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C H Hsu

Publications and source records attributed to C H Hsu.

At least 37 records · Page 2Linked to original sources
PubMed2000

The proneural gene amos promotes multiple dendritic neuron formation in the Drosophila peripheral nervous system.

In the Drosophila peripheral nervous system, proneural genes direct the formation of different types of sensory organs. Here, we show that amos is a novel proneural gene that promotes multiple dendritic (MD) neuron formation. amos encodes a basic-helix-loop-helix (bHLH) protein of the Atonal family. During embryonic development, amos is expressed in patches of ectodermal cells, and the expression is quickly restricted to sensory organ precursors. Loss of amos function eliminates MD neurons that remain in ASC;atonal mutants. Misexpression of amos generates ectopic MD and other types of neurons. Amos interacts with the ubiquitously expressed Daughter-less protein in vivo and in vitro. Our final misexpression experiments suggest that a domain located outside the DNA-binding domain of Amos determines the MD neuronal specificity.

Animals↗
PubMed2000

Association of CTLA4 gene A-G polymorphism with type 1 diabetes in Chinese children.

OBJECTIVE: The CTLA4 (cytotoxic T lymphocyte associated antigen-4) gene encodes the T cell receptor involved in the control of T cell proliferation and mediates T cell apoptosis. Thus it is a strong candidate gene for T cell-mediated autoimmune disease. There is polymorphism at position 49 in exon 1 of the CTLA4 gene, providing a A-G exchange. This polymorphism is reportedly associated with type 1 diabetes in Caucasians but not in a small data set of Chinese. We wished to test this polymorphism in a larger and more homogeneous data set of Chinese children with type 1 diabetes and normal adult controls. DESIGN: A population-based case-control study of a CTLA4 gene 49 A-G polymorphism was performed to look for an association with type 1 diabetes in Chinese children. PATIENTS: We analysed this polymorphism in 253 unrelated children (128 boys) with type 1 diabetes (age at diagnosis 7.1 +/- 3.7 years) and 91 randomly selected normal adults. All individuals were Han Chinese. RESULTS: The genotype and gene frequencies of children with type 1 diabetes differed significantly from those of adult controls (P = 0.0091 and P = 0.0051, respectively). Genotype CTLA4 49 G/G and G allele conferred a risk of type 1 diabetes (RR = 2.13, 95% CI = 1.31-3.46, P = 0.0022; RR = 1.68, 95% CI = 1.17-2.43, P = 0.0051, respectively). CONCLUSIONS: This study demonstrates that CTLA4 49 A-G polymorphism is associated with type 1 diabetes in Han Chinese children. The CTLA4 49 G allele confers an increased risk of type 1 diabetes.

Abatacept↗
PubMed2000

Decreased GTPase activity of K-ras mutants deriving from human functional adrenocortical tumours.

Our previous studies have shown that seven out of 15 patients with adrenocortical tumours contained K-ras gene mutation. In addition, the mutation type was a multiple-site mutation, and the hot spots were located at codons 15, 16, 18 and 31, which were different from those reported before (codons 12, 13 and 61). To understand whether the mutation hot spots in human adrenocortical tumours were associated with activation of K-Ras oncogene and the alterations of its biocharacteristics, mutant K-Ras genes were cloned from tumour tissues and then constructed with expression vector pBKCMV. Mutant K-Ras genes were expressed at high levels in Escherichia coli and the resultant K-Ras proteins were shown to be functional with respect to their well-known specific, high-affinity, GDP/GTP binding. The purified K-Ras protein from E. coli were then measured for their intrinsic GTPase activity and the GTPase activity in the presence of GTPase-activating protein for Ras. The results showed that the wild-type cellular K-Ras protein (p21BN) exhibits about ten times higher intrinsic GTPase activity than the activated protein (p21BM3) encoded by mutant K-Ras gene, which mutated at codon 60. With regards to the codon 15, 16, 18 and 31 mutant K-Ras proteins (p21BM2), the GTPase activity in the presence of GAP is much lower than that of the normal K-Ras protein, whereas the intrinsic GTPase activity is nearly the same as that of the normal K-Ras protein. These results indicated that mutations at these hot spots of K-Ras gene were indeed activated K-Ras oncogene in adrenocortical tumours; however, their association with tumors needs further experiments to prove.

Adrenal Cortex Neoplasms↗
PubMed2000

Prolonged and enhanced suppression of thymidylate synthase by weekly 24-h infusion of high-dose 5-fluorouracil.

We have recently demonstrated that HDFL (high-dose 5-FU 2600 mg m-2 week-1 and leucovorin 500 mg m-2 week-1, weekly 24-h infusion) is highly active in the treatment of gastric cancer. To further clarify the possible mechanism underlying the improved activity of HDFL compared with conventional 5-FU regimens, we conducted in vitro studies examining the effect of these regimens on the differential regulation of thymidylate synthase (TS) in NCI-N87, a human gastric cancer cell line. The expected serum concentrations of 5-FU are 100-200 mM (lasting for less than 30 min) and 5-10 mM (lasting for 24 h) for the conventional 5-FU regimens (bolus injection or short intravenous infusion of 5-FU 370-500 mg m-2) and the HDFL regimens, respectively. Western blot analysis revealed that 24-h exposure of NCI-N87 to 2.5-10.0 mM of 5-FU resulted in a dose-dependent depletion of free TS, lasting for more than 24 h. In contrast, 30-min exposure of NCI-N87 to 200 mM of 5-FU resulted in a less than 12-h depletion of free TS. Moreover, 24-h exposure to 5-FU resulted in a higher S-phase blockade and enhanced cytotoxicity. In both modes of 5-FU treatment, the initial rapid depletion of free TS was accompanied by a rapid increment of a higher-molecular-weight TS molecule, suggesting that rapid formation of the ternary complex was the key mechanism of 5-FU action during this period. Northern blot analysis showed that the steady-state mRNA of TS was not affected by either of the schedules. We conclude that 24-h exposure of gastric cancer cells to low concentration of 5-FU resulted in better suppression of free TS, a higher degree of S-phase blockade, and enhanced cytotoxicity compared to 30-min exposure to high concentration of 5-FU. These in vitro results may help explain the improved clinical efficacy of HDFL regimens compared to conventional 5-FU regimens.

Antimetabolites, Antineoplastic↗
PubMed2000

Curcumin-containing diet inhibits diethylnitrosamine-induced murine hepatocarcinogenesis.

Curcumin has been widely used as a spice and coloring agent in foods. Recently, curcumin was found to possess chemopreventive effects against skin cancer, forestomach cancer, colon cancer and oral cancer in mice. Clinical trials of curcumin for prevention of human cancers are currently ongoing. In this study, we examine the chemopreventive effect of curcumin on murine hepatocarcinogenesis. C3H/HeN mice were injected i.p. with N-diethylnitrosamine (DEN) at the age of 5 weeks. The curcumin group started eating 0.2% curcumin-containing diet 4 days before DEN injection until death. The mice were then serially killed at the scheduled times to examine the development of hepatocellular carcinoma (HCC) and changes in intermediate biological markers. At the age of 42 weeks, the curcumin group, as compared with the control group (DEN alone), had an 81% reduction in multiplicity (0.5 versus 2.57) and a 62% reduction in incidence (38 versus 100%) of development of HCC. A series of intermediate biological markers were examined by western blot. While hepatic tissues obtained from the DEN-treated mice showed a remarkable increase in the levels of p21(ras), PCNA and CDC2 proteins, eating a curcumin-containing diet reversed the levels to normal values. These results indicate that curcumin effectively inhibits DEN-induced hepatocarcinogenesis in the mouse. The underlying mechanisms of the phenomenon and the feasibility of using curcumin in the chemoprevention of human HCC should be further explored.

Animals↗
PubMed2000

Increased frequency of angiotensin-converting enzyme DD genotype in patients with type 2 diabetes in Taiwan.

BACKGROUND: Diabetes is one of the major causes of end-stage renal failure in the Taiwanese population. Previous studies have shown that angiotensin-converting enzyme (ACE) inhibitor can improve glucose utilization and suppress hepatic glucose production and the renin-angiotensin system may play an important role in the initiation and progression of diabetic nephropathy. Thus, ACE gene polymorphism may be associated with type 2 diabetes and diabetic nephropathy. METHODS: To investigate the distribution of ACE-I/D genotype in type 2 diabetes and diabetic nephropathy, we examined 336 patients with type 2 diabetes (157 without nephropathy and 179 with nephropathy) and 263 age-matched normal controls. The diagnosis of nephropathy was made when daily protein loss exceeded 500 mg. ACE gene polymorphism was analysed by use of polymerase chain reaction. RESULTS: Our study revealed that the frequency of the D allele of the ACE gene was 29.3% in normal controls. The frequency of ACE DD genotype was significantly higher in type 2 diabetics compared with normal controls (18.2 vs 9.1%, P<0.01). The frequency of ACE DD genotype in patients with diabetic nephropathy was significantly higher than in patients without nephropathy (22.3 vs 13.4%, P<0.05). To determine whether ACE gene polymorphism was associated with the severity of diabetic nephropathy, we divided patients with diabetic nephropathy into dialysis and non-dialysis groups. The frequency of ACE DD genotype in the dialysis group was significantly higher than in non-dialysis group (28.7 vs 15.3%, P<0.05). CONCLUSION: Our results indicate that the frequency of ACE DD genotype is markedly higher in patients with type 2 diabetes, and the ACE DD genotype is significantly associated with diabetic nephropathy.

Adult↗
PubMed2000

Comparison of hemocytometer leukocyte counts and standard urinalyses for predicting urinary tract infections in febrile infants.

OBJECTIVES: To compare the accuracy of standard and hemocytometer white blood cell (WBC) counts and urinalyses for predicting urinary tract infection (UTI) in febrile infants. METHODS: Enrolled were 230 febrile infants < 12 months of age. All urine specimens were obtained by suprapubic bladder aspiration and microscopically analyzed by the standard urinalysis (UA) and by hemocytometer WBC counts simultaneously, and quantitative urine cultures were performed. Receiver-operating characteristic (ROC) curves were constructed for each method of UA. The optimal cutoff point of the UA test in predicting UTI was determined by ROC analysis. RESULTS: There were 37 positive urine cultures of at least 1,000 CFU/ml. Of these 37 patients, 9 females and 28 males, 1 had a positive blood culture (Escherichia coli). Thirty (81%) of the positive urine cultures had a bacterial colony count > or = 100,000 colony-forming units/ml, whereas the remaining had between 1,000 and 50,000 colony-forming units/ml. The area under the ROC curve for standard UA was 0.790 +/- 0.053, compared with 0.900 +/- 0.039 for hemocytometer WBC counts (P < 0.05). For hemocytometer WBC counts, the presence of < or =10 WBC/microl appeared to be the most useful cutoff point, yielding a high sensitivity (83.8%) and specificity (89.6%). Standard UA, with a cutoff point of 5 WBC/high power field, had a lower sensitivity (64.9%) and similar specificity (88.1%). The hemocytometer WBC counts showed significantly greater sensitivity and positive predictive value (83.8 and 60.8%, respectively) than the standard urinalysis (64.9 and 51.1%, respectively) (P < 0.05). The accuracy, specificity and likelihood ratio of hemocytometer WBC counts were also greater than that of standard UA (88.7, 89.6 and 8.08% vs. 84.3, 88.1 and 5.44%). CONCLUSION: Hemocytometer WBC counts provide more valid and precise prediction of UTI in febrile infants than standard UA. The presence of > or =10 WBC/microl in suprapubic aspiration specimens is the optimum cutoff value for identifying febrile infants for whom urine culture is warranted.

Chi-Square Distribution↗
PubMed2000

Capture-recapture when time and behavioral response affect capture probabilities.

We consider a capture-recapture model in which capture probabilities vary with time and with behavioral response. Two inference procedures are developed under the assumption that recapture probabilities bear a constant relationship to initial capture probabilities. These two procedures are the maximum likelihood method (both unconditional and conditional types are discussed) and an approach based on optimal estimating functions. The population size estimators derived from the two procedures are shown to be asymptotically equivalent when population size is large enough. The performance and relative merits of various population size estimators for finite cases are discussed. The bootstrap method is suggested for constructing a variance estimator and confidence interval. An example of the deer mouse analyzed in Otis et al. (1978, Wildlife Monographs 62, 93) is given for illustration.

Animals↗
PubMed2000

Increased renal medullary endothelin-1 synthesis in prehypertensive DOCA- and salt-treated rats.

To investigate the role of renal endothelin-1 (ET-1) synthesis in water-sodium homeostasis, we measured mRNA expressions, protein levels, enzyme activity, and receptor binding of the renal ET-1 system in a DOCA- and salt-treated rat model. Male Wistar rats were divided into control and DOCA- and salt-treated (DOCA-Salt) groups. The DOCA-Salt group received 25 mg/kg body wt DOCA and was maintained on 1% NaCl drinking water. Rats were killed on days 1, 2, 4, and 10 of the experiment. Urinary ET-1-like immunoreactivity significantly increased from the second day in the DOCA-Salt group and correlated well with the urinary sodium excretion rate (r = 0.81, P < 0.001). Renal endothelin-converting enzyme (ECE) activity, ET-1, and ECE-1 mRNA expressions were significantly increased in the renal medullary area of DOCA-Salt rats. In situ hybridization and immunohistochemical studies showed that the increase in ET-1 synthesis was mainly localized in the inner medullary collecting ducts. The maximum binding of endothelin B receptor also increased from the second day in the renal medulla of the DOCA-Salt group. Our results suggest that renal medullary synthesized ET-1 may be a natriuretic factor and may participate in the intrarenal regulation of water and salt homeostasis in prehypertensive DOCA-and salt-treated rats.

Animals↗
PubMed2000

Polymorphism of transmembrane region of MICA gene and Kawasaki disease.

Kawasaki disease is a febrile disease of children complicated with vasculitis of the coronary arteries and potential aneurysm formation. It has been recognized worldwide and appears to be increasing in frequency. Studies have found that Kawasaki disease is associated with major histocompatibility complex (MHC) class I B antigens. The MHC-class-I-chain-related gene A (MICA) is located near HLA-B. It has a triplet repeat microsatellite polymorphism in the transmembrane region. We investigated the microsatellite polymorphism in children with Kawasaki disease and controls. Seventy children (46 boys), age at diagnosis 1.68 +/- 1.69 years, with Kawasaki who were treated with aspirin as well as intravenous gamma-globulin were enrolled. Control subjects consisted of 154 children (87 boys), age 2.81 +/- 2.12 years. Phenotype frequency of allele A4 in patients with aneurysm formation was significantly lower than in patients without aneurysms [relative risk (RR) = 0.06, 95% confidence interval (CI) = 0.01-0.48, p = 0.00469, pc = 0.0232] and showed a similar tendency when compared with controls. Gene frequency of allele A4 was also significantly lower in patients who developed aneurysms than in patients who did not (RR = 0.07, 95% CI = 0.01-0.57, p = 0.0057, pc = 0.0282). Gene frequency of allele A5 showed a tendency to be higher in patients who developed aneurysms than in controls (RR = 2.35, 95% CI = 0.98-5.63, p = 0.0486, pc = 0. 220). Allele A5.1 tended to be negatively associated with Kawasaki disease (RR = 0.57, 95% CI = 0.35-0.93, p = 0.022, pc = 0.105). Our study showed that allele A4 was negatively associated with coronary aneurysm formation in Kawasaki disease. This suggests that allele A4 protects the children with Kawasaki disease from developing coronary aneurysms after aspirin and gamma globulin therapy.

Alleles↗
PubMed2000

Polymorphism in the transmembrane region of the MICA gene and type 1 diabetes.

Although MHC class II genes have a stronger association with type 1 diabetes than MHC class I genes, studies have shown that MHC class I molecules play an independent role in the etiology of type 1 diabetes, and the existence of susceptibility genes within a segment of MHC between the HLA-B and TNF genes has been predicted, where MHC class I chain-related gene A (MICA) resides. MICA has a triplet repeat polymorphism in the transmembrane region consisting of five alleles. We analyzed this polymorphism in 162 unrelated children (82 boys) with type 1 diabetes (age at diagnosis 7.01 +/- 3.76 yr) and 154 randomly selected unrelated children (87 boys), age 2.81 +/- 2.12 yr. Phenotype frequency of allele A9 in children with type 1 diabetes was significantly higher than in controls (RR = 2.42, 95% CI = 1.52-3.85, p = 0.000162, pc = 0.00081). Gene frequency of allele A9 was also significantly higher in children with type 1 diabetes when compared with control children (RR = 2.73, 95% CI = 1.85-4.03, p = 2.62 x 10(-7), pc = 1.31 x 10(-6)). This study demonstrates that MICA allele A9 confers risk of type 1 diabetes.

Alleles↗
PubMed2000

Urinary tract infection in febrile infants younger than eight weeks of Age.

OBJECTIVE: To assess the usefulness of laboratory parameters, including peripheral white blood cell (WBC) count, C-reactive protein (CRP) concentration, erythrocyte sedimentation rate (ESR), and microscopic urinalysis (UA), for identifying febrile infants younger than 8 weeks of age at risk for urinary tract infection (UTI), and comparison of standard UA and hemocytometer WBC counts for predicting the presence of UTI. METHODS: A total of 162 febrile children <8 weeks of age were enrolled in this prospective study. All underwent clinical evaluation and laboratory investigation, including WBC count and differential; ESR; CRP; blood culture; a lumbar puncture for cell count and differential, glucose level, protein level, Gram stain, and culture; and a UA and urine culture. All urine specimens were obtained by suprapubic aspiration and microscopically analyzed with standard UA as well as with hemocytometer WBC counts. Quantitative urine cultures were performed. Sensitivity, specificity, accuracy, likelihood ratios, and receiver operating characteristic (ROC) curves were determined for each of the screening tests. RESULTS: There were 22 positive urine culture results of at least 100 colony-forming unit/mL. Eighteen of these 22 patients were males, and all were uncircumcised. There were significant differences for pyuria >/=5 WBCs/hpf, pyuria >/=10 WBC/microL, CRP >20 mg/L, and ESR >30 mm/hour between culture-positive and culture-negative groups (P <.05). The ROC area for hemocytometer WBC count, standard UA, peripheral WBC count, ESR, and CRP concentration were.909 +/-.045,.791 +/-.065,.544 +/-.074,. 787 +/-.060, and.822 +/-.036, respectively. The ROC curve analysis indicates that the CRP, ESR, and standard UA were powerful but imperfect tools with which to discriminate for UTI in potentially infected neonates. Hemocytometer WBC counts had the highest sensitivity, specificity, accuracy, and likelihood ratios for identifying very young infants with positive urine culture results. For all assessments, hemocytometer WBC counts were significantly different, compared with the standard urinalysis. ESR, CRP, and peripheral WBC counts were not helpful in identifying UTI in febrile infants. CONCLUSION: UTI had a prevalence of 13.6% in febrile infants <8 weeks of age. The CRP, ESR, and standard UA were imperfect tools in discriminating for UTI, and the sensitivity of these laboratory parameters was relatively low. Hemocytometer WBC count was a significantly better predictor of UTI in febrile infants.

Female↗
PubMed2000

Convulsions during superior laryngeal nerve block--a case report.

Complications following local anesthesia for fiberoscope-assisted intubation are rare. We report a case with surgical condition indicating awake endotracheal intubation for general anesthesia, suffering from convulsions after receiving left superior laryngeal nerve block to facilitate the procedure. The possible cause may be accidental injection of the local anesthetic into the vertebral artery. Although the amount of local anesthetic injected was small, its concentration in the brain might be high enough to cause convulsion. The central nervous system toxicity of local anesthetic depends not only on the dosage used, but also on the rate of injection, as well as the site at which it is injected. Starting from a small dose together with careful monitoring of patient's response is advised when nerve block in the neck is performed. Here, we also emphasize the importance of availability of resuscitation equipment for maintaining adequate ventilation and circulation in case of emergency.

Adult↗
PubMed2000

Clinical presentation of acute mastoiditis in children.

Nineteen children with 21 episodes of acute mastoiditis were treated in our hospital from 1989 to 1998. The diagnosis was based on physical, radiologic, and surgical findings. The affected children were aged from 1 year old to 17 years old, with the peak incidence at 4 years old (23.8%). Postauricular pain (90.5%) and fever (81%) were the most common harbingers of incipient acute mastoiditis. Streptococcus pneumoniae (38.1%) was the most common organism isolated followed by Pseudomonas aeruginosa (23.8%). Underlying diseases such as leukemia and myeloid metaplasia were found in 38.6% of patients. All of the patients were initially treated with intravenous antibiotics during hospitalization. Six patients were managed with an adjunctive drainage procedure such as myringotomy or mastoidectomy. The most common complication of acute mastoiditis was hearing loss (31.6%); the second was meningitis (21.1%). Subperiosteal abscess was found in two patients and brain abscess in one. Although acute mastoiditis is an uncommon condition, early diagnosis and management are necessary to prevent more serious complications.

Acute Disease↗
PubMed2000

Congenital rhabdomyosarcoma--a case report.

A term female newborn was noted to have a tumor mass in the oral cavity soon after birth. Oral computer tomography revealed a well-enhanced soft tissue mass about 4 x 4 x 3 cm in size in the left buccal area. Group III embryonal type congenital rhabdomyosarcoma was diagnosed after biopsy (gross removal was not feasible). Respiratory distress exacerbated due to rapid tumor growth compressing airway with the result that endotracheal tube had to be intubated. Chemotherapy was done and complicated by two episodes of neutropenic fever and sepsis. Radiotherapy was suggested but refused by the family. Tumor size was slightly reduced and endotracheal tube could be removed four months later. She was taken home under regular chemotherapy. Radiotherapy, was, however, clearly indicated.

Female↗
PubMed1999

DNA adduct formation by secondary metabolites of cyclopenta[cd]pyrene in vitro.

In this study, calf thymus DNA was reacted in vitro with cyclopenta[cd]pyrene 3,4-epoxide (CPPE) or its metabolites, 3,4-dihydroCPP-3,4-diol (CPP-3,4-diol) and 4-hydroxy-3,4-dihydroCPP (4-OH-DCPP), activated with sulfotransferase. The adducts formed were analyzed by HPLC with fluorescence detection following enzymatic digestion of DNA to deoxynucleosides. We have shown previously that the major CPPE-reacted DNA adducts are cis-3-(deoxyguanosin-N2-yl)-4-hydroxy-3,4-dihydroCPP. Sulfotransferase activation of trans-CPP-3,4-diol yielded two adducts that were identical to the products resulting from the reaction of CPPE with DNA, while cis-CPP-3,4-diol gave very low covalent binding. Two adducts formed by sulfotransferase activation of 4-OH-DCPP were identical to the products of the reaction of synthetic 4-NaO3S-O-DCPP or sulfotransferase-activated 4-OH-DCPP with deoxyguanosine. These results indicate that guanine is the predominant site of CPP adduct formation in DNA, and that the 4-hydroxy-3-dGuo adducts can arise by reaction of DNA with either CPPE or sulfotransferase-activated trans-CPP-3,4-diol.

Animals↗
PubMed1999

Mutational spectrum of p53 gene in arsenic-related skin cancers from the blackfoot disease endemic area of Taiwan.

To understand the role of p53 tumour suppressor gene in the carcinogenesis of arsenic-related skin cancers from the blackfoot disease endemic area of Taiwan, we collected tumour samples from 23 patients with Bowen's disease, seven patients with basal cell carcinomas (BCC) and nine patients with squamous cell carcinomas (SCC). The result showed that p53 gene mutations were found in 39% of cases with Bowen's disease (9/23), 28.6% of cases with BCC (2/7) and 55.6% of cases with SCC (5/9). Most of the mutation sites were located on exon 5 and exon 8. Moreover, the results from direct sequencing indicated that missense mutations were found at codon 149 (C-->T) in one case, codon 175 (G-->A) in three cases, codon 273 (G-->C) in three cases, codon 292 (T-->A) in one case, codon 283 (G-->T) in one case, codon 172 (T-->C) in one case and codon 284 (C-->A) in one case. In addition, silent mutations were also found in four cases. These mutations were located at codons 174, 253, 289 and 298 respectively. In immunohistochemistry analysis, p53 overexpression was found in 43.5% (10/23) of cases with Bowen's disease, 14% (1/7) of cases with BCC and 44% (4/9) of cases with SSC. These findings showed that p53 gene mutation rate in arsenic-related skin cancers from the blackfoot disease endemic area of Taiwan is high and that the mutation types are different from those in UV-induced skin cancers.

Aged↗