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X Kang

Publications and source records attributed to X Kang.

At least 55 records · Page 3Linked to original sources
PubMed1997

Genomic structure of the human GT334 (EHOC-1) gene mapping to 21q22.3.

Several inherited diseases have been mapped to the distal tip of human chromosome 21. In our recent efforts to clone candidate genes for some of these disorders, we have assembled a cosmid and BAC contig spanning 770 kb. We have identified expressed sequences from this contig by means of a cDNA hybrid selection scheme. We present here the isolation, cDNA sequence, genomic organization, and polymorphisms analysis of one such expressed sequence, GT334, which had been identified independently and designated EHOC-1. GT334 is split into 23 exons, and spans an estimated 95 kb of genomic DNA. A pseudogene of the histone H2AZ gene has been identified, and maps within the third intron. We have identified an ORF potentially encoding a protein 1259 amino acids in length, longer than that described in the EHOC-1 gene. The GT334 gene was screened for single base pair changes using single-strand conformation polymorphism (SSCP) analysis and we have identified seven sequence variations within this gene. These polymorphisms can be used as markers in the genetic mapping of other diseases localized to this region.

Amino Acid Sequence↗
PubMed1997

Incremental prognostic value of adenosine stress myocardial perfusion single-photon emission computed tomography and impact on subsequent management in patients with or suspected of having myocardial ischemia.

We examined 1,159 consecutive patients who underwent adenosine stress dual isotope single-photon emission computed tomography (SPECT) and had follow-up performed at a mean of 27.5 +/- 9.1 months (94% complete) for hard events (cardiac death and myocardial infarction) and referral to cardiac catheterization after nuclear testing. During follow-up, 120 hard events occurred (11.0% hard event rate; 72 cardiac deaths [6.7% cardiac death rate] and 57 myocardial infarctions [5.3% myocardial infarction rate]). Cox proportional hazards analysis revealed that nuclear testing added incremental value after adjusting for clinical and historical variables (global chi-square increased 13 to 98 for cardiac death as the end point, global chi-square increased 19 to 105 for hard events as the end point; p <0.0001 for both). Kaplan-Meier analysis demonstrated that after clinical risk stratification of the patient population, the results of nuclear testing were further able to significantly stratify both low- and intermediate- to high-risk patients. Patients with both normal and mildly abnormal scans were at low risk of cardiac death (<1% cardiac death per year of follow-up) and the risk of events increased significantly with worsening scan result. Multivariable analysis revealed that the only predictor of referral to catheterization was the extent and severity of reversible defect present on the scan. Referral rates to early catheterization were very low in patients with normal scans and increased significantly as a function of worsening scan results. In patients who underwent myocardial perfusion SPECT using adenosine stress, the results of nuclear testing yielded incremental prognostic information and clinically relevant risk stratification. Referring physicians predominantly utilized nuclear information when referring patients to catheterization after nuclear testing and do so at rates comparable with those after exercise SPECT despite the higher risk of events in patients undergoing pharmacologic stress.

Adenosine↗
PubMed1997

Identification of severe or extensive coronary artery disease in women by adenosine technetium-99m sestamibi SPECT.

To assess the ability of adenosine technetium-99m sestamibi myocardial perfusion single-photon emission computed tomography (SPECT) to identify high-risk women with severe or extensive coronary artery disease (CAD), we studied 130 consecutive women who underwent adenosine sestamibi myocardial perfusion SPECT and catheterization within 2 months. Severe (> or = 50% stenosis of left main coronary artery, > or = 90% stenosis in the proximal left anterior descending or in > or = 2 coronary arteries) or extensive (> or = 70% stenosis in 3 vessels) CAD was present in 54 patients, whereas 76 had no CAD or mild to moderate CAD. Semiquantitative visual SPECT analysis used 20 segments and a 5-point scoring system (0 = normal, 4 = absent uptake). Among the clinical, hemodynamic and nuclear variables analyzed, univariate predictors of severe or extensive CAD included a higher prescan likelihood of CAD, history of myocardial infarction, a higher heart rate at rest, a lower increase in heart rate during adenosine infusion, a higher summed stress score, summed reversibility score, and multivessel scan abnormality. Multivariate logistic analysis of the most predictive clinical (prescan likelihood of CAD), hemodynamic (increase in heart rate during adenosine infusion), and scan variables (summed stress score) revealed summed stress score (chi-square = 32; p <0.0001) and prescan likelihood of CAD (chi-square = 6.4; p <0.05) as the only independent predictors of severe or extensive CAD. Based on these logistic models, we determined the probability for the presence of severe or extensive CAD in patients with low, intermediate, and high prescan likelihood of CAD across the range of values of a summed stress score. This revealed that there were incremental increases in the probability for severe or extensive CAD both as a function of prescan likelihood of CAD and summed stress score. A severely abnormal scan (summed stress score > 8) during adenosine technetium-99m sestamibi myocardial perfusion SPECT had a high sensitivity of 91% and a moderately high specificity of 70% for identifying high-risk women with severe or extensive CAD. These results coupled with the previously defined prognostic significance of these findings suggest this test to be a useful diagnostic tool for the evaluation of CAD in women.

Adenosine↗
PubMed1997

Induction of melanoma reactive T cells by stimulator cells expressing melanoma epitope-major histocompatibility complex class I fusion proteins.

Several epitopes in the human melanoma antigens recognized by HLA-A2-restricted CTLs have a relatively low MHC-binding affinity and as a result may be expressed at very low densities on the cell surface, indicating that these epitopes may not be efficient immunogens. To express these epitopes at higher densities on the surface of antigen-presenting cells and therefore improve their immunogenicity, a DNA construct in which a cDNA fragment encoding the melanoma epitope MART-1(27-35) or gp100(280-288) was inserted between sequences encoding the leader and the HLA-A*0201 protein. Cells transfected with these epitope-HLA fusion constructs were recognized by HLA-A2-restricted melanoma-reactive CTLs specific for the MART-1 or gp100 epitope. In addition, tumor-reactive CTLs could be induced from PBMCs of patients with metastatic melanoma by in vitro stimulation with HMY-C1R B-cell lines expressing the MART-1 or gp100 epitope-HLA-A*0201 fusion protein. These epitope-HLA fusion constructs may be useful for the development of immunotherapies for patients with melanoma.

Animals↗
PubMed1997

Clinical validation of automatic quantitative defect size in rest technetium-99m-sestamibi myocardial perfusion SPECT.

UNLABELLED: We examined the relationships of automatic quantitative perfusion defect size and defect severity to rest left ventricular ejection fraction and semiquantitative visual sestamibi defect size in rest 99mTc-sestamibi SPECT in 40 consecutive patients with a history of myocardial infarction more than 30 days prior to testing. The purpose of this investigation was to validate the use of automatic quantitative rest sestamibi SPECT as a clinical measure of assessing relative infarction size. METHODS: All patients received 20-30 mCi of 99mTc-sestamibi followed by SPECT imaging. Quantitative defect analysis used previously developed resting normal limits and an automatic version of a commercially available quantitative program (CEqual). Semiquantitative visual defect interpretation used a 20 segment/scan and five-point scoring analysis. First-pass (FP) radionuclide ventriculography (RVG) and gated sestamibi perfusion SPECT were each performed in 31 patients. RESULTS: LVEF assessed by FP RVG was 37% +/- 15% (range 14%-62%) and 37% +/- 16% (range 12%-63%) by gated perfusion SPECT with high linear correlation (r = 0.96, n = 22) between the two methods. Myocardial perfusion defect size was 24% +/- 15% of LV (range 0%-50%) and defect severity was 1103 +/- 864 (range 0 to 2825) by automatic quantitative rest sestamibi. Perfusion defect size and defect severity both had close correlations with LVEF by FP RVG (r = -0.78, r = -0.86) and by gated perfusion SPECT (r = -0.75, r = -0.79). High linear correlations were observed between quantitative defect size and summed visual score of segments with score > or = 2 (r = 0.82) and the number of visually abnormal segments (r = 0.77), as well as between defect severity and visual summed rest score (r = 0.86) and the number of visually abnormal segments (r = 0.76). CONCLUSION: Quantitation of rest sestamibi SPECT defect extent and severity using automatic CEqual correlates well with rest LVEF and with semiquantitative expert visual analysis. Results of this study define a strong relationship between measurements of 99mTc-sestamibi perfusion defect as measured by an automatic software program and global left ventricular function. The automatic quantitative program appears to be a useful measure of assessing infarct size in patients with remote myocardial infarction.

Adult↗
PubMed1996

Isolation and characterization of GT335, a novel human gene conserved in Escherichia coli and mapping to 21q22.3.

As part of efforts to identify candidate genes for disorders mapped to 21q22.3, we have constructed a 405-kb cosmid contig encompassing five tightly linked markers mapping to this region. A subset of these cosmids was used to identify cDNA fragments by the method of hybrid selection. We present here the cDNA sequence of one such gene (GT335) mapping to this region. The gene is expressed as a 1.7-kb transcript predominantly in heart and skeletal muscle, potentially displays alternate splicing, and is predicted to encode a protein 268 amino acids in length. GT335 spans an estimated 13 kb of genomic DNA and is split into seven exons. Five of the six introns conform to the GT . . . AG consensus for intronic splice junctions; the sixth contains nonconventional (AT . . . AC) intronic junctions. We screened this gene for single-basepair mutations using single-strand conformation polymorphism and sequence analysis of both cDNA and genomic DNA from a number of unrelated individuals and have identified several sequence variations, two of which cause conservative amino acid substitutions. This gene is well conserved evolutionarily, with homologs identified in zebrafish and Escherichia coli, suggesting that it plays an important role in basic cellular metabolism.

Amino Acid Sequence↗
PubMed1996

Does coronary artery screening by electron beam computed tomography motivate potentially beneficial lifestyle behaviors?

We evaluated the extent to which cardiovascular risk-reducing behaviors are initiated as a result of knowledge of newly detected coronary artery disease, based on test results from noninvasive electron beam computed tomography (EBCT). A total of 703 men and women, aged 28 to 84 years, asymptomatic and without prior coronary disease, who had a baseline EBCT coronary artery scan and basic medical history and risk factor information completed a follow-up survey questioning them about health behaviors undertaken since their scan. Baseline calcium scores were significantly higher in those who subsequently reported consulting with a physician, or reported new hospitalization, coronary revascularization, beginning aspirin usage, blood pressure medications, cholesterol-lowering therapy, decreasing dietary fat, losing weight, beginning vitamin E, and under more worry (all p <0.01). Other factors, including reducing time worked, obtaining life insurance, losing employment, increased work absenteeism, increasing exercise, or stopping smoking were not associated with coronary calcium. In logistic regression, after adjusting for age, gender, pre-existing high cholesterol, high blood pressure, cigarette smoking, and a positive family history of coronary disease, the natural log of total calcium score remained associated with new aspirin usage, new cholesterol medication, consulting with a physician, losing weight, decreasing dietary fat, new coronary revascularization (all p <0.01), but also new hospitalization (p <0.05) and increased worry (p <0.001). The results suggest that potentially important risk-reducing behaviors may be reinforced by the knowledge of a positive coronary artery scan, independent of preexisting coronary risk factor status.

Adult↗
PubMed1996

Identification of TRP-2 as a human tumor antigen recognized by cytotoxic T lymphocytes.

The infusion of TIL586 along with interleukin-2 into the autologous patient with metastatic melanoma resulted in the objective regression of tumor. A gene encoding a tumor antigen recognized by TIL586 was previously isolated and shown to encode gp75 or TRP-1. Here we report that TRP-2 was identified as a second tumor antigen recognized by a HLA-A31-restricted CTL clone derived from the TIL586 cell line. The peptide LLPGGRPYR epitope was subsequently identified from the coding region of TRP-2 based on studies of the recognition of truncated TRP-2 cDNAs and the HLA-A31 binding motif. This epitope peptide was capable of sensitizing target cells for lysis by a CTL clone at 1 nM peptide concentration. Although some modified peptides could be recognized by the CTL clone, none were found to be better recognized by T cells than the parental peptide. Like other melamona differentiation antigens, TRP-2 was only expressed in melanoma, melanocytes, and retina, but not in other human tissues tested.

Amino Acid Sequence↗
PubMed1996

Genomic structure of the human D-site binding protein (DBP) gene.

The human gene for the D-Site Binding Protein (DBP) has been sequenced and characterized. This gene is a member of the b/ZIP family of transcription factors and is one of three genes forming the PAR subfamily. DBP has been implicated in the diurnal regulation of a variety of liver-specific genes. Examination of the genomic structure of DBP reveals that the gene is divided into four exons and is contained within a relatively compact region of approximately 6 kb. These exons appear to correspond to functional divisions of the DBP protein. Exon 1 contains a long 5' UTR, and conservation between the rat and the human genes of the presence of small open reading frames within this region suggests that it may play a role in translational control. Exon 2 contains a limited region of similarity to the other PAR domain genes, which may be part of a potential activation domain. Exon 3 contains the PAR domain and differs by only 1 of 71 amino acids between rat and human. Exon 4, containing both the basic and the leucine zipper domains, is likewise highly conserved. The overall degree of homology between the rat and the human cDNA sequences is 82% for the nucleic acid sequence and 92% for the protein sequence. Comparison of the rat and human proximal promoters reveals extensive sequence conservation, with two previously characterized DNA binding sites being conserved at the functional and sequence levels.

Amino Acid Sequence↗
PubMed1996

Effects of steroid on diaphragmatic functions in rabbits.

The effects of steroid on diaphragmatic contractility and endurance were examined in 24 New Zealand rabbits. Diaphragmatic contractility was determined by measuring gastric pressure (Pga) with the lower thorax and the abdomen of the animal being fixed with a rigid cast. Endurance procedure was done by continuous 15 Hz stimulation of the bilateral phrenic nerves, and diaphragmatic endurance was expressed as the time from the initiation of the endurance procedure to the moment when transdiaphragmatic pressure 15 Hz (Pdi-15 Hz) decreased to 25% of Pdimax-15 Hz. Our data suggested that intravenous administration of dexamethasone 2.5 mg daily for 7 days did not affect the diaphragmatic contractility significantly, but could cause a significant decrease in diaphragmatic endurance. When delivered intravenously at the dose of 2.0 mg daily for 14 days, dexamethasone induced a significant decrease both in diaphragmatic contractility and endurance. The recovery of the diaphragmatic strength from fatigue, however, was not influenced by dexamethasone in either circumstance. The influence of dexamethasone on diaphragmatic contractility and endurance may have important clinical implications.

Animals↗
PubMed1996

In vitro atherosclerotic plaque and calcium quantitation by intravascular ultrasound and electron-beam computed tomography.

The purpose of this investigation was to compare the accuracy of intravascular ultrasound (IVUS) and electron-beam computed tomography (EBCT) in quantitating human atherosclerotic plaque and calcium. In experiment 1, 12 human atherosclerotic arterial segments were obtained at autopsy and imaged by using IVUS and EBCT. The plaque from each arterial segment was dissected and a volume measurement of the dissected plaque was obtained by water displacement. The plaque from each arterial segment was ashed at 700 degrees F, and the weight of the remaining ashes was used as an estimate of the calcium mass. In experiment II, 11 calcified arterial segments were obtained at autopsy and imaged by using IVUS at one site along the artery. A corresponding histologic cross section stained with Masson's trichrome was prepared. In experiment I, the mean plaque volume measured by water displacement was 165.3 +/- 118.4 microliters. The mean plaque volume calculated by IVUS was 166.1 +/- 114.4 microliters and correlated closely with that by water displacement (r = 0.98, p < 0.0001). The mean calcium mass measured by ashing was 19.4 +/- 15.8 mg. The mean calculated calcium mass by EBCT was 19.9 mg and correlated closely with that by ashing (r=0.98, p<0.001). The mean calculated calcium volume by IVUS was 18.6 +/- 11.2 microliters and correlated linearly with the calcium mass by ashing (r = 0.87, p < 0.0003). In experiment II, the mean cross-sectional area of the calcified matrix was 1.71 +/- 0.66 mm2 by histologic examination compared with 1.44 +/- 0.66 mm2 by IVUS. There was a good correlation between the calcified cross-sectional area by histologic examination and IVUS (r = 0.76, p < 0.007); however, IVUS may underestimate the amount of calcium present depending on the intralesional calcium morphologic characteristics. In conclusion, IVUS accurately quantitates atherosclerotic plaque volume as well as the cross-sectional area and volume of intralesional calcium, especially if the calcium is localized at the base of the plaque. IVUS underestimates the amount of calcium present because of signal drop-off when the calcium is too thick for the ultrasound to completely penetrate. In comparison, EBCT accurately quantitates calcium mass regardless of the intralesional calcium morphologic characteristics; however, EBCT does not accurately quantitate plaque volume and will miss noncalcified atherosclerotic lesions.

Adolescent↗
PubMed1996

[Bi-pedical and bi-muscle flap reconstruction of the laryngeal function].

The method of reconstruction of laryngeal function by bi-pedical and bi-muscle flap (DP-DMF) was presented. The DP-DMF was obtained from sternohyoid muscle, sternothyroid muscle and thyrohyoid muscle. It had enough length, width and plasticity, applicable to all patients with T3 and T4 laryngeal carcinoma. Up to now, 102 patients were treated by expanded horizontal hemilaryngectomy and repaired with unilateral or bilateral DP-DMF. After operation, the swallow function returned to normal in 7 to 11 days. The tracheal tube extraction rate was 66.7% (72/108). The 5-year survival rate was 76.5% (62/81), and recurrence rate was 13.9% (15/108). With the application of DP-DMF, the patients who might have been treated formerly by total laryngectomy could be treated by partial laryngectomy. This method expanded the indication of partial laryngectomy, improved the life quality and survival rate.

Adult↗
PubMed1995

Identification of a tyrosinase epitope recognized by HLA-A24-restricted, tumor-infiltrating lymphocytes.

A number of Ags recognized by class I-restricted, melanoma-specific T cells have recently been identified. In this report we demonstrated that tumor-infiltrating lymphocytes (TIL) from melanoma patient 1413 recognize a tumor Ag, tyrosinase, in the context of HLA-A24. This Ag had previously been shown to be recognized by an HLA-A24-restricted TIL, TIL 888, as well as HLA-A2-restricted, melanoma-specific T cells isolated from two additional patients. The peptide epitope recognized by TIL 1413 was then identified through the use of sequential deletions of the tyrosinase cDNA, as well as through prediction of HLA-A24 binding peptides based on a previously identified motif. Two peptides, a 9-amino acid peptide (AFLPWHRLF) and an overlapping 10-amino acid peptide (AFLPWHRLFL) containing an additional leucine at the carboxyl terminus, were both recognized by TIL 1413. Anti-peptide-specific CTL could be induced by repeated stimulation of peripheral blood lymphocytes from melanoma patient 1413, and this CTL line specifically recognized both HLA-A24+ B cell lines pulsed with the peptide and HLA-A24+ tyrosinase+ melanoma cells. This peptide thus represents a reagent that may be used to generate melanoma-specific T cells for adoptive immunotherapy, as well as in peptide vaccines for HLA-A24+ melanoma patients.

Amino Acid Sequence↗
PubMed1995

Recognition of multiple epitopes in the human melanoma antigen gp100 by tumor-infiltrating T lymphocytes associated with in vivo tumor regression.

Four of ten HLA-A2-restricted melanoma specific CTL that were derived from tumor-infiltrating lymphocytes (TIL) and administered to patients recognized the gp100 melanoma Ag and nine of ten recognized the MART-1 Ag. Adoptive transfer of the four gp100-reactive CTL, but not the other TIL, resulted in tumor regression when infused into autologous patients along with IL-2. Tumor regression was thus correlated with the recognition of gp100 by the administered T cells (p = 0.0048). To identify the epitopes recognized by these four gp100-reactive CTL, 169 peptides containing HLA-A2.1 binding motifs were synthesized and screened for their recognition by TIL using cytotoxicity and IFN-gamma release assays. Five gp100 epitopes (two for TIL620, three for TIL660, one for TIL1143, and two for TIL1200) were recognized by CTL derived from different patients. Five of eight HLA-A2 binding melanoma epitopes (five gp100, one MART-1/Melan-A, two tyrosinase) had intermediate binding affinity to HLA-A2.1. These gp100 epitopes may be responsible for mediating tumor rejection in vivo and thus may be useful for the development of immunotherapies for patients with melanoma.

Amino Acid Sequence↗