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S Lin

Publications and source records attributed to S Lin.

At least 181 records · Page 10Linked to original sources
PubMed2000

Monte Carlo methods for linkage analysis of two-locus disease models.

Parametric linkage analysis of simultaneous mapping of the two disease loci of a qualitative trait governed by a two-locus model has been shown to provide greater power in detecting linkage than standard lod-score analysis that maps a single disease locus. Despite its great potential for power gains, two-locus parametric analysis has not been used routinely in disease gene mapping. due to the computational intensity of currently available methods and programs. In this paper, we propose a Markov chain Monte Carlo (MCMC) method for performing lod-score analysis of qualitative traits governed by two-locus models. This method obtains lod-score estimates that can be arbitrarily close to their corresponding exact values. The algorithm implementing this MCMC method is linear in the number of markers. This feature enables us to perform two-locus analysis mapping each trait to a set of markers, instead of just to a single marker. We analyzed an alcohol dependence dataset composed of 105 pedigrees with various sizes and various degrees of missingness in the observed marker and disease data. The estimates from our MCMC procedure match up well with the lod scores from exact analysis, but it took much less time for the MCMC procedure to obtain the results. We also performed a simulation study to investigate power gains with additional markers. Our results indicate that an additional marker on each map can provide a great deal more information for linkage measured in terms of the magnitude of lod scores.

Alcoholism↗
PubMed2000

Antitumour activity of novel taxanes that act at the same time as cytotoxic agents and P-glycoprotein inhibitors.

Taxanes antitumour agents such as paclitaxel and docetaxel represent a successful family of chemotherapeutic drugs. Unfortunately, acquired and innate resistance represents a clinical problem for these drugs. We investigated, on a panel of 7 human cancer cell lines, the growth inhibition effect of 3 newly developed taxanes (SB-T-1213, SB-T-1250 and SB-T-101187) with modification at the C10 and C3' positions of the taxane framework. These positions have been previously characterized as critical to make taxanes highly active against cells overexpressing the efflux pump P-glycoprotein (P-gp). Paclitaxel and docetaxel were used as reference compounds. Results unambiguously indicate the exceptional activity of the novel taxanes toward P-gp positive cells (up to >400 fold higher potency than that of paclitaxel). SB-T-1213 and SB-T-1250 are also substantially more active than the reference compounds against P-gp negative cells. To better understand the mechanisms underlying the enhanced activity of the newly developed taxanes, we performed cell cycle and apoptosis analysis. This study demonstrates that the striking growth inhibition effect exhibited by the novel taxanes is ascribed to their increased ability in inducing apoptosis and G(2)/M cell cycle block. SB-T-1213 and SB-T-1250 are also more active than reference compounds in inducing intracellular accumulation of the beta-tubulin subunits. Finally, it is revealed that these novel taxanes have ability to inhibit the function of the P-gp efflux pump on the basis of the Rhodamine 123 assay. These findings strongly suggest that SB-T-1213, SB-T-1250 and SB-T-101187 represent a new tool to overcome innate or acquired P-gp mediated taxane-resistance.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2000

Esophagogastric junction pressure topography after fundoplication.

OBJECTIVES: This study compared the pressure topography after laparoscopic Nissen fundoplication to that of normal subjects and patients with hiatal hernia and reflux disease. METHODS: Seven patients with fundoplication, 7 normal subjects and 7 patients with hiatal hernia, were studied. The squamocolumnar junction and intragastric margin of the esophagogastric junction (EGJ) were marked with metal clips. Axial and radial characteristics of EGJ pressure were mapped relative to the hernia and clipped during concurrent fluoroscopy and manometry. Responses to inspiration and abdominal compression were also analyzed. RESULTS: Fundoplication modifies the EGJ by restoration of the hiatal component of EGJ pressure and elongation of the subdiaphragmatic component. Maximal EGJ pressure after fundoplication is mainly dependent on the extrinsic effect of the hiatal canal that compresses the esophagus; the resultant length of the EGJ reflects the length of the fundic wrap. Integrity of the EGJ after fundoplication is independent of the intrinsic lower esophageal sphincter itself. CONCLUSIONS: Fundoplication alters the pressure topography of the EGJ by reducing the hiatal hernia, tightening the hiatal orifice, and constructing a subdiaphragmatic wrap of variable length. Each effect depends on different technical aspects of the surgery with the potential of substantial variability in the resultant pressure topography.

Adult↗
PubMed2000

Temperature-dependent pharmacokinetics and pharmacodynamics of vecuronium.

BACKGROUND: The authors evaluated the influence of temperature on the pharmacokinetics and pharmacodynamics of vecuronium because mild core hypothermia doubles its duration of action. METHODS: Anesthesia was induced with alfentanil and propofol and maintained with nitrous oxide and isoflurane in 12 healthy volunteers. Train-of-four stimuli were applied to the ulnar nerve, and the mechanical response of the adductor pollicis was measured. Volunteers were actively cooled or warmed until their distal esophageal temperatures were in one of four ranges: < 35.0 degrees C, 35.0-35.9 degrees C, 36.0-36.9 degrees C, and > or = 37.0 degrees C. With temperature stabilized, vecuronium was infused at 5 microg x kg(-1) x min(-1) until the first response of each train-of-four had decreased by 70%. Arterial blood (for vecuronium analysis) was sampled at intervals until the first response recovered to at least 90% of its prevecuronium level. Vecuronium, 20 microg x kg(-1) x min(-1), was then infused for 10 min, and arterial blood was sampled at intervals for up to 7 h. Population-based nonlinear mixed-effects modeling was used to examine the effect of physical characteristics and core temperature on vecuronium pharmacokinetics and pharmacodynamics. RESULTS: Decreasing core temperature over 38.0-34.0 degrees C decreases the plasma clearance of vecuronium (11.3% per degrees C), decreases the rate constant for drug equilibration between plasma and effect site (0.023 min(-1) per degrees C), and increases the slope of the concentration-response relationship (0.43 per degrees C). CONCLUSIONS: Our results show that reduced clearance and rate of effect site equilibration explain the increased duration of action of vecuronium with reducing core temperature. Tissue sensitivity to vecuronium is not influenced by core temperature.

Adult↗
PubMed2000

Three-dimensional finite element analyses of four designs of a high-strength silicon nitride implant.

The effects of implant shape and size on the stress distribution around high-strength silicon nitride implants under vertical and oblique forces were determined using a three-dimensional finite element analysis. Finite element models were designed using as a basis the serial sections of the mandible. Using Auto-CAD software, the model simulated the placement of implants in the molar region of the left mandible. Results of the analyses demonstrated that mainly the implant root shape and the directions of bite forces influence the stress distributions in the supporting bone around each implant. Implant size is a lesser factor. The serrated implants presented a larger surface area to the bone than either the cylindrical or tapered implants, which resulted in lower compressive stress around the serrated implants. With increasing implant diameter and length, compressive stress decreased. The mean compressive stress distribution on the serrated implants was more flat (platykurtic) than on either the cylindrical or tapered implants. Results of studies on two load directions (vertical and oblique) showed that, in either case, the compressive stress in the cortical bone around the neck of the implant was higher than in the cancellous bone along the length of the implant. The most extreme principal compressive stress was found with oblique force. This study provides the first information on the relationship between shape of the silicon nitride implant and stress on the supporting bone.

Alveolar Process↗
PubMed2000

Delta9-THC training dose as a determinant for (R)-methanandamide generalization in rats: a systematic replication.

Järbe et al. (1998a) trained rats to discriminate between (-)-delta9-tetrahydrocannabinol (delta9-THC) and vehicle, using different training doses in order to create assays with different efficacy demands, to examine whether (R)-methanandamide, an analog of the endogenous ligand anandamide, had lower efficacy than delta9-THC. Rats were initially trained with 3 mg/kg delta9-THC, then tested with (R)-methanandamide and delta9-THC. Thereafter, the rats were split into two groups and retrained with either 1.8 or 5.6 mg/kg delta9-THC, followed by additional tests with the two agonists. The current study systematically replicated this study in two groups of rats, trained from the outset to discriminate between vehicle and either 1.8 or 5.6 mg/kg delta9-THC, respectively. Two-lever operant drug discrimination procedures were used. The outcomes in the two studies were similar. In tests with (R)-methanandamide, full substitution occurred in the low-dose delta9-THC training group, whereas substitution was partial in the high-dose delta9-THC training group. (R)-Methanandamide in higher doses exerted marked suppression of lever pressing. In tests with delta9-THC, full substitution occurred in both delta9-THC-trained groups, and rates of responding were comparable to those observed during regular drug training sessions. In conclusion, both sets of data indicate that cannabinoid agonists either can have varying degrees of efficacy at a receptor site, or may produce their behavioral actions through multiple mechanisms, or both. Prevailing training-dose condition rather than prior training-dose history is the major determinant for the substitution pattern.

Animals↗
PubMed2000

Bacterial activity in South Pole snow.

Large populations (200 to 5,000 cells ml(-1) in snowmelt) of bacteria were present in surface snow and firn from the south pole sampled in January 1999 and 2000. DNA isolated from this snow yielded ribosomal DNA sequences similar to those of several psychrophilic bacteria and a bacterium which aligns closely with members of the genus Deinococcus, an ionizing-radiation- and desiccation-resistant genus. We also obtained evidence of low rates of bacterial DNA and protein synthesis which indicates that the organisms were metabolizing at ambient subzero temperatures (-12 to -17 degrees C).

Antarctic Regions↗
PubMed2000

Down-regulation of cyclin D1 expression by prostaglandin A(2) is mediated by enhanced cyclin D1 mRNA turnover.

Prostaglandin A(2) (PGA(2)), an experimental chemotherapeutic agent, causes growth arrest associated with decreased cyclin D1 expression in several cancer cell lines. Here, using human non-small-cell lung carcinoma H1299 cells, we investigated the mechanisms whereby PGA(2) down-regulates cyclin D1 expression. Transcription rates of the cyclin D1 gene, studied using a cyclin D1 promoter-luciferase construct and nuclear run-on assays, were not affected by PGA(2) treatment. Instead, the cyclin D1 mRNA was rendered unstable after exposure to PGA(2). Since the stability of labile mRNA is modulated through binding of proteins to specific mRNA sequences, we sought to identify protein(s) recognizing the cyclin D1 mRNA. In electrophoretic mobility-shift assays using radiolabeled RNA probes derived from different regions of cyclin D1 mRNA, we observed that (i) lysates prepared from PGA(2)-treated cells exhibited enhanced protein-cyclin D1 RNA complex formation; (ii) the kinetics of complex formation correlated closely with that of cyclin D1 mRNA loss; and (iii) binding occurred within a 390-base cyclin D1 3' untranslated region (UTR) (K12). This binding activity could be cross-linked, revealing proteins ranging from 30 to 47 kDa. The RNA-binding protein AUF1, previously associated with the degradation of target mRNAs, bound cyclin D1 mRNA, because anti-AUF1 antibodies were capable of supershifting or immunoprecipitating cyclin D1 mRNA-protein complexes. Finally, insertion of K12 in the 3'UTR of reporter genes markedly reduced the expression and half-life of the resulting chimeric mRNAs in transfected, PGA(2)-treated cells. Our data demonstrate that PGA(2) down-regulates cyclin D1 expression by decreasing cyclin D1 mRNA stability and implicates a 390-base element in the 3'UTR in this regulation.

3' Untranslated Regions↗
PubMed2000

Comparative polymerase chain reaction analysis of c-myc amplification on archival breast fine-needle aspiration materials.

The oncogene c-myc is a key regulator of cell cycle progression (from G1 to S phase). The amplification of c-myc can either induce cell proliferation or apoptosis. As a part of our ongoing effort to develop methods for multiple tumor marker analysis, this study was carried out to determine whether biomarkers such as c-myc amplification could be analyzed on genetic materials collected from archival fine-needle aspiration (FNA) smears. A novel comparative PCR analysis was used to analyze c-myc amplification semiquantitatively. Genomic DNA was prepared using cells obtained from archival FNA materials that had undergone quantitative fluorescence image analysis (QFIA) for other biomarkers. Of the 72 cases selected from 1995 for this study, 53 had an adequate amount of DNA for analysis. A novel comparative PCR analysis was used to analyze c-myc amplification quantitatively. For each batch of experiments, DNA from the high c-myc expressing cells, HL-60, and DNA from the low expressing cells, K562, were served as positive and negative controls, respectively. c-myc amplification was observed in 16 (94.1%) of 17 malignant lesions, 5 (41.7%) of 12 proliferative breast diseases with nuclear atypia, and 4 (16.7%) of 24 other benign lesions (fibroadenoma or fibrocystic disease). The overall difference of c-myc expression among these groups was highly significant by chi2 analysis (P = 0.0002). We conclude that multiple phenotypic markers and genotypic markers may be combined in a risk assessment biomarker profile on small FNA samples that can be obtained on multiple occasions relatively noninvasively from the patient. The results of this study suggest that c-myc amplification may be a biomarker of breast cancer risk. However, additional large, prospective studies are needed to confirm the current observation.

Adult↗
PubMed2000

Androgenetic alopecia in heterozygous carriers of a mutation in the human hairless gene.

BACKGROUND: Androgenetic alopecia is considered to be genetically determined. Recently, a rare autosomal recessive form of hereditary alopecia, termed atrichia with papular lesions (APL), was found to result from mutations in the human hairless gene. OBJECTIVE: Our aim was to assess the pattern of androgenetic alopecia in heterozygous carriers of a deleterious mutation in the human hairless gene. METHODS: Healthy male second-degree relatives (n = 31) of patients affected with APL and belonging to a large consanguineous kindred were interviewed and given a Hamilton score of baldness. DNA was obtained from each subject and analyzed for the presence of a mutation in the human hairless gene known to affect this family. The age at onset and extent of baldness were compared in healthy homozygotes and heterozygous carriers of the mutation. RESULTS: Statistical analysis of the results revealed no differences in age at onset and extent of androgenetic alopecia between the two groups of subjects. CONCLUSION: The present study reports the first attempt to characterize the phenotype of heterozygous carriers of a mutation in the human hairless gene. It indicates that the presence of a deleterious mutation in one allele of the hairless gene does not affect the pattern of androgenetic hair loss.

Adult↗
PubMed2000

Plasma CPU-86017 concentrations regarding suppression of ouabain-induced cardiac arrhythmias and decrease of heart rate in guinea pigs.

AIM: To determine the effective plasma levels of CPU-86017 which could suppress the cardiac arrhythmias induced by i.v. ouabain in guinea pigs. METHODS: The cardiac arrhythmias and the heart rate were monitored by ECG traces. Blood samples were collected to determine plasma levels using HPLC assay. TXB2 and 6-keto-PGF1 alpha were measured in plasma. RESULTS: The plasma concentrations of CPU-86017 which were effective to suppress ventricular fibrillation (VF) and heart rate were 0.13-0.23 mg/L and 0.13-0.31 mg/L, respectively. A reduction of TXB2 levels and an elevation of 6-keto-PGF1 alpha levels were observed after CPU-86017 i.v. administration. CONCLUSION: The arrhythmia-suppressing and heart rate-slowing effect of CPU-86017 followed a linear relationship with its concentrations in plasma.

6-Ketoprostaglandin F1 alpha↗
PubMed2000

Ozonation and alkaline-peroxide pretreatment of wheat straw for Cryptococcus curvatus fermentation.

Crop residues in an Advanced Life Support System (ALS) contain many valuable components that could be recovered and used. Wheat is 60% inedible, with approximately 90% of the total sugars in the residue cellulose and hemicellulose. To release these sugars requires pretreatment followed by enzymatic hydrolysis. Cryptococcus curvatus, an oleaginous yeast, uses the sugars in cellulose and hemicellulose for growth and production of storage triglycerides. In this investigation, alkaline-peroxide and ozonation pretreatment methods were compared for their efficiency to release glucose and xylose to be used in the cultivation of C. curvatus. Leaching the biomass with water at 65 degrees C for 4 h prior to pretreatment facilitated saccharification. Alkaline-peroxide and ozone pretreatment were almost 100% and 80% saccharification efficient, respectively. The sugars derived from the hydrolysis of alkaline-peroxide-treated wheat straw supported the growth of C. curvatus and the production of edible single-cell oil.

Biomass↗
PubMed2000

[Effect of foliar leaching on growth and mineral nutrition of maize under NaCl stress].

The impact of foliar leaching on growth and mineral nutrition maize under NaCl stress was investigated. The results showed that there was no difference in biomass between leaching and control treatments under low NaCl stress (0 and 50 mmol.L-1), but under high NaCl stress (100 and 200 mmol.L-1), the biomass of leaching treatment was higher, with a better at pH 3.5 than at pH 7.0. The shoot K+ content in leaching treatments was higher than that of control under no NaCl stress, but lower under 200 mmol.L-1 NaCl stress. Shoot Na+ content of leaching treatments was lower than that of control under high NaCl stress, and shoot Ca2+ and Mg2+ contents of leaching treatments were higher under no NaCl stress. Root K+, Na+, Ca2+ and Mg2+ content and relative water content of leaching treatments had no significant changes, compared with those of control. It was suggested that foliar leaching could alleviate harmful degree of maize under serious salt stress, which was related with the decrease of shoot Na+ content by foliar leaching.

Minerals↗
PubMed2000

Synergetic effect of dialyzer membrane and lipopolysaccharide on peripheral blood mononuclear cell cytokine production in uremic patients.

OBJECTIVE: To investigate the effect of lipopolysaccharide(LPS) and dialyzer membrane on cytokine gene expression and protein production in uremic patients on continuous ambulatory peritoneal dialysis (CAPD) and regular hemodialysis(HD). METHODS: Interleukin-1 beta (IL-1 beta) and interleukin-1 receptor antagonist (IL-1Ra) produced by cultured peripheral blood mononuclear cells (PBMC) after exposure to cuprammonium (Cup) membrane, polysulfone (PS) membranes or endotoxin were detected using enzyme-linked immunoabsorbent assay. mRNA expression was determined simultaneously by in situ hybridization. RESULTS: In the absence of endotoxin, a small amount of IL-1 beta and IL-1 Ra was produced by PBMC harvested from HD and CAPD patients after incubation with Cup or PS during subsequent 24-hour culture. For healthy controls, IL-1 beta was barely detectable just above the detection limit. Although no differences could be found in protein synthesis between Cup and PS, in situ hybridization showed that Cup induced markedly higher level mRNA coding for IL-1 beta and IL-1Ra. In contrast, when subsequently stimulated with endotoxin, PBMC incubated with Cup could produce significantly larger amount of IL-1 beta and IL-1Ra compared with either unstimulated cells or post-incubation PBMC with PS. LPS-stimulated PBMC in healthy subjects produced similar amount of IL-1 beta and markedly lower IL-1Ra as compared with uremic patients on HD and CAPD. CONCLUSIONS: Two steps are required in healthy control for IL-1 beta and IL-1Ra production: induction of mRNA transcription by membrane contact, followed by LPS-induced translation, while in uremic patients on HD or CAPD bioincompatibility-membrane and LPS have a synergetic effect on IL-1 beta and IL-1Ra production. There exists an unbalance between IL-1 beta and its specific inhibitor in maintenance dialysis patients.

Adult↗
PubMed2000

Dysregulation of apoptosis: a possible mechanism leading to chronic progressive renal histological changes in lupus nephritis.

OBJECTIVE: To evaluate apoptosis in lupus nephritis and the relationship between the existence of apoptotic cells in renal tissue and histopathological or clinical changes. METHODS: Apoptosis was detected by in situ nick-end labeling techniques (TUNEL) in renal biopsies from 25 patients with type IV lupus nephritis (LN), 12 patients with IgA nephropathy IgAN, 4 patients with idiopathic mesangioproliferative glomerulonephritis (MsPGN) and 3 patients with acute poststreptococcal glomerulonephritis (APGN). Normal renal tissue obtained at nephrectomy for hypernephroma in 4 adults was used as control. Proliferating cells were identified by proliferating cell nuclear antigen (PCNA) in these patients. RESULTS: Compared to other proliferative glomerulonephritis and controls, the patients with lupus nephritis had less apoptotic cells, a higher ratio of PCNA + cells/TdT + cells (P/T) in renal tissues; and their P/T ratio in glomeruli and tubulointerstitium correlated with the chronicity index, r = 0.4983 (P = 0.0132), r = 0.8399 (P < 0.001), r = 0.6614 (P = 0.0033), respectively. P/T ratios in the glomerulus and tubule had a positive correlation with 24-hour urinary protein, r = 0.8554 (P < 0.001) and r = 0.7134 (P = 0.001); and a negative correlation with creatinine clearance (Ccr), r = -0.4880 (P = 0.0133) and r = -0.7229 (P = 0.001), which in tubules positively correlated with serum creatinine (Scr), r = 0.4107 (P = 0.0414). CONCLUSIONS: Apoptosis is reduced in proliferative lupus nephritis. Intense proliferation without a commensurate increase in apoptosis is a possible mechanism that leads to chronic progressive renal histopathological changes.

Adult↗