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Biomedical subjects

W C Shen

Publications and source records attributed to W C Shen.

At least 19 recordsLinked to original sources

Phenotype-dependent synthesis of transferrin receptor in rat alveolar epithelial cell monolayers.

The iron carrier protein transferrin plays a prominent antioxidant and anti-bacterial role in the lower respiratory tract and is present at elevated concentrations in lung epithelial lining fluid relative to plasma. The level of transferrin receptor synthesis in primary cultures of rat alveolar epithelial cells (AECs) was investigated. Transferrin receptor was found to be synthesized early in AEC cultures with the alveolar type II cell-like phenotype. Cell-surface receptor localization was attenuated upon apparent transdifferentiation to the alveolar type I cell-like phenotype later in culture. Binding of (125)I-labeled transferrin to the receptor indicated that surface and total cellular transferrin receptor levels were decreased in the type I-like cells. Inclusion of keratinocyte growth factor (KGF) in culture media (10 ng/ml) resulted in retention of transferrin receptor localized to the basolateral surface. Transferrin-receptor-specific internalization of (59)Fe-transferrin was also limited to the basolateral surface of KGF-treated monolayers. These data suggest that alveolar type II (but not type I) cells express functional transferrin receptor in adult rat alveolar epithelium.

Animals↗

Bowman-Birk protease inhibitor and its palmitic acid conjugate prevent 7,12-dimethylbenz[a]anthracene-induced transformation in cultured mouse mammary glands.

The chemopreventive effects of Bowman-Birk protease inhibitor (BBI), a soybean polypeptide, and its palmitic acid conjugate, Pal-BBI, on 7,12-dimethylbenz[a]anthracene (DMBA)-induced transformation were investigated by using an in vitro whole organ culture system of mouse mammary glands. The transformation incidence was measured as the number of glands containing nodule-like alveolar lesions (NLAL). Both BBI and Pal-BBI were effective in preventing DMBA-induced transformation, especially when added to the medium during the developing period after the exposure of mammary glands to DMBA, i.e. 35.9 and 53.4% prevention, respectively. However, when only present in the medium before the promotion period, Pal-BBI was effective in decreasing the transformation incidence (32.2%) while BBI was not (10.3%). This difference could possibly be due to the high lipophilicity and tissue retention of Pal-BBI in mammary gland cultures.

9,10-Dimethyl-1,2-benzanthracene↗

Presentation of striatal hyperintensity on T1-weighted MRI in patients with hemiballism-hemichorea caused by non-ketotic hyperglycemia: report of seven new cases and a review of literature.

Recent studies have shown unique clinicoradiologic characteristics in patients with hemiballism-hemichorea (HB-HC) caused by non-ketotic hyperglycemia; however, there is still a limited number of patients being reported. We report 7 patients (3 males and 4 females) with this type of dyskinesia, whose ages ranged from 60 to 84 years. Brain CT of these patients showed hyperdensity in the contralateral striatum, corresponding with MRI studies that showed an increased signal intensity on T1-weighted images and a decreased signal on T2-weighted images. After metabolic control had been achieved, the hyperkinetic state of these patients abruptly ceased. Follow-up neuroimaging studies in 2 patients documentied complete resolution of the striatal hyperintensity on brain CT and MRI after 3 months and 6 months, respectively. A review of patients with HB-HC caused by non-ketotic hyperglycemia reported formerly and in the present study shows that the dyskinesia tends to occur in aged diabetic patients. The age of patients with dyskinesia secondary to cerebral infarction is generelly much lower. We also found that 86% (30 out of 35 cases) patients reported with HB-HC caused by non-ketotic hyperglycemia were Asians. The prognosis of the dyskinesia was excellent, and the radiological abnormalities are completely reversible.

Aged↗

Tyrphostin-8 enhances transferrin receptor-mediated transcytosis in Caco-2- cells and inreases hypoglycemic effect of orally administered insulin-transferrin conjugate in diabetic rats.

PURPOSE: To investigate the effect of tyrphostin 8 (T-8), a GTPase inhibitor, on transferrin receptor (TfR)-mediated transcytosis of insulin-transferrin (In-Tf) conjugate in cultured enterocyte-like Caco-2 cells and on gastrointestinal (GI) absorption of In-Tf in streptozotocin (STZ)-induced diabetic rats. METHODS: Caco-2 cells and diabetic rats were used as in vitro and in vivo models, respectively. TfR-mediated transcytosis was measured using 125I-In-Tf. The absorption of insulin in diabetic rats was demonstrated by the hypoglycemic effect. Rat blood glucose level was determined using a ONE TOUCH blood glucose monitoring system. RESULTS: T-8 increased apical-to-basolateral transport of In-Tf conjugate by enhancing TfR-mediated transcytosis in filter-grown Caco-2 cell monolayer, and this enhancement was higher and faster than the previously reported brefeldin A (BFA)-induced effect. The measurement of transepithelial electrical resistance (TEER) during the transport study showed that T-8 was less destructive on the cell tight junction than BFA. The GI absorption of In-Tf was evaluated by its hypoglycemic effect after oral administration in STZ-induced diabetic rats. The glucose-lowering effect of orally administered In-Tf in STZ-induced diabetic rats was improved by either T-8 or BFA. However, the effect of T-8 was more potent than that of BFA, especially at 7 h after administration. Either non-conjugated insulin or insulin-human serum albumin (In-HSA) conjugate by itself or in combination with T-8 did not show any hypoglycemic effect after oral administration, indicating that T-8-enhanced hypoglycemic activity of In-Tf was due to a selective enhancement of TfR-mediated transcytosis. CONCLUSIONS: Our data indicated that T-8 could be used to increase the GI absorption of insulin as a transferrin conjugate. T-8, as an enhancer of TfR-mediated transcytosis, is better than the previously reported BFA. T-8 produces a higher increase on the transport of In-Tf and a lower toxicity on epithelial cells. Our findings provide an alternative approach to promote the GI absorption of insulin, as well as other peptide or protein drugs.

Animals↗

Antley-Bixler syndrome, description of two new cases and review of the literature.

OBJECTIVE: Antley-Bixler syndrome (ABS) is a rare disorder characterized by multiple malformations of cartilage and bone including multisynostotic osteodysgenesis, midface hypoplasia, choanal atresia or stenosis, femoral bowing, neonatal fractures and multiple joint contractures and, occasionally, urogenital, gastrointestinal or cardiac defects. Since the first report in 1975, at least 34 cases (including this report) have been described. We present 2 cases of congenital hydrocephalus, suggesting the cause of craniosynostosis and midface hypoplasia is associated with ABS. CLINICAL PRESENTATION: The first case was a 1-day-old female with Arnold-Chiari malformation, multiple cranial synostosis, obstructive hydrocephalus and radioulnahumeral synostosis. Ventriculoperitoneal (V-P) shunting was performed when she was 7 days old. She died 42 days later due to cardiopulmonary failure. The second case was a 2-month-old female with bilateral coronal synostosis, obstructive hydrocephalus and brachycephaly. V-P shunting was done soon after her admission, and bilateral lateral canthal advancement with the floating forehead procedure was performed 1 month later. She is still alive with good development. DISCUSSION: The main anomalies of the ABS can be divided into 4 categories: craniofacial, skeletal, extremity and urogenital anomalies. They may be the result of mutation in the fibroblast growth factor receptor 2 (Ser351Cys) gene, which was confirmed in our case 2. Craniosynostosis combined with hydrocephalus created congenital increased intracranial pressure (IICP). Early V-P shunt implantation and surgical release of the closed suture and lateral canthal advancement should be done as soon as possible, ideally when the patient is younger than 3 months. CONCLUSION: Early correction of craniosynostosis was feasible and safe for one of our patients. We offer our experience in the treatment of hydrocephalus and correction of craniosynostosis to relieve IICP.

Abnormalities, Multiple↗

Gastric retention and stability of lipidized Bowman-Birk protease inhibitor in mice.

Bowman-Birk protease inhibitor (BBI) was modified with a reversible lipidizing agent. The palmitoylated product, Pal-BBI, and BBI were iodinated and orally administered to mice using a gavage needle. A prolonged retention of Pal-BBI was found in the stomach. Furthermore, a significant amount of Pal-BBI was detected as intact polypeptide in the stomach of mice fed with Pal-BBI, while only degradation products were detected with BBI. There was also a significant increase of radioactivity in the blood and liver in mice 1.5 h post-administration of Pal-BBI. These results indicate that lipidized polypeptide can have a longer retention and lower digestion in the stomach. They also suggest that the Pal-BBI may have a higher gastrointestinal absorption than the original polypeptide.

Animals↗

Congenital enterovirus 71 infection: a case study with virology and immunohistochemistry.

Previously reported enterovirus 71 (EV71) infections associated with hand-foot-mouth disease, aseptic meningitis, encephalitis, polio-like myelitis, and paralysis all have involved young children. We report a 28-year-old woman who possibly contracted EV71 infection during pregnancy. Obstetric ultrasonograms at 25 weeks of gestation revealed an abnormal placenta, as well as hepatosplenomegaly, liver calcification, excessive ascites, and mild hydrocephalus of the fetus. Presence of EV71 was determined by immunodot blotting, virus culture, and partial sequencing of the amplified product of nested reverse transcription-polymerase chain reaction. Postmortem immunohistochemistry further identified EV71 in the fetal midbrain and liver. The findings indicate that intrauterine EV71 infection is possible during pregnancy.

Adult↗

Redundant roles for the TFIID and SAGA complexes in global transcription.

The transcription factors TFIID and SAGA are multi-subunit complexes involved in transcription by RNA polymerase II. TFIID and SAGA contain common TATA-binding protein (TBP)-associated factor (TAF(II)) subunits and each complex contains a subunit with histone acetyltransferase activity. These observations have raised questions about whether the functions of the two complexes in vivo are unique or overlapping. Here we use genome-wide expression analysis to investigate how expression of the yeast genome depends on both shared and unique subunits of these two complexes. We find that expression of most genes requires one or more of the common TAF(II) subunits, indicating that the functions of TFIID and SAGA are widely required for gene expression. Among the subunits shared by TFIID and SAGA are three histone-like TAF(II)s, which have been proposed to form a sub-complex and mediate a common function in global transcription. Unexpectedly, we find that the histone-like TAF(II)s have distinct roles in expression of the yeast genome. Most importantly, we show that the histone acetylase components of TFIID and SAGA (TAF(II)145 and Gcn5) are functionally redundant, indicating that expression of a large fraction of yeast genes can be regulated through the action of either complex.

Acetyltransferases↗

Dermal sinus with dermoid cyst in the upper cervical spine: case note.

We describe a 5 year-old girl who had a skin dimple of the back of her upper neck. MRI showed a dermal sinus tract in the upper cervical spine, associated with an intramedullary dermoid cyst at C 2-3, and spina bifida. A laminectomy was performed, the dermoid cyst and the sinus tract were completely removed. This congenital complex is very rare.

Cervical Vertebrae↗

MRI of Enterovirus 71 myelitis with monoplegia.

We report two boys diagnosed as having herpangina and hand-foot-mouth disease complicated by monoplegia during the outbreak enterovirus infection in Taiwan in 1998. Enterovirus 71 was identified in the stool and throat swab; neither polio nor Coxsackie viruses was identified. MRI showed unilateral lesions in the anterior horns of the spinal cord at T11-12 and C2-5. Although the MRI findings and sites of these lesions were similar to those of poliovirus-associated poliomyelitis, the virological data indicated that these boys were infected with enterovirus type 71.

Diagnosis, Differential↗

Dural cavernous angioma mimicking a meningioma and causing facial pain.

An 18-year-old girl who had severe headaches in the left temporal and facial regions was found to have a small enhanced dural-based parietal convexity mass. On magnetic resonance imaging (MRI), this mass was homogeneously enhanced with "dural tail sign," and was similar to a meningioma. This mass was completely removed surgically, and pathology proved it to be a cavernous angioma without previous hemorrhages. The patient's facial pain was dramatically relieved after surgery. A small dural mass causing severe facial pain is an unusual situation. The lack of hemosiderin in the extra-axial cavernous angioma often leads to the preoperative diagnosis of meningioma.

Adolescent↗

Signal transduction cascades regulating fungal development and virulence.

Cellular differentiation, mating, and filamentous growth are regulated in many fungi by environmental and nutritional signals. For example, in response to nitrogen limitation, diploid cells of the yeast Saccharomyces cerevisiae undergo a dimorphic transition to filamentous growth referred to as pseudohyphal differentiation. Yeast filamentous growth is regulated, in part, by two conserved signal transduction cascades: a mitogen-activated protein kinase cascade and a G-protein regulated cyclic AMP signaling pathway. Related signaling cascades play an analogous role in regulating mating and virulence in the plant fungal pathogen Ustilago maydis and the human fungal pathogens Cryptococcus neoformans and Candida albicans. We review here studies on the signaling cascades that regulate development of these and other fungi. This analysis illustrates both how the model yeast S. cerevisiae can serve as a paradigm for signaling in other organisms and also how studies in other fungi provide insights into conserved signaling pathways that operate in many divergent organisms.

Calcineurin↗

Hypoglycemic effect of insulin-transferrin conjugate in streptozotocin-induced diabetic rats.

Transferrin (Tf) receptor-mediated transcytosis of insulin-transferrin conjugate (In-Tf) has been demonstrated in cultured human enterocyte-like Caco-2 cells. In the present report, oral delivery of insulin as a Tf conjugate in streptozotocin (STZ)-induced diabetic rats was investigated. Human insulin was conjugated at a 1:1 molar ratio to iron-loaded human Tf by a disulfide linkage. The stability of In-Tf and the free insulin released from In-Tf was studied in the presence of rat liver slices by using radioimmunoassay. The release of free insulin involved a disulfide reduction reaction that was inhibited by the pretreatment of the liver slice with a sulfhydryl-reactive reagent N-ethylmaleimide. A protease inhibitor cocktail also showed a partial inhibition of insulin degradation. The biological activity of the conjugate was tested in STZ-induced diabetic rats with s.c. administration, and the conjugate exhibited a slow but prolonged hypoglycemic effect compared with that of the native human insulin. In-Tf also displayed a slow but prolonged hypoglycemic effect after oral administration in fasted STZ-induced diabetic rats in a dose-dependent manner. Furthermore, In-Tf was detected in the serum of rats at 4 h after oral administration of the conjugate, indicating that In-Tf can overcome the barriers in the gastrointestinal tract and be absorbed as an intact conjugate. These results demonstrate that transepithelial transport via TfR-mediated transcytosis is a feasible approach for developing the oral delivery of insulin, as well as other peptide drugs.

Administration, Oral↗