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Biomedical subjects

Y C Lin

Publications and source records attributed to Y C Lin.

At least 55 records · Page 3Linked to original sources
PubMed2001

Structure-activity studies of FIV and HIV protease inhibitors containing allophenylnorstatine.

The interaction of P1 and P3 side chains with the combining S1 and S3 hydrophobic subsites of HIV and FIV proteases has been explored using asymmetric competitive inhibitors. The inhibitors evaluated contained (2S,3S)-3-amino-2-hydroxy-4-phenylbutyric acid (allophenylnorstatine) as the hydroxymethylcarbonyl isostere, (R)-5,5-dimethyl-1, 3-thiazolidine-4-carbonyl as P1', Val as P2 and P2' residues, and a variety of amino acids at the P3 and P3' positions. All inhibitors showed competitive inhibition of both enzymes with higher potency against the HIV protease in vitro. Within this series, 31 (VLE776) is the most effective inhibitor against FIV protease, and it contains Phe at P3, but no P3' residue. VLE776 also exhibited potent antiviral activities against the drug-resistant HIV mutants (G48V and V82F) and the TL3-resistant HIV mutants. Explanation of the inhibition activities was described. In addition, a new strategy was described for development of bifunctional inhibitors, which combine the protease inhibitor and another enzyme inhibitor in one molecule.

Aspartic Acid Endopeptidases↗
PubMed2001

The heterogeneity in risk factors of lung cancer and the difference of histologic distribution between genders in Taiwan.

OBJECTIVE: The difference in histologic patterns of lung cancer between men and women in Taiwan may be associated with the heterogeneity in causal factors of lung cancer between the sexes. A sex- and age-matched case-control study was designed to investigate such a relationship. METHODS: Cases consisted of 236 male and 291 female incident cases with newly diagnosed and histologically confirmed primary carcinoma of the lung, and were compared to one or two individually matched controls. RESULTS: Cigarette smoking, occupations, and previous tuberculosis history were found to independently correlate with an elevated risk of squamous/small cell carcinoma and adenocarcinoma for male patients. However, there was little difference in the effect of these risk factors except smoking. The use of fume extractors in the kitchen, and the habit of waiting to fry after the fumes were emitted, separately explained the majority of the attributable fraction of female squamous/small cell carcinoma (28.2%) and adenocarcinoma (47.7%). With the exception of a kitchen with fume extractors and a clinical history of tuberculosis, the environmental causal factors of lung cancer were heterogeneous between these two histologic cell groups. CONCLUSIONS: Our results suggested that the causal factors of lung cancer might be specific for the type of tumor concerned. The gender-specific risk factors of lung cancer could partly explain the difference in cell-type distribution between men and women.

Adenocarcinoma↗
PubMed2001

Tests for physical function of the elderly with knee and hip osteoarthritis.

This study reports the results of a battery of physical function tests used to assess physical function of older patients with clinical knee and/or hip osteoarthritis (OA), and the correlation to the WOMAC Index (disease-specific questionnaire). A total of 106 sedentary subjects, aged >60 years (mean 69.4, S.D. 5.9) with hip and/or knee OA (mean 12.2 yrs, S.D. 11.0) participated in the study. Mobility, joint flexibility and muscle strength were evaluated by recording time to: walk a distance of 8', ascend/descend 4 stairs, rise from/sit down from a chair (5 times). Hip/knee flexion and isometric quadriceps strength were also measured. Categories of performance were formed by dividing data into quartiles for each test (1=highest, 4=lowest score, 5=unable to complete) and, by summing the category scores, a total summary score (TSS) was obtained. The battery of physical function tests showed an acceptable test-retest reliability (ICC of all tasks > or =0.80) and internal consistency (Cronbach's alpha > or =0.80). Performance scores on walking, stair climb, chair-rise and ROM of affected OA joints were significantly correlated with each other, and with the WOMAC Index (P<0.05, Spearman's correlation). Lower scores on the TSS were associated with lower scores on all the WOMAC Index items (P<0.001). This study shows that a simple battery of physical function tests in combination with the WOMAC Index are reliable and may be useful outcome measures in the evaluation of therapeutic interventions and geriatric rehabilitation.

Aged↗
PubMed2001

Cell cycle effects of IL-10 on malignant B-1 cells.

IL-10 is overexpressed in human chronic lymphocytic leukemia (CLL), and is an autocrine growth factor involved in the development of malignant B1 clones in NZB mice, a murine model for CLL. Antisense IL-10 oligonucleotide treatment induces apoptosis and cell cycle disruption in these cells both in vitro and in vivo. In addition, NZB IL-10 knock-out mice fail to develop the B-1 clones. Dampening of IL-10 protein production via antisense IL-10 oligonucleotide treatment is correlated with decreased p27/Kip1 protein expression which results in increased cyclin D2, cyclin E and cyclin A associated kinase activity. The action of the antisense oligonucleotides is through alterations in cell cycle regulation, resulting in accelerated cell cycle progression, a G2/M block which culminates in apoptosis induction in the malignant cells. This implies that the role of IL-10 as an autocrine growth factor in malignant B-1 cells lies in its ability to inhibit apoptosis induction through the maintenance of sustainable cell cycle progression in malignant cells.

Animals↗
PubMed2001

Anisocoria from transdermal scopolamine.

A transdermal scopolamine patch is an effective medication for relieving motion sickness, treating nausea and vomiting from chemotherapy and decreasing withdrawal side-effects from wearing off opioids. A 14-year-old boy with chronic granulomatous disease and severe infection was admitted to the hospital because of left shoulder aspergillus' infection and pain. The patient required high dose opioid to control the shoulder pain. A unilateral fixed and dilated pupil was noted. We assumed this to be related to the advancing central nervous system aspergillosis. After extensive neurological 'work up', we realized that the anisocoria was related to the transdermal scopolamine patch that we had prescribed for weaning off the opioid.

Adjuvants, Anesthesia↗
PubMed2001

Coordination exercise and postural stability in elderly people: Effect of Tai Chi Chuan.

OBJECTIVE: To evaluate the effects of coordination exercise on postural stability in older individuals by Chinese shadow boxing, Tai Chi Chuan (TCC). DESIGN: Cross-sectional study. SETTING: Research project in a hospital-based biomechanical laboratory. PARTICIPANTS: The TCC group (n = 25) had been practicing TCC regularly for 2 to 35 years. The control group (n = 14) included healthy and active older subjects. INTERVENTION: Static postural stability test: progressively harder sequential tests with 6 combinations of vision (eyes open, eyes closed, sway-referenced) and support (fixed, sway-referenced); and dynamic balance test: 3 tests of weight shifting (left to right, forward-backward, multidirectional) at 3 speeds. MAIN OUTCOME MEASURES: Static and dynamic balance of Sensory Organization Testing (SOT) of the Smart Balance Master System. RESULTS: In static postural control, the results showed no differences between the TCC or control group in the more simple conditions, but in the more complicated SOT (eyes closed with sway surface, sway vision with sway surface), the TCC group had significantly better results than the control group. The TCC group also had significantly better results in the rhythmic forward-backward weight-shifting test. Duration of practice did not seem to affect the stability of elder people. CONCLUSION: The elderly people who regularly practiced TCC showed better postural stability in the more challenged conditions than those who do not (eg, the condition with simultaneous disturbance of vision and proprioception). TCC as a coordination exercise may reduce the risk of a fall through maintaining the ability of posture control.

Adolescent↗
PubMed2001

Combustion modeling and performance evaluation in a full-scale rotary kiln incinerator.

This work summarizes the results of numerical investigations and in situ measurements for turbulent combustion in a full-scale rotary kiln incinerator (RKI). The three-dimensional (3D) governing equations for mass, momentum, energy, and species, together with the kappa - epsilon turbulence model, are formulated and solved using a finite volume method. Volatile gases from solid waste were simulated by gaseous CH4 distributed nonuniformly along the kiln bed. The combustion process was considered to be a two-step stoichiometric reaction for primary air mixed with CH4 gas in the combustion chamber. The mixing-controlled eddy-dissipation model (EDM) was employed to predict the conversion rates of CH4, O2, CO2, and CO. The results of the prediction show that reverse flows occur near the entrance of the first combustion chamber (FCC) and the turning point at the entrance to the second combustion chamber (SCC). Temperature and species are nonuniform and are vertically stratified. Meanwhile, additional mixing in the SCC enhances postflame oxidation. A combustion efficiency of up to 99.96% can be achieved at approximately 150% excess air and 20-30% secondary air. Reasonable agreement is achieved between numerical predictions and in situ measurements.

Air Pollution↗
PubMed2001

Weekly high-dose 5-fluorouracil (5-FU), leucovorin (LV) and bimonthly cisplatin in patients with advanced gastric cancer.

BACKGROUND: A phase II clinical trial was performed to evaluate the activity and toxicity of bimonthly cisplatin and weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin in patients with advanced gastric cancer. PATIENTS AND METHODS: From September 1997 to March 1998, 23 chemo-naive patients of advanced gastric cancer were enrolled in this study. The regimen consisted of weekly 24-h infusion of 5-FU (2,600 mg/m2) and LV 150 mg and bimonthly cisplatin (25-50 mg/m2) bolus for 12 weeks followed by a 2-week break. RESULTS: There were 10 male and 13 female patients with a median age of 52 years. A total of 428 chemotherapy treatments were given with a mean of 11. Seventeen patients were evaluable for response. There were 41% (7/17) partial response, 18% (3/17) stable disease and 41% (7/17) progressive disease. The grade III or IV toxicity included anorexia 35% (8/23), fatigue 26% (6/23), vomiting 17% (4/23) and mucositis 9% (2/23). One patient developed perforated duodenal stump after chemotherapy. One patient died of hyperammonemia-related coma. The median times to disease progression and overall survival were 3.5 and 7 months, respectively. CONCLUSIONS: This regimen showed modest activity against gastric cancer. However, there was no survival advantage and there was greater toxicity than with weekly high-dose 5-FU-LV alone.

Adult↗
PubMed2001

Phase II study of a weekly 8-hour 5-fluorouracil and leucovorin infusion for patients with advanced colorectal cancer: dose adjusted according to its toxicity.

BACKGROUND: 5-fluorouracil (5-FU) clearly behaves as two different drugs according to the schedules for its administration. A weekly, 8-h 5-FU continuous infusion (CI) regimen may produce a dual effect, because it elicits both a high plasma 5-FU level and also a durable exposure to 5-FU, which may have the advantage of inhibiting both DNA synthesis and RNA activities. The plasma 5-FU level, however, cannot be monitored in most hospitals, so we initiated a pragmatic clinical trial with this weekly 8-h 5-FU Cl regimen and adjusted the drug's dose according to the detected toxicity. METHODS: The initial dose of 5-FU was 1200 mg/m2 and this was escalated by 200 mg/m2 weekly, provided that no evidence of significant (grade 2 or greater) toxicity became apparent. Twenty-six patients entered the study from June 1998 to March 1999. RESULTS: The median dose of 5-FU delivered was 1600 mg/m2. The major symptoms precluding dose escalation were nausea and vomiting. Seven patients demonstrated a partial response (26.9%), 11 patients revealed stable disease (42.3%) and eight exhibited progressive disease (30.8%). CONCLUSION: This weekly 8-h CI 5-FU protocol with the adjustment of dose according to toxicity was not able to achieve the same 5-FU dose and response rate as in previous studies with pharmacokinetic monitoring of 5-FU levels. However, with the concurrent administration of intensive anti-emetic premedication, it is still possible to achieve adequate plasma 5-FU levels by adjusting the 5-FU dose according to elicited toxicity.

Adult↗
PubMed2001

Cloning and characterization of a complementary DNA encoding a human epididymis-associated disintegrin and metalloprotease 7 protein.

Mammalian spermatozoa interact with the proteins secreted by the epididymis to develop fertility. Transmembrane proteins that possess a disintegrin and metalloprotease (ADAM) domains are shown to be closely related to spermatogenesis and fertilization. Our previous study demonstrated that GP-83, a glycoprotein secreted by the epididymis, was conjugated to mature sperm. In this study, a 2.1-kilobase (kb) GP-83-expressing insert was isolated from a cDNA library of human epididymis by immunoscreening using GP-83-specific antiserum. The 5' end rapid amplification of cDNA ends (RACE) and 3'-RACE of the 2.1-kb insert elucidated two isoforms of GP-83-encoding cDNA sequences, an alpha-form of 3451 base pairs (bp) and beta-form of 2643 bp. Both forms exhibit the same open reading frame of 2262 bp predicting a peptide of 754 amino acid residues. Deduced amino acid sequence revealed signal sequence, prodomain, metalloproteinase, disintegrin, cysteine-rich, epidermal growth factor-like, transmembrane, and cytoplasmic domains. The GP-83-encoding sequence was recognized as human ADAM7 due to significant homology to other ADAM7s. According to the DNA sequences elucidated in the Human Genome Project, h-ADAM7 was located at chromosome 8p22. Ex vivo expression confirmed that h-ADAM7 cDNA did encode GP-83. Northern blot analysis revealed two transcripts of 4 kb and 3 kb in the epididymis, but not in testis or other major tissues. These results indicate that the GP-83-encoding gene is a human epididymis-associated ADAM7 gene (human ADAM7, h-ADAM7) and may be involved in the sperm-egg interaction.

ADAM Proteins↗
PubMed2001

Modulations of spinal serotonin activity affect the development of morphine tolerance.

To test whether modulations of spinal serotonin (5-HT) levels would affect the development of morphine tolerance, we treated rats with either intrathecal 5-HT or 5,7-dihydroxytryptamine (5,7-DHT; a 5-HT neurotoxin) in addition to systemic infusion with morphine (2 mg x kg(-1) x h(-1)). Continuous infusion of 5-HT (10 microg x 6 microL(-1) x h(-1)) into the lumbar subarachnoid space of rats for 9 h accelerated the development of morphine tolerance. The area under the curve for the tail-flick latency test was 454.1 +/- 35.1 in the Sham Control group vs 327.6 +/- 41.0 in the 5-HT-Infused group. mu-opioid receptor binding in the lumbar spinal cord showed a decrease in the Bmax (maximal binding -46.5%), but not the binding affinity (Kd), in 5-HT-infused rats. However, intrathecal injection of 5,7-DHT (50 microg), which resulted in a 48% reduction in 5-HT and 51% reduction in 5-hydroxyindoleacetic acid concentrations, led to an attenuation of morphine tolerance (the area under the curve was 613.0 +/- 24.7 in the 5,7-DHT-Lesioned group). The binding study indicated that the affinity of lumbar micro-opioid receptors decreased 196% in 5-HT-depleted rats, whereas there was no effect on apparent binding. The infusion of 5-HT (10 microg x 6 microL(-1) x h(-1)) was not analgesic and the 5,7-DHT-induced lesion did not affect acute morphine-induced analgesia. We conclude that activity of spinal 5-HT-containing neurons plays a crucial role during the development of morphine tolerance.

5,7-Dihydroxytryptamine↗
PubMed2001

Mitomycin C with weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin in patients with biliary tract and periampullar carcinomas.

We have reported a 33% partial response rate with acceptable toxicity using weekly 24-h infusion of high-dose 5-fluorouracil (5-FU) and leucovorin (LV) in patients with far advanced biliary tract cancers (BTC). In this study, we added mitomycin (MMC) to 5-FU and LV in an attempt to improve the response rate and survival. From July 1997 to September 1999, 25 chemotherapy-naive patients with pathology-proven far advanced BTC and periampullar cancers were enrolled. The regimen consisted of MMC 10 mg/m(2) every 8 weeks combined with 5-FU 2600 mg/m(2) and LV 150 mg at a schedule of 24-h infusion weekly for 6 weeks followed by a 2 week break. There were 10 males and 15 females with a median age of 57 years (range 40-76). The sites of primary tumor were 15 intrahepatic cholangiocarcinomas (CC), one perihilar CCs, three distal BTC, three gallbladder cancers (GB) and three periampullar cancers. A total of 148 sessions of chemotherapy were given with a mean of 8 (range 2-18). Nineteen patients were evaluable for response. The response rate was: 26% (five of 19) partial response, 42% (eight of 19) stable disease and 32% (six of 19) progressive disease. All of the patients were evaluable for toxicity. Toxicities more than grade III-IV were thrombocytopenia 16% (four of 25), leukopenia 12% (three of 25) and vomiting 4% (one of 25). There were four treatment-related deaths. The median time to disease progression was 3 months. The median survival was 6 months. A combination of MMC with weekly high-dose 5-FU and LV in patients with BTC did not improve the response rate, but produced more toxicity than weekly high-dose 5-FU and LV alone.

Adenocarcinoma↗
PubMed2001

Long-term care services needs for spinal-cord injury patients in Taiwan.

According to official health statistics, accidents and their adverse effects are the third leading cause of death in Taiwan. More accident victims are surviving thanks to treatment using high medical technology, but this results in many disabled patients with irreversible impairments. The demand for long-term care (LTC) services for spinal cord injury (SCI) patients has thus become a major concern. However, homebound SCI patients may easily face exclusion from LTC services because they are often ineligible for benefits under the regulations of National Health Insurance (NHI). The purposes of this study were: 1. To quantify the LTC needs of SCI patients, and 2. To evaluate the correlation between SCI patient health status and LTC needs. A total of 133 samples were visited from Kaohsiung City and Pingtung County. The results of this study showed that the average age of subjects was 43.15, with 72.9% male. The health status of most of the research subjects was fair (M = 2.33). The test of physiological health status was a 20-item scale with a five-point response format. The worst dysfunctions were urination (M = 3.36, SD = 1.06), sexual function (M = 3.30, SD = 0.88), excretion (M = 3.26, SD = 1.06), comfort (M = 3.25, SD = 0.84), and mobility (M = 2.75, SD = 1.11). All of the above items showed higher mean scores than average. More than one third of the subjects (36.8%) used wheelchairs, had better mobility and went out often. However, half of subjects were completely bedridden (45.9%). The mean psychosocial health status was poor with a mean score of 2.80 which showed higher mean score than average. The subjects were less satisfied with role function (M = 2.92), emotional stability (M = 2.92), and application for community resources (M = 2.79). The most needed LTC services for SCI patients was home-making services; referral and monitoring services ranked second. Suggestions derived from this study were to coordinate nursing care services with social support services for LTC patients and to allocate LTC resources based on patients' health status and their need for LTC services.

Activities of Daily Living↗
PubMed2001

Molecular basis for the relative substrate specificity of human immunodeficiency virus type 1 and feline immunodeficiency virus proteases.

We have used a random hexamer phage library to delineate similarities and differences between the substrate specificities of human immunodeficiency virus type 1 (HIV-1) and feline immunodeficiency virus (FIV) proteases (PRs). Peptide sequences were identified that were specifically cleaved by each protease, as well as sequences cleaved equally well by both enzymes. Based on amino acid distinctions within the P3-P3' region of substrates that appeared to correlate with these cleavage specificities, we prepared a series of synthetic peptides within the framework of a peptide sequence cleaved with essentially the same efficiency by both HIV-1 and FIV PRs, Ac-KSGVF/VVNGLVK-NH(2) (arrow denotes cleavage site). We used the resultant peptide set to assess the influence of specific amino acid substitutions on the cleavage characteristics of the two proteases. The findings show that when Asn is substituted for Val at the P2 position, HIV-1 PR cleaves the substrate at a much greater rate than does FIV PR. Likewise, Glu or Gln substituted for Val at the P2' position also yields peptides specifically susceptible to HIV-1 PR. In contrast, when Ser is substituted for Val at P1', FIV PR cleaves the substrate at a much higher rate than does HIV-1 PR. In addition, Asn or Gln at the P1 position, in combination with an appropriate P3 amino acid, Arg, also strongly favors cleavage by FIV PR over HIV PR. Structural analysis identified several protease residues likely to dictate the observed specificity differences. Interestingly, HIV PR Asp30 (Ile-35 in FIV PR), which influences specificity at the S2 and S2' subsites, and HIV-1 PR Pro-81 and Val-82 (Ile-98 and Gln-99 in FIV PR), which influence specificity at the S1 and S1' subsites, are residues which are often involved in development of drug resistance in HIV-1 protease. The peptide substrate KSGVF/VVNGK, cleaved by both PRs, was used as a template for the design of a reduced amide inhibitor, Ac-GSGVF Psi(CH(2)NH)VVNGL-NH(2.) This compound inhibited both FIV and HIV-1 PRs with approximately equal efficiency. These findings establish a molecular basis for distinctions in substrate specificity between human and feline lentivirus PRs and offer a framework for development of efficient broad-based inhibitors.

Amino Acid Substitution↗
PubMed2001

Viral evolution in response to the broad-based retroviral protease inhibitor TL-3.

TL-3 is a protease inhibitor developed using the feline immunodeficiency virus protease as a model. It has been shown to efficiently inhibit replication of human, simian, and feline immunodeficiency viruses and therefore has broad-based activity. We now demonstrate that TL-3 efficiently inhibits the replication of 6 of 12 isolates with confirmed resistance mutations to known protease inhibitors. To dissect the spectrum of molecular changes in protease and viral properties associated with resistance to TL-3, a panel of chronological in vitro escape variants was generated. We have virologically and biochemically characterized mutants with one (V82A), three (M46I/F53L/V82A), or six (L24I/M46I/F53L/L63P/V77I/V82A) changes in the protease and structurally modeled the protease mutant containing six changes. Virus containing six changes was found to be 17-fold more resistant to TL-3 in cell culture than was wild-type virus but maintained similar in vitro replication kinetics compared to the wild-type virus. Analyses of enzyme activity of protease variants with one, three, and six changes indicated that these enzymes, compared to wild-type protease, retained 40, 47, and 61% activity, respectively. These results suggest that deficient protease enzymatic activity is sufficient for function, and the observed protease restoration might imply a selective advantage, at least in vitro, for increased protease activity.

Amino Acid Sequence↗
PubMed2001

Calcium currents from jellyfish striated muscle cells: preservation of phenotype, characterisation of currents and channel localisation.

When striated muscle cells of the jellyfish Polyorchis penicillatus were dissociated at 30 degrees C they retained their in vivo morphology and the integrity of ionic currents. This contrasted with cells dissociated at room temperature that rarely expressed any inward currents. Whole-cell, patch-clamp recordings from dissociated muscle cells revealed that the inward component of the total ionic current consisted of only one calcium current. This calcium current activated at -70 mV, peaked at -30 mV, and inactivated within 5 ms. In comparison with barium and strontium ions, calcium ions were the preferred current carriers. Calcium channels can be blocked by dihydropyridines and nickel ions at micromolar levels. Several properties of this current are reminiscent of T-type calcium currents. Localisation of this channel using the fluorescent channel blocker fDHP and the fluorescent dye RH414 indicated that myofibres had a higher density of these channels than the somata.

Adenosine Triphosphate↗
PubMed2001

Localisation of intracellular calcium stores in the striated muscles of the jellyfish Polyorchis penicillatus: possible involvement in excitation-contraction coupling.

When jellyfish striated muscles were stimulated directly, the amplitude of contractile tension increased as the stimulation frequency increased. Application of 10 mmol l(-1) caffeine reduced the amplitude of contractile tension and abolished this facilitatory relationship, indicating that calcium stores participate in excitation-contraction coupling. Calcium stores were identified ultrastructurally using enzymatic histochemistry to localize CaATPases, and potassium dichromate to precipitate calcium. Electron energy-loss spectroscopy was used to verify the presence of calcium in precipitates. Both CaATPase and calcium were localised in membrane-bound vesicles beneath the sarcolemma. We concluded that sub-sarcolemmal vesicles could act as calcium stores and participate in excitation-contraction coupling.

Animals↗