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Biomedical subjects

S C Hsu

Publications and source records attributed to S C Hsu.

At least 91 records · Page 5Linked to original sources
PubMed1994

Glucose metabolism in photoreceptor outer segments. Its role in phototransduction and in NADPH-requiring reactions.

Glucose metabolism in the photoreceptor rod outer segment produces both ATP (GTP) and NADPH to support phototransduction and NADPH-requiring processes in this organelle. Glycolysis in isolated bovine rod outer segments produces 44.0 +/- 6.4 nmol of ATP/min/mg of protein or 5.7 mM ATP/min. This rate of ATP production is more than sufficient to maintain the basal rate of cGMP synthesis (0.86 mM cGMP/min) in the dark requiring 1.7 mM ATP/min. Following photoexcitation, the 4.5-fold increase in the turnover of cGMP requires an ATP synthesis rate of up to 7.7 mM ATP/min (Ames, A., Walseth, T. F., Heyman, R. A., Barad, M., Graeff, R. M., and Goldberg, N. D. (1986) J. Biol. Chem. 261, 13034-13042). Under these conditions the rate of ATP production by glycolysis as measured in isolated rod outer segments is not sufficient for the regeneration of cGMP. Additional energy is most likely provided by the phosphocreatine shuttle which transports high energy phosphate groups in the form of creatine phosphate from the rod inner segment to the rod outer segment for conversion to ATP. The hexose monophosphate pathway in bovine rod outer segments can produce up to 39.8 +/- 2.2 nmol of NADPH/min/mg of protein. This rate of NADPH production is sufficient to support both the reduction of retinal to retinol (1.2 +/- 0.2 nmol of NADPH/min/mg of protein) following the photobleaching of rhodopsin and glutathione reduction (1.1 +/- 0.1 nmol of NADPH/min/mg of protein) for the protection of rod outer segments from oxidative damage. These studies provide insight into the contribution of anaerobic glycolysis and the hexose monophosphate pathway in providing energy and nucleotides for phototransduction and other outer segment processes.

Adenosine Triphosphate↗
PubMed1994

n-Sec1: a neural-specific syntaxin-binding protein.

We have identified n-Sec1, a rat brain homolog of the yeast Sec1p protein that participates in the constitutive secretory pathway between the Golgi apparatus and the plasma membrane. The rat brain cDNA is predicted to encode a 68-kDa protein with 65% amino acid identity to Drosophila rop, 59% identity to Caenorhabditis elegans unc-18, and 27% identity to Saccharomyces cerevisiae Sec1p. By RNA blot analysis, n-Sec1 mRNA expression is neural-specific. An anti-peptide antiserum directed against the n-Sec1 carboxyl terminus detects a 68-kDa protein in rat brain cytosol and membranes, but not in peripheral tissues. In the presence of syntaxin 1a, a plasma membrane protein implicated in synaptic vesicle docking, n-Sec1 becomes membrane-associated. n-Sec1 binds to syntaxin 1a, 2, and 3 fusion proteins coupled to agarose beads, but not to syntaxin 4 fusion protein or beads coupled to a variety of other proteins. These findings indicate that n-Sec1 is a neural-specific, syntaxin-binding protein that may participate in the regulation of synaptic vesicle docking and fusion.

Amino Acid Sequence↗
PubMed1994

Specificity and regulation of a synaptic vesicle docking complex.

Synaptic vesicles are proposed to dock at the presynaptic plasma membrane through the interaction of two integral membrane proteins of synaptic vesicles, VAMP and synaptotagmin, and two plasma membrane proteins, syntaxin and SNAP-25. We have characterized the binding properties of these proteins and observed SNAP-25 potentiation of VAMP 2 binding to syntaxins 1a and 4 but not syntaxins 2 or 3. n-sec1, a neuron-specific syntaxin-binding protein, bound syntaxin with nanomolar affinity, forming a complex that is distinct from the previously identified 7S and 20S syntaxin-containing complexes. This suggests that syntaxin exists in at least three states: bound to n-sec1, in a 7S particle, and in a 20S particle. Recombinant n-sec1 inhibited VAMP or SNAP-25 binding to syntaxin. We propose that the specific associations of VAMP, SNAP-25, and syntaxin mediate vesicle docking and that a syntaxin/n-sec1 complex precedes and/or regulates formation of these complexes.

Amino Acid Sequence↗
PubMed1994

Differential diagnosis of extrahepatic biliary atresia from neonatal hepatitis: a prospective study.

The clinical presentations of cholestasis in infancy caused by neonatal hepatitis and biliary atresia are very similar. Diagnosis may be difficult on many occasions, but the surgical treatment of biliary atresia should be performed as early as possible. We established a 3-day workup protocol for the differential diagnosis of biliary atresia and neonatal hepatitis and compared the diagnostic accuracy, sensitivity, specificity, and predictive values of various methods. One hundred and twenty-six infants, including 84 with neonatal hepatitis (age, 65.1 +/- 24.1 days) and 42 with biliary atresia (age, 60.3 +/- 31.1 days), were studied prospectively from July 1982 to December 1990. The diagnostic accuracy of various methods was as follows: liver histology, 96.8%; color of duodenal juice, 91.6%; peak radioisotope count in duodenal juice, 84.2%; ultrasonographic examination of the hepatobiliary system, 80.2%; and persistence of clay-colored stool, 80.2%. After stepwise logistic regression, the diagnostic methods of significance were liver biopsy, color of duodenal juice, abdominal ultrasonography, and stool color. However, stool color and the onset of jaundice could not differentiate severe neonatal hepatitis from biliary atresia. The diagnostic methods of significance then were liver biopsy and duodenal juice color. With this 3-day protocol, no biliary atresia was missed although four cases of neonatal hepatitis were misdiagnosed, resulting in unnecessary laparotomy; we found an overall diagnostic accuracy of 96.8%. We conclude that this 3-day diagnostic protocol is very helpful in the differential diagnosis of neonatal hepatitis and biliary atresia. Liver histologic examination is the most reliable single test for the differential diagnosis.

Biliary Atresia↗
PubMed1993

Horizontal transmission of hepatitis B virus in children.

Horizontal transmission of hepatitis B virus (HBV) is responsible for about half of the hepatitis B surface antigen (HBsAg) carriers in Taiwan. To investigate the routes and risk factors of horizontal HBV transmission, 131 HBsAg carrier children of HBsAg seronegative mothers were compared with 98 age-matched children seronegative for all hepatitis B markers. Possible factors influencing transmission of HBV, including family size, age at attending kindergarten, frequency of intramuscular injection during infancy and at the toddler stage, contact with HBsAg carriers, and HBV status of parents, siblings and caretakers were studied by questionnaire survey. Intramuscular injection frequency during infancy and at the toddler stage and prevalence of HBsAg positivity among siblings were significantly higher in carrier children than in the control group. Other factors studied were not different in these two groups. The results indicated that unsterilized, multiple intramuscular injections and intrafamilial spread among siblings might be the major routes of horizontal HBV transmission in children in Taiwan.

Adolescent↗
PubMed1993

Carcinoma of the ampulla of Vater: long-term survival after surgical treatment.

Ninety-one patients were identified as having carcinoma arising from the ampulla of Vater. Radical pancreaticoduodenectomy, using either a standard or pylorus-preserving method, was performed in 69 consecutive patients over a 30-year period. Frequent clinical findings included jaundice (84%), a weight loss of more than 10% of the body weight (75%), abdominal pain (59%), chills and fever (52%), pruritus (48%) and a palpable gallbladder (38%). Acute pancreatitis was present in 10%. Postoperative mortality was 11.6%. Surgical mortality was 23.1% from 1962 to 1971 and 12.5% from 1972 to 1981, but was reduced to 6.3% from 1982 to 1991. Surgical mortality was primarily due to pancreaticojejunostomy leaks. The five-year survival rate was 52% and the 10-year rate was 50%. Radical pancreaticoduodenectomy for ampullary carcinoma has a low mortality and should remain the procedure of choice for ampullary carcinoma.

Adult↗
PubMed1992

Cell cycle regulation of glucocorticoid receptor function.

Glucocorticoid receptor (GR) nuclear translocation, transactivation and phosphorylation were examined during the cell cycle in mouse L cell fibroblasts. Glucocorticoid-dependent transactivation of the mouse mammary tumor virus promoter was observed in G0 and S phase synchronized L cells, but not in G2 synchronized cells. G2 effects were selective on the glucocorticoid hormone signal transduction pathway, since glucocorticoid but not heavy metal induction of the endogenous Metallothionein-1 gene was also impaired in G2 synchronized cells. GRs that translocate to the nucleus of G2 synchronized cells in response to dexamethasone treatment were not efficiently retained there and redistributed to the cytoplasmic compartment. In contrast, GRs bound by the glucocorticoid antagonist RU486 were efficiently retained within nuclei of G2 synchronized cells. Inefficient nuclear retention was observed for both dexamethasone- and RU486-bound GRs in L cells that actively progress through G2 following release from an S phase arrest. Finally, site-specific alterations in GR phosphorylation were observed in G2 synchronized cells suggesting that cell cycle regulation of specific protein kinases and phosphatases could influence nuclear retention, recycling and transactivation activity of the GR.

Animals↗
PubMed1992

Tumorigenicity of interleukin-2 (IL-2)-cDNA-transfected L1210 lymphoma and its in vivo variants is modulated by changes in IL-2 expression; potential therapeutic implications.

To study parameters that affect the tumorigenicity of L1210 lymphoma we have analyzed the structure of MHC class I antigens of this tumor. In addition this tumor was transfected with interleukin-2 (IL-2) cDNA in order to determine the effects of high concentrations of IL-2 within the tumor environment. The nucleotide sequence of the class I Kd, Dd and Ld mRNAs from this tumor showed that the encoded amino acid sequence of the corresponding antigens is normal, thus suggesting that the tumorigenicity of L1210 lymphoma is not due to defective antigen presentation to tumor-specific cytotoxic T cells. In contrast, induction of IL-2 expression by cDNA transfection led to loss of tumorigenicity of the IL-2-secreting tumor cells. However, a fraction of long-term-surviving mice developed progressively growing variant tumors that showed substantial decrease or loss of IL-2 expression. These results suggest that IL-2 secretion by tumors is suicidal but, because of tumor heterogeneity, IL-2-loss-variant tumors may arise that are able to escape the immune defenses of the host. The observed consistent loss of IL-2 expression in variant tumors implies that specific targeting of large quantities of IL-2 to tumor cells may be a valuable approach to immunotherapy of cancer. In addition we find that under specific gamma ray irradiation IL-2-secreting tumor cells lose their ability to multiply yet continue to secrete IL-2 at levels equivalent to those secreted by unirradiated cells. Such IL-2-secreting irradiated tumor cells were found to be superior immunogens in comparison to the irradiated parental tumor cells, suggesting their use as tumor vaccines.

Animals↗
PubMed1992

Production and characterisation of a monoclonal antibody (Cx-99) against cervical carcinoma.

An IgG1 monoclonal antibody (MAb Cx-99) has been established which recognises a surface antigen on epithelial cells, but not on fibroblastic or hematopoietic cells. Immunohistochemical studies showed that this antigen was present in all 37 squamous cell carcinomas (SCC) including 33 cervical SCC, and 30 of the 32 adenocarcinomas examined; most of the 33 cervical SCC were stained extensively. It was also detected in the culture medium of cervical cancer cell lines. In the normal cervix, this antigen was restricted to the undifferentiated basal cells. This observation suggests that the widespread expression of the antigen was triggered by oncogenesis. The MAb Cx-99 recognised an epitope on an asialyted glycoprotein which has an apparent molecular weight of 37 kilodaltons (kD) (and 2 minor proteins at 18 and 27 kD) and an isoelectric point (pI) of 5.3. It may have potential for studies on differentiation and oncogenesis and for diagnostic applications.

Animals↗
PubMed1992

[Factors in recurrence after curative resection of rectal cancer].

Data on 409 Patients who had a curative resection for rectal cancer at the National Taiwan University Hospital between 1977 and 1989 were analysed to determine the independent effect on recurrence. In our series, the total operative mortality rate was 1.7% and the resectability rate was 88.1%. For these cases who received curative resection, the overall 5-year survival rate was 62.6%. The 5-year survival rate varied according to the Dukes' stage: stage A, 96.4%; stage B, 73.3% and stage C, 39.6%. The total recurrence rate after curative resection was 35.9%, including local recurrence 18.3%, systemic recurrence 12.0%, and combined recurrence 5.6%. According to Dukes' staging system, the recurrence rate for stage A, B and C were 0%, 22.4% and 63.8%, respectively. We used Cox's regression model to analyse the patients characteristics and pathological variables on recurrence and to assess the independent influence of each when all other factors were held constant. The pathological stage of the cancer had the strongest association. Other variables found to have an independent yet significant importance, were CEA level and tumor size. The identification of the patient group, at a high risk of recurrence, might promote a more judicious selection for surgical procedure and trials of adjuvant therapy.

Adult↗
PubMed1991

Glycolytic enzymes and a GLUT-1 glucose transporter in the outer segments of rod and cone photoreceptor cells.

The presence of glycolytic enzymes and a GLUT-1-type glucose transporter in rod and cone outer segments was determined by enzyme activity assays, glucose uptake measurements, Western blotting, and immunofluorescence microscopy. Enzyme activities of six glycolytic enzymes including hexokinase, phosphofructokinase, aldolase, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, pyruvate kinase, and lactate dehydrogenase, were found to be present in purified rod outer segment (ROS) preparations. Immunofluorescence microscopy of bovine and chicken retina sections labeled with monoclonal antibodies against glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, and lactate dehydrogenase have confirmed that these enzymes are present in rod and cone outer segments and not simply contaminants from the inner segments or other cells. Rod outer segments were also found to contain glucose transport activity as detected by 3-O-[14C]methylglucose uptake and exchange. The glucose transporter had a Km of 6.3 mM and a Vmax of 0.15 nmol of 3-O-methylglucose/s/mg of ROS membrane protein for net uptake and a Km of 29 mM and a Vmax of 1.06 nmol of 3-O-methylglucose/s/mg of ROS membrane protein for equilibrium exchange. These Km values for net uptake and equilibrium exchange are similar to values obtained for human red blood cells and are characteristic of GLUT-1-type glucose transporter. The transport was inhibited by both cytochalasin B and phloretin. Western blot analysis and immunofluorescence microscopy using type-specific glucose transporter antibodies indicated that both rod and cone outer segment plasma membranes have a GLUT-1 glucose transporter of Mr 45K as found in red blood cells and brain microsomal membranes. Solid-phase radioimmune competitive inhibition studies indicated that rod outer segment plasma membranes contained 15% the number of glucose transporters found in human red blood cell membranes and had an estimated density of 400 glucose transporter per micron2 of plasma membrane. These studies support the view that outer segments can generate energy in the form of ATP and GTP by anaerobic glycolysis to supply at least some of the energy requirements for phototransduction and other metabolic processes.

3-O-Methylglucose↗
PubMed1991

Non-A, non-B hepatitis in children: a clinical, histologic, and serologic study.

Twenty-seven children with non-A, non-B hepatitis were studied with regard to their clinical, serologic, and histologic features. In contrast to adult patients, non-A, non-B hepatitis developed in most pediatric patients (19 out of 27) in the absence of identifiable parenteral exposure, probably because of fewer chances for exposure of children to blood or blood-contaminated products. Perinatal transmission was considered possible in one of the patients. Fulminant hepatitis had occurred in six patients, two of whom died. It is noteworthy that fulminant hepatitis usually occurred in children with sporadic non-A, non-B hepatitis. The progression to chronic hepatitis after acute illness is less likely in children than in adults. Chronic hepatitis developed in four patients. Two of these were asymptomatic at presentation, suggesting that in some patients, non-A, non-B hepatitis infections may remain undetected and progress to chronic hepatitis. Liver histologic examination was performed in 11 patients. There were no characteristic histologic findings which could differentiate non-A, non-B from B hepatitis. Antibodies to hepatitis C virus (anti-HCV) were tested in 22 of the 27 patients and 8 (36%) were seropositive for anti-HCV.

Child↗
PubMed1991

Gastroesophageal reflux in children with chronic recurrent bronchopulmonary infection.

To evaluate the role of gastroesophageal reflux (GER) as a possible cause of recurrent bronchopulmonary infection in Chinese children, 23 patients were studied prospectively with 24-h pH monitoring. Their ages ranged from 3 to 25 months. The patients studied were chosen by the criterion of repeated, radiographically documented bronchopulmonary infection with a frequency of two or more episodes in the most recent 6 months, or a single episode with a protracted course longer than 3 months. Twenty-one of the 23 showed abnormal GER on 24-h pH monitoring. Twenty children received medical therapy, 17 of whom were followed regularly for 14-29 months. Eleven had subsidence or improvement of symptoms at follow-up. Follow-up pH monitoring was performed in 5 of the 11 patients, and showed improvement. Six failed to show improvement with medical therapy. Follow-up pH monitoring revealed increased reflux in two of them. Three of the six received fundoplication and had marked improvement of reflux and symptoms postoperatively. Clinical resolution corresponded well to 24-h pH monitoring. GER may be considered one of the possible contributing factors in any child with chronic recurrent bronchopulmonary infection, and antireflux therapy might be beneficial. Twenty-four hour pH monitoring was the best single test for diagnosing GER and determining the severity of the disease.

Bronchitis↗
PubMed1990

Glyceraldehyde-3-phosphate dehydrogenase is a major protein associated with the plasma membrane of retinal photoreceptor outer segments.

A major 38-kDa protein associated with bovine rod outer segment plasma membranes, but not disk membranes, has been identified as glyceraldehyde-3-phosphate dehydrogenase on the basis of its N-terminal sequence and specific enzyme activity. This enzyme was extracted from lysed rod outer segments or isolated rod outer segment plasma membrane with 0.15 M NaCl and purified to homogeneity by affinity chromatography on a NAD(+)-agarose column. A specific activity of 90-100 units/mg of protein is within the range of activity obtained for glyceraldehyde-3-phosphate dehydrogenase isolated from other mammalian cells. Enzyme activity measurements indicate that this enzyme makes up approximately 2% of the total rod outer segment protein and over 11% of the plasma membrane protein. Protease digestion and binding studies on purified rod outer segment plasma and disk membranes suggest that glyceraldehyde-3-phosphate dehydrogenase reversibly interacts with a protease-sensitive plasma membrane-specific protein of rod outer segments. The finding that glyceraldehyde-3-phosphate dehydrogenase is present in large quantities in rod outer segments suggests that at least some of the energy required for the synthesis of ATP and GTP for phototransduction and other processes of the outer segment is derived from glycolysis which takes place within this organelle.

Amino Acid Sequence↗
PubMed1990

[Age changes in location of mandibular foramen].

In order to understand the changes in location of the mandibular foramen with age in children, lateral cephalometric radiographs from 112 child and adult patients, including both males and females, were randomly selected according to age. The subjects were divided into 6 age-groups; 3, 5, 7, 9, 11 and adult. Certain lines and points were traced on the radiographs used. The location of the mandibular foramen was identified by two persons. The perpendicular distance from the center of the mandibular foramen to the occlusal plane and the location of the mandibular foramen relative to the ramus height (Ar-Kk), as well as to the ramus width (a-p), were measured. The mandibular foramen was located 4.12 mm below the occlusal plane at the age of 3. It subsequently moved upward with age. By the age of 9, it had reached approximately the same level as the occlusal plane. The foramen continued to move upward to 4.16 mm above the occlusal plane in the adult group. The height percentage averages ranged from the lower 1/3 of the ramus height in the 3 year-old group to the middle of the ramus height in adults. The depth percentage averages ranged from 67.8% in 3 year-old children to 61.7% in adults. For greater accuracy in anesthetic procedures, dentists should relate the locational changes in the mandibular foramen with age when performing block anesthesia for the inferior alveolar nerve.

Adult↗
PubMed1989

Ischemic colitis as a cause of massive lower gastrointestinal bleeding and peritonitis. Report of five cases.

Vascular disorders of the colorectum are considered rare in Taiwan, however, recently the authors encountered five cases of ischemic colitis, all in men over 50 years of age. Cases one and five involved stricture, case two was secondary to obstructive colon cancer, and case three was of the gangrenous type presenting with peritonitis due to colonic perforation. Case four was of the transient type with acute massive lower gastrointestinal bleeding secondary to traumatic shock. All five patients were treated successfully by resection.

Aged↗