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Eugene Lin

Publications and source records attributed to Eugene Lin.

13 recordsLinked to original sources
PubMed2007

Pattern-recognition techniques with haplotype analysis in pharmacogenomics.

Single nucleotide polymorphisms (SNPs) can be used in clinical association studies to determine the contribution of genes to drug efficacy. However, it would be extremely inefficient to test all the 10 million common SNPs for an association study. Here we review haplotype analysis and pattern-recognition techniques to systematically select candidate SNPs for candidate-gene association studies in pharmacogenomics. First, we survey linkage disequilibrium methods to identify tag SNPs and explore the use of haplotypes as genetic markers that are correlated and associated with drug efficacy. Secondly, we investigate pattern-recognition algorithms and statistical analyses to assess drug efficacy based on SNPs and other factors. Finally, we study pattern-recognition approaches to evaluate the epistasis among genes and SNPs. These techniques may provide tools for clinical association studies and help find genes/SNPs involved in responses to therapeutic drugs or adverse drug reactions.

Animals↗
PubMed2006

Impaired baseline regional cerebral perfusion in patients referred for coronary artery bypass.

BACKGROUND: Cognitive dysfunction and cerebral vascular accidents remain some of the most devastating problems related to cardiac surgery. Despite the major advances in perioperative care and operative technique in coronary artery bypass, this cohort of patients appears to have poor cerebral physiologic reserve. The aim of this study was to describe regional cerebral perfusion of patients with coronary artery disease referred for coronary artery bypass grafting. METHODS: Eighty-two consecutive patients with coronary artery disease referred for coronary artery bypass grafting were enrolled after providing informed consent in an institutional review board-approved study. Patients with prior cerebral vascular accident, transient ischemic attacks, head trauma, or other neurologic afflictions were excluded from the study. We prospectively measured preoperative regional cerebral perfusion using single photon emission computed tomography (SPECT) imaging of 12 regions. Patients were determined to have an abnormal SPECT if regional cerebral perfusion was less than 2 standard deviations below the mean of age-matched controls. RESULTS: The mean age was 67.5 (range, 34-89) years. The study group comprised 22% women and 78% men with known risk factors for atherosclerosis: current tobacco use (30%), hypertension (69%), and diabetes (27%). Seventy-five percent of the SPECT scans demonstrated abnormal regional cerebral perfusions, which were associated with older age (P < .008), current tobacco use (P < .005), and diabetes mellitus (P < .005). The incidence of postoperative cerebral vascular accident was 5% and only occurred in patients with abnormal regional cerebral perfusion. CONCLUSION: Seventy-five percent of patients undergoing coronary bypass grafting have a significant impairment in regional cerebral perfusion compared with published age-matched controls, which may contribute to their proclivity for cerebral complications.

Adult↗
PubMed2006

A case study of the utility of the HapMap database for pharmacogenomic haplotype analysis in the Taiwanese population.

BACKGROUND: Single nucleotide polymorphisms (SNPs) can be used in clinical association studies to determine the contribution of genes to drug efficacy. The goal of this work was to evaluate the feasibility of using SNP information of the Han Chinese in Beijing (CHB) population from the HapMap database for clinical association studies in the Taiwanese (TWN) population. METHODS: We compared the HapMap populations with our TWN study population with regard to allele frequencies for common SNPs in two candidate genes for antidepressant treatment response to determine the applicability of the HapMap CHB data for SNP selection in the TWN population. RESULTS AND CONCLUSION: Our preliminary results suggest that there was no significant difference, in terms of allele and haplotype frequencies, between the CHB population of the HapMap database and the TWN population collected by Vita Genomics Inc. Therefore, it is possible to use the CHB population of the HapMap database for SNP selection in association studies for the TWN population. Using haplotype analysis, we generated a panel of SNPs that may be strongly relevant to antidepressant response in this population.

Asian People↗
PubMed2006

An artificial neural network approach to the drug efficacy of interferon treatments.

INTRODUCTION: Interferon taken alone or in combination with ribavirin can be used for the treatment of persons with chronic hepatitis C. It is highly desirable, both clinically and economically, to establish tools to distinguish responders from nonresponders and to predict possible outcomes of the treatments. In this work, our goal is to develop a prediction model resulting from the analysis of chronic hepatitis C patients' single nucleotide polymorphisms, viral genotype, viral load, age and gender, to predict the responsiveness of interferon combination treatment. MATERIALS AND METHODS: We collected blood samples from 523 chronic hepatitis C patients that had received interferon and ribavirin combination therapy. Based on the current treatment strategy for chronic hepatitis C patients, we focused our search for candidate genes involved in pathways related to interferon signaling and immunomodulation. With artificial neural network algorithms, we then developed pattern recognition methodologies to achieve predictions among the patients. The artificial neural network model was trained by an algorithm with an adaptive momentum and learning rate. RESULTS: There were seven single nucleotide polymorphisms selected from six candidate genes including adenosine deaminase-RNA-specific, caspase 5, interferon consensus sequence binding protein 1, interferon-induced protein 44, phosphoinositide-3-kinase catalytic gamma polypeptide and transporter 2 ATP-binding cassette subfamily B genes. We further applied the artificial neural network algorithms with these seven single nucleotide polymorphisms, viral genotype, viral load, age and gender information to build tools for predicting the responsiveness of interferon. Based on the fivefold cross-validation method to evaluate the performance, the model achieved a high success rate of prediction. CONCLUSION: We demonstrated that a trained artificial neural network model is a promising method for providing the inference from factors such as single nucleotide polymorphisms, viral genotype, viral load, age and gender to the responsiveness of interferon.

Aging↗
PubMed2005

Neuronal CXCL10 directs CD8+ T-cell recruitment and control of West Nile virus encephalitis.

The activation and entry of antigen-specific CD8(+) T cells into the central nervous system is an essential step towards clearance of West Nile virus (WNV) from infected neurons. The molecular signals responsible for the directed migration of virus-specific T cells and their cellular sources are presently unknown. Here we demonstrate that in response to WNV infection, neurons secrete the chemokine CXCL10, which recruits effector T cells via the chemokine receptor CXCR3. Neutralization or a genetic deficiency of CXCL10 leads to a decrease in CXCR3(+) CD8(+) T-cell trafficking, an increase in viral burden in the brain, and enhanced morbidity and mortality. These data support a new paradigm in chemokine neurobiology, as neurons are not generally considered to generate antiviral immune responses, and CXCL10 may represent a novel neuroprotective agent in response to WNV infection in the central nervous system.

Animals↗
PubMed2005

Is Fournier's gangrene severity index useful for predicting outcome of Fournier's gangrene?

OBJECTIVES: Fournier's gangrene (FG) is a rare but life-threatening disease. Although antibiotics and aggressive debridement have been broadly accepted as the standard treatment, the mortality rate remains high. We conducted a retrospective study to analyze the outcome and identify the risk factors and prognostic indicators. METHODS: We retrospectively reviewed the medical records of 25 patients diagnosed with FG between July 1993 and August 2003. Data collected included age, predisposing factors, treatment modalities, length of hospital stay, surgical debridement times, and outcome. The FG severity index was used to predict outcome. Univariate analysis of the different prognostic factors was performed using t test and Fisher's exact probability test. RESULTS: All patients were male, 60% were diabetic, and the mean age was 55.8 years. The mean hospital stay was 20 days and the mortality rate was 32%. The mean age of 53.8+/-18.3 (SD) years in the survival group (n=17) was significantly lower than the 59.9+/-10.2 years (n=8) of the non-survival group (p<0.05). Non-survival group patients had lower serum hematocrit (mean 28.9, p=0.019) and albumin (mean 1.93, p=0.024) levels. In our series, the mean FG severity index for survivors was 4.41+/-2.45 (range 2-9) compared to 12.75+/-2.82 (range 9-18) for those who died (t test, p<0.0001). CONCLUSION: The survival rate of younger patients with FG was higher. We agree that a FG severity index cutoff value of 9 is an excellent predictor of outcome.

Adult↗
PubMed2004

IFN-inducible protein 10/CXC chemokine ligand 10-independent induction of experimental autoimmune encephalomyelitis.

In multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), autoaggressive T cells traffic into the CNS and induce disease. Infiltration of these pathogenic T cells into the CNS has been correlated with the expression of the chemokine IFN-inducible protein (IP)10/CXC chemokine ligand (CXCL)10, a chemoattractant for activated T cells, and its receptor CXCR3, in the CNS of both MS patients and mice with EAE. In the present study, we report that targeted deletion of IP-10 did not diminish the expression, severity, or histopathology of EAE induced by active immunization with 100 micro g of myelin oligodendrocyte glycoprotein peptide (MOG)p35-55. However, we found that IP-10-deficient mice had a lower threshold for expression of disease compared with wild-type littermates. EAE induced by immunization with 5 micro g of MOGp35-55 resulted in more severe disease characterized by a greater number of CNS lesions and infiltrating mononuclear cells in IP-10-deficient mice compared with wild-type controls. IP-10-deficient mice immunized with MOGp35-55 demonstrated increased levels of IFN-inducible T cell alpha-chemokine/CXCL11 mRNA in the CNS and decreased levels of monokine induced by IFN-gamma/CXCL9 mRNA in draining lymph nodes, suggesting differential compensation for loss of IP-10 in lymphoid vs parenchymal tissue compartments. EAE in IP-10-deficient mice induced by low-dose immunization was associated with enhanced Ag-specific Th1 responses in the draining lymph node, which corresponded with diminished lymph node TGF-beta1 expression. Our data demonstrated that IP-10 was not required for the trafficking of pathogenic T cells into the CNS in EAE but played an unexpected role in determining the threshold of disease susceptibility in the periphery.

Animals↗
PubMed2004

Recovery from and consequences of severe iatrogenic lymphopenia (induced to treat autoimmune diseases).

To ascertain the consequences of severe leukopenia and the tempo of recovery, we studied the immunity of 56 adult patients treated for multiple sclerosis or systemic sclerosis with autologous CD34 cell transplantation using extremely lymphoablative conditioning. NK cell, monocyte, and neutrophil counts recovered to normal by 1 month; dendritic cell and B cell counts by 6 months; and T cell counts by 2 years posttransplant, although CD4 T cell counts remained borderline low. Initial peripheral expansion was robust for CD8 T cells but only moderate for CD4 T cells. Subsequent thymopoiesis was slow, especially in older patients. Importantly, levels of antibodies, including autoantibodies, did not drop substantially. Infections were frequent during the first 6 months, when all immune cells were deficient, and surprisingly rare (0.21 per patient year) at 7-24 months posttransplant, when only T cells (particularly CD4 T cells) were deficient. In conclusion, peripheral expansion of CD8 but not CD4 T cells is highly efficient. Prolonged CD4 lymphopenia is associated with relatively few infections, possibly due to antibodies produced by persisting pretransplant plasma cells.

Adult↗
PubMed2004

Oncolytic viral therapies.

Molecular research has vastly advanced our understanding of the mechanism of cancer growth and spread. Targeted approaches utilizing molecular science have yielded provocative results in the treatment of cancer. Oncolytic viruses genetically programmed to replicate within cancer cells and directly induce toxic effect via cell lysis or apoptosis are currently being explored in the clinic. Safety has been confirmed and despite variable efficacy results several dramatic responses have been observed with some oncolytic viruses. This review summarizes results of clinical trials with oncolytic viruses in cancer.

Genetic Therapy↗
PubMed2004

Bacteria in the treatment of cancer.

Incidental observations of cancer regression following spontaneous bacterial infection have led to the preclinical development of bacteria as potential therapeutics in the treatment of cancer. A variety of natural and gene-modified bacterial species have now been explored as potential cancer treatments. The selectivity of bacterial species towards cancer will be discussed, direct bacterial oncolytic activity will be summarized and the use of bacteria as gene and/or protein delivery vehicles will be described. Preclinical and early clinical results presented indicate a high safety profile and demonstrate clear anticancer activity, thereby justifying further investigation of bacteria as a therapeutic approach in the treatment of cancer.

Animals↗
PubMed2003

Lack of synergy of erythromycin combined with penicillin or cefotaxime against Streptococcus pneumoniae in vitro.

We investigated a possible synergistic effect of a macrolide and beta-lactams against Streptococcus pneumoniae strains with different resistance profiles. Checkerboard and time-kill assays of erythromycin combined with penicillin or cefotaxime essentially showed indifference, suggesting that these antibiotics in combinations in vitro act substantially as individuals in their activity against S. pneumoniae.

Anti-Bacterial Agents↗