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Biomedical subjects

L S Lin

Publications and source records attributed to L S Lin.

At least 37 records · Page 2Linked to original sources

Changes of superoxide dismutase (SOD) mRNA and activity in response to hypoxic stress in cultured Wistar rat glioma cells.

In an attempt to understand the change of superoxide dismutase (SOD) in tumor cells by hypoxia and hypoxia-normoxia exposure, the present study performed an in vitro investigation using rat glioma cell line in culture. Hypoxia was induced by an incubation with nitrogen gas for 15 h followed the normoxia exposure with air for 30 min. Activity of SOD in cytosolic and particulate of cells was determined by the reduction of nitroblue tetrazolium. Changes of mRNA for Cu,Zn-SOD or Mn-SOD were also characterized using Northern blotting analysis. Hypoxic stress decreased the activity of SOD, both Cu,Zn-SOD and Mn-SOD, in glioma cells. Expression of mRNA for SOD was elevated by hypoxic stress and the increase of mRNA level for Cu,Zn-SOD was more marked than that for Mn-SOD. In response to hypoxia-normoxia exposure, an increase of activity with a lower mRNA level for Mn-SOD was observed in glioma cells. However, changes of Cu,Zn-SOD both the activity and the level of mRNA were not found in glioma cells by hypoxia-normoxia. The obtained results suggest that the SOD in glioma cells can be activated to compensate the damage from free radicals during hypoxic stress.

Animals↗

Epidemiological study of moyamoya disease in Taiwan.

From January 1978 to December 1995, 92 cases of Moyamoya disease were collected from seven major medical centers in Taiwan. The data gave an annual incidence rate of 0.048 per 100,000 population. There were 40 males and 52 females and the ages ranged from 2 to 62 years with the peak incidence in the 31-40 year age group (23 cases). Cerebral infarction occurred in 20 out of 24 juvenile patients (83%), and in 24 out of 68 adult patients (35%). The difference was statistically significant. Haemorrhagic stroke was more frequent in adult patients. Computed tomographic scans following stroke showed cerebral infarction in 44 cases, ventricular haemorrhage in 26 cases, intracerebral haemorrhage in 14 cases and pure subarachnoid haemorrhage in eight. The most frequent initial symptom was motor disturbance (59%), followed by headache (49%) and impaired consciousness (35%). This survey showed an incidence rate much lower than that in Japan, but comparable with those in other Oriental countries and higher than those in Western countries. The male-to-female ratio once differed considerably from that of the Japanese series, but from the present study is now quite similar.

Adolescent↗

Social-cognitive predictors of fruit and vegetable intake in children.

Social-cognitive theory (SCT) was used to explain the fruit and vegetable intake of 1,398 3rd graders. SCT variables assessed included self-efficacy, outcome expectations, preferences, social norms, asking skills, and knowledge. Fruit and vegetable intake was assessed with 7-day records. Bivariate correlations with fruit and vegetable intake ranged from .17 for asking skills to .29 for fruit and vegetable preferences. In analyses controlling for school-level clustering, only preferences and positive outcome expectations remained significantly associated with fruit and vegetable intake, accounting for approximately 10%-11% of the variance. Limitations in the conceptualization, scope, and measurement of the variables assessed may have contributed to the weak associations observed. Models incorporating factors other than individual-level social-cognitive variables may be required to more fully explain children's dietary behavior.

Child↗

A nationwide epidemiological study of spinal cord injuries in Taiwan from July 1992 to June 1996.

This prospective epidemiological survey of spinal cord injury (SCI) in Taiwan was carried out by recruiting patients attended by physicians from various medical centers and general hospitals all over Taiwan from July 1992 to June 1996. A total of 6,410 cases of traumatic spinal fracture were registered among which were 1,586 new cases of SCI. The results represented 70% of the scope of SCI in Taiwan. The observed average annual incidence of SCI in Taiwan was 18.8 per million population. The mean age was 46.1 years-old with a plateau distribution for over 20 years and older. Geriatric victims are a major group of SCI in Taiwan. The male to female ratio was 3 to 1. The leading causes of SCI were traffic accidents and accidental falls. Motorcycle collisions accounted for 62% of the traffic accidents, and as most of the motorcycle riders were not helmet users, head injury became the major associated injury of SCI in Taiwan. The effectiveness of the comprehensive care system for SCI patients in Taiwan is relatively good, as reflected by the low rates of complications of SCI, the low mortality rate (6.6%) and the high percentage (67.4%) of SCI patients achieving self-care ultimately at home after rehabilitation. The analysis of person days healthy life loss and quality adjusted survival time revealed that SCI patients in Taiwan required 4 years to cope with the morbidity, and on average, could return to the main stream of life for another 30 years.

Accidental Falls↗

Patterns in children's fruit and vegetable consumption by meal and day of the week.

OBJECTIVE: To assess differences in children's consumption of fruit and vegetables (F&V) by day of the week and meal of the day. DESIGN: Baseline data from two school based nutrition education studies were combined for analysis. SUBJECTS/SETTING: 2984 third grade students from 48 participating elementary schools in three school districts in the metropolitan Atlanta area. MEASURES OF OUTCOME: The frequency of consumption of F&V abstracted by trained registered dietitians from prompted 7-day food records. STATISTICAL-ANALYSES PERFORMED: Mixed model analysis with meals and days as terms, controlling for the within school correlation, gender and ethnic group. RESULTS: F&V were most frequently consumed at weekday lunch, and second most frequently at dinner. Participation in school lunch accounted for a substantial proportion of F&Vs consumed at lunch. Few F&Vs were consumed at breakfast or snack. CONCLUSIONS: School lunch makes an important contribution to elementary school students' F&V consumption. Dietary change programs should target parents to increase F&V consumption at dinner, and target students for the meals over which they assert the most control: breakfast and snacks.

Adolescent↗

A nationwide epidemiological study of spinal cord injury in geriatric patients in Taiwan.

This prospective epidemiological survey of spinal cord injury (SCI) in Taiwan was carried out among patients attended by physicians from various medical centers and general hospitals all over Taiwan from July 1992 to June 1996. In all, 1,586 new cases of SCI were registered, representing about 70% of all possible SCI cases in Taiwan. The observed average annual incidence of SCI in Taiwan was 18.8 per million people, whereas it was 47.5 for the geriatric section. The mean age was 46.1 years with a plateau distribution after 20 years and older. Geriatric victims (297 cases, 18.7%, group II) formed a major section of SCI cases in Taiwan. Another group of younger SCI patients (15-64 years old, 1,232 cases, group I) was selected for comparison. The results showed that the male-to-female ratio, pattern of neurological deficits, and causes of injury and death of geriatric SCI patients differed significantly from those of the younger SCI group. Elderly women were exposed to a higher risk of SCI than younger women (M/F ratio 1.7:1). Falls were the leading cause of geriatric SCI, and two thirds of them occurred on level ground. Traffic accidents accounted for a third of SCI cases, half of which involved motorcycle accidents, a fifth of them pedestrians. Quadriplegia and quadriparesis occurred more frequently among elderly cases of SCI than in the younger group and a higher proportion of them died of SCI complications. Two thirds of elderly SCI patients recovered well enough after comprehensive treatment to be able to take care of themselves at home. The government should initiate programs of prevention to reduce the prevalence of geriatric SCI in Taiwan.

Age Factors↗

Serum responses to the combination of Epstein-Barr virus antigens from both latent and acute phases in nasopharyngeal carcinoma: complementary test of EBNA-1 with EA-D.

Elevated serum IgA to antigens of EBV is associated with nasopharyngeal carcinoma (NPC). We have tested 620 NPC sera by ELISA for the presence of antibodies to EBV-encoded DNA binding protein, EBV-specific DNA polymerase, early antigen-diffused (EA-D), EBV nuclear antigen 1 (EBNA-1), EBV-specific thymidine kinase, and BamHI Z fragment EBV replication antigen. Sensitivity of these proteins was in the range of 51.5-79.5% for IgA and 69.4-82.8% for IgG. The complementary use of EBNA-1 with EA-D, however, could increase the sensitivity significantly to 98.1%. Western blot analysis further showed that the combination of EBNA-1 and EA-D is most useful for the detection of NPC. This is the first report of using double biomarkers including EBV gene products from both latent and active infections. The results of this study suggest that EBV in NPC may not be latent alone and that the method may be valuable for the early detection, early treatment, and better survival rate of patients with NPC. Because the application of recombinant EBV protein in ELISA is cost-effective and feasible for mass screening, the method may be of worth for further clinical investigation.

Adult↗

Evaluation of the drug interaction between intravenous high-dose fluconazole and cyclosporine or tacrolimus in bone marrow transplant patients.

The purpose of this open-label, prospective study was to compare steady state concentrations and clearances of intravenously administered cyclosporine or tacrolimus with and without concomitant high-dose (400 mg/day) fluconazole in allogeneic BMT patients. Twenty-one patients were evaluable. The mean steady state cyclosporine and tacrolimus concentrations without fluconazole were 320.3 and 18.2 ng/ml and increased to 389.2 and 21.2 ng/ml, respectively, after the addition of fluconazole, corresponding to a 21% (P=0.031) and 16% (P=0.125) increase. The mean steady state clearance of cyclosporine and tacrolimus without fluconazole was 6.82 and 1.28 ml/min/kg, which decreased to 5.57 and 1.10 ml/min/kg with fluconazole, corresponding to a 21% (P=0.031) and 16% (P=0.125) decrease, respectively. The 21% difference in the cyclosporine concentration and clearance was not thought to be clinically significant. These results suggest that fluconazole's interaction with cyclosporine or tacrolimus may be a result of fluconazole's inhibition of gut metabolism, resulting in a greater extent of absorption.

Antifungal Agents↗

Hypothalamic serotonin release and raised blood pressure after raphe nuclei stimulation in rats.

Electrical stimulation of dorsal raphe (DR) nuclei, in addition to enhancing serotonin (5-HT) release in the hypothalamus, elicited proportional hypertension and tachycardia in anesthetized rats. This could be mimicked by microinjection of two excitatory amino acids, kainic acid and glutamate, into the DR of rat brain. Intrahypothalamic administration of DOI (a 5-HT2 agonist), but not 8-OH DPAT (a 5-HT1 agonist) or 2-methyl-serotonin (a 5-HT3 agonist), also produced both hypertension and tachycardia in rats. The DR stimulation-induced hypertension, tachycardia, or increased hypothalamic 5-HT release were attenuated by prior destruction of the ascending serotonergic system produced by ICV injection of 5,7-dihydroxytryptamine and by prior blockade of postsynaptic serotonergic receptors produced by intrahypothalamic injection of 5-HT2 antagonists, cyproheptadine and ketanserin. The DOI-induced hypertension and tachycardia were also reduced by prior blockade of 5-HT2 receptors with cyproheptadine or ketanserin. Thus, it appears that DR stimulation activates the 5-HT release in the hypothalamus, then activates the hypothalamic 5-HT2 receptors and results in both hypertension and tachycardia in rats.

5,7-Dihydroxytryptamine↗

Association of busulfan area under the curve with veno-occlusive disease following BMT.

Busulfan pharmacokinetics, specifically area under the concentration curve (AUC), have been correlated with the occurrence of veno-occlusive disease (VOD) following BMT. To evaluate the risk of VOD, we studied 66 patients who received pharmacotherapeutically monitored busulfan regimens in combination with CY, etoposide (VP16) and/or Ara-C in preparation for BMT. These patients received a total of 16 doses of busulfan dosed as 1 mg/kg/dose q 6 h beginning at 09.00 (n = 39), 18.00 (n = 2), 21.00 (n = 1) or 24.00 (n = 24) h. With the first dose, blood samples were obtained at baseline, every 15-30 min for 2 h, then every 1-2 h for 4 h. Blood was analyzed for busulfan concentration by high performance liquid chromatography and AUC calculated by the trapezoidal rule. Seventeen patients (25.8%) were not evaluable for AUC calculation due to slow absorption and/or elimination: 13 of 27 (48.1%) received the first dose between 18.00-24.00 vs four of 39 (10.2%) patients who received the first dose at 09.00 (P < 0.001). Eighteen of 51 (35.3%) evaluable patients had an AUC > 1500 mumol x min/l; 10 of whom received doses reduced proportionally to achieve an AUC = 1200 mumol x min/l starting with the 10th to 15th dose. Six of 18 (33.3%) patients with an initial AUC > 1500 mumol x min/l developed VOD vs one of 33 (3.0%) patients with an initial AUC < 1500 mumol x min/l (relative risk = 11.1; P = 0.0056). Other pharmacokinetic parameters, age, gender, type of BMT, previous therapy or pre-transplant liver function tests were not predictive of VOD. A higher incidence of VOD occurred in patients receiving BUCY (4 of 10) compared to those receiving BUCYAra-C (1 of 18) or BUCYVP16 (7 of 38), which could not be attributed to increased busulfan exposure in the BUCY patients. Routine pharmacotherapeutic monitoring of busulfan is recommended with further study to evaluate the impact of earlier and greater overall dose reduction in patients with high initial busulfan exposures.

Adolescent↗

Use of recombinant Epstein-Barr virus early antigen for detection of antibody in patients with nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is one of the most common cancers in southern China and Taiwan. Serological studies revealed the close-relationship between NPC and Epstein-Barr virus (EBV). Elevated serum and saliva levels of anti-EBV antibodies are detected in patients with NPC. Therefore, Development Center for Biotechnology prepared the EBV-early antigen (EA-D) by recombinant DNA technique for screening the serum and throat washing samples from patients with head and neck cancers. METHODS: The BMRF1 gene for EBV early antigen (EA-D) was placed into the plasmid pDB18, then transformed into an Escherichia coli strain containing the lambda cI857 temperature-sensitive repressor. Heat treatment of the transformant, at exponential growth phase, inactivated the cI protein and induced an over-expression of the EA-D protein. Next, the EA-D was purified by chromatography and characterized as a protein of molecular weight 47 kDa, by sodium dodecyl sulfate-polyacry lamide gel electrophoresis (SDS-PAGE) and Western blot analysis using monoclonal anti-EA antibody and sera from patients with nasopharyngeal carcinoma (NPC). Enzyme-linked immunosorbent assay (ELISA) with the purified EA-D antigen was used to screen 129 serum and throat washing (TW) samples from patients with head and neck tumors, 24 from patients with a nonmalignant disease and 44 from normal donors. RESULTS: Experimental results indicated significantly higher positive rates of EA-D IgA (69%) and EA-D IgG (91%) in NPC sera than in the sera of patients with other head and neck tumors and normal controls. TW samples from patients with NPC also showed a higher positive rate (34%) than the other groups (7-20%). CONCLUSIONS: Results in this study demonstrate that the bacterially expressed EA-D antigen could be recognized by sera from patients with NPC and monoclonal anti-EA antibody. Thus, it has potential use in ELISA for screening EBV-related diseases such as NPC.

Antibodies, Viral↗

Risk factors predicting surgically significant intracranial hematomas in patients with head injuries.

This population-based study was designed to determine the risk of patients with head injuries to develop surgically significant intracranial hematomas (SSIHs). A total of 28,500 cases of head injury were reviewed in Taipei City and Hualien County from 1988 to 1992. The Glasgow Coma Scale (GCS) was used to determine the severity of head injury. The presence of skull fracture and intracranial hematoma was determined by x-ray and computed tomographic (CT) scan, respectively. Those patients suffering from both loss of consciousness and skull fracture had a significantly greater risk of developing SSIHs than those having none or only one of these conditions. The relationship between skull fracture and severity of head injury revealed that the presence of a skull fracture in mildly head-injured patients could be used as an indicator to investigate the development of SSIHs before the occurrence of irreversible damage. The distribution of hematomas by location showed that a higher rate of SSIH resulting in parenchymal damage occurred when consciousness was lost. It also showed that epidural hematomas occurred more frequently with skull fractures. Skull fracture and impaired consciousness are important indices in determining the risk of developing SSIH.

Adult↗

Functional analysis of EA-D of Epstein-Barr virus.

Different mutations were generated in the diffused-form early antigen (EA-D) of Epstein-Barr virus (EBV) for study of the effects of these mutations in DNA binding, stimulating the activity of EBV-specific DNA polymerase (EBV-DP), and binding to monoclonal antibody R3. Results revealed that the N-terminal 303 amino acids were essential for DNA binding and were sufficient for the enhancement of the activity of EBV-specific DNA polymerase. Deletion study also showed that the region recognized by the R3 monoclonal antibody was located between aa 315 and aa 377. Our results failed to demonstrate the binding between EA-D and EBV-DP, using the proteins synthesized in vitro, suggesting that direct contact between the two proteins is not required for the EBV-DP activity in vitro. We have generated fusion between EA-D and DNA-binding domain of yeast GAL4 protein; however, this fusion protein was not able to transactivate the promoter containing UAS sequence in P3HR1 cells.

Antigens, Viral↗

Characterization of Epstein-Barr virus DNase and its interaction with the major DNA binding protein.

Bacterially expressed Epstein-Barr virus (EBV) DNase was purified to 98% purity and used as the source for characterization of the enzyme activities. Complete digestion of DNA by EBV DNase yielded 5'-monophosphate nucleosides as the final products. During the logarithmic phase of the reaction, EBV DNase acted processively on dsDNA but distributively on ssDNA. Both 5' to 3' and 3' to 5' exonuclease activities were present, although the former was shown to be 10-fold stronger. No significant discrepancy was seen in the liberation of end-labeled nucleotides by DNase when substrates with 5'-protruding, blunt, or 3'-protruding ends were used. EBV DNase was demonstrated also to have an endonuclease activity using supercoiled plasmid DNA as substrate. Two preferential dsDNA cleavage sites were mapped on pBS-TR, a pBlueScript vector containing one copy of the EBV terminal repeat; both are in vector sequences. Finally, an N-terminally truncated EBV major DNA binding protein, but not EA-D, was shown to inhibit EBV DNase activity. This inhibitory effect may due to direct protein-protein interactions between EBV DNase and the major DNA binding protein. The biological significance of these characteristics is discussed.

Antigens, Viral↗