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Biomedical subjects

T Y Wang

Publications and source records attributed to T Y Wang.

At least 37 records · Page 2Linked to original sources

The human VASA gene is specifically expressed in the germ cell lineage.

To understand the origins and function of the human germ cell lineage and to identify germ cell-specific markers we have isolated a human ortholog of the Drosophila gene vasa. The gene was mapped to human chromosome 5q (near the centromere) by radiation hybrid mapping. We show by Northern analysis of fetal and adult tissues that expression of the human VASA gene is restricted to the ovary and testis and is undetectable in somatic tissues. We generated polyclonal antibodies that bind to the VASA protein in formalin-fixed, paraffin-embedded tissue and characterized VASA protein expression in human germ cells at various stages of development. The VASA protein is cytoplasmic and expressed in migratory primordial germ cells in the region of the gonadal ridge. VASA protein is present in fetal and adult gonadal germ cells in both males and females and is most abundant in spermatocytes and mature oocytes. The gene we have isolated is thus a highly specific marker of germ cells and should be useful for studies of human germ cell determination and function.

Adult↗

Fluorescence-based evaluation of the partitioning of lipids and lipidated peptides into liquid-ordered lipid microdomains: a model for molecular partitioning into "lipid rafts".

A fluorescence-quenching assay is described that can directly monitor the relative extents of partitioning of different but structurally homologous fluorescent molecules into liquid-ordered (l(o)) domains in lipid vesicles exhibiting liquid-ordered/liquid-disordered (l(o)/l(d)) phase coexistence. Applying this assay to a series of bimane-labeled diacyl phospholipid probes in cholesterol-containing ternary lipid mixtures exhibiting l(o)/l(d) phase separation, we demonstrate that partitioning into l(o)-phase domains is negligible for diunsaturated species and greatest for long-chain disaturated species. These conclusions agree well with those derived from previous studies of the association of lipids and lipid-anchored molecules with l(o)-phase domains, using methods based on the isolation of a detergent-insoluble fraction from model or biological membranes at low temperatures. However, we also find that monounsaturated and shorter-chain saturated species partition into l(o) phases with significant, albeit modest affinities, and that the level of partitioning of these latter species into l(o)-phase domains is significantly underestimated (relative to that of their long-chain saturated counterparts) by the criterion of low-temperature detergent insolubility. Finally, applying the fluorescence-quenching method to a family of lipid-modified peptides, we demonstrate that the S-palmitoyl/S-isoprenyl dual-lipidation motif found in proteins such as H- and N-ras and yeast Ste18p does not promote significant association with l(o) domains in l(o)/l(d)-phase-separated bilayers.

Binding Sites↗

Different sphingolipids show differential partitioning into sphingolipid/cholesterol-rich domains in lipid bilayers.

Two fluorescence-based approaches have been applied to examine the differential partitioning of fluorescent phospho- and sphingolipid molecules into sphingolipid-enriched domains modeling membrane "lipid rafts." Fluorescence-quenching measurements reveal that N-(diphenylhexatrienyl)propionyl- (DPH3:0-)-labeled gluco- and galactocerebroside partition into sphingolipid-enriched domains in sphingolipid/phosphatidylcholine/cholesterol bilayers with substantially higher affinity than do analogous sphingomyelin, ceramide, or phosphatidylcholine molecules. By contrast, the affinity of sphingomyelin and ceramide for such domains is only marginally greater than that of a phosphatidylcholine with similar hydrocarbon chains. By using direct measurements of molecular partitioning between vesicles of different compositions, we show that the relative affinities of different C(6)-NBD- and C(5)-Bodipy-labeled sphingolipids for sphingolipid-enriched domains are quantitatively, and in most circumstances even qualitatively, quite different from those found for species whose N-acyl chains more closely resemble the long saturated chains of cellular sphingolipids. These findings lend support in principle to previous suggestions that differential partitioning of different sphingolipids into "raft" domains could contribute to the differential trafficking of these species in eukaryotic cells. However, our findings also indicate that short-chain sphingolipid probes previously used to examine this phenomenon are in general ill-suited for such applications.

Cholesterol↗

Adenoid basal carcinomas of the cervix: a unique morphological evolution with cell cycle correlates.

Adenoid basal carcinoma (ABC) is a rare cervical carcinoma of postmenopausal women composed of small basal-type (basaloid) cells with focal endocervical ("adenoid") differentiation. ABCs are associated with high-grade squamous intraepithelial lesions (HSIL) and contain integrated human papillomavirus type 16 DNA. However, ABCs have a favorable prognosis and do not metastasize. Five (5) ABCs were analyzed histologically for a marker distinguishing basal/ squamous from columnar (adenoid) differentiation (p63) and cell cycle activity (Ki-67), and compared with 20 cervical (CC) carcinomas. In contrast to other CCs, ABCs contained 4 distinct components, including (1) a classic HSIL; (2) a limited invasive component with squamoid maturation, often with a discrete layer of peripheral basal cells; (3) outgrowth of small basal cells from either HSIL or squamoid areas; (4) focal endocervical (adenoid) differentiation. ABCs showed distinct differences in cell cycle activity relative to CCs. Ki-67 positivity was high in associated HSILs but remained high and concentrated in the suprabasal cells of the invasive squamoid component of ABC. Moreover, proliferative index was variable to sharply reduced in areas of basaloid and adenoid differentiation, in contrast to conventional CCs. ABC is a unique neoplasm, not only by its transition through multiple phenotypes during invasion, but also by a proliferative index that is high in more mature neoplastic cells during the infiltrative process and reduced with progressive basal differentiation. The precise mechanism underlying this unique process of tumor evolution is unclear. However, the postmenopausal status of these patients suggests that host factors related to aging may influence tumor evolution and morphology after HPV 16 infection.

Basal Cell Carcinoma↗

Endometrial stromal sarcoma of the vagina.

Endometrial stromal sarcoma is a rare tumor and has unique histopathologic features. Most tumors of this kind occur in the uterus; thus, the vagina is an extremely rare site. A 34-year-old woman presented with endometrial stromal sarcoma arising in the vagina. No correlative endometriosis was found. Because of the uncommon location, this tumor was differentiated from other more common neoplasms of the vagina, particularly embryonal rhabdomyosarcoma and other smooth muscle tumors. Although the pathogenesis of endometrial stromal tumors remains controversial, the most common theory of its origin is heterotopic Müllerian tissue such as endometriosis tissue. Primitive cells of the pelvis and retroperitoneum are an alternative possible origin for the tumor if endometriosis is not present. According to the literature, the tumor has a fairly good prognosis compared with other vaginal sarcomas. Surgery combined with adjuvant radiotherapy appears to be an adequate treatment.

Adult↗

Prenatal diagnosis of a fetus with distal 10q trisomy.

Distal 10q trisomy is a well-defined but rare syndrome. Most cases are diagnosed in infancy or in childhood and rarely include prenatal findings. We present a case of fetal distal 10q trisomy with abnormal prenatal sonographic findings. A 19-year-old primigravida was referred for genetic counselling at 18 gestational weeks because her husband had a familial history of congenital anomalies. Genetic amniocentesis was thus performed and showed fetal distal 10q trisomy (10q24.1-->qter), 46,XX,der(22)t(10;22)(q24.1;p11.2)pat, resulting from paternal t(10;22) reciprocal translocation. Level II ultrasonograms further demonstrated bilateral hydronephrosis, ventricular septal defect and facial dysmorphism ascertained by three-dimensional ultrasound. The pregnancy was terminated at 22 gestational weeks. Post-mortem autopsy confirmed the sonographic findings. We suggest that abnormal prenatal sonographic findings such as cardio-vascular, renal and facial malformations should alert cytogeneticists to search for subtle chromosomal abnormalities.

Adult↗

A frame shift mutation in the DNA-binding domain of the androgen receptor gene associated with complete androgen insensitivity, persistent müllerian structures, and germ cell tumors in dysgenetic gonads.

OBJECTIVE: To describe the molecular, cytogenetic, immunohistochemical, and endocrinologic characteristics of a young 46,XY female with persistent müllerian structures and germ cell tumors in dysgenetic gonads. DESIGN: Descriptive case study. SETTING: Mackay Memorial Hospital and National Yang-Ming University, Taipei, Taiwan. PATIENT(S): A 22-year-old 46,XY female with persistent müllerian structures, a low level of serum testosterone, and no apparent adnexal masses. INTERVENTION(S): Laparoscopic removal of the dysgenetic gonads. MAIN OUTCOME MEASURE(S): Detection of an androgen receptor gene mutation by a semiautomated DNA sequencer, of the chromosomal complement by cytogenetic examination, of placental alkaline phosphatase activity by immunohistochemical analysis, and of neoplasms in dysgenetic gonads by histologic studies. RESULT(S): A unilateral gonadoblastoma and a contralateral gonadoblastoma associated with a dysgerminoma were found in the excised gonads. The tumors had a 46,XY complement. Placental alkaline phosphatase was present in the tumor cells. A frameshift mutation in the DNA-binding domain of the androgen receptor gene was detected in the patient's blood and the tumor tissues. A five-nucleotide "AGGAA" deletion at codons 608 and 609 of the androgen receptor gene resulted in a missing arginine and lysine as well as a frameshift that introduced a stop codon 12 amino acid downstream from the mutation. CONCLUSION(S): Molecular genetic analysis of the androgen receptor gene aids in the rapid diagnosis of complete androgen insensitivity irrespective of atypical clinical phenotypes and endocrinologic parameters.

Adult↗

Androgen receptor gene mutations in 46,XY females with germ cell tumours.

We present clinical findings and molecular characterization in two patients previously diagnosed as 46,XY female gonadal dysgenesis with germ cell tumour. Both patients showed a female general phenotype with unambiguously female external genitalia and primary amenorrhoea compatible with complete androgen insensitivity syndrome. The first patient, at the age of 31 years, developed a dysgerminoma measuring 8 x 13 x 10 cm in one abdominal testis. Genetic analysis revealed a single nucleotide substitution on exon 4 in the hormone-binding domain of the androgen receptor (AR) gene, resulting in a change of codon 681 GAG (glutamic acid) to AAG (lysine). The second patient, at the age of 17 years, developed a dysgerminoma measuring 12 x 10 x 7 cm in one abdominal testis and gonadoblastoma in the other testis. Genetic analysis showed a point mutation on exon 3 in the DNA-binding domain of the AR gene resulting in a change of codon 607 CGA (arginine) to CAA (glutamine). Arg607-Gln and Arg608-Lys point mutations in the DNA-binding domain of the AR gene have been associated with male breast cancer in partial androgen insensitivity syndrome. A codon 607 mutation in the DNA-binding domain of the AR gene in our patient 2 is associated with early development of germ cell tumour. We suggest regular molecular genetic analysis of the AR gene in 46,XY females with germ cell tumour and androgen insensitivity syndrome to detect differences in the specific regions of AR gene involved in early progression toward oncogenesis of the dysgenetic gonads.

Adolescent↗

Comparison of pylorus-preserving and classic pancreaticoduodenectomy.

BACKGROUND: The authors present their recent experience with the treatment of periampullary lesions to compare the surgical technique, safety and prognosis between pylorus-preserving pancreaticoduodenectomy (PPPD) and classic pancreaticoduodenectomy (CPD). METHODS: Prospective data from 100 patients with periampullary lesions treated with either PPPD or CPD between January, 1991, and June, 1997, were evaluated, including demographic data, surgical technique, surgical risk and prognosis. RESULTS: There were 35 patients treated with PPPD and 65 treated with CPD. The operating time was significantly shorter in the PPPD group (9.3 +/- 0.3 hours) than in CPD (10.4 +/- 0.3 hours). The average overall blood loss was 1,275 +/- 71 ml, with no statistical difference between PPPD and CPD groups. The overall complication rate was 56%, with 54% in the PPPD group and 57% in the CPD group (p = 0.755). The overall mortality was 4%, with 0% in the PPPD group and 6.2% in CPD (p = 0.655). There was no statistical difference in survival time for overall periampullary cancers between the PPPD and CPD groups (median = 28.0 vs 26.5 months, p = 0.393). The difference in survival time was still of no significance between the PPPD and CPD groups when the periampullary cancers were further stratified into pancreatic head cancer and nonpancreatic periampullary cancer. CONCLUSIONS: Morbidity and mortality of PPPD did not exceed that of CPD, and the prognosis after PPPD was not compromised in patients with periampullary cancer. PPPD, with a shorter operating time, can be a safe and effective alternative to CPD in the treatment of periampullary lesions.

Ampulla of Vater↗

Comparison of fluid-based, thin-layer processing and conventional Papanicolaou methods for uterine cervical cytology.

This study was conducted to compare the diagnoses and specimen adequacy of the ThinPrep (Cytyc Corporation, Boxborough, MA, USA) and conventional Papanicolaou preparation methods for cervical cytology. Cervical specimens from 972 patients from our gynecology clinic were analyzed. A single sample of the uterine cervix taken from each patient was first used to prepare the conventional Papanicolaou smear. Afterward, the residual tissue on the sampling device was rinsed into a fluid preservative from which two slides were prepared by means of the ThinPrep method. Conventional and ThinPrep slides were examined independently. Cytologic diagnoses and specimen adequacy were classified according to the Bethesda System. The diagnoses based on the ThinPrep and conventional smears matched in 939 (96.6%) cases. Low-grade squamous epithelial or higher grade lesions were detected with at least one of the methods in 59 cases and with both methods in 42 cases. Fifteen more cases of low-grade squamous epithelial or higher grade lesions (58 vs 43; p < 0.001) and 10 more cases of high-grade squamous epithelial lesions or carcinoma (42 vs 32; p = 0.006), were detected with ThinPrep than with conventional smears. The ThinPrep method yielded a higher rate of specimens that were satisfactory for cytologic examination than the conventional smears (89.8% vs 70.9%, p < 0.001). The detection rate of infectious agents was also higher with the ThinPrep method (14.9% vs 6.6%; p < 0.001). The reproducibility rate of the twin slides prepared with the ThinPrep method was greater than 99%. In conclusion, the ThinPrep method yielded a significantly higher positive detection rate of cervical abnormalities and more satisfactory specimens than conventional Papanicolaou smears.

Adult↗

Prenatal diagnosis of partial trisomy 3p(3p23-->pter) and monosomy 7q(7q36-->qter) in a fetus with microcephaly alobar holoprosencephaly and cyclopia.

We report the prenatal diagnosis of partial trisomy 3p(3p23-->pter) and monosomy 7q(7q36-->qter) in a fetus with microcephaly, alobar holoprosencephaly and cyclopia. A 26-year-old primigravida woman was referred for genetic counselling at 23 gestational weeks due to sonographic findings of intra-uterine growth retardation and cranio-facial abnormalities. Level II ultrasonograms further demonstrated alobar holoprosencephaly, a proboscis above the eye and a single median orbit consistent with cyclopia. Genetic analysis and fluorescence in situ hybridization on cells obtained from amniocentesis showed distal 3p trisomy (3p23-->pter) and 7q36 deletion, 46,XX,der(7)t(3;7)(p23;q36), resulting from a paternal t(3;7) reciprocal translocation. The pregnancy was terminated. Autopsy further confirmed the presence of arrhinencephaly, agenesis of the corpus callosum and a single ventricle of the brain. The phenotype of this antenatally diagnosed case is compared with those observed in 10 previously reported cases with simultaneous occurrence of partial trisomy 3p and terminal deletion 7q. All cases are associated with severe forms of holoprosencephaly and facial dysmorphism. This delineates an autosomal imbalance syndrome or a dosage effect involving duplication of distal 3p/deficiency of terminal 7q and dysmorphogenesis of the forebrain and mid-face.

Abnormalities, Multiple↗

12-O-Tetradecanoylphorbol-13-acetate (TPA)-induced increase in depressed white blood cell counts in patients treated with cytotoxic cancer chemotherapeutic drugs.

Fifty-two patients with solid tumors had depressed white blood cell and neutrophil counts because of prior treatment with cytotoxic cancer chemotherapeutic drugs. These patients were given one or more i.v. infusions of 0.125-0.25 mg of 12-O-tetradecanoylphorbol-13-acetate (TPA), and this treatment increased the low white blood cell and neutrophil counts toward the normal range. The average white blood cell and neutrophil counts were 2.55 x 10(9)/liter and 1.76 x 10(9)/liter, respectively, before treatment with TPA. After one or more i.v. infusions of TPA, the white blood cell and neutrophil counts increased to peak values of 5. 92 x 10(9)/liter and 4.76 x 10(9)/liter, respectively, within a few days. Most patients had increased levels of white blood cells and neutrophils by 24 hr after a single i.v. infusion of 0.25 mg TPA. Elevated levels were observed for at least 3 days. This study demonstrates that treatment with parenteral TPA is feasible with useful biological activity. Only mild and reversible side effects were observed.

Antineoplastic Agents↗

Is the short insulin tolerance test safe and reproducible?

The short insulin tolerance test (SITT) is described as a simple method to measure insulin sensitivity. To investigate the safety and reproducibility of the SITT, 16 healthy volunteers underwent two SITTs within 1 week. Intravenous insulin (0.05 U kg(-1) body weight) was injected into an antecubital vein. Blood samples were collected from the contralateral antecubital vein. The insulin-induced glucose disposal rate (Kitt) was calculated from the slope of the regression line of the logarithm of blood glucose against time during the first 3-15 min. Plasma glucose concentrations fell below 2.8 mmol l(-1) in 4 of the 32 tests and below 2.2 mmol I(-1) in 1 of these 4. Five subjects had mild hypoglycaemic symptoms, three of whom had plasma glucose concentrations below 2.8 mmol l(-1) in at least one SITT. The mean Kitt was 4.2% min(-1) (range 0.8-8.4) for the first test and 3.4% min(-1) (range 0.1-6.8) for the second test. The mean within-subject coefficient of variation was 30.7%. We conclude that SITT should be applied with caution especially on insulin sensitive subjects and has poor reproducibility using 0.05 U kg(-1) body weight of insulin injection, venous sampling, uncontrolled physical activity and uncontrolled dietary composition. Whether 0.1 U kg(-1) body weight of insulin injection and arterialized venous blood sampling as in the original description of this test can improve the reproducibility of the SITT needs further investigation.

Adult↗

Sonographic findings in a fetus with megacystis-microcolon-intestinal hypoperistalsis syndrome.

We describe the perinatal findings in a female fetus with megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS). Prenatal sonography performed during 18-21 weeks' gestation showed a normal amount of amniotic fluid, but the fetus was seen to have a persistently distended stomach, a hugely distended bladder, and bilateral dilated renal calyces. Genetic analysis of amniotic fluid revealed a 46,XX karyotype. The pregnancy was terminated at 22 weeks' gestation. At necropsy, the fetus was found to have prune-belly syndrome, gastric dilatation, pronounced megacystis, bilateral hydronephrosis and megaureters, short bowel, microileum, microcolon, and malrotation of the intestines. This fetus showed the typical clinical and sonographic features of MMIHS, as well as the rare antenatal finding of persistent gastric distention.

Abnormalities, Multiple↗

Accuracy of frozen section diagnosis in gynecology.

OBJECTIVE: A retrospective study was undertaken to evaluate the accuracy of frozen section diagnosis in gynecological surgery. METHODS: We compared the results of 792 consecutive gynecological frozen section diagnoses with their final diagnoses from January 1991 to June 1996. Slides for which the frozen section diagnosis was uncertain or incompatible with the final diagnosis were reviewed by an attending pathologist to determine the possible causes. RESULTS: A total of 299 ovarian, 390 lymph node, 56 uterine lesions, and 77 other tissue samples were obtained. The frozen section diagnosis was compatible with the final diagnosis in 97.5% of cases. The sensitivity for nonbenign lesions was 90.9%, and the specificity was 99.5%. There were no false positives or overestimated cases; 1.3% of cases were falsely negative, 0.4% underestimated the degree of malignancy, and 0.9% were uncertain. Possible causes for incompatible or uncertain frozen section diagnoses were analyzed. The accuracy of frozen section diagnoses for ovarian, lymph node, uterine, and other tissues was also evaluated. Frozen section was found to identify correctly 13 of 17 ovarian malignancies metastaic from other organs, 14 of 15 germ cell malignancies, and 3 of 4 dysgerminomas. The low sensitivity in ovarian borderline malignancy was due to the even lower sensitivity in its mucinous subgroup. The relationship between section numbers and accuracy of frozen section diagnosis in mucinous ovarian tumors was assessed. CONCLUSIONS: Frozen section diagnosis in gynecology is sufficiently accurate for clinical use, with a low false negative rate and an even lower false positive rate. Most incompatible frozen section diagnoses occurred in ovarian lesions, especially in mucinous ovarian tumors. Performing multiple sections (at least one section for every 10 cm in diameter) is recommended in the frozen section diagnosis of mucinous ovarian tumors.

Female↗

Effects of puerarin against glutamate excitotoxicity on cultured mouse cerebral cortical neurons.

AIM: To study the effects of puerarin (Pue) against injury of cultured neurons by sodium glutamate (Glu). METHODS: Neuronal damage induced by Glu, N-methyl-D-asparate (NMDA), and kainic acid (KA), as well as the actions of Pue and some excitatory amino acid antagonists (EAAA), were measured by determining the leakage of lactate dehydrogenase (LDH) from nerve cells. RESULTS: The 24-h leakage of LDH was increased from cells exposed either to Glu 100 and 500 mumol.L-1 for 15 min (from 20 +/- 4 kU/g protein in control group to 35 +/- 3 kU/g protein in Glu 100 mumol.L-1 group and to 46 +/- 6 kU/g protein in Glu 500 mumol.L-1 group) or to NMDA 500 mumol.L-1 or KA 500 mumol.L-1 for 45 min (from 19 +/- 4 kU/g protein in control group to 27 +/- 3 kU/g protein in NMDA group and to 30 +/- 5 kU/g protein in KA group). Pre and post-treatment with Pue (100 mumol.L-1) decreased the leakage of LDH, which was similar to the effects of EAAA kynurenic acid (from 35 +/- 3 kU/g protein in Glu 100 mumol.L-1 to 20 +/- 5 kU/g protein in kynurenic acid group and to 22 +/- 3 kU/g protein in Pue group), DL-2-amino-5-phosphonovaleric acid (APV) (from 27 +/- 3 kU/g protein in NMDA damaged group to 183 kU/g protein in APV group and to 19 +/- 5 kU/g protein in Pue group) or 6,7-dinitroquinoxaline-2,3(1H,4H)-diane (DNQX) (from 30 +/- 5 kU/g protein in KA damaged control to 22 +/- 5 kU/g protein in DNQX group and to 20 +/- 4 kU/g protein in Pue group). Post-treatment with Pue (100 mumol.L-1) was able to reduce 24-h leakage of LDH from neurons expos ed to Glu 100 mumol.L-1 for 15 min (from 35 +/- 3 kU/g protein to 27 +/- 4 kU/g protein). CONCLUSION: Pue had protective effects on neurons damaged by Glu, NMDA, or KA.

Animals↗

Metastatic leiomyosarcoma of the thyroid: a case report.

Metastatic malignant tumors of the thyroid are rarely encountered clinically. Most arise from primary sites in the lung, breast, kidney or gastrointestinal tract. Their clinical presentation may mimic a primary thyroid tumor and include signs and symptoms such as enlargement of the neck, hoarseness and dysphagia. Without a history of carcinoma in other organs, management as for primary thyroid tumor is often undertaken and misdiagnosis is common. This report concerns a 63-year-old female patient with a rapidly progressive enlargement of the neck. She had had a primary leiomyosarcoma lesion in her left leg that had been well controlled after wide excision. Bilateral pulmonary metastases were noted two years later without local recurrence. She receive wedge lung resections several times. To relieve progressive shortness of breath, debulking surgery of the thyroid was performed and metastatic leiomyosarcoma was proved. The related clinical data of this rare metastatic leiomyosarcoma of the thyroid is presented and the literature is reviewed.

Female↗