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Biomedical subjects

T Y Chen

Publications and source records attributed to T Y Chen.

At least 55 records · Page 3Linked to original sources

Cysteine modification of a putative pore residue in ClC-0: implication for the pore stoichiometry of ClC chloride channels.

The ClC channel family consists of chloride channels important for various physiological functions. Two members in this family, ClC-0 and ClC-1, share approximately 50-60% amino acid identity and show similar gating behaviors. Although they both contain two subunits, the number of pores present in the homodimeric channel is controversial. The double-barrel model proposed for ClC-0 was recently challenged by a one-pore model partly based on experiments with ClC-1 exploiting cysteine mutagenesis followed by modification with methanethiosulfonate (MTS) reagents. To investigate the pore stoichiometry of ClC-0 more rigorously, we applied a similar strategy of MTS modification in an inactivation-suppressed mutant (C212S) of ClC-0. Mutation of lysine 165 to cysteine (K165C) rendered the channel nonfunctional, but modification of the introduced cysteine by 2-aminoethyl MTS (MTSEA) recovered functional channels with altered properties of gating-permeation coupling. The fast gate of the MTSEA-modified K165C homodimer responded to external Cl(-) less effectively, so the P(o)-V curve was shifted to a more depolarized potential by approximately 45 mV. The K165C-K165 heterodimer showed double-barrel-like channel activity after MTSEA modification, with the fast-gating behaviors mimicking a combination of those of the mutant and the wild-type pore, as expected for the two-pore model. Without MTSEA modification, the heterodimer showed only one pore, and was easier to inactivate than the two-pore channel. These results showed that K165 is important for both the fast and slow gating of ClC-0. Therefore, the effects of MTS reagents on channel gating need to be carefully considered when interpreting the apparent modification rate.

Animals↗

A quasi-experimental study on a quality circle program in a Taiwanese hospital.

OBJECTIVE: To explore the impact of quality circles on job satisfaction, absenteeism, and turnover among hospital nurses in Taiwan. DESIGN: A quasi-experimental research design. SETTING: In November 1995, a study was initiated to establish quality circles in a 500-bed community hospital in Taiwan. After the administrative process and a pilot study, three of the experimental units began implementing the quality circle program in January 1997. For the comparison group, three non-quality circle medical-surgical units were selected from another building. STUDY PARTICIPANTS: All registered nurses on the three selected units who met the criteria of having worked full-time on those units for > or = 6 months were included in the study. There were 53 full-time registered nurses (49 female, four male) who met the criteria and 100% participated. There were no significant differences between the quality circle group and the non-quality circle group in terms of sex, age, and number of years of working experience, education or marital status. INTERVENTIONS: After obtaining administrative approval and support, the pilot study began with 3-month quality circle courses and 3-month quality circle process training for the experimental group nurses. Each circle has been meeting for 1 hour each week to identify problems, barriers, and solutions for effective implementation since 1997. MAIN OUTCOME MEASURES: (i) Demographic data questionnaire; (ii) Stamps and Piedmont's Index of Work Satisfaction; (iii) hospital records for absenteeism and turnover data. RESULTS: The data reveal that nurses of the three quality circle units felt more satisfied (P < 0.01) than did nurses from the three non-participating units. In the non-participating group, 36% had considered leaving the units, compared to 10% of nurses from the quality circle group. The turnover rate was significantly higher for the non-participating group (40%) than for the quality circle group (13%). CONCLUSION: This quality circle program in a Taiwanese hospital significantly improved satisfaction, reduced absenteeism, and lowered turnover of nurses. The findings support other studies reported in the literature.

Absenteeism↗

Comparison of in vitro growth-inhibitory activity of carboplatin and cisplatin on leukemic cells and hematopoietic progenitors: the myelosuppressive activity of carboplatin may be greater than its antileukemic effect.

BACKGROUND: Carboplatin [cis-diammine(cyclobutane-1, 1-dicarboxylato)platinum(II)] has been shown to be an active agent for acute myeloid leukemia. This second-generation platinum drug has less nephrotoxicity and ototoxicity but more myelotoxicity than does the first-generation platinum drug cisplatin. The study was designed to elucidate whether their myelosuppressive activities equal their antileukemic effects. METHODS: Cisplatin and carboplatin were used to treat four leukemic cell lines (CEM, HL60, K562 and U937), blast cells from 10 leukemic patients and hematopoietic progenitors from five umbilical cord blood samples. RESULTS: The mean IC50 of leukemic cell lines was 0.4 and 6.2 microg/ml, the mean IC50 of patients' leukemic blasts was 2.0 and 22.4 microg/ml and the mean IC50 of hematopoietic progenitors (BFU-E, CFU-E and CFU-GM) was 1.8 and 1.7 microg/ml for cisplatin and carboplatin, respectively. CONCLUSIONS: Carboplatin required a 10 times higher drug concentration than cisplatin to induce a similar degree of growth inhibition on leukemic cells. However, the hematopoietic progenitors responded equally to cisplatin and carboplatin at the same drug concentration. The results suggest that the myelosuppressive activity of carboplatin is greater than its antileukemic effect.

Antineoplastic Agents↗

Effects of the chitin synthesis inhibitor buprofezin on survival and development of immatures of Chrysoperla rufilabris (Neuroptera: Chrysopidae).

Effects of buprofezin (Applaud), a chitin synthesis inhibitor, on survival and development of eggs, three instars, and pupae of Chrysoperla rufilabris (Burmeister) were determined in the laboratory. Buprofezin at three tested concentrations (100, 500, and 1,000 mg [AI]/liter) did not affect the viability and development of eggs when the eggs were treated, or third instars and pupae when those stages were treated. Although the degree of effects by buprofezin on larvae varied with instar, buprofezin at the higher concentrations (500 and 1,000 mg [AI]/liter) reduced survival rates 17-47% and prolonged the overall development from first instars to adult emergence by 2 or 3 d when first instars were treated, indicating that the first instar is the most vulnerable stage. When second instars were treated, the survival of C. rufilabris from second instars to pupae was not significantly affected. However, the developmental time from second instar to adult emergence was longer in the treatments with the highest concentration (1,000 mg [AI]/liter) than that with the lowest concentration (100 mg [AI]/liter). The compatibility of buprofezin with natural enemies in integrated pest management programs is discussed.

Animals↗

Bezoars in children: report of four cases.

We reviewed the histories of four children (2 boys and 2 girls, aged 6 mo to 10 yr) with surgically proven bezoars, treated from 1991 to 1998. Two had gastric bezoars and two had intestinal bezoars. All four patients presented with gastrointestinal symptoms and none had undergone previous surgery. Three had a history of abnormal ingestion, including one who ate a pickled fruit from the Boraginaceae (locally known as Po-pu-tsu) plant for 1 year. Plain radiographs revealed intestinal obstruction in all four patients. Abdominal sonography disclosed a hyperechoic band-like lesion and acoustic shadow in both cases of gastric bezoar, and these bezoars were subsequently confirmed by gastric endoscopy. Lower gastrointestinal studies showed obstruction considered most likely to be due to bezoar in one case, while computed tomography (CT) revealed a characteristic small bowel mottled gas pattern in another. Surgical treatment relieved obstruction in all four patients. Bezoar should be suspected in patients with intestinal obstruction who have a history of ingestion of unusual substances. The findings of this report suggest that sonography and endoscopy are useful in the diagnosis of gastric bezoar, while CT is useful in the detection of intestinal bezoar.

Bezoars↗

Reversible hypertensive retinopathy in a child with bilateral pheochromocytoma after tumor resection.

Pheochromocytoma is very rare in children. We report a case of bilateral pheochromocytoma in a 12-year-old boy who had blurred vision due to hypertensive retinopathy. Abdominal ultrasound and computed tomography revealed bilateral suprarenal tumors. Resection of the bilateral tumors along with right total and left subtotal adrenalectomy were performed. Blood pressure and visual acuity returned to normal after surgery.

Adrenal Gland Neoplasms↗

Magnetic resonance of the hepatic veins with angular reconstruction: application in living-related liver transplantation.

BACKGROUND: Preoperative mapping of the hepatic venous system of the partial liver graft is indispensable to the success of living-related liver transplantation. We assessed the accuracy of magnetic resonance (MR) venography with angular reconstruction in depicting the tributaries of the middle hepatic vein and left hepatic vein in the donors, which was essential in graft retrieval and venoplasty. METHODS: Nineteen living-related liver transplantation donors underwent a pretransplantation survey, including sonography and MRI for hepatic venous evaluation. T1-weighted images were reconstructed manually, using the inferior vena cava as a fixed point for tilting to produce an oblique plane image where both the middle hepatic vein and left hepatic vein could be demonstrated draining into the inferior vena cava. The reconstructed images of the hepatic veins were compared with preoperative sonography, intraoperative sonography, and operative findings. RESULTS: Preoperative sonography and MR findings correlated well with the operative findings in the major hepatic veins. The MR venography of the ramification of the hepatic veins has an accuracy of 93%, the sonography, 84%. Sonography is slightly inferior in the evaluation of the hepatic vein in segment 4 and the left superior hepatic vein, with an accuracy of 73% and 67%, respectively. CONCLUSION: MR venography with angular reconstruction is accurate in depicting the complex distribution of the hepatic veins of the left liver, providing important information for decision making as to the cutting plane during graft retrieval and the method of venoplasty and anastomosis. Thus, unnecessary blood loss could be avoided and vascular complications could be prevented, as these conditions would be unacceptable for a healthy living donor. We propose that MR venography, a rapid and reliable technique, is an appropriate alternative examination or complementary modality to sonography in the pretransplantation evaluation of the living donor.

Adult↗

Recombinant protein composed of Pseudomonas exotoxin A, outer membrane proteins I and F as vaccine against P. aeruginosa infection.

We have constructed a chimeric protein composed of the receptor binding and membrane translocation domains of Pseudomonas exotoxin A (PE) with the outer membrane proteins I and F, together designated as PEIF. The potential of PEIF as a vaccine against Pseudomonas infection was evaluated in BALB/c mice and New Zealand white rabbits. We examined titers of anti-PE and anti-OprF antibodies, and the ability both to neutralize PE cytotoxicity and to increase opsonophagocytic uptake of Pseudomonas aeruginosa strain PAO1, serogroups 2 and 6. The results showed that PEIF can induce antibodies not only to neutralize the PE cytotoxicity but also to promote the uptake of various strains of P. aeruginosa by murine peritoneal macrophages. In a burned mouse model, PEIF afforded significant protection against infection by the homologous P. aeruginosa strain PAO1, heterologous serogroup 2, and the PE hyperproducing strain PA103. These observations thus indicate that PEIF may be used as a novel vaccine against P. aeruginosa infection.

ADP Ribose Transferases↗

Elimination of the slow gating of ClC-0 chloride channel by a point mutation.

The inactivation of the ClC-0 chloride channel is very temperature sensitive and is greatly facilitated by the binding of a zinc ion (Zn2+) from the extracellular side, leading to a Zn2+-induced current inhibition. To further explore the relation of Zn2+ inhibition and the ClC-0 inactivation, we mutated all 12 cysteine amino acids in the channel and assayed the effect of Zn2+ on these mutants. With this approach, we found that C212 appears to be important for the sensitivity of the Zn2+ inhibition. Upon mutating C212 to serine or alanine, the inactivation of the channel in macroscopic current recordings disappears and the channel does not show detectable inactivation events at the single-channel level. At the same time, the channel's sensitivity to Zn2+ inhibition is also greatly reduced. The other two cysteine mutants, C213G and C480S, as well as a previously identified mutant, S123T, also affect the inactivation of the channel to some degree, but the temperature-dependent inactivation process is still present, likewise the high sensitivity of the Zn2+ inhibition. These results further support the assertion that the inhibition of Zn2+ on ClC-0 is indeed due to an effect on the inactivation of the channel. The absence of inactivation in C212S mutants may provide a better defined system to study the fast gating and the ion permeation of ClC-0.

Amino Acid Sequence↗

Effects of a nitric oxide scavenger, carboxy-PTIO, on isoflurane MAC and cerebellar nitric oxide synthase activity in rats.

Recent studies have indicated that nitric oxide may play a role in inhalation anaesthesia. Inhibition of nitric oxide synthase reduces the minimum alveolar concentration (MAC) for inhalation anaesthetics and decreases cerebellar nitric oxide synthase (NOS) activity in rats. In this study, we have explored further the role of nitric oxide in isoflurane anaesthesia by examining the effects of a nitric oxide scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO 0.075-0.6 mg kg-1) on MAC values and cerebellar NOS activity in rats. Bolus injection of carboxy-PTIO at doses greater than 0.15 mg kg-1 reduced the MAC value of isoflurane (mean 1.36 (SEM 0.07)% at 0.15 mg kg-1, 1.39 (0.14)% at 0.3 mg kg-1 and 1.31 (0.06)% at 0.6 mg kg-1 vs control value of 1.61 (0.19)%. Administration of carboxy-PTIO 0.125 and 0.15 mg kg-1 resulted in increased cerebellar NOS activity during isoflurane anaesthesia (P < 0.05). These findings suggest that the level of nitric oxide may set a baseline from which isoflurane then acts.

Anesthetics, Inhalation↗

Presentation of autoantibody to proliferating cell nuclear antigen in patients with chronic hepatitis B and C virus infection.

OBJECTIVES: To study the association of antibodies to proliferating cell nuclear antigen (PCNA) in patients with chronic hepatitis B (HBV) and C (HCV) virus infection. METHODS: Sera from 243 patients with chronic HBV infection; 379 patients with chronic HCV infection; 80 patients with systemic lupus erythematosus (SLE); 28 patients with rheumatoid arthritis; 15 patients with Sjogren's syndrome; eight with polymyositis; eight with primary biliary cirrhosis; and 33 healthy control subjects were tested for the presentation of anti-PCNA antibodies by enzyme linked immunosorbent assay (ELISA) and immunoblotting using recombinant PCNA as antigen. The distribution of immunoglobulin isotypes of anti-PCNA antibody was measured by ELISA assay. RESULTS: By ELISA, anti-PCNA antibodies were detected in 30 (12.3%) patients with chronic HBV infection, 71 (18.7%) patients with chronic HCV infection, and five (6.3%) patients with SLE. The inhibition of binding with these sera by purified PCNA was shown to exceed 71%. By immunoblotting, the frequency of anti-PCNA in patients with chronic HBV and HCV infection was 17 of 243 (7%) and 41 of 379 (11%), respectively. Absorption studies on indirect immunofluorescence showed the typical nuclear speckled staining pattern by anti-PCNA sera was abolished by preincubation of sera with PCNA. Anti-PCNA antibody was not detected in sera from patients with autoimmune diseases except SLE. Anti-PCNA antibodies in patients with chronic HBV and HCV infection were predominantly IgG. CONCLUSION: These data suggest that anti-PCNA antibody are also present in patients with chronic HBV and HCV infection. Anti-PCNA antibody may not be specific for SLE.

Animals↗

The dose effect of propofol on cerebrovascular reactivity to carbon dioxide in rabbits.

BACKGROUND: Propofol has several properties beneficial to intracranial operation such as reduction in cerebral metabolic rate and cerebral blood flow (CBF) in a dose-dependent manner while leaving autoregulation intact. Several studies have demonstrated that the responsiveness of CBF to changes in arterial carbon dioxide tension (PaCO2) is maintained during propofol anesthesia in both humans and animals. These studies showed a significant difference in the CBF-CO2 reactivity slope between awake and propofol anaesthetized groups, but no comparison with different doses of propofol was made. To determine the dose effect of propofol on cerebrovascular CO2 reactivity, we used laser Doppler flowmetry (LDF) to detect the changes of CBF during propofol anesthesia. METHODS: Ten rabbits were studied using LDF on the parietal cortex. After surgical preparation, anesthesia was maintained with 66% N2O in O2, morphine 10 mg/kg and pancuronium. Three experimental conditions were studied sequentially with intravenous administration of the following drugs: (1) normal saline (control), (2) propofol 20 mg/kg/h i.v., (3) propofol 40 mg/kg/h i.v. Mean arterial pressure, rectal temperature and hematocrit were kept constant. The arterial carbon dioxide tension (PaCO2) was adjusted to three levels during each condition: 20-25 mmHg (hypocapnia), 35-40 mmHg (normocapnia) and 45-50 mmHg (hypercapnia). CBF was measured continuously and recorded after the target PaCO2 had been reached. RESULTS: There were no differences among all conditions in mean arterial pressure and heart rate. The changes of CBF as PaCO2 increased at the three different CO2 levels during each of the conditions were significantly different. The slope of CBF-CO2 reactivity among three different propofol doses was not significantly different. CONCLUSIONS: These data indicate that cerebral vasomotor responsiveness to CO2 during propofol anesthesia is preserved and that the slope of CBF-CO2 reactivity is independent of propofol doses as mean arterial blood pressure is maintained.

Anesthetics, Intravenous↗

The role of decompression for acute incomplete cervical spinal cord injury in cervical spondylosis.

STUDY DESIGN: A prospective study was conducted in 37 patients with cervical spondylosis with incomplete cord injury to assess the role of decompression in these patients. OBJECTIVES: To evaluate surgical and nonsurgical outcomes in patients with pre-existing cervical spondylosis of the spine, in whom an incomplete spinal cord syndrome developed after a minor neck injury. SUMMARY OF BACKGROUND DATA: The benefits of surgical treatment of incomplete cord injury with cervical spondylosis is controversial but remains a treatment option. The results of this study clarified the benefits of surgery in such patients. METHODS: Radiographic findings and outcomes based on post-spinal injury motor function score were compared retrospectively in 37 patients with cervical spondylosis. Sixteen patients were treated operatively and 21 were treated nonoperatively. RESULTS: The neurologic conditions of 13 of the 16 patients (81.2%) treated surgically improved within 2 days of surgery. Comparing the improvement of the two groups at defined intervals, there were statistically significant differences (P < 0.006) between the surgical and nonsurgical patients at 1-month and 6-month follow-ups. Nevertheless, 13 of the 21 patients (62%) treated nonoperatively had recovered to at least muscle Grade 3 at the 2-year follow-up, but their recovery was slower than that of the surgical group. CONCLUSION: Although neurologic improvement after an incomplete spinal cord injury when no bony lesion was present was slow during the first few months after trauma, more than 60% of the patients showed neurologic recovery with a muscle grade higher than 3 at 2-year follow-up. Surgical decompression, however, was associated with immediate neurologic improvement, faster recovery of neurologic function, early mobilization, better long-term neurologic outcome, briefer hospital stays, and fewer complications related to long confinements in bed than was nonoperative treatment.

Adult↗

Functional co-assembly among subunits of cyclic-nucleotide-activated, nonselective cation channels, and across species from nematode to human.

Cyclic-nucleotide-activated, nonselective cation channels have a central role in sensory transduction. They are most likely tetramers, composed of two subunits (alpha and beta or 1 and 2), with the former, but not the latter, being able to form homomeric cyclic-nucleotide-activated channels. Identified members of this channel family now include, in vertebrates, the rod and cone channels mediating visual transduction and the channel mediating olfactory transduction, each apparently with distinct alpha- and beta-subunits. Homologous channels have also been identified in Drosophila melanogaster and Caenorhabditis elegans. By co-expressing any combination of two alpha-subunits, or alpha- and beta-subunits, of this channel family in HEK 293 cells, we have found that they can all co-assemble functionally with each other, including those from fly and nematode. This finding suggests that the subunit members so far identified form a remarkably homogeneous and conserved group, functionally and evolutionarily, with no subfamilies yet identified. The ability to cross-assemble allows these subunits to potentially generate a diversity of heteromeric channels, each with properties specifically suited to a particular cellular function.

Animals↗