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Biomedical subjects

D Lin

Publications and source records attributed to D Lin.

At least 55 records · Page 3Linked to original sources
PubMed2000

Chronic alcohol ingestion induces osteoclastogenesis and bone loss through IL-6 in mice.

To investigate the role of IL-6 in alcohol-mediated osteoporosis, we measured a variety of bone remodeling parameters in wild-type (il6(+/+)) or IL-6 gene knockout (il6(-/-)) mice that were fed either control or ethanol liquid diets for 4 months. In the il6(+/+) mice, ethanol ingestion decreased bone mineral density, as determined by dual-energy densitometry; decreased cancellous bone volume and trabecular width and increased trabecular spacing and osteoclast surface, as determined by histomorphometry of the femur; increased urinary deoxypyridinolines, as determined by ELISA; and increased CFU-GM formation and osteoclastogenesis as determined ex vivo in bone marrow cell cultures. In contrast, ethanol ingestion did not alter any of these parameters in the il6(-/-) mice. Ethanol increased receptor activator of NF-kappaB ligand (RANKL) mRNA expression in the bone marrow of il6(+/+) but not il6(-/-) mice. Additionally, ethanol decreased several osteoblastic parameters including osteoblast perimeter and osteoblast culture calcium retention in both il6(+/+) and il6(-/-) mice. These findings demonstrate that ethanol induces bone loss through IL-6. Furthermore, they suggest that IL-6 achieves this effect by inducing RANKL and promoting CFU-GM formation and osteoclastogenesis.

Absorptiometry, Photon↗
PubMed2000

On asymmetries in cross-modal spatial attention orienting.

In a previous study, Ward (1994) reported that spatially uninformative visual cues orient auditory attention but that spatially uninformative auditory cues fail to orient visual attention. This cross-modal asymmetry is consistent with other intersensory perceptual phenomena that are dominated by the visual modality (e.g., ventriloquism). However, Spence and Driver (1997) found exactly the opposite asymmetry under different experimental conditions and with a different task. In spite of the several differences between the two studies, Spence and Driver (see also Driver & Spence, 1998) argued that Ward's findings might have arisen from response-priming effects, and that the cross-modal asymmetry they themselves reported, in which auditory cues affect responses to visual targets but not vice versa, is in fact the correct result. The present study investigated cross-modal interactions in stimulus-driven spatial attention orienting under Ward's complex cue environment conditions using an experimental procedure that eliminates response-priming artifacts. The results demonstrate that the cross-modal asymmetry reported by Ward (1994) does occur when the cue environment is complex. We argue that strategic effects in cross-modal stimulus-driven orienting of attention are responsible for the opposite asymmetries found by Ward and by Spence and Driver (1997).

Adolescent↗
PubMed2000

[Genetic polymorphism in hOGG1 and susceptibility to esophageal cancer in Chinese].

OBJECTIVE: To examine the association between Ser326Cys polymorphism in hOGG1 gene, which is involved in the repair of 8-hydroxyguanine in damaged DNA, and investigate the risk of squamous cell carcinoma of the esophagus in Chinese. METHODS: Ser326Cys polymorphism in hOGG1 gene was determined by PCR-SSCP approach among 201 normal controls and 196 patients with squamous cell carcinoma of the esophagus. The association between this genetic polymorphism and the risk of the cancer was examined by a multivariate analysis. RESULTS: The Cys/Cys genotype of hOGG1 was found in 21.4% of patients with the cancer and in 13.4% of controls (P<0.05). Homozygosity for the Cys/Cys genotype significantly increased the risk of developing esophageal cancer, with the odds ratio adjusted for age, sex and smoking being 1.9(95% CI 1.3-2.6). Smoking also significantly increased esophageal cancer risk in this case-control study (adjusted OR 2.6; 95% CI 1.7- 3.9). No interaction between smoking and Cys/Cys genotype was observed for the risk of esophageal cancer. CONCLUSION: Polymorphism of hOGG1 Ser326Cys may play a role in esophageal carcinogenesis.

Adult↗
PubMed2000

[The effect of polylactide screws on fracture healing].

This experiment aimed at investigating the effect of a kind of home-bred poly-DL-lactide screws on fracture healing. An operation was performed so as to make bilateral lateral condylar fractures of the femur in 8 dogs. The left sides were fixed with 2 home-bred PDLLA(Mv = 43 x 10(4)) screws, and the contralateral sides were fixed with 2 metalic screws to be used as controls. The animals were sacrificed at 2, 4, 8, and 12 weeks after surgery. Optic microscopy and SEM photography were done. The results of optic microscopy showed that fibrous callus formed already in both groups by 2 weeks after surgery, and bilateral fractures united uneventfully by 12 weeks. Although the course of fracture healing in experimental group was slower than that in control group, the osteogenesis in experimental group appeared to be normal. The SEM examination demonstrated that collagenous fibers arranged regularly and calcified normally in both groups at 12 weeks. And many square and rhomboid granules produced from the degradation of PDLLA material were found in experimental group at 12 weeks. Therefore, it is suggested that this kind of home-bred PDLLA screws should be applicable to fractures where the tissues are rich in blood supply.

Animals↗
PubMed2000

[Geographic information systems spatial analysis on transmission of schistosomiasis in China].

OBJECTIVE: To understand the epidemiologic status and geographical distribution of schistosomiasis in China. METHODS: Relevant detabases were set up after collection of data from two National Sampling Surveys on Schistosomiasis, in 1989 and 1995. Spatial analysis was undertaken after the database linked to the GIS software which was supported by Arc View 3.0a. Correlation analysis was performed to understand the relationship between rates of human infection and cattle infection. RESULTS: The epidemic areas of schistosomiasis with high risk are mainly distributed in the marshland along the Yangtze River and can be identified as five spatial distribution regions based on the results of spatial analysis. Both epidemic areas and positive rates of stool examination in cattle and water buffalo are much wider and higher than that in humans. The positive correlation was seen between infection rate in human and in cattle from data of both sampling surveys. CONCLUSION: The relevant strategy for schistosomiasis control in different spatial regions should be performed accordingly and the measures of control for cattle and water buffalo should be strengthened in the endemic areas.

Adolescent↗
PubMed2000

[Experimental studies on exons 5-8 of p53 gene mutation in laryngeal squamous cell carcinoma].

This study was designed to detect the point mutations of exons 5-8 of p53 gene in laryngeal squamous cell carcinoma (LSCC) and analyze their relationship. The detection of fresh tumor samples from LSCC patients was performed using silver staining PCR-SSCP method. From among 60 patients samples, 47 were positive in SSCP. Mutation rate was 78.3% (47/60). The results showed that the prevalence of p53 mutations in LSCC subjected to silver staining PCR-SSCP test were 50% (30/60) in exon 5, 11.67%(7/60) in exon 6, 41.6%(25/60) in exon 7, and 25%(15/60) in exon 8. The majority of the mutations were found in exon 5 and exon 7. Exon 5 and exon 7 of p53 gene may be the mutation hotspot in LSCC; they may be the critical position easily attacked by some carcinogen factors relating to LSCC.

Carcinoma, Squamous Cell↗
PubMed1999

Functional consequences of troponin T mutations found in hypertrophic cardiomyopathy.

Missense mutations in the cardiac thin filament protein troponin T (TnT) are a cause of familial hypertrophic cardiomyopathy (FHC). To understand how these mutations produce dysfunction, five TnTs were produced and purified containing FHC mutations found in several regions of TnT. Functional defects were diverse. Mutations F110I, E244D, and COOH-terminal truncation weakened the affinity of troponin for the thin filament. Mutation DeltaE160 resulted in thin filaments with increased calcium affinity at the regulatory site of troponin C. Mutations R92Q and F110I resulted in impaired troponin solubility, suggesting abnormal protein folding. Depending upon the mutation, the in vitro unloaded actin-myosin sliding speed showed small increases, showed small decreases, or was unchanged. COOH-terminal truncation mutation resulted in a decreased thin filament-myosin subfragment 1 MgATPase rate. The results indicate that the mutations cause diverse immediate effects, despite similarities in disease manifestations. Separable but repeatedly observed abnormalities resulting from FHC TnT mutations include increased unloaded sliding speed, increased or decreased Ca(2+) affinity, impairment of folding or sarcomeric integrity, and decreased force. Enhancement as well as impairment of contractile protein function is observed, suggesting that TnT, including the troponin tail region, modulates the regulation of cardiac contraction.

Amino Acid Sequence↗
PubMed1999

The carboxyl terminus of B class ephrins constitutes a PDZ domain binding motif.

Ephrin B proteins function as ligands for B class Eph receptor tyrosine kinases and are postulated to possess an intrinsic signaling function. The sequence at the carboxyl terminus of B-type ephrins contains a putative PDZ binding site, providing a possible mechanism through which transmembrane ephrins might interact with cytoplasmic proteins. To test this notion, a day 10.5 mouse embryonic expression library was screened with a biotinylated peptide corresponding to the carboxyl terminus of ephrin B3. Three of the positive cDNAs encoded polypeptides with multiple PDZ domains, representing fragments of the molecule GRIP, the protein syntenin, and PHIP, a novel PDZ domain-containing protein related to Caenorhabditis elegans PAR-3. In addition, the binding specificities of PDZ domains previously predicted by an oriented library approach (Songyang, Z., Fanning, A. S., Fu, C., Xu, J., Marfatia, S. M., Chishti, A. H., Crompton, A., Chan, A. C., Anderson, J. M., and Cantley, L. C. (1997) Science 275, 73-77) identified the tyrosine phosphatase FAP-1 as a potential binding partner for B ephrins. In vitro studies demonstrated that the fifth PDZ domain of FAP-1 and full-length syntenin bound ephrin B1 via the carboxyl-terminal motif. Lastly, syntenin and ephrin B1 could be co-immunoprecipitated from transfected COS-1 cells, suggesting that PDZ domain binding of B ephrins can occur in cells. These results indicate that the carboxyl-terminal motif of B ephrins provides a binding site for specific PDZ domain-containing proteins, which might localize the transmembrane ligands for interactions with Eph receptors or participate in signaling within ephrin B-expressing cells.

Amino Acid Sequence↗
PubMed1999

Differential effects of withdrawal from chronic amphetamine or fluoxetine administration on brain stimulation reward in the rat--interactions between the two drugs.

RATIONALE: Withdrawal from chronic amphetamine administration is characterized by deficits in reward that resemble some symptoms of depression. Nevertheless, the effects of long-term administration and withdrawal from other drugs, such as fluoxetine, that have the potential to elevate mood in depressed individuals have not been characterized. OBJECTIVES: The purpose of this study was to characterize the effects of withdrawal from chronic amphetamine or fluoxetine administration on central reward function. Furthermore, the effects of acute or chronic pretreatment with fluoxetine on responsiveness to an acute amphetamine challenge were examined to identify potential interactions between the two drugs. METHODS: A rate-independent discrete-trial threshold procedure was used to characterize self-stimulation behavior in rats prepared with bipolar electrodes in the medial forebrain bundle. RESULTS: Elevations in intracranial self-stimulation (ICSS) thresholds, reflecting a decrease in the reward value of the stimulation, were associated with withdrawal from various chronic amphetamine treatment regimens (1-5 mg/kg, three injections per day for 1, 2, 4 or 6 days). The magnitude and duration of threshold elevations were proportional to the duration and dose of amphetamine treatment prior to withdrawal. In contrast, no alterations in ICSS thresholds were associated with withdrawal from chronic fluoxetine treatment (5 mg/kg/day for 15 days). While neither acute nor chronic administration of fluoxetine alone altered ICSS thresholds, chronic pretreatment with fluoxetine blocked the threshold-lowering effect of acute amphetamine administration (4 mg/kg), but acute pretreatment did not. Amphetamine-induced decreases in response latency, a measure of motor performance, were not affected by either chronic or acute fluoxetine pretreatment. CONCLUSIONS: The results of these experiments suggest that chronic fluoxetine treatment may induce adaptive changes in serotonergic transmission that, in themselves, do not alter the function of central reward processes, but may alter the ability of amphetamine to potentiate ICSS reward. In addition, the lack of change in ICSS thresholds during withdrawal from the chronic fluoxetine treatment regimen used suggests that withdrawal from all mood-altering drugs may not necessarily produce changes in central reward functions.

Amphetamine↗
PubMed1999

On the use of survival analysis techniques to estimate medical care costs.

Measurement of treatment costs is important in the evaluation of medical interventions. Accurate cost estimation is problematic, when cost records are incomplete. Methods from the survival analysis literature have been proposed for estimating costs using available data. In this article, we clarify assumptions necessary for validity of these techniques. We demonstrate how assumptions needed for valid survival analysis may be violated when these methods are applied to cost estimation. Our observations are confirmed through simulations and empirical data analysis. We conclude that survival analysis approaches are not generally appropriate for the analysis of medical costs and review several valid alternatives.

Costs and Cost Analysis↗
PubMed1999

The protein data bank. Bridging the gap between the sequence and 3D structure world.

The protein data bank (PDB), at Brookhaven National Laboratory, is a database containing information on experimentally determined three-dimensional structures of proteins, nucleic acids, and other biological macromolecules, with approximately 9000 entries. The PDB has a 27-year history of service to a global community of researchers, educators, and students in a wide variety of scientific disciplines. Data are easily submitted via PDB's WWW-based tool AutoDep, in either PDB or mmCIF format, and are most conveniently examined via PDB's WWW-based tool 3DB Browser. Collaborative centers have been, and continue to be, established worldwide to assist in data deposition, archiving, and distribution.

Databases, Factual↗
PubMed1999

Structural genomics: beyond the human genome project.

With access to whole genome sequences for various organisms and imminent completion of the Human Genome Project, the entire process of discovery in molecular and cellular biology is poised to change. Massively parallel measurement strategies promise to revolutionize how we study and ultimately understand the complex biochemical circuitry responsible for controlling normal development, physiologic homeostasis and disease processes. This information explosion is also providing the foundation for an important new initiative in structural biology. We are about to embark on a program of high-throughput X-ray crystallography aimed at developing a comprehensive mechanistic understanding of normal and abnormal human and microbial physiology at the molecular level. We present the rationale for creation of a structural genomics initiative, recount the efforts of ongoing structural genomics pilot studies, and detail the lofty goals, technical challenges and pitfalls facing structural biologists.

Computational Biology↗
PubMed1999

Assessment and control for confounding by indication in observational studies.

In the evaluation of pharmacologic therapies, the controlled clinical trial is the preferred design. When clinical trial results are not available, the alternative designs are observational epidemiologic studies. A traditional concern about the validity of findings from epidemiologic studies is the possibility of bias from uncontrolled confounding. In studies of pharmacologic therapies, confounding by indication may arise when a drug treatment serves as a marker for a clinical characteristic or medical condition that triggers the use of the treatment and that, at the same time, increases the risk of the outcome under study. Confounding by indication is not conceptually different from confounding by other factors, and the approaches to detect and control for confounding--matching, stratification, restriction, and multivariate adjustment--are the same. Even after adjustment for known risk factors, residual confounding may occur because of measurement error or unmeasured or unknown risk factors. Although residual confounding is difficult to exclude in observational studies, there are limits to what this "unknown" confounding can explain. The degree of confounding depends on the prevalence of the putative confounding factor, the level of its association with the disease, and the level of its association with the exposure. For example, a confounding factor with a prevalence of 20% would have to increase the relative odds of both outcome and exposure by factors of 4 to 5 before the relative risk of 1.57 would be reduced to 1.00. Observational studies have provided important scientific evidence about the risks associated with several risk factors, including drug therapies, and they are often the only option for assessing safety. Understanding the methods to detect and control for confounding makes it possible to assess the plausibility of claims that confounding is an alternative explanation for the findings of particular studies.

Antihypertensive Agents↗
PubMed1999

Initial clinical experience with a fully automatic in-hospital external cardioverter defibrillator.

Sudden cardiac death due to ventricular tachyarrhythmia remains a significant problem in the in-hospital setting. Although the probability of survival is closely correlated with the rapidity of a response by qualified personnel, response times can be prolonged, even in specialized care units. In an effort to decrease response time, a fully automatic external cardioverter defibrillator was recently devised. This device was evaluated in the in-hospital setting to assess safety and efficacy. A total of 79 patients were studied in a multicenter trial. Patients were monitored with fully functional devices in the electrophysiology laboratory (51 patients) and in the cardiac care unit (28 patients). Performance of the device was assessed by comparing automatic responses to any sustained change in cardiac rhythm, either spontaneous or induced, to a retrospective review of stored ECG data and programmed parameters. During a total duration of 964 hours of monitoring, there were 99 episodes of sustained tachycardia. Therapy was appropriately delivered or advised in all episodes. Therapy was advised in one episode of supraventricular tachycardia. There were no episodes of inappropriate therapy delivery. There were no complications or adverse events. The device performed with a sensitivity of 100% and specificity of 98.8% with an average response time of 22 seconds. In conclusion, this automatic external defibrillator was safe, effective, and functioned as designed. Significant improvement in response time to life-threatening ventricular tachyarrhythmia in the in-hospital setting would be expected if this technology was widely adopted.

Adult↗