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Biomedical subjects

Yu-Ching Lin

Publications and source records attributed to Yu-Ching Lin.

11 recordsLinked to original sources

A web-based decision support system for slopeland hazard warning.

A WebGIS decision support system for slopeland hazard warning based on real-time monitored rainfall is introduced herein. This paper presents its framework, database, processes of setting up the threshold line for debris flow triggering and the calculation algorithm implemented in the system. The web-based GIS via the Microsoft Internet Explorer is designed for analysis of areas prone to debris flows outburst and landslides during torrential rain. Its function is to provide suggestions to commander for immediate response to the possibility of slopeland hazards, and determine if pre-evacuation is necessary. The defining characteristics of the internet-based decision support system is not to automatically show the dangerous areas but acts as part of the decision process via information collection to help experts judge the prone debris flow creeks and the tendency of landslides initiation. The combination with real-time rainfall estimation by the QPESUMS radar system is suggested for further enhancement.

Decision Support Techniques↗

Wnt inhibitory factor-1, a Wnt antagonist, is silenced by promoter hypermethylation in malignant pleural mesothelioma.

Wnt inhibitory factor-1 (WIF-1) is a secreted protein that antagonizes Wnt signaling. We recently demonstrated the importance of aberrant activation of the Wnt signaling pathway in various cancers including malignant pleural mesothelioma. In this study, we revealed downregulated WIF-1 expression in cell lines and primary tissue when compared to normal mesothelial cell lines and adjacent pleura, respectively. We observed hypermethylation in four of four mesothelioma cell lines, but not in two normal mesothelial cell lines. In primary tissue samples, we observed methylation in three paired tumor specimens compared to their adjacent normal pleura and methylation in eight of nine unpaired tumor tissue samples. Taken together, our studies suggest that WIF-1 silencing due to its promoter hypermethylation is an important mechanism underlying the constitutively activated Wnt signaling in mesothelioma. New therapies toward inhibition of the Wnt pathway through WIF-1 might be promising for the future treatment of malignant mesothelioma.

Adaptor Proteins, Signal Transducing↗

Wnt signaling activation and WIF-1 silencing in nasopharyngeal cancer cell lines.

Aberrant activation of Wingless-type (Wnt) signaling pathway plays a critical role in oncogenesis of various human cancers. Wnt inhibitory factor-1 (WIF-1) is a secreted antagonist of Wnt signaling and acts through direct binding to Wnt in the extracellular space. Recently, we reported Wnt signaling in various human malignancies. In addition, we identified in lung cancer that WIF-1 is silenced due to promoter hypermethylation. In this study, we found constitutive activation of Wnt signaling and WIF-1 silencing in nasopharyngeal carcinoma (NPC) cell lines. Furthermore, by utilizing methylation-specific PCR and sequence analysis, we demonstrated that frequent hypermethylation of the WIF-1 promoter correlates with WIF-1 silencing in NPC cell lines. Our results indicate that aberrant Wnt signaling is a common event in NPC carcinogenesis linked with WIF-1 silencing in at least cell lines. Strategies targeting these molecules should be potentially promising in treating NPC.

Adaptor Proteins, Signal Transducing↗

Dramatic and prolonged decrease of whole salivary secretion in nasopharyngeal carcinoma patients treated with radiotherapy.

OBJECTIVES: This study evaluates: (1) the change in whole salivary secretion rates of nasopharyngeal carcinoma patients before, during, and after radiotherapy, especially during the first week of irradiation; (2) the recovery capability of salivary glands up to 2 years postirradiation; and (3) the possible prognostic factors affecting salivary gland functions. STUDY DESIGN: Fifty patients who completed conventional radiotherapy using either once-per-day or hyperfractionated technique were included. Both unstimulated and stimulated whole salivary flow rates and ratios (flow rate compared with baseline) were measured before, during, 1, 3, and 6 months, and 1 and 2 years after radiotherapy. Multivariate analysis of potential prognostic factors affecting the salivary secretion ratio was made. RESULTS: Salivary glands were very radiosensitive and responded to radiation very early. After 720 cGy at the fourth day of the 8-week treatment, the unstimulated and stimulated salivary flow rates had decreased by 40%-50%. The nadir was reached in many patients after 3600 cGy (4 weeks). A second phase of decrease in salivary secretion was noted after completion of radiotherapy. CONCLUSIONS: Different mechanisms may be responsible for salivary response after low and high dose of radiation. This study shows no recovery of salivary secretion during the follow-up period, and the best strategy for managing radiation-induced salivary gland damage may be reduction of radiation dose to the glands.

Adolescent↗

Structural and DNA-binding studies on the bovine antimicrobial peptide, indolicidin: evidence for multiple conformations involved in binding to membranes and DNA.

Indolicidin, a l3-residue antimicrobial peptide-amide, which is unusually rich in tryptophan and proline, is isolated from the cytoplasmic granules of bovine neutrophils. In this study, the structures of indolicidin in 50% D3-trifluoroethanol and in the absence and presence of SDS and D38-dodecylphosphocholine were determined using NMR spectroscopy. Multiple conformations were found and were shown to be due to different combinations of contact between the two WPW motifs. Although indolicidin is bactericidal and able to permeabilize bacterial membranes, it does not lead to cell wall lysis, showing that there is more than one mechanism of antimicrobial action. The structure of indolicidin in aqueous solution was a globular and amphipathic conformation, differing from the wedge shape adopted in lipid micelles, and these two structures were predicted to have different functions. Indolicidin, which is known to inhibit DNA synthesis and induce filamentation of bacteria, was shown to bind DNA in gel retardation and fluorescence quenching experiments. Further investigations using surface plasmon resonance confirmed the DNA-binding ability and showed the sequence preference of indolicidin. Based on our biophysical studies and previous results, we present a diagram illustrating the DNA-binding mechanism of the antimicrobial action of indolicidin and explaining the roles of the peptide when interacting with lipid bilayers at different concentrations.

Amino Acid Motifs↗

Directed evolution of Streptomyces clavuligerus deacetoxycephalosporin C synthase for enhancement of penicillin G expansion.

The deacetoxycephalosporin C synthase from Streptomyces clavuligerus was directly modified for enhancement of penicillin G expansion into phenylacetyl-7-aminodeacetoxycephalosporanic acid, an important intermediate in the industrial manufacture of cephalosporin antibiotics. Nine new mutants, mutants M73T, T91A, A106T, C155Y, Y184H, M188V, M188I, H244Q, and L277Q with 1.4- to 5.7-fold increases in the kcat/Km ratio, were obtained by screening 6,364 clones after error-prone PCR-based random mutagenesis. Subsequently, DNA shuffling was carried out to screen possible combinations of substitutions, including previous point mutations. One quaternary mutant, the C155Y/Y184H/V275I/C281Y mutant, which had a kcat/Km ratio that was 41-fold higher was found after 10,572 clones were assayed. The distinct mutants obtained using different mutagenesis methods demonstrated the complementarity of the techniques. Interestingly, most of the mutated residues that result in enhanced activities are located within or near the unique small barrel subdomain, suggesting that manipulation of this subdomain may be a constructive strategy for improvement of penicillin expansion. Several mutations had very distinct effects on expansion of penicillins N and G, perhaps due to different penicillin-interacting modes within the enzyme. Thus, the present study provided not only promising enzymes for cephalosporin biosynthesis but also a large number of mutants, which provided new insights into the structure-function relationship of the protein that should lead to further rational engineering.

Amino Acid Sequence↗

Leptospirosis presenting with fever and pulmonary hemorrhage.

Reports of leptospirosis have recently been increasing in Taiwan. We report a case of leptospirosis with the unusual initial manifestation of pulmonary hemorrhage. The patient presented with cough for 1 week and was admitted. After admission, fever, hemoptysis and severe dyspnea developed suddenly. Chest radiograph showed bilateral diffuse pulmonary infiltrates and he was transferred to the emergency room of our hospital. Oxygen saturation was 86% under room air and respiratory rate was 30 per minute. After admission to the thoracic ward on the third morning, parenteral penicillin and trimethoprim-sulfamethoxazole were given empirically, and a dramatic recovery ensued. Microscopic agglutination test showed an increased titer of 1:6400 against Leptospira interrogans serogroup shermani on the fourth day of hospitalization. Neither jaundice nor renal insufficiency occurred during treatment. Pulmonary hemorrhage may be an under-recognized manifestation of leptospirosis in Taiwanese patients. Leptospirosis should be taken into consideration in the differential diagnosis of pulmonary hemorrhage. Early treatment can lead to cure with reduced morbidity.

Adult↗

Cardiac catheterization in low birth weight infants.

BACKGROUND AND PURPOSE: The increased survival of low birth weight infants means that more of these infants may be candidates for cardiac catheterization. There is a lack of data from Taiwan on the results of cardiac catheterization in these infants. This study investigated the outcome of cardiac catheterization in infants weighing less than 2500 g in a single hospital over an 11-year period. METHODS: The records of 41 infants (17 males and 24 females) weighing less than 2500 g at the time of cardiac catheterization from August 1993 to July 2004 were reviewed. Morbidity and mortality were compared between diagnostic and intervention groups. RESULTS: Interventional procedures were performed in 14 and diagnostic catheterizations in 27 infants. These interventional procedures included 5 balloon valvuloplasties for pulmonary stenosis and 1 for aortic stenosis, 1 balloon angioplasty for critical coarctation, 1 aortic valvuloplasty, 1 dilatation for coarctation plus aortic valvuloplasty, 1 temporary pacemaker implantation, and 5 balloon atrioseptostomies. The median age at catheterization was 5 days and the median weight was 2.35 kg. All diagnostic and interventional procedures were successfully performed without mortality. Complications included 2 cases each of arrhythmia, bleeding, apnea, and thromboembolism in the diagnostic group and, in the intervention group, 2 cases each of supraventricular tachycardia and bleeding, and 1 case of linear dissection of a coarctation. CONCLUSIONS: None of the 41 catheterized low birth weight infants died. Furthermore, the complication rate in the intervention group was no higher than in the diagnostic group. We conclude that cardiac catheterization, even with an interventional procedure, can be performed safely in low birth weight infants.

Cardiac Catheterization↗

Balloon valvuloplasty for critical aortic stenosis in a low birth weight baby with tracheoesophageal fistula.

The use of valvuloplasty in low birth weight infants with valvular aortic stenosis has not been widely reported. We report a 1556 g 3-day-old female infant with complex heart disease including critical valvular aortic stenosis, bicuspid aortic valve, mitral stenosis, patent ductus arteriosus, and secundum type atrial septal defect. She also had esophageal atresia with a distal tracheoesophageal fistula and trisomy 18. Balloon valvuloplasty was considered to be more dangerous in this patient than in infants with simple critical aortic stenosis without other associated anomalies or low birth weight. Retrograde aortic balloon valvuloplasty was done carefully with the patient intubated and mechanically ventilated. We successfully dilated the stenotic aortic valve, which resulted in a dramatic decrease of the left ventricular pressure from 139/12 mm Hg to 81/11 mm Hg. Despite the high operative risk and poor prognosis, balloon valvuloplasty may be the first feasible step towards the survival of low birth weight infants with valvular aortic stenosis.

Aortic Valve Stenosis↗

Outcome of lung cancer patients with acute respiratory failure requiring mechanical ventilation.

To assess the weaning outcome of lung cancer patients with acute respiratory failure (ARF) requiring mechanical ventilation, we retrospectively analyzed the database of the respiratory intensive care unit at a university-affiliated tertiary care hospital. Charts were reviewed for cancer status, biochemistries before respiratory failure, causes of respiratory failure, acute physiology and chronic health evaluation (APACHE) III score, ventilatory settings, data recorded during spontaneous breathing, duration of ventilator days, and weaning outcome. Ninety-five consecutive respiratory failure events in 81 patients were recorded from January 1, 1995 through June 30, 1999. Twenty-six episodes ended with successful weaning (27.4%). Age, gender, and cancer status did not affect the weaning outcome. Serum albumin level, APACHE III score, highest fractional inspired O2 (FiO2) and highest positive end-expiratory pressure, organ failure, ability to shift to partial ventilatory support, and duration of mechanical ventilation could significantly influence the weaning outcome statistically. The overall hospital mortality rate was 85.2%. Our results suggested that lung cancer patients with ARF will have a better chance to wean if the initial APACHE III score was less than 70, use of FiO2 never exceeded 0.6, or less than 2 additional organ systems failed during the treatment course.

APACHE↗