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Biomedical subjects

J Chang

Publications and source records attributed to J Chang.

At least 163 records · Page 9Linked to original sources
PubMed2000

The 3T3-L1 fibroblast to adipocyte conversion is accompanied by increased expression of angiopoietin-1, a ligand for tie2.

The tie2 receptor tyrosine kinase plays a key role in angiogenesis, and the remodeling and maturation of blood vessels. In this study we have used a factor-dependent cell line (Ba/F3) expressing a chimeric receptor containing the extracellular domain of mouse tie2 and the transmembrane and cytoplasmic domain of the erythropoietin receptor to identify specific binding activity associated with an adipogenic sub-line of 3T3 fibroblasts (3T3-L1). 3T3-L1 fibroblasts are capable of undergoing differentiation to adipocytes under specific culture conditions. When compared to 3T3-L1 cells, the adipocyte differentiated cultures, which contain both pre-adipocytes and adipocytes, exhibited a significantly increased ability to support the growth of Ba/F3 cells expressing the chimeric receptor. Using probes specific for two recently described ligands for tie2, Ang-1 and Ang-2, we have shown that mRNA encoding Ang-1 is upregulated when 3T3-L1 fibroblasts are differentiated to adipocytes. These results suggest that the levels of Ang-1 protein and mRNA in 3T3-L1 cells can be regulated by cellular differentiation in adipose development.

1-Methyl-3-isobutylxanthine↗
PubMed2000

A case of endobronchial aspergilloma.

Pulmonary aspergillosis may be classified under three categories, depending upon whether the host is atopic or immunocompromised: invasive aspergillosis, allergic bronchopulmonary aspergillosis (ABPA) or aspergilloma. However, it is not always possible to effectively categorize this disease. We experienced a case of endobronchial aspergilloma, which was difficult to categorize, in a healthy male patient. The chest X-ray and computed tomography showed an ill-defined nodule mimicking lung cancer. Fiberoptic bronchoscopy revealed an aspergilloma without cavity formation in the left lower laterobasal segmental bronchial orifice. The aspergilloma was removed and the patient's symptoms were relieved. We present this unusual case with a review of the literature.

Adult↗
PubMed2000

Prediction of clinical outcome from primary tamoxifen by expression of biologic markers in breast cancer patients.

The aim of this study was to evaluate pretreatment clinical features and biological markers together with changes in these factors as predictors of response and relapse in patients receiving tamoxifen for primary breast cancer. Fine-needle aspiration cytology of the primary breast cancer was performed before tamoxifen treatment in 54 patients and repeated after therapy on day 14, day 60, or on both days in a subset of 35 patients. These samples were evaluated for estrogen receptor (ER), progesterone receptor (PgR), Ki67, S-phase fraction and ploidy. The overall response to tamoxifen was 57% (31 of 54 patients). Pretreatment ER and PgR significantly predicted for response by univariate analysis (P < 0.0001 and P < 0.003, respectively). By multivariate analysis, ER expression was the only independent predictor of response, and it was associated with 27 times the likelihood of response (95% confidence interval, 6-136). Increase in PgR and decrease in Ki67 on day 14 significantly predicted for response to tamoxifen (P < 0.03 and P < 0.04, respectively). Lack of ER, clinical node-positive disease, and failure to decrease Ki67 on day 14 were significantly associated with increased risk of relapse (P < 0.05). By multivariate analysis, ER expression was the only independent predictor of relapse (P < 0.005). Pretreatment and early changes in molecular marker expression may assist in the prediction of response and clinical outcome in primary breast cancer patients receiving tamoxifen.

Aged↗
PubMed2000

Macrophage inflammatory protein 1alpha attenuates the toxic effects of temozolomide in human bone marrow granulocyte-macrophage colony-forming cells.

Macrophage inflammatory protein 1alpha (MIP-1alpha) is a chemokine that may act principally by preventing hemopoietic cells from entering G1, thereby attenuating the cytotoxic effects of cell cycle-specific chemotherapeutic agents. Here we examine the effect of MIP-1alpha on the sensitivity of human granulocyte-macrophage hemopoietic progenitor cells (granulocyte-macrophage colony-forming cells; GM-CFCs) with the cytotoxic effects of antitumor agents that act mainly via alkylation at the O6 position of guanine in DNA. Mononuclear cell preparations from human bone marrow were used in an in vitro GM-CFC colony-forming assay. The GM-CFC survival from individual patients displayed a range of sensitivities to the methylating agent temozolomide [(Tz) 20-55% survival at 10 microg/ml Tz]. However, in all 16 cases, MIP-1alpha (50 ng/ml) protected against GM-CFC killing: survival in the presence of MIP-1alpha ranged from 65-97% at 10 microg/ml Tz, with GM-CFCs being 1.5-4.5-fold more resistant than control cells from the same patient. The highest levels of protection were seen in the GM-CFCs with the highest sensitivity in the absence of MIP-1alpha. Similar degrees of protection were seen for the methylating agent streptozotocin, but no protection was detected for the chloroethylating agents carmustine or mitozolomide in the samples for which there was protection against the toxic effects of Tz. Whereas the mechanism of this effect remains to be established, the results may have potential immediate clinical application in the attenuation of hematological toxicity after administration of methylating antitumor agents.

Antineoplastic Agents, Alkylating↗
PubMed2000

Immunohistochemical analyses of focal adhesion kinase expression in benign and malignant human breast and colon tissues: correlation with preinvasive and invasive phenotypes.

The focal adhesion kinase (FAK) is a protein tyrosine kinase linked to signaling events between cells and the extracellular matrix. Studies at the Western blot level have demonstrated up-regulation of FAK expression in invasive breast and colon cancers. To assess p125FAK expression at the cellular level, we developed monoclonal antibodies that specifically detected FAK in formalin-fixed, paraffin-embedded tissue sections and analyzed the levels of FAK expression in human breast and colon tissues. Monoclonal antibody 4.47 demonstrated FAK-specific focal adhesion staining by immunofluorescence assays on BT-474 breast cancer cells and detected a Mr 125,000 protein by both Western blotting and immunoprecipitation analyses. Using immunohistochemical techniques, the expression of p125FAK was analyzed in 36 normal and 43 preinvasive or invasive human breast and colon tissues from individual patients. FAK was weakly expressed in most benign breast epithelium but was up-regulated at moderate or strong levels in 14 of 18 invasive breast carcinomas. In seven samples of ductal carcinoma-in situ, FAK was overexpressed. Borderline-to-weak expression of FAK was detected in the normal colonic epithelium. In the invasive colon cancers, FAK was overexpressed at moderate or strong levels in 13 of 15 tumors. Furthermore, FAK expression was up-regulated in areas of dysplastic, premalignant colon epithelium. These results provide the first evidence at the cellular level that FAK expression is variably overexpressed in breast and colon cancer and suggest that up-regulation occurs at an early stage of tumorigenesis.

Animals↗
PubMed2000

Interleukin-12 induces gene expression in interleukin-2 stimulated human T lymphocytes.

IL-12 is a critical immunoregulatory cytokine that promotes cell-mediated immune responses by inducing the differentiation of Th1 cells. To better clarify the molecular basis of IL-12 action, we compared the gene expression in human T lymphocytes activated by IL-2 and IL-12. mRNAs from T lymphocytes activated by either IL-2 alone or IL-2 plus IL-12 were transcribed into cDNAs. A differential mRNA display was conducted. As a result, differential display of five cDNA fragments was obtained. Sequence analysis suggests that they had high homology with recorded genes as found by a computer search against GenBank. Two full genes of the five fragments were cloned, which activation-induced C-type lectin and glucose transporter-like protein. Interestingly, these proteins were expressed in the T cells stimulated by IL-2 and IL-12, but not in the T cells stimulated by IL-2 alone. These results suggest that C-type lectin and glucose transporter-like protein may play an important role in the T lymphocyte activation induced by IL-12.

Base Sequence↗
PubMed2000

[Nutrition of wheat under wet injury and its regulation].

With pot experiment, this paper dealt with the effects of different nutrition regulations on nutrient absorption and crop yield of wheat under waterlogged condition. N, P, K, Zn, Cu uptakes by wheat were greatly inhibited by waterlogging. The total amounts of reusable elements N, P, K and Zn in leaves decreased obviously in stems but did not in ears, compared with control; while the total amount of element Cu in all parts was reduced by waterlogging. The yield of individual wheat plant was significantly reduced under waterlogging. Additional N-fertilizer or spraying N, P and K significantly increased the uptake of nutrients and the yield for Wanmai 19 under light waterlogging, but were not effective for Yanmai 158 under heavy waterlogging. A positive correlation was found between the yield of wheat under waterlogging and the N accumulation in leaves.

Copper↗
PubMed2000

[Point mutations of N-ras oncogene and abnormal expression of rasp21, p53 proteins in orbital rhabdomyosarcoma].

OBJECTIVE: The point mutations of N-ras oncogene and the abnormal expression of rasp21 and p53 proteins in orbital rhabdomyosarcoma (RMS) were analyzed in order to explore the role of oncogene mutations in the pathogenesis of orbital RMS and its relation to patients' prognosis. METHOD: 21 human orbital RMS tissues were analyzed by dot-blot hybridization and immunohistochemistry using synthetic specific oligonucleotide probes and mutant rasp21, p53 monoclonal antibodies. RESULTS: The second base mutation of codon 12 of the N-ras oncogene was found in 4 patients. The third base mutation of codon 61 was found in 5 patients. The mutant rate was 33.3%. By immunohistochemistry analysis, the overexpression of rasp21 and p53 protein level was found in 42.9% and 76.2% respectively. The prognosis of patients with overexpression of ras p21, p53 was worse than that of normal expression (P < 0.01). CONCLUSION: The mutants of ras and p53 oncogene play important roles in the pathogenesis of orbital RMS, and the abnormal expression of their protein products is related to patients' prognosis.

Adolescent↗
PubMed1999

High frequency of deletion on chromosome 9p21 may harbor several tumor-suppressor genes in human prostate cancer.

Chromosome 9p has been reported to be a critical region of loss in various cancers. Our present study was designed to determine the frequency of deletions at different loci of chromosome 9p in microdissected samples of normal prostatic epithelium and carcinoma from the same patients. For this purpose, DNA was extracted from the microdissected sections of normal and tumor cells of 40 prostate specimens, amplified by PCR and analyzed for loss of heterozygosity (LOH) on chromosome 9p using 15 microsatellite markers. Only 6 of 15 microsatellite markers exhibited LOH in prostate cancer specimens (D9S162, D9S1748, D9S171, D9S270, D9S273 and D9S153). LOH on chromosome 9p was identified in 29 of 40 cases (72.5%) with at least 1 marker. The main deletion was found on 9p21, at loci D9S1748 (50%), D9S171 (51.4%) and D9S270 (21.8%). There was also a deletion on 9p22 at locus D9S162 (8.3%), on 9p13 at locus D9S273 (13.8%) and on 9p11 at locus D9S153 (7.7%). LOH data were correlated with stage of prostate cancer and revealed a high frequency of LOH at 3 or more loci in samples with stage T(3)N(0)M(0) (46%) compared with stage T(2)N(0)M(0) (15%), which suggests a higher incidence of LOH in the advanced stage of prostate cancer. One of the candidate target tumor-suppressor genes, p16 (MTS-1/CDKN2), has been identified within the 9p21 deleted region in tumor cell lines. Expression of P16 protein was either absent or very low in prostate cancer samples, suggesting that loss of the p16 gene may be involved in prostatic carcinogenesis.

Chromosomes, Human, Pair 9↗
PubMed1999

Type 2 diabetes: evidence for linkage on chromosome 20 in 716 Finnish affected sib pairs.

We are conducting a genome scan at an average resolution of 10 centimorgans (cM) for type 2 diabetes susceptibility genes in 716 affected sib pairs from 477 Finnish families. To date, our best evidence for linkage is on chromosome 20 with potentially separable peaks located on both the long and short arms. The unweighted multipoint maximum logarithm of odds score (MLS) was 3.08 on 20p (location, chi = 19.5 cM) under an additive model, whereas the weighted MLS was 2.06 on 20q (chi = 57 cM, recurrence risk,lambda(s) = 1. 25, P = 0.009). Weighted logarithm of odds scores of 2.00 (chi = 69.5 cM, P = 0.010) and 1.92 (chi = 18.5 cM, P = 0.013) were also observed. Ordered subset analyses based on sibships with extreme mean values of diabetes-related quantitative traits yielded sets of families who contributed disproportionately to the peaks. Two-hour glucose levels in offspring of diabetic individuals gave a MLS of 2. 12 (P = 0.0018) at 9.5 cM. Evidence from this and other studies suggests at least two diabetes-susceptibility genes on chromosome 20. We have also screened the gene for maturity-onset diabetes of the young 1, hepatic nuclear factor 4-a (HNF-4alpha) in 64 affected sibships with evidence for high chromosomal sharing at its location on chromosome 20q. We found no evidence that sequence changes in this gene accounted for the linkage results we observed.

Adult↗
PubMed1999

Factor VIIa's first epidermal growth factor-like domain's role in catalytic activity.

Factor VIIa-tissue factor complex formation initiates the extrinsic blood coagulation pathway. We investigated factor VIIa's first epidermal growth factor-like (egf1) domain's role in the catalytic activity increase caused when factor VIIa binds tissue factor. Starting with a factor VIIa with factor IX's egf1 domain (factor VII(IXegf1)a), we made 4 proteins with egf1 residues changed to those in factor VIIa, including E51A, D64Q, FG74-75PA, and K79R. We measured each enzyme's affinity for tissue factor and determined the enzymes' kinetic constants with and without tissue factor. The Kd for factor VII(IXegf1)a binding to tissue factor was 60-200-fold higher than that of factor VIIa depending on the assay employed. Only factor VII(IXegf1)a with the K79R (K79Ra) mutation, among all the mutants, had an effect on binding with a Kd 3-8-fold lower than that of factor VII(IXegf1)a. In kinetic analyses with a small peptide substrate, in the absence of tissue factor, factor VIIa, factor VII(IXegf1)a, and K79Ra had similar kcat's and Km's. With tissue factor, due to a kcat decrease, factor VII(IXegf1)a's catalytic efficiency (kcat/Km) was 2-fold lower than factor VIIa's. K79Ra's catalytic efficiency was intermediate between those of factor VIIa and factor VII(IXegf1)a. With factor X as substrate, in the absence of tissue factor, K79Ra and factor VII(IXegf1)a had catalytic efficiencies 1.5-fold and 2-fold lower than that of factor VIIa. In contrast, with tissue factor and with factor X as substrate, due to higher Km's, factor VII(IXegf1)a and K79Ra had only 9% and 33% of factor VIIa's catalytic efficiency. Our results suggest the egf1 domain's role in tissue factor binding involves critical alignment of tissue factor with factor VIIa's catalytic domain. Proper alignment in turn promotes optimal catalytic activities.

Amino Acid Substitution↗
PubMed1999

Mutational inactivation of transforming growth factor beta receptor type II in microsatellite stable colon cancers.

We previously demonstrated that mutational inactivation of transforming growth factor beta type II receptors (RIIs) is very common among the 13% of human colon cancers with microsatellite instability. These mutations principally cluster in the BAT-RII polyadenine sequence repeat. Among microsatellite stable (MSS) colon cancers, we now find that non-BAT-RII point mutations inactivate RII in another 15% of cases, thus doubling the known number of colon cancers in which RII mutations are pathogenetic. Functional analysis confirms that these mutations inactivate RII signaling. Moreover, another 55% of MSS colon cancers demonstrate a transforming growth factor beta signaling blockade distal to RII. The transforming growth factor beta pathway and RII in particular are major targets for inactivation in MSS colon cancers as well as in colon cancers with microsatellite instability.

Adult↗
PubMed1999

Electrocardiogram abnormalities among men with stress-related psychiatric disorders: implications for coronary heart disease and clinical research.

Research suggests psychological distress could result in arterial endothelial injury and coronary heart disease (CHD). Studies also show Posttraumatic Stress Disorder (PTSD) victims have higher circulating catecholamines and other sympathoadrenal-neuroendocrine bioactive agents implicated in arterial damage. Here we analyzed resting 12-lead electrocardiographic (ECG) results among a national sample of 4,462 nonhospitalized male veterans (mean age = 38) about 20 years after military service by current posttraumatic stress (n = 54), general anxiety (n = 186), and depression (n = 157) disorders. ECGs were interpreted by board-certified cardiologists and summarized using the Minnesota Code Manual of Electrocardiographic Findings. Psychiatric disorders were diagnosed based on the Diagnostic Interview Schedule, Version III. Controlling for age, place of service, illicit drug use, medication use, race, body mass index, alcohol use, cigarette smoking, and education, PTSD (odds ratio [OR] = 2.23, 95% confidence interval [CI] = 1.17-4.26, p < 0.05), anxiety (OR = 1.51, 95% CI = 1.03-2.22, p < 0.05), and depression (OR = 1.71, 95% CI = 1.13-2.58, p < 0.01) were associated with having a positive ECG finding. Specific results indicate PTSD was associated with atrioventricular (AV) conduction defects (OR = 2.81, 95% CI = 1.03-7.66, p < 0.05) and infarctions (OR = 4.44, 95% CI = 1.20-16.43, p < 0.05), while depression was associated with arrhythmias (OR = 1.98, 95% CI = 1.22-3.23, p < 0.01). The PTSD associations for AV conduction defects and infarctions held, even after controlling for current anxiety and depression. These findings suggest psychological distress may result in CHD, because we controlled for obvious biases and confounders, the men studied had current PTSD due to combat exposures 20 years ago, combat exposure was associated with anxiety and depression among these men, and the men were disease free a military induction. These findings suggest the need for clinical surveillance among combat veterans, better psychobiologic models of CHD pathogenesis, and additional research.

Age of Onset↗
PubMed1999

Identification and Expression Pattern of DNA Polymerase alpha Gene in a Marine Diatom, Skeletonema costatum.

: To investigate the potential of DNA polymerase alpha as a marker for DNA replication in phytoplankton, two gene fragments that showed a high degree of similarity with eukaryotic DNA polymerase alpha were cloned from two strains of a diatom, Skeletonema costatum (Greville) Cleve. The gene fragments amplified with the polymerase chain reaction were 397 and 396 bp in length, respectively. The deduced amino acid sequences showed 44% to 61% similarity to the corresponding regions of DNA polymerase alpha sequences of eukaryotic organisms ranging from yeast to humans. The similarity was especially high in three evolutionarily conserved regions within the amplified fragments. Further, hybridization patterns from Southern blotting confirmed that the amplified fragments were an integral part on the genome of S. costatum. In batch cultures abundant messenger of DNA polymerase alpha appeared in the late exponential phase and the early stationary phase. This pattern suggests that DNA polymerase alpha expression is associated with actively dividing cells.

Journal Article↗
PubMed1999

Splenic rupture in a patient with acute myeloid leukemia undergoing peripheral blood stem cell transplantation.

Splenic rupture is a rare but well-recognized complication of hematological malignancies. Here, we present the case of a 22-year-old woman with the diagnosis of acute myeloid leukemia who was undergoing peripheral blood stem cell transplantation. On day + 10 she developed a hypovolemic shock due to rupture of her spleen and went to emergency laparotomy. This is the first report of splenic rupture during peripheral blood stem cell transplantation.

Adult↗