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Y T Chen

Publications and source records attributed to Y T Chen.

At least 127 records · Page 7Linked to original sources
PubMed1999

Antigens recognized by autologous antibody in patients with renal-cell carcinoma.

The screening of cDNA expression libraries derived from human tumors with autologous antibody (SEREX) is a powerful method for defining the structure of tumor antigens recognized by the humoral immune system. Sixty-five distinct antigens (NY-REN-1 to NY-REN-65) reactive with autologous IgG were identified by SEREX analysis of 4 renal cancer patients and were characterized in terms of cDNA sequence, mRNA expression pattern, and reactivity with allogeneic sera. REN-9, -10, -19, and -26 have a known association with human cancer. REN-9 (LUCA-15) and REN-10 (gene 21) map to the small cell lung cancer tumor suppressor gene locus on chromosome 3p21.3. REN-19 is equivalent to LKB1/STK11, a gene that is defective in Peutz-Jeghers syndrome and cancer. REN-26 is encoded by the bcr gene involved in the [t(9:22)] bcr/abl translocation. Genes encoding 3 of the antigens in the series showed differential mRNA expression; REN-3 displays a pattern of tissue-specific isoforms, and REN-21 and REN-43 are expressed at a high level in testis in comparison to 15 other normal tissues. The other 62 antigens were broadly expressed in normal tissues. With regard to immunogenicity, 20 of the 65 antigens reacted only with autologous sera. Thirty-three antigens reacted with sera from normal donors, indicating that their immunogenicity is not restricted to cancer. The remaining 12 antigens reacted with sera from 5-25% of the cancer patients but not with sera from normal donors. Seventy percent of the renal cancer patients had antibodies directed against one or more of these 12 antigens. Our results demonstrate the potential of the SEREX approach for the analysis of the humoral immune response against human cancer.

Aged↗
PubMed1999

Age-associated rapid and Stat6-independent IL-4 production by NK1-CD4+8- thymus T lymphocytes.

The source of IL-4 required for priming naive T cells into IL-4-secreting effectors has not been clearly identified. Here we show that upon TCR stimulation, thymus NK1-CD4+8- T cells produced IL-4, the magnitude of which was inversely correlated with age. This IL-4 production response by Th2-prone BALB/c mice was approximately 9-fold that of Th1-prone C57BL/10 mice. More than 90% of activated NK1-CD4+8- thymocytes did not use the invariant V alpha 14-J alpha 281 chain characteristic of typical CD1-restricted NK1+CD4+ T cells. Stat6-null NK1-CD4+8- thymocytes produced bioactive IL-4, with induction of IL-4 mRNA expression within 1 h of stimulation. Our results support the possibility that TCR repertoire-diverse conventional NK1-CD4+ T cells are a potential IL-4 source for directing naive T cells toward Th2/type 2 CD8+ T cell (Tc2) effector development.

Aging↗
PubMed1999

Humoral immune responses of cancer patients against "Cancer-Testis" antigen NY-ESO-1: correlation with clinical events.

Humoral immune responses against the "Cancer-Testis" (CT) antigen NY-ESO-1 are frequently observed in patients with NY-ESO-1 expressing tumors. This is in contrast to other known tumor antigens (TA) defined by antibody or cytotoxic T cell (CTL) reactivity, i.e., MAGE-1, MAGE-3, SSX2, Melan A, and tyrosinase. No NY-ESO-1 antibody has been detected in healthy controls and patients with NY-ESO-1 negative tumors. In this study, we have assessed the NY-ESO-1 serum antibody response in patients with NY-ESO-1 positive tumors of different histological types and stages using Western blotting and an ELISA. Of the 12 patients analyzed, 10 had demonstrable NY-ESO-1 antibodies at the start of the study. All patients were followed for changes in NY-ESO-1 antibody titers during the course of tumor treatment and clinical evolution. In 4 patients, an increase of NY-ESO-1 antibody titer was observed with progression of disease or extensive tumor necrosis under treatment. One patient showed a stable NY-ESO-1 antibody titer over 3 years along with gradual regression of a large tumor mass. In 5 patients, a decrease of NY-ESO-1 antibody was detected: in 1 patient after curative tumor resection, in 3 patients with partial regression of metastatic disease under chemo- and immunotherapy, and in another patient with a NY-ESO-1 negative tumor relapse. Our results indicate that the induction and maintenance of NY-ESO-1 antibody is dependent on the presence of NY-ESO-1 expressing tumors. Furthermore, changes in NY-ESO-1 antibody titers correlate with the evolution of NY-ESO-1 positive disease.

Adult↗
PubMed1999

Systemic correction of the muscle disorder glycogen storage disease type II after hepatic targeting of a modified adenovirus vector encoding human acid-alpha-glucosidase.

This report demonstrates that a single intravenous administration of a gene therapy vector can potentially result in the correction of all affected muscles in a mouse model of a human genetic muscle disease. These results were achieved by capitalizing both on the positive attributes of modified adenovirus-based vectoring systems and receptor-mediated lysosomal targeting of enzymes. The muscle disease treated, glycogen storage disease type II, is a lysosomal storage disorder that manifests as a progressive myopathy, secondary to massive glycogen accumulations in the skeletal and/or cardiac muscles of affected individuals. We demonstrated that a single intravenous administration of a modified Ad vector encoding human acid alpha-glucosidase (GAA) resulted in efficient hepatic transduction and secretion of high levels of the precursor GAA proenzyme into the plasma of treated animals. Subsequently, systemic distribution and uptake of the proenzyme into the skeletal and cardiac muscles of the GAA-knockout mouse was confirmed. As a result, systemic decreases (and correction) of the glycogen accumulations in a variety of muscle tissues was demonstrated. This model can potentially be expanded to include the treatment of other lysosomal enzyme disorders. Lessons learned from systemic genetic therapy of muscle disorders also should have implications for other muscle diseases, such as the muscular dystrophies.

Adenoviridae↗
PubMed1999

Comparing AMI mortality among hospitals in patients 65 years of age and older: evaluating methods of risk adjustment.

BACKGROUND: Interest in the reporting of risk-adjusted outcomes for patients with acute myocardial infarction is growing. A useful risk-adjustment model must balance parsimony and ease of data collection with predictive ability. METHODS AND RESULTS: From our analysis of 82 359 patients >/=65 years of age admitted with acute myocardial infarction to 2401 hospitals, we derived a parsimonious model that predicts 30-day mortality. The model was validated on a similar group of 78 699 patients from 2386 hospitals. Of the 73 candidate predictor variables examined, 7 variables describing patient characteristics on arrival were selected for inclusion in the final model: age, cardiac arrest, anterior or lateral location of myocardial infarction, systolic blood pressure, white blood cell count, serum creatinine, and congestive heart failure. The area under the receiver-operating characteristic curve for the final model was 0.77 in the derivation cohort and 0.77 in the validation cohort. The rankings of hospitals by performance (in deciles) with this model were most similar to a comprehensive 27-variable model based on medical chart review and least similar to models based on administrative billing codes. CONCLUSIONS: A simple 7-variable risk model performs as well as more complex models in comparing hospital outcomes for acute myocardial infarction. Although there is a continuing need to improve methods of risk adjustment, our results provide a basis for hospitals to develop a simple approach to compare outcomes.

Age Factors↗
PubMed1999

Isoforms of the human PDZ-73 protein exhibit differential tissue expression.

Patients with renal and colon cancer frequently develop IgG autoantibodies toward the NY-CO-38/PDZ-73 antigen, a protein of 652 amino acids (73 kDa) which contains three copies of the PDZ protein-protein interaction domain. The gene encoding PDZ-73 mapped to chromosome 11p15.4-p15.1. Additional tissue-specific isoforms were identified: PDZ-45, which lacks the third PDZ domain and the putative PEST protein degradation motif, is expressed in kidney, colon, small intestine, brain and testis; PDZ-54 and PDZ-59, which also lack the third PDZ domains, have unique carboxyl terminal amino acids and are expressed in brain, kidney, bladder, colon cancer and renal cancer; and a putative PDZ-37 isoform, containing only the third PDZ domain, that is expressed in the central nervous system. Immunohistochemical staining with anti-PDZ 73 monoclonal antibodies showed strong cytoplasmic reactivity in epithelial cells of the small intestine, colon and kidney tubules, with a prominent apical staining pattern in cells of the small intestine. The reactivity pattern of the antibodies with various tissues correlated with the mRNA expression pattern of the PDZ-45 isoform. The existence of multiple PDZ-73 isoforms with variations in tissue distribution, PDZ domains, protein degradation sequences and carboxyl terminal structure indicate that these isoforms have distinct tissue-specific functions.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Coupling assembly of the E-cadherin/beta-catenin complex to efficient endoplasmic reticulum exit and basal-lateral membrane targeting of E-cadherin in polarized MDCK cells.

The E-cadherin/catenin complex regulates Ca++-dependent cell-cell adhesion and is localized to the basal-lateral membrane of polarized epithelial cells. Little is known about mechanisms of complex assembly or intracellular trafficking, or how these processes might ultimately regulate adhesion functions of the complex at the cell surface. The cytoplasmic domain of E-cadherin contains two putative basal-lateral sorting motifs, which are homologous to sorting signals in the low density lipoprotein receptor, but an alanine scan across tyrosine residues in these motifs did not affect the fidelity of newly synthesized E-cadherin delivery to the basal-lateral membrane of MDCK cells. Nevertheless, sorting signals are located in the cytoplasmic domain since a chimeric protein (GP2CAD1), comprising the extracellular domain of GP2 (an apical membrane protein) and the transmembrane and cytoplasmic domains of E-cadherin, was efficiently and specifically delivered to the basal-lateral membrane. Systematic deletion and recombination of specific regions of the cytoplasmic domain of GP2CAD1 resulted in delivery of <10% of these newly synthesized proteins to both apical and basal-lateral membrane domains. Significantly, >90% of each mutant protein was retained in the ER. None of these mutants formed a strong interaction with beta-catenin, which normally occurs shortly after E-cadherin synthesis. In addition, a simple deletion mutation of E-cadherin that lacks beta-catenin binding is also localized intracellularly. Thus, beta-catenin binding to the whole cytoplasmic domain of E-cadherin correlates with efficient and targeted delivery of E-cadherin to the lateral plasma membrane. In this capacity, we suggest that beta-catenin acts as a chauffeur, to facilitate transport of E-cadherin out of the ER and the plasma membrane.

Amino Acid Sequence↗
PubMed1999

Prenatal diagnosis of glycogen storage disease type IV using PCR-based DNA mutation analysis.

Deficiency of glycogen branching enzyme activity causes glycogen storage disease type IV (GSD-IV). Clinically, GSD-IV has variable clinical presentations ranging from a fatal neonatal neuromuscular disease, to a progressive liver cirrhosis form, and to a milder liver disease without progression. Current methods for prenatal and postnatal diagnosis are based on an indirect method of measuring the enzyme activity, which has a limited sensitivity and cannot be used to distinguish patients with these variable clinical phenotypes. In this study, a GSD-IV family with a non-progressive hepatic form of the disease requested prenatal diagnosis. Determination of the branching enzyme activity in cultivated amniocytes showed 20 per cent residual activity overlapping with the level detected in the heterozygotes. Mutation analysis revealed that the fetus carried two mutant alleles, L224P and Y329S, the same as the proband of this family. The fetus was predicted to be affected and postnatally his clinical presentation is consistent with the diagnosis. We conclude that DNA mutation analysis should be used in the prenatal diagnosis of GSD-IV, especially in the situation of high residual enzyme activity.

Child, Preschool↗
PubMed1999

Coronary artery aneurysms: A 25-patient study.

Coronary artery aneurysm is a rare disorder, characterized by abnormal dilatation of a localized portion or diffuse segments of the coronary artery. We studied clinical demographics, catheterization findings, and clinical outcomes in an Asian patient cohort with documented coronary artery aneurysms. Compared to a Caucasian adult population, our patient cohort had a lower incidence of coronary artery aneurysm (0.25% vs. 2.6%), and more patients with nonobstructive coronary artery aneurysms (70%); age, gender, and coronary distribution were comparable. The initial presentation of myocardial infarction occurred in five patients (5/17, 30%) with nonobstructive coronary artery aneurysms; however, none who were receiving preventive medications consisting of anticoagulant and antiplatelet agents subsequently developed myocardial infarction. We conclude that the incidence of coronary artery aneurysms with or without associated significant coronary stenosis seems to be lower in the Asian population. In contrast, the incidence of nonobstructive coronary artery aneurysms is considerably high and should not be thought of as a relatively benign disease entity if not treated with preventive medications. Rheumatoid arthritis-related vasculitis might be a cause of coronary artery aneurysm. Surgical intervention is based on the severity of coronary artery stenosis. The result of medical treatment has been compatible with long-term survival. Cathet. Cardiovasc. Intervent. 48:31-38, 1999.

Adult↗
PubMed1999

Liver transplantation for glycogen storage disease types I, III, and IV.

UNLABELLED: Glycogen storage disease (GSD) types I, III, and IV can be associated with severe liver disease. The possible development of hepatocellular carcinoma and/or hepatic failure make these GSDs potential candidates for liver transplantation. Early diagnosis and initiation of effective dietary therapy have dramatically improved the outcome of GSD type I by reducing the incidence of liver adenoma and renal insufficiency. Nine type I and 3 type III patients have received liver transplants because of poor metabolic control, multiple liver adenomas, or progressive liver failure. Metabolic abnormalities were corrected in all GSD type I and type III patients, while catch-up growth was reported only in two patients. Whether liver transplantation results in reversal and/or prevention of renal disease remains unclear. Neutropenia persisted in both GSDIb patients post liver transplantation necessitating continuous granulocyte colony stimulating factor treatment. Thirteen GSD type IV patients were liver transplanted because of progressive liver cirrhosis and failure. All but one patient have not had neuromuscular or cardiac complications during follow-up periods for as long as 13 years. Four have died within a week and 5 years after transplantation. Caution should be taken in selecting GSD type IV candidates for liver transplantation because of the variable phenotype, which may include life-limiting extrahepatic manifestations. It remains to be evaluated, whether a genotype-phenotype correlation exists for GSD type IV, which may aid in the decision making. CONCLUSION: Liver transplantation should be considered for patients with glycogen storage disease who have developed liver malignancy or hepatic failure, and for type IV patients with the classical and progressive hepatic form.

Adolescent↗
PubMed1999

Expression of melanocyte-associated markers gp-100 and Melan-A/MART-1 in angiomyolipomas. An immunohistochemical and rt-PCR analysis.

Angiomyolipomas are tumours of uncertain histogenesis, most often occurring in association with the kidney. A characteristic finding is their reactivity with HMB-45, a monoclonal antibody to the melanocyte-associated antigen gp-100. We tested 18 angiomyolipomas for their reactivity with A103, a monoclonal antibody to Melan-A (MART-1), another melanocyte-associated marker, and compared it with HMB-45. All cases were positive with both antibodies, yet most cases showed a more homogeneous staining pattern with A103. Normal kidney was immunohistochemically negative for both antibodies. We also performed RT-PCR assays for gp-100 and Melan-A in 4 of the 18 angiomyolipoma samples and in three normal kidney samples. All 4 angiomyolipoma specimens revealed mRNA for both melanocyte differentiation markers. gp-100 mRNA was found in the samples of normal kidney, but Melan-A mRNA was not. Our study shows that angiomyolipomas express the melanocyte-associated antigens Melan-A and gp-100 at the protein and at the mRNA level, suggesting a true expression of these antigens rather than cross-reacting epitopes. Based on the mRNA expression pattern, immunohistochemical analysis is the preferred method for the detection of gp-100, while Melan-A can be used at the protein and mRNA levels. Our study demonstrates that A103 is a useful marker for the diagnosis of angiomyolipomas.

Angiomyolipoma↗
PubMed1999

Sex differences in the clinical care and outcomes of congestive heart failure in the elderly.

BACKGROUND: There is evidence for sex differences in treatment and outcome of ischemic heart disease. However, little and conflicting data exist about sex differences in the care and outcome of elderly patients with heart failure. METHODS: We compared mortality rate, readmission, and use of selected treatments and procedures between women and men in a database of 2445 patients (1426 women) aged >/=65 admitted for heart failure to 18 Connecticut hospitals in 1994 and 1995. Demographic and clinical data were abstracted from the medical records. RESULTS: Women were older and more likely to have a history of hypertension whereas men more often had previous coronary heart disease. Women had more preserved left ventricular systolic function and higher systolic blood pressure on presentation than men. Treatments on day 1 (aspirin, angiotensin-converting enzyme [ACE] inhibitors, and diuretics), procedures during admission (assessment of left ventricular function, coronary angiography, and revascularization), and use of ACE inhibitors among ideal candidates at discharge were similar in men and women. Six-month rehospitalization rates were also similar. Although 30-day mortality rate did not differ between men and women, 6-month and 1-year mortality rates were lower in women after age adjustment (relative risk for 6-month death 0.81, 95% confidence interval, 0.68-0.95). In multivariable analysis, sex differences in mortality rate were reduced (relative risk 0.90, 95% confidence intervals, 0.75-1.08). History of hypertension, systolic blood pressure on admission, and left ventricular function mostly explained the observed sex differences in mortality rate. CONCLUSIONS: Female and male patients hospitalized for heart failure have a similar hospital course, treatment pattern, and readmission rates, but women live longer than men. When baseline differences are accounted for, the mortality risk of women and men becomes very similar.

Aged↗
PubMed1999

Quality of care for patients hospitalized with heart failure at academic medical centers.

BACKGROUND: The purpose of this study was to determine the standard of care provided by academic medical centers for the management of congestive heart failure (CHF). METHODS AND RESULTS: The standard of care was estimated by assessing adherence to the treatment guidelines published by the US Agency for Health Care Policy and Research among 522 patients hospitalized at 7 university hospitals with a diagnosis of CHF. Data were abstracted by retrospective chart review. Of the 522 patients analyzed, 435 (83%) had a left ventricular ejection fraction (LVEF) measured or documented. Among these patients, 192 were considered "ideal" candidates for angiotensin-converting enzyme (ACE) inhibitor therapy (ie, with systolic dysfunction [LVEF <40%] and no contraindications to ACE inhibitors). In this cohort of "ideal" candidates, 138 (72%) were receiving ACE inhibitors at hospital discharge, including 60 (44%) who were prescribed doses recommended in large clinical trials. Compliance with patient education guidelines was assessed in all 487 patients who were alive at the time of discharge. Of these patients, 365 (75%) received dietary counseling, 404 (83%) were educated about exercise, 54 (11%) were instructed to follow daily weights, and 468 (96%) were counseled regarding medication compliance. Among the 87 smokers who were alive at time of discharge, 8 (9%) had documented advice to quit smoking. CONCLUSIONS: This study indicates that academic medical centers performed fairly well on the assessment of LVEF, the prescription of ACE inhibitors at discharge, and on education regarding diet, exercise, and compliance with medications. However, the results suggest opportunities for improvement in ACE inhibitor dosing and patient education regarding the importance of monitoring daily weights and smoking cessation.

Academic Medical Centers↗
PubMed1999

A prognostic rule for elderly patients admitted with community-acquired pneumonia.

PURPOSE: We sought to identify admission characteristics predicting mortality in elderly patients hospitalized with community-acquired pneumonia and to develop a prognostic staging system and discriminant rule. PATIENTS AND METHODS: We retrospectively analyzed data from 2,356 patients aged > or = 65 years admitted with community-acquired pneumonia. Multivariable analyses of a derivation cohort (n = 1,000) identified characteristics associated with hospital mortality. A staging system and discriminant rule based on these characteristics were tested in a validation cohort (n = 1,356). Our discriminant rule was compared with a rule formulated from a heterogeneous adult population with community-acquired pneumonia. RESULTS: Hospital mortality rates were 9% (derivation cohort) and 12% (validation cohort). We identified five independent predictors of mortality: age > or = 85 years [odds ratio 1.8 (95% confidence interval 1.1-3.1)], comorbid disease [odds ratio 4.1 (2.1-8.1)], impaired motor response [odds ratio 2.3 (1.4-3.7)], vital sign abnormality [odds ratio 3.4 (2.1-5.4)], and creatinine level > or = 1.5 mg/dL [odds ratio 2.5 (1.5-4.2)]. These variables stratified patients into four distinct stages with increasing mortality in the derivation cohort (Stage 1, 2%; Stage 2, 7%; Stage 3, 22%; Stage 4, 45%; P = 0.001) as well as in the validation cohort (Stage 1, 4%; Stage 2, 11%; Stage 3, 23%; Stage 4, 41%; P = 0.001). The discriminant rule developed from the derivation cohort had greater overall accuracy (77.1%) in the validation cohort than a rule formulated from a heterogeneous adult population (68.0%, P = 0.001). CONCLUSION: Elderly patients with community-acquired pneumonia have characteristics at admission that can predict mortality. Our staging system and discriminant rule improve prognostic stratification of these patients.

Aged↗
PubMed1999

Risk factors for heart failure in the elderly: a prospective community-based study.

PURPOSE: The risk factors for the development of heart failure are not clearly defined, particularly for older adults. We undertook the current investigation to examine the associations of traditional cardiovascular risk factors, comorbidity, and psychosocial factors with the risk of heart failure during 10 years of follow-up in a community-based elderly population. SUBJECTS AND METHODS: We evaluated 1,749 subjects, 65 years of age or older, free of heart failure, myocardial infarction, and angina at baseline, who were participating in the New Haven, Connecticut cohort of the Established Population for Epidemiologic Studies of the Elderly program. Cox proportional hazards regression models were used to determine risk ratios (RR) and 95% confidence intervals (CI). RESULTS: During 13,811 person-years of follow-up, 173 subjects developed incident heart failure, as confirmed by chart review. Five factors were independent predictors of heart failure: male sex (RR = 1.7; CI, 1.3 to 2.4), older age (RR = 1.9; CI, 1.3 to 2.7 for age 75 to 84 years, RR = 3.0; CI, 1.7 to 5.5 for age 85 years and older, compared with < or = 74 years), diabetes (RR = 2.9; CI, 2.0 to 4.3), pulse pressure > or = 70 mm Hg (RR = 2.3; CI, 1.3 to 4.3, compared with <50 mm Hg), and body mass index > or = 28 kg/m2 (RR = 1.6; CI, 1.0 to 2.4, compared with <24 kg/ m2). Myocardial infarction occurred during follow-up in 8% of the cohort and was also an important predictor of heart failure (RR = 21; CI, 15 to 31). CONCLUSIONS: Age and traditional cardiovascular risk factors are associated with the development of heart failure in the elderly. Preventive strategies should focus on the management of diabetes, blood pressure, and weight, in addition to the prevention and management of myocardial infarction.

Aged↗
PubMed1999

Lack of association between genetic variation in the beta3-adrenergic receptor gene and insulin resistance in patients with coronary heart disease.

The beta-adrenergic system plays a critical role in regulating lipolysis and thermogenesis. Recent studies have suggested that a missense Trp64Arg mutation in the beta3-adrenergic receptor gene is involved in visceral obesity and insulin resistance. We investigated the effect of this mutation on insulin resistance in patients with angiographically documented coronary heart disease ([CHD]n = 137) and normal subjects (n = 188). Plasma glucose and insulin responses to a 75-g oral glucose tolerance test and insulin resistance measured by the insulin suppression test, were determined in 58 (42%) patients with CHD and 121 (64%) controls. The genotype and allele frequency of the beta3-adrenergic receptor did not differ between patients with CHD and controls. The blood pressure, body mass index (BMI), waist to hip ratio, fasting plasma glucose, insulin, and lipid, and plasma glucose and insulin responses to the glucose load were relatively similar in subjects with and without the mutation in CHD and normal groups. The degree of insulin sensitivity, ie, the steady-state plasma glucose concentration, was not significantly different between subjects with and without the mutation in the CHD group (11.3 +/- 1.2, n = 11 v 11.9 +/- 0.6 mmol/L, n = 47, P = NS) and control group (8.4 +/- 0.7, n = 30 v 8.2 +/- 0.4 mmol/L, n = 91, P = NS). We conclude that Trp64Arg polymorphism of the beta3-adrenergic receptor gene does not likely play a major role in the development of CHD in the Chinese population. In addition, it appears to have no association with the insulin resistance syndrome in either CHD or non-CHD subjects.

Alleles↗