Biomedical subjects

Y Lin

Publications and source records attributed to Y Lin.

At least 163 records · Page 9Linked to original sources

PubMed2000

Comparative in vitro metabolism of indinavir in primates--a unique stereoselective hydroxylation in monkey.

1. The in vitro metabolism of indinavir (CRIXIVAN, MK-0639, L-735,524), an HIV protease inhibitor, was evaluated using liver microsomes from cynomolgus monkey, rhesus monkey, chimpanzee and human. Indinavir exhibited marked species differences in metabolism. The overall rate of indinavir metabolism varied > 4-fold among primates (84 pmol/min/mg protein in cynomolgus monkey versus 20.4 pmol/min/mg protein in human) and followed the rank order: cynomolgus monkey > rhesus monkey > chimpanzee > human. 2. The cis-(indan)hydroxylated metabolite of indinavir was formed only in cynomolgus and rhesus monkey livers, whereas trans-(indan)hydroxylation and N-dealkylation were observed as the major metabolites in all primates tested. Inhibition studies with P450-selective inhibitors (ketoconazole, quinine, quinidine) and monoclonal antibodies (against CYP2D6 or CYP3A4) indicated that a cytochrome P450 isoform of the CYP2D subfamily is involved in the formation of the unique cis-(indan) hydroxylated metabolite in monkey, whereas all other oxidative metabolites, including the trans-(indan)hydroxylated metabolite, are formed by CYP3A isoform(s). 3. The present study has demonstrated that monkeys were unique in their abilities to form the stereoselective metabolite and were not appropriate surrogates for the qualitative prediction of indinavir metabolism in human.

Animals↗

PubMed2000

Variability of the conversion of beta-carotene to vitamin A in women measured by using a double-tracer study design.

BACKGROUND: Blood beta-carotene and vitamin A responses to oral beta-carotene are variable in humans. Some individuals are characterized as responders and others as low- or nonresponders. A better understanding of the conditions that produce the variability is important to help design public health programs that ensure vitamin A sufficiency. OBJECTIVE: Our objective was to assess variability in absorption and conversion of beta-carotene to vitamin A in vivo in humans by using a novel double-tracer ¿hexadeuterated (D(6)) beta-carotene and D(6) retinyl acetate approach. DESIGN: Eleven healthy women were housed at the US Department of Agriculture Western Human Nutrition Research Center metabolic unit for 44 d, where they consumed diets adequate in vitamins and minerals except for carotenoids. After an adaptation period, the women were given 30 micromol D(6) retinyl acetate orally, followed 1 wk later with 37 micromol D(6) beta-carotene (approximately equimolar doses). Time-dependent plasma concentration curves were determined for D(6) retinol, D(6) beta-carotene, and trideuterated (D(3)) retinol (derived from D(6) beta-carotene). RESULTS: Mean (+/-SE) absorption of D(6) beta-carotene was 3.3 +/- 1.3% for all subjects. The mean conversion ratio was 0.81 +/- 0.34 mol D(3) retinol to 1 mol D(6) beta-carotene for all subjects. However, only 6 of the 11 subjects had plasma D(6) beta-carotene and D(3) retinol concentrations that we could measure. The mean absorption of D(6) beta-carotene in these 6 subjects was 6.1 +/- 0.02% and their conversion ratio was 1.47 +/- 0.49 mol D(3) retinol to 1 mol D(6) beta-carotene. The remaining 5 subjects were low responders with </=0.01% absorption and a mean conversion ratio of 0.014 +/- 0.004 mol D(3) retinol to 1 mol D(6) beta-carotene. CONCLUSION: Variable absorption and conversion of beta-carotene to vitamin A both contribute to the variable response to consumption of beta-carotene. Our double-tracer approach is adaptable for identifying efficient converters of carotenoid to retinoid.

Absorption↗

PubMed2000

The effect of diclofenac on the expression of spinal cord c-fos-like immunoreactivity after ischemia-reperfusion-induced acute hyperalgesia in the rat tail.

Ischemia-reperfusion of the rat tail for 20 min induces local acute hyperalgesia of approximately 1-h duration. We studied how this stimulus affected the expression of c-fos-like immunoreactivity (c-fos-LI) labeling of neurons of the sacral spinal cord, and how diclofenac pretreatment influenced the outcome. After ischemia, the number of c-fos-LI-labeled neurons was significantly increased when assessed at 60, 90, and 120 min after reperfusion (to 183%, 283%, and 164% of control, respectively; all P < 0.01). At 90 min, the number of regional c-fos-LI-labeled neurons was increased to 585% in laminae I-II, 183% in laminae III-IV, 270% in laminae V-X, and 286% in total, compared with respective control values (all P < 0.01). After diclofenac pretreatment (subcutaneous 40 mg/Kg, 30 min before insult) the number of c-fos-LI-labeled neurons at 90 min was increased to 424% in laminae I-II, 150% in laminae III-IV, 142% in laminae V-X, and 183% in total (all P < 0.01). Thus diclofenac pretreatment partially prevented the insult-induced increase in total and regional neuronal c-fos-LI. This acute nociceptive model involves only natural algogens. However, the results were similar to acute chemically induced or chronic adjuvant induced arthritic inflammatory pain models in which increases in c-Fos were partially inhibited by nonsteroidal antiinflammatory drugs.

Acute Disease↗

PubMed2000

Cigarette smoking as a risk factor for chronic pancreatitis: a case-control study in Japan. Research Committee on Intractable Pancreatic Diseases.

We conducted a hospital-based, case-control study to examine the association of cigarette smoking with chronic pancreatitis. Ninety-one male patients with chronic pancreatitis newly diagnosed from July 1997 to December 1998 were recruited as cases, and 175 controls were individually matched to each case for gender, age (+/- 5 years), hospital, and time of the first visit to a hospital (+/- 1 year). A self-administered questionnaire was used to collect information on tobacco and alcohol use, diet, and other factors. The odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated by multiple conditional logistic models, adjusting for body mass index, education level, and alcohol consumption. Compared with nonsmokers, the ORs (95% CIs) were 7.8 (2.2-27.3) for all current smokers, and 14.7 (3.1-69.9), 5.5 (1.5-20.1), 12.2 (2.4-71.0) for those consuming < 20, 20-39, and > or = 40 cigarettes per day, respectively. Much greater risk was observed for those who had smoked for > or = 25 years. Risk of chronic pancreatitis significantly increased with increasing cumulative amount of smoking (p < 0.05). Analysis for the effect of combined use of tobacco and alcohol showed that cigarette smoking was associated with the higher risk in both of the two alcohol consumption levels. Our findings indicated that cigarette smoking may be an independent and significant risk factor for chronic pancreatitis.

Aged↗

PubMed2000

Genetic interactions between the chlorate-resistant mutant cr 8 8 and the photomorphogenic mutants cop1 and hy5.

The chlorate-resistant mutant cr88 is defective in photomorphogenesis, as shown by the phenotypes of long hypocotyls in red light and yellow cotyledons under all light conditions. A subset of light-regulated genes is expressed at subnormal levels in cr88. To analyze further the role that CR88 plays in photomorphogenesis, we investigated the genetic interactions between cr88 and mutants of two other loci affecting photomorphogenesis, CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1) and LONG HYPOCOTYL5 (HY5). COP1 represses the expression of light-regulated genes in the dark, and HY5 inhibits hypocotyl elongation in the light. Using morphological, cellular, and gene expression criteria for epistasis analyses to position CR88 in the genetic hierarchy of the photomorphogenesis pathway, we determined that CR88 acts downstream of COP1 but in a branch separate from HY5. In the course of our analysis, we discovered that light causes extensive destruction of plastids in dark-grown cop1 seedlings and that cr88 prevents this destruction.

Arabidopsis Proteins↗

PubMed2000

Crystallization and preliminary crystallographic study of cucurmosin, a ribosome-inactivating protein from the sarcocarp of Cucurbita moschata.

Cucurmosin, a ribosome-inactivating protein purified from pumpkin, the sarcocarp of Cucurbita moschata, has been crystallized using polyethylene glycol as a precipitant. The crystals belong to space group P2(1)2(1)2(1) and have unit-cell parameters a = 41.91, b = 59. 48, c = 98.78 A. There is one molecule in the asymmetric unit. The diffraction data to 3.0 A resolution were collected on a MAR Research image-plate detector.

Crystallization↗

PubMed2000

The death domain kinase RIP is essential for TRAIL (Apo2L)-induced activation of IkappaB kinase and c-Jun N-terminal kinase.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) (Apo2 ligand [Apo2L]) is a member of the TNF superfamily and has been shown to have selective antitumor activity. Although it is known that TRAIL (Apo2L) induces apoptosis and activates NF-kappaB and Jun N-terminal kinase (JNK) through receptors such as TRAIL-R1 (DR4) and TRAIL-R2 (DR5), the components of its signaling cascade have not been well defined. In this report, we demonstrated that the death domain kinase RIP is essential for TRAIL-induced IkappaB kinase (IKK) and JNK activation. We found that ectopic expression of the dominant negative mutant RIP, RIP(559-671), blocks TRAIL-induced IKK and JNK activation. In the RIP null fibroblasts, TRAIL failed to activate IKK and only partially activated JNK. The endogenous RIP protein was detected by immunoprecipitation in the TRAIL-R1 complex after TRAIL treatment. More importantly, we found that RIP is not involved in TRAIL-induced apoptosis. In addition, we also demonstrated that the TNF receptor-associated factor 2 (TRAF2) plays little role in TRAIL-induced IKK activation although it is required for TRAIL-mediated JNK activation. These results indicated that the death domain kinase RIP, a key factor in TNF signaling, also plays a pivotal role in TRAIL-induced IKK and JNK activation.

Animals↗

PubMed2000

Repression of c-myc is necessary but not sufficient for terminal differentiation of B lymphocytes in vitro.

The importance of c-myc as a target of the Blimp-1 repressor has been studied in BCL-1 cells, in which Blimp-1 is sufficient to trigger terminal B-cell differentiation. Our data show that Blimp-1-dependent repression of c-myc is required for BCL-1 differentiation, since constitutive expression of c-Myc blocked differentiation. Furthermore, ectopic expression of cyclin E mimicked the effects of c-Myc on both proliferation and differentiation, indicating that the ability of c-Myc to drive proliferation is responsible for blocking BCL-1 differentiation. However, inhibition of c-Myc by a dominant negative form was not sufficient to drive BCL-1 differentiation. Thus, during Blimp-1-dependent plasma cell differentiation, repression of c-myc is necessary but not sufficient, demonstrating the existence of additional Blimp-1 target genes.

B-Lymphocytes↗

PubMed2000

Mooren's ulcer in China: a study of clinical characteristics and treatment.

AIMS: To investigate the clinical characteristics and compare the effects of several methods of treatment of Mooren's corneal ulcer. METHODS: 550 consecutive cases of Mooren's corneal ulcer were analysed in patients, including age, sex, laterality of eye, ulcer location, perforative rate, cure rate of surgeries, recurrent rate, the effects of conjunctiva excision, lamellar keratoplasty (LKP), and LKP plus 1% cyclosporin A eye drops. RESULTS: The average age of onset was 48.4 years of age. The ratio of males to females was 1:0. 74. 165 (30%) cases had the disease bilaterally, of which 52 (31.5%) occurred in the young age group and 113 (68.5%) in the old age group. Ulcers of 501 eyes (70.1%) were located at the limbus of the palpebral fissure. The perforation rate was 13.3%, with perforation of 41 eyes (43.2%) occurring in the young age group and 54 (56.8%) in the old age group. Postoperative recurrence rate was 25.6%. The cure rate of the first procedure of LKP plus 1% cyclosporin A eye drops was 73.7%. The final cure rate was 95.6%, and the postoperative preservation rate of the eye globe was 99.7%. CONCLUSION: This primary study provided the clinical characteristics of patients with Mooren's corneal ulcer in China. LKP plus 1% cyclosporin A eye drops was an effective treatment.

Administration, Topical↗

PubMed2000

Hypoplasia of the bony canal for the cochlear nerve in patients with congenital sensorineural hearing loss: initial observations.

PURPOSE: To evaluate the length and width of the bony canal of the cochlear nerve in patients with congenital sensorineural hearing loss (SNHL) who have "normal" findings at thin-section computed tomography (CT) of the temporal bone. MATERIALS AND METHODS: The authors retrospectively evaluated the length and width of the bony canal for the cochlear nerve in two groups of patients. The first group was composed of 33 patients with profound SNHL and no demonstrable abnormality at thin-section CT. The control group was composed of 50 patients who underwent temporal bone CT for causes unrelated to SNHL. The mean value +/- SD was calculated for both cohorts. Statistical analysis consisted of the nonparametric Wilcoxon rank sum test with the NPAR1WAY program. RESULTS: The length and width of the bony canal for the cochlear nerve were significantly smaller in patients with SNHL than in the control group (P <.05) CONCLUSION: The hypoplastic bony canal for the cochlear nerve in patients with SNHL may be indicative of a previously unrecognized embryologic malformation of the cochlear nerve.

Adolescent↗

PubMed2000

Origins of circulating endothelial cells and endothelial outgrowth from blood.

Normal adults have a small number of circulating endothelial cells (CEC) in peripheral blood, and endothelial outgrowth has been observed from cultures of blood. In this study we seek insight into the origins of CEC and endothelial outgrowth from cultures of blood. Fluorescence in situ hybridization analysis of blood samples from bone marrow transplant recipients who had received gender-mismatched transplants 5-20 months earlier showed that most CEC in fresh blood had recipient genotype. Endothelial outgrowth from the same blood samples after 9 days in culture (5-fold expansion) was still predominantly of the recipient genotype. In contrast, endothelial outgrowth after approximately 1 month (102-fold expansion) was mostly of donor genotype. Thus, recipient-genotype endothelial cells expanded only approximately 20-fold over this period, whereas donor-genotype endothelial cells expanded approximately 1000-fold. These data suggest that most CEC in fresh blood originate from vessel walls and have limited growth capability. Conversely, the data indicate that outgrowth of endothelial cells from cultures of blood is mostly derived from transplantable marrow-derived cells. Because these cells have more delayed outgrowth but a greater proliferative rate, our data suggest that they are derived from circulating angioblasts.

Adult↗

PubMed2000

Glutamate and kynurenate in the rat central nervous system following treatments with tail ischaemia or diclofenac.

Kynurenate is an endogenous antagonist at the allosteric glycine site on the N-methyl-D-aspartate (NMDA) receptor, and may have a role in ameliorating nociceptive processes through modulation of NMDA receptor function. While antinociceptive effects of nonsteroidal anti-inflammatory drugs (NSAIDs) are mediated peripherally and possibly centrally through inhibition of prostaglandin synthesis, there is also evidence for centrally mediated prostaglandin-independent antinociceptive effects that may result from increased central nervous system (CNS) concentrations of kynurenate. We have investigated the effects of the NSAID diclofenac, (40 mg kg(-1), s.c.; administered to rats 1 h before killing) or the exposure of rats to noxious stimulation (tail ischaemia for 20 min before killing), on the concentrations of glutamate and kynurenate in discrete CNS regions. Regional CNS tissue concentrations of diclofenac were between 3.0-3.8 nmolg(-1). The corresponding regional glutamate concentrations ranged between 4.8-10.6 micromol g(-1), and were significantly lower in the ischaemia group when compared with both control (15%, P < 0.05) and diclofenac-treated (19%, P < 0.002) groups. Kynurenate concentrations in these CNS regions ranged between 3.3-45.8 pmol g(-1). Pairwise comparisons between the control and diclofenac-treated groups found significant increases in kynurenate concentrations in the diencephalon and lumbo-sacral regions of the CNS (P = 0.05). Noxious stimulation from tail ischaemia appeared to be associated with increased release of glutamate. Additionally, NSAIDs appeared to increase kynurenate concentrations in the spinal cord and diencephalon. Antagonism by kynurenate of glutamate effects at NMDA receptors may contribute to the antinociceptive effects of NSAIDs.

Animals↗

PubMed2000

Molecular characterization of a novel yeast cell-wall acid phosphatase cloned from Kluyveromyces marxianus.

A novel Kluyveromyces marxianus gene that encodes an acid phosphatase, Pho610, was cloned in Saccharomyces cerevisiae. The deduced amino acid sequence was distinct from S. cerevisiae phosphatases but similar to some fungal enzymes. A peculiar feature of the sequence is that it has hydrophobic stretches both at the N- and C-termini, which is a characteristic of the precursors of glycosylphosphatidylinositol(GPI)-anchored proteins. When the gene was expressed in S. cerevisiae, the active enzyme was recovered in the periplasmic fraction by glucanase digestion. The Pho610 polypeptide was highly glycosylated and a significant portion was covalently linked to the cell-wall glucan. The enzyme was secreted when the C-terminal region was truncated to remove the GPI signal. Therefore, Pho610 is a novel cell-wall protein having an enzyme activity.

Acid Phosphatase↗

PubMed2000

Cardiovascular responses to glutamate and angiotensin II in ventrolateral medulla of hypertension induced by chronic inhibition of nitric oxide.

It has been suggested that nitric oxide (NO) influences the actions of L-glutamate and angiotensin II in the brain. In the present study, we examined whether cardiovascular responses to L-glutamate and angiotensin II would be altered in the rostral ventrolateral medulla (RVLM) of rats treated with an NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME). Wistar rats were treated with either L-NAME (100 mg/kg/day, n=9) or vehicle (n=8) for 4 weeks. L-glutamate (2 nmol/50 nl) or angiotensin 11 (100 pmol) was then microinjected into unilateral RVLM of anesthetized rats. Upon completion of the experiments, angiotensin-converting enzyme (ACE) activity of the brain stem was measured. The systolic blood pressure after 4 weeks of the treatment was significantly higher in the L-NAME group (203+/-8 mmHg) than in the control group (142+/-3 mmHg, p< 0.01). The pressor response to L-glutamate microinjected into the RVLM was significantly greater in the L-NAME group (31+/-2 mmHg) than in the control group (24+/-1 mmHg, p< 0.01). Similarly, angiotensin II showed a greater pressor response in the L-NAME group. ACE activity of the brain stem did not differ between the groups. In conclusion, NO may have an inhibitory influence on the actions of L-glutamate and angiotensin II in the RVLM.

Angiotensin II↗

PubMed2000

Incidence of intravenous site reactions in neurotrauma patients receiving valproate or phenytoin.

OBJECTIVE: To determine the incidence of intravenous site reactions to phenytoin and valproate in a large population of patients with neurotrauma. DESIGN: Retrospective chart review of two double-blind, randomized clinical trials evaluating the use of antiepileptic drugs to prevent posttraumatic seizures in patients with neurotrauma: phenytoin versus placebo (n = 390), and valproate versus phenytoin with placebo (n = 385). Information collected from the charts included the number, type, and location of intravenous lines and intravenous site events. SETTING: Tertiary care trauma and university teaching hospital. MAIN RESULTS: Intravenous site reactions occurred in 18% and 25% of patients receiving valproate or phenytoin, respectively, with the majority of events (70%) occurring in the first intravenous site. Patients received the neurosurgery study drug (NSSD) by either central or peripheral lines; all intravenous site reactions occurred in peripheral administration sites. When patients who received the drug by central line during the course of therapy were excluded, the estimated incidence of site reactions was 21% and 30% for valproate and phenytoin, respectively (p = 0.056). The time to the first event was shorter with phenytoin compared with valproate (2.0 +/- 1.3 vs. 3.0 +/- 1.9 d; p = 0.009). Fewer adverse events were noted with phenytoin in the phenytoin-without-valproate study than in the phenytoin-with-valproate study, with 4.3% and 8.2% of intravenous site events recorded in patients receiving placebo or phenytoin, respectively. There was no significant difference in the number of intravenous lines per patient used during NSSD drug infusion for phenytoin versus placebo or phenytoin versus valproate. CONCLUSIONS: Both intravenous phenytoin and valproate resulted in intravenous site reactions, with the loading doses responsible for the majority of the events.

Adult↗

PubMed2000

Sleep patterns and total mortality: a 12-year follow-up study in Japan.

A population-based cohort study was conducted to assess the relationship between total mortality and self-reported sleep patterns as regards not only to sleep duration but also subjective sleep quality. A total of 5,322 inhabitants in Gifu Prefecture, Japan, completed a self-administered questionnaire on health status and lifestyles including habitual sleep patterns, and were followed-up for an average of 11.9 years. Relative risks were computed by using Cox proportional hazards models. Both longer and shorter sleep, compared to 7-8 hour-sleep, was related to significantly increased risk of total mortality in males (relative risk [RR] for > or = 10 hours = 1.94, and RR for < 7 hour = 1.90), but not in females. Females complaining of poor awakening state experienced a higher mortality risk compared to those who woke up normally (RR: 1.97). Males who usually fell asleep easily showed a marginally lower mortality risk compared to those who fell asleep normally (RR: 0.70). Female users of sleeping pills were at an elevated risk (RR: 1.89). These findings were almost unchanged after adjustment for sleep duration and other confounders. Poor self-reported quality of sleep seemed to be associated with an increased risk of mortality independently of sleep duration.

Adult↗

PubMed2000

Has the mammography quality standards act affected the mammography quality in North Carolina?

OBJECTIVE: The United States Food and Drug Administration implemented federal regulations governing mammography under the Mammography Quality Standards Act (MQSA) of 1992. During 1995, its first year in implementation, we examined the impact of the MQSA on the quality of mammography in North Carolina. MATERIALS AND METHODS: All mammography facilities were inspected during 1993-1994, and again in 1995. Both inspections evaluated mean glandular radiation dose, phantom image evaluation, darkroom fog, and developer temperature. Two mammography health specialists employed by the North Carolina Division of Radiation Protection performed all inspections and collected and codified data. RESULTS: The percentage of facilities that met quality standards increased from the first inspection to the second inspection. Phantom scores passing rate was 31.6% versus 78.2%; darkroom fog passing rate was 74.3% versus 88.5%; and temperature difference passing rate was 62.4% versus 86.9%. CONCLUSION: In 1995, the first year that the MQSA was in effect, there was a significant improvement in the quality of mammography in North Carolina. This improvement probably resulted from facilities' compliance with federal regulations.

Mammography↗

PubMed2000

Neuroprotective efficacy and therapeutic window of the high-affinity N-methyl-D-aspartate antagonist conantokin-G: in vitro (primary cerebellar neurons) and in vivo (rat model of transient focal brain ischemia) studies.

Conantokin-G (Con-G), a 17-amino-acid peptide derived from marine snails and a potent N-methyl-D-aspartate (NMDA) antagonist, was evaluated for its neuroprotective properties in vitro and in vivo. In primary cerebellar neurons, Con-G was shown to decrease excitotoxic calcium responses to NMDA and to exhibit differential neuroprotection potencies against hypoxia/hypoglycemia-, NMDA-, glutamate-, or veratridine-induced injury. Using the intraluminal filament method of middle cerebral artery occlusion as an in vivo rat model of transient focal brain ischemia, the neuroprotective dose-response effect of Con-G administration beginning 30 min postocclusion was evaluated after 2 h of ischemia and 22 h of reperfusion. In the core region of injury, an 89% reduction in brain infarction was measured with significant neurological and electroencephalographic recovery at the maximal dose tested (2 nmol), although mild sedation was noted. Lower doses of Con-G (0.001-0.5 nmol) were significantly neuroprotective without causing sedation. Postinjury time course experiments demonstrated a therapeutic window out to at least 4 to 8 h from the start of the injury, providing a 47% reduction in core injury. The neuroprotective effect of Con-G (0. 5 nmol) was also evaluated after 72 h of injury, where a 54% reduction in core brain infarction was measured. Critically, in both recovery models (i.e., 24 and 72 h), the reduction in brain infarction was associated with significant improvements in neurological and electroencephalographic recovery. These data provide evidence for the potent and highly efficacious effect of Con-G as a neuroprotective agent, with an excellent therapeutic window for the potential intervention against ischemic/excitotoxic brain injury.

Animals↗