line C33A. Correspondingly, interrupting the IL-6 autocrine machinery with either anti-IL-6 or anti-IL-6 receptor antibody markedly reduced the expression of VEGF at the transcriptional level in SiHa cells. Significantly higher levels of IL-6 in cancer tissues were observed in patients older than 45 (P < 0.01), patients with tumors >2 cm (P < 0.01), patients with oncogenic HPV-16 or -18 infections (P < 0.01), and patients with squamous cell carcinoma (P = 0.02). Patients with a deeper stromal invasion, vaginal invasion, lymphovascular emboli, or lymph node metastasis appeared to have higher intratumoral IL-6 levels, although the differences were statistically insignificant. CONCLUSIONS: Substantially high microenvironmental IL-6 levels promote tumor angiogenesis and the development of cervical cancer. Thus, inhibition of the biological activity of IL-6 may be potentially beneficial.

Adult↗

Decreased maternal serum placenta growth factor in early second trimester and preeclampsia.

OBJECTIVE: To compare early second-trimester maternal serum placenta growth factor concentrations in patients with subsequent development of preeclampsia and those with normal pregnancies. METHODS: We conducted a case-control analysis of stored maternal serum of 27 women who subsequently developed preeclampsia and 227 randomly selected normal controls during the gestational period of 14-19 weeks. Using such a sample size, there was a greater than 95% power to test a difference in the primary study interest. A quantitative sandwich enzyme immunoassay was used to measure the maternal serum placenta growth factor concentration. For statistical analysis, Mann-Whitney U tests, multiple linear regression analysis, multivariable logistic regression model, and receiver-operating characteristic (ROC) curve were used. P <.05 was considered statistically significant. RESULTS: Maternal serum placenta growth factor concentration was associated with the occurrence of subsequent preeclampsia (P <.001) and gestational age (P <.001). The median (interquartile range) of multiples (MoM) of the gestational age stratified median for placenta growth factor in preeclampsia was 0.55 (0.33, 0.85). The ROC curve revealed that the specificity was 70% when the diagnostic sensitivity was 70%, and the optimal cutoff value of placenta growth factor MoM was 0.76. The risk of developing preeclampsia subsequently was increased 2.5-fold for maternal serum placenta growth factor concentration decrements of 0.1 MoM. CONCLUSION: A decreased maternal serum placenta growth factor concentration in the early second trimester is highly associated with the subsequent development of preeclampsia, but a large prospective study is needed to explore its use as an early predictor for the condition.

Adolescent↗

Noninvasive assessment of laryngeal phonation function using color Doppler ultrasound imaging.

Color Doppler imaging (CDI) was used to identify the morphology of vocal folds (VF) and to quantify the tissue horizontal displacement velocity (HDV) in the vibrating portion of VF. Mucosal HDV that gives an estimate of the stiffness of the VF cover is very important clinically. The VF and its cover were shown to be very hypoechoic and not adequately visible in B-scan image. However, in this study, we found that the structure of the true VF, especially the mucosa and the superficial layer of the lamina propria, the so-called "cover," can be easily identified and evaluated using CDI. The mean VF displacement velocity was measured by decoding the pseudocolor codes of the ultrasound (US) image at the vibrating sites. The mucosal mean HDV obtained from 10 normal men of age 34 +/- 8 years phonating at their most comfortable pitch and intensity (98 +/- 12 Hz, 55-65 dB) was about 68 +/- 10 cm/s, which agreed reasonably with the literature. Therefore, the CDI could be used as a potential tool for assessing the phonation function in the larynx nonintrusively.

Adult↗

Noninvasive assessment of vocal fold mucosal wave velocity using color doppler imaging.

The vibratory movement of the vocal folds (VF) plays an important role in normal function of phonation. We developed a noninvasive technique to quantify the human mucosal wave velocity (MWV) in vivo using color Doppler imaging (CDI). During phonation, the motion of mucosa-air interface generates a unique pattern of US color artefacts that assist the identification of true VF location. An in vitro study using a vibrating string phantom was conducted to investigate how the CDI displayed a vibrating soft tissue at high frequency. The vibrating amplitude, frequency, mass density and the acoustic impedance of the soft tissues were found to dominate the formation of color artefacts. Based on the model of finite string with fixed ends, we estimated the mean MWV for 10 adult volunteers (6 men, 4 women, ages 34 +/- 5 years) with normal VF function. The mean MWVs for the men were found to vary from 2.1 to 10 m/s in a frequency range of 85 to 310 Hz at their comfortable pitch and intensity, and the women typically had higher MWVs that varied from 5.0 to 16.5 m/s in a frequency range of 180 to 480 Hz. The MWV increased linearly with the frequency and there was no observable difference in mucosa stiffness due to the effect of gender. The variation in MWV as it propagates vertically can be seen from the color and shape of the artefacts. The VF polyp resulted in abnormal MWV and different CDI vibratory artefacts. The CDI artefacts provide insight on the dynamics of mucosa structure during phonation, and the method presented is promising for noninvasive monitoring of laryngeal functions clinically.

Adult↗

Relationship between fetal nuchal translucency and crown-rump length in an Asian population.

OBJECTIVES: To investigate the relationship between the nuchal translucency (NT) thickness and crown-rump length (CRL) in normal Asian fetuses during the first trimester. DESIGN: A prospective observational study was conducted. Ultrasound measurement of NT and CRL was offered in 879 consecutive Taiwanese fetuses between 9 weeks and 14 weeks of gestation. Regression analysis was used to analyze the relationship between the NT thickness and CRL. Fetal sex was also considered in the analysis. The distribution of multiple of median (MoM) values of the NT measurements with CRL in 10-mm intervals and the 95th centile of MoM were also calculated. RESULTS: The present study shows that NT measurements increase with increasing CRL. A fixed cut-off point through the first trimester is not appropriate. The NT thickness has no relationship with fetal sex. Expressing the NT thickness by MoM values provides a simple method for clinical practice. CONCLUSIONS: The present study offers normative data of the fetal NT thickness in an Asian population, which may improve the performance of NT measurement during the first-trimester as a screening tool for chromosomal aberrations or other congenital abnormalities in the first trimester.

Adult↗

Three-dimensional ultrasonography in early pregnancy.

Three-dimensional ultrasound was introduced into clinical use over a decade ago. Early attempts on three-dimensional ultrasound were primitive and limited to experimental use only. Recently, it was used as a powerful tool to display three-dimensional fetal appearance and assess normal and pathological conditions. Because of the improvement in image resolution and reconstruction speed, three-dimensional ultrasound is now more and more popular in many centers, and used commonly as an adjunct in prenatal diagnosis. Indeed, a skillful sonographer may usually make the correct diagnosis of fetal anomaly with simply two-dimensional ultrasound. Nonetheless, the situation is gradually changing, because some anomalies have been diagnosed only based on the findings of three-dimensional ultrasound. In spite of that, the application of three-dimensional ultrasound is still less discussed in early pregnancy. In this article, the authors clarify the capability of three-dimensional ultrasound in different anatomic areas, and catalog its clinical merits in the early pregnancy to date. We also present the safety guidelines for its use in the first trimester.

Embryonic and Fetal Development↗

First-trimester Down's syndrome screening by fetal nuchal translucency measurement in Taiwan.

BACKGROUND: Fetal nuchal translucency (NT) measurement is now widely used in many Western countries as a screening tool for Down's syndrome during the first trimester. However, at present there is no data on its use in Taiwan. The purpose of the present study was to evaluate the efficacy of NT measurement in first-trimester Down's syndrome screening in Taiwan. METHODS: We conducted a prospective study from October 1997 to May 1999. Sonographic measurement of fetal NT was performed in 1,249 fetuses at 9-14 weeks of gestation. Transabdominal ultrasound scanning was performed to obtain a sagittal section of the fetus for measuring the crown-rump length (CRL) and the maximum thickness of the subcutaneous translucency between the skin and the soft tissue overlying the cervical spine. Two different cut-off points were used for screening: a fixed cut-off point of at least 2.5 mm and a CRL-related cut-off point. In the latter method, fetuses with an NT measurement in the 95th percentile were considered at high risk for Down's syndrome. RESULTS: Three fetuses had Down's syndrome, with NT measurements of 2.1 mm, 2.7 mm, and 4.0 mm. The false positive rates for the fixed cut-off point and CRL-related cut-off point were 6.3% and 4.6%, respectively. Both methods had a sensitivity of 66.7%. However, the screening program using the CRL-related cut-off point had two advantages: a higher specificity (95.5% vs 93.8%) and a more reasonable distribution pattern for screening. CONCLUSION: This study showed that NT measurement is a potential screening tool for Down's syndrome during the first trimester in Taiwan. Using CRL-related cut-off points for screening is more reasonable than using a fixed cut-off point.

Adult↗

In utero progressive pulmonary stenosis successfully treated with transcatheter intervention after delivery.

It is unclear whether pulmonary stenosis with intact ventricular septum is a secondary cardiac malformation. We report an infant with pulmonary stenosis (diagnosed by fetal echocardiography) with progressive obstruction in late gestation who presented with increasing transvalvular pressure gradients (15 mm Hg at 22 weeks' gestation to 47 mm Hg at 35 weeks). The tricuspid/mitral valve annulus ratio decreased from 1.25 at 24 weeks' gestation to 0.96 at 33 weeks. At 38 weeks' gestation, a male infant weighing 3,524 g, with Apgar scores of 9 and 9 at 1 and 5 minutes, respectively, was delivered by cesarean section. Critical pulmonary stenosis was confirmed by postnatal catheterization. These findings support the postulation that pulmonary stenosis is a progressive disorder. After percutaneous balloon dilatation, the transvalvular pressure gradient decreased and the right ventricular cavity increased gradually. The transvalvular pressure gradient had decreased to 15 mm Hg and the tricuspid/mitral valve annulus ratio was 0.93 at the age of 2 years.

Adult↗

Color Doppler vascularity index can predict distant metastasis and survival in colon cancer patients.

The purpose of this study was to investigate the clinical usefulness of the color Doppler vascularity index (CDVI) in patients with colon cancer before surgery. Forty-four patients with sonographically visible tumor mass of colon cancer were investigated. The CDVI of each tumor was determined using transabdominal color Doppler ultrasound. The CDVI was defined as the ratio of the number of the colored pixels within a tumor section to the number of total pixels in that specific tumor section and was calculated by using Encomate software (Electronic Business Machine Co. Ltd., Taipei, Taiwan). The correlation between the CDVI and clinicopathological factors, mode of recurrence, and patient survival was studied. For comparison, microvessel density (the mean number of microvessels in three areas of highest vascular density at x200 magnification) of the tumors of these 44 patients was also evaluated by using immunohistochemical staining of surgical specimens with anti-CD34. The microvessel density was not correlated with Dukes' classification, clinicopathological factors, and survival. The CDVI was significantly higher in the patients with lymph node metastases and vascular invasion than in those without such metastases and invasion (P = 0.006 and P = 0.0098, respectively). Moreover, in patients with a high CDVI (> 15%) and positive vascular invasion, survival was significantly poorer than in those with low CDVI (< or = 15%) and negative invasion (P = 0.0037 and 0.0039, respectively). Multivariate analysis indicated that liver metastasis, vascular invasion, and CDVI are independent prognostic factors in the patients with colon cancer. According to the mode of recurrence in 36 patients who underwent curative resection, the frequency of the distant organ recurrence was significantly higher in the high CDVI group (40%) than in the low CDVI group (0%). The CDVI is a good preoperative indicator of recurrence and patient survival in colon cancer. Thus, the CDVI may be helpful in stratifying patients for adjuvant therapy.

Adult↗

A probability prediction rule for malignant cervical lymphadenopathy using sonography.

BACKGROUND: Our purpose was to weigh various sonographic parameters as predicting malignant cervical lymphadenopathy and build a reliable prediction rule. METHODS: One hundred and eighty-nine cervical lymph node lesions from 125 consecutive patients were used for building the prediction model. Sonographic variables, including 15 morphologic features of B-mode, 5 vascular parameters of color Doppler mode, along with age and sex, were analyzed with multivariate logistic regression to evaluate the joint effect of a set of independent variables. A prediction rule for malignant lymphadenopathy was established, and prospective validation was assessed on a new group consisting of 100 lymph nodes from another 60 consecutive patients. RESULTS: The association of heterogeneous content, long transverse diameter, pathologic vascular pattern, high vascular density, and older age provided the most robust prediction value. Scoring scale was designed as 1x (age) + 2x (vascularity index) + 3x (short axis) + 4x (vascular pattern) + 4x (internal echo) according to the parameter estimates of multivariate logistic regression analysis. Cut-off value of score >==10 as malignancy resulted in 89.2% sensitivity and 85.2% specificity. Prospective validation also showed satisfactory results (sensitivity, 82.9%; specificity, 86.2%). CONCLUSIONS: By measuring only 4 sonographic parameters and age, this prediction rule could provide the physician a nonconfusing and reliable probability reference for managing cervical lymphadenopathy.

Adolescent↗

Angiogenesis of endometrial carcinomas assessed by measurement of intratumoral blood flow, microvessel density, and vascular endothelial growth factor levels.

OBJECTIVE: To evaluate the relationship between blood flow in the tumor assessed by color Doppler ultrasound, microvessel density, and vascular endothelial growth factor levels in endometrial carcinoma. METHODS: Forty-nine patients undergoing surgery for endometrial carcinoma were enrolled. Transvaginal color Doppler ultrasound was performed preoperatively and the lowest resistance index (RI) in the tumor was recorded for analysis. Vascular endothelial growth factor in the tumor was quantified by enzyme immunoassay. The microvessel density of the excised tumor was assessed immunohistochemically. The relationships between the corresponding RI, microvessel density, and vascular endothelial growth factor level of the tumor tissues and clinical and pathologic parameters were analyzed. RESULTS: Significantly lower RIs were noted in tumors of stage II or greater (0.37 compared with 0.50, P <.001), of high histologic grade (grade 3) (0.34 compared with 0.49, P =.004), with deep myometrial invasion (one-half depth or greater) (0.39 compared with 0.49, P =.002), with lymphovascular emboli (0.38 compared with 0.49, P <.001), or with lymph node metastasis (0.30 compared with 0.49, P <.001) compared with stage I tumors and tumors of histologic grade 1 or 2, with superficial myometrial invasion, without lymphovascular emboli, or with no lymph node metastasis. Increased vascular endothelial growth factor levels and microvessel density (x200 field) also were detected in tumors of stage II or greater (975 compared with 129 pg/mg, P =.014; and 88 compared with 61, P =.018, respectively), with lymphovascular emboli (1138 compared with 120 pg/mg, P =.002; and 86 compared with 63, P =.023), or with lymph node metastasis (1011 compared with 95 pg/mg, P <.001; and 98 compared with 61, P =. 019). Resistance index, microvessel density, and vascular endothelial growth factor levels in the tumor showed linear correlations (RI compared with microvessel density: r = -.32, P =. 03; RI compared with vascular endothelial growth factor levels: r = -.40, P =.004; microvessel density compared with vascular endothelial growth factor levels: r =.36, P =.011). CONCLUSION: Blood flow assessed by color Doppler ultrasound has histologic and biologic correlations with angiogenesis and vascular endothelial growth factor levels and might play an important role in predicting tumor progression and metastasis in endometrial carcinoma.

Adult↗

Vascular endothelial growth factor and prognosis of cervical carcinoma.

OBJECTIVE: To evaluate vascular endothelial growth factor (VEGF) as a marker for predicting lymph node metastasis and an independent prognostic factor of early-stage cervical carcinoma. METHODS: One hundred thirty-five women with stage IB-IIA cervical carcinoma had radical abdominal hysterectomies and pelvic lymph node dissections. Intratumoral cytosol VEGF concentrations were assayed with enzyme immunoassay. Histopathologic items and cytosol VEGF-influencing clinical outcomes were compared. RESULTS: Twenty-two women (16.3%) who had disease recurrence had higher levels of cytosol VEGF (1020 versus 112 pg/mg protein, P <.001) than those without recurrence. Using a cutoff value of 400 pg/mg protein resulted in best sensitivity of 75%, best specificity of 70%, positive predictive value of 41%, and negative predictive value of 92%. Only overexpressed cytosol VEGF (hazard ratio 6.44, P <.001) was an independent prognostic factor of disease-free survival. The overexpressed cytosol VEGF (hazard ratio 4.50, P =.021) and positive lymphovascular emboli (hazard ratio 4.11, P =.045) were independent prognostic factor of overall survival. CONCLUSION: Cytosol VEGF might be a biomarker for the status of pelvic lymph nodes in early-stage cervical carcinoma and an independent prognostic indicator of its outcome.

Adult↗

Gynecology.

Explore the source record for details and available documents.

Female↗

Prenatal depiction of angioarchitecture of an aneurysm of the vein of Galen with three-dimensional color power angiography.

A fetus with a large supratentorial cyst and cardiomegaly was encountered at 33 weeks of gestation. The cyst appeared as an aneurysmal, fluid-filled structure extending posteriorly with a finger-like appendage. Using color flow mapping, we disclosed rapid in-and-out blood flow with marked turbulence within the cyst. For evaluation of its blood supply and venous drainage of the vascular malformation, a three-dimensional reconstruction of the power Doppler image was conducted. The results revealed that the vascular malformation was supplied by a small contralateral aneurysm from the branches of Willis' circle, draining posteriorly into an abnormal falcine sinus and then into the superior sagittal sinus. No other fetal abnormality such as hydrocephalus or hydrops was discovered. The prenatal diagnosis of an aneurysm of the vein of Galen was made on the basis of the gray-scale, color Doppler findings, and also the angioarchitecture obtained by three-dimensional power Doppler imaging. The woman was admitted at 37 weeks of gestation due to labor onset and delivered the baby via the vaginal route without complication. Postnatal angiography and magnetic resonance imaging confirmed the diagnosis of an aneurysm of the vein of Galen, and the angioarchitecture depicted it before birth. We suggest that three-dimensional power Doppler ultrasonography may assist in the diagnosis of an aneurysm of the vein of Galen, and precisely delineate the complicated corresponding vasculature. This may guide postnatal management and predict the prognosis more accurately.

Adult↗

Antenatal diagnosis of congenital hepatoblastoma in utero.

A fetus with a huge hepatic tumor was detected by sonography at 36 weeks of gestation. The mass appeared as a single, solid and polylobular tumor located in the right lobe of the liver. Foci of hemorrhage, necrosis and some tiny calcifications were seen. The adjacent right kidney appeared normal but was displaced. The right adrenal gland was not visualized. Three-dimensional power Doppler sonography further depicted the corresponding vascular anatomy of the tumor, including its vascularization pattern and blood supply. The tumor was situated to the right of the umbilical vein and portal sinus, possibly deriving its blood supply from the portal circulation. The fundamental findings suggested the diagnosis of hepatoblastoma by exclusion of other possibilities. The baby was delivered by Cesarean section at 36 weeks' gestation, due to signs of fetal distress. Unfortunately, hypotension, tachycardia, and tachypnea developed shortly after birth. Surgical intervention was performed, but intractable bleeding occurred intra-operatively. The infant died at 6 days of age. Autopsy confirmed the diagnosis of hepatoblastoma. We believe this is the first reported case of the antenatal diagnosis of congenital hepatoblastoma.

Adult↗