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Biomedical subjects

J C Chang

Publications and source records attributed to J C Chang.

At least 19 recordsLinked to original sources
PubMed1996

NRF2, a member of the NFE2 family of transcription factors, is not essential for murine erythropoiesis, growth, and development.

The locus control region of the beta-globin gene is composed of four erythroid-specific hypersensitive sites. Hypersensitive site 2 has been shown to be a powerful enhancer and contains a tandem repeat sequence for the transcription factors AP1 and NFE2 (activating protein 1 and nuclear factor erythroid 2, respectively). The human NRF2 (NFE2 related factor 2) has been isolated by bacterial expression screening using this core sequence as a probe. p45-NFE2, NRF1, and NRF2 belong to the CNC ("cap 'n' collar") subfamily of the basic region-leucine zipper transcription factors, which exhibits strong homology at specific regions such as the "CNC" and the DNA binding and leucine zipper domains. Although the erythroid-specific p45-NFE2 has been implicated in globin gene regulation, p45-NFE2 null mice succumb to bleedings due to lack of platelets and those that survive exhibit only a mild anemia. To determine the function of NRF2, which we found to be widely expressed in vivo, we have characterized the genomic structure of the mouse NRF2 gene, disrupted the Nrf2 gene by homologous recombination in mouse embryonic stem cells (ES cells), and generated NRF2-/- mice. Homozygous mutant mice developed normally, were not anemic, reached adulthood, and reproduced. Our studies indicate that NRF2 is dispensable for mouse development.

Aging↗
PubMed1996

Chemokine expression by intraepithelial gamma delta T cells. Implications for the recruitment of inflammatory cells to damaged epithelia.

T cells expressing gamma delta TCR may have evolved to recognize Ag in a different manner as well as perform a broader set of functions than T cells with alpha beta TCR. In this study, we tested the hypothesis that dendritic epidermal T cells (DETC) bearing the invariant V gamma 3V delta 1 TCR may be able to signal the migration of peripheral alpha beta T cells to the epidermis by secreting specific chemokines. Expression of macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, RANTES, and lymphotactin was inducible in DETC 7-17 cells, whereas mRNA for monocyte chemoattractant protein (MCP)-1 could not be detected. Strikingly, lymphotactin was the most abundant chemokine produced by activated DETC 7-17 cells. Activated primary DETC cultures also produced copious amounts of lymphotactin mRNA. Similarly, freshly isolated and activated intestinal intraepithelial T cells (i-IEL) with gamma delta TCR expressed high levels of lymphotactin mRNA. In contrast, lymphotactin mRNA was present in activated spleen gamma delta T cells at low basal levels. Migration of CD8+ T cells induced by culture supernatants from stimulated DETC 7-17 cells was strongly reduced in the presence of a neutralizing anti-lymphotactin antiserum and to a lesser extent by neutralizing anti-MIP-1 alpha, anti-MIP-1 beta, or anti-RANTES antiserum. The presence of lymphotactin in supernatants from activated DETC 7-17 cultures was directly demonstrated by Western blot analysis. These observations are consistent with a model in which gamma delta IEL play an active multi-faceted role in the maintenance of epithelia homeostasis.

Animals↗
PubMed1996

Selective killing of AFP-positive hepatocellular carcinoma cells by adeno-associated virus transfer of the herpes simplex virus thymidine kinase gene.

The use of viral thymidine kinase (TK) gene coupled with the administration of ganciclovir to render cancer cell death has been studied extensively. Many of these experiments utilized retrovirus to transfer the TK gene under the control of a nonspecific promoter. Because nonspecific expression of the viral TK gene may cause death of proliferating cells, other than cancer cells, we explored the use of a liver-specific promoter and a tumor-specific AFP enhancer to achieve regulated viral TK gene expression for treatment of hepatocellular carcinoma. We also used the adeno-associated virus (AAV) as vector for the delivery of the TK gene because this virus is not associated with any pathological consequences in humans. Because it can infect nondividing S-phase cells, AAV can transfer genes into noncycling tumor cells. A recombinant AAV virus was constructed to include the selectable marker neoR gene and the herpes simplex virus (HSV)-TK gene driven by the human AFP enhancer and the albumin promoter. The liver-predominant expression pattern of the TK gene was observed when this construct was tested in transgenic mice. When human hepatocellular carcinoma cell lines displaying different levels of AFP and albumin and nonhepatocyte tumor cell lines were infected with the recombinant AAV virus, ganciclovir treatment caused only AFP and albumin-positive hepatocellular carcinoma cells death, but not nonhepatocyte tumor cells or AFP and albumin-negative hepatic tumor cells. Moreover, the dose required to kill the cancer cells was inversely proportional to the level of AFP expression in the cells.

Albumins↗
PubMed1996

Postoperative thrombotic thrombocytopenic purpura following cardiovascular surgeries.

Among 47 patients with thrombotic thrombocytopenic purpura (TTP), 8 patients were diagnosed to have postoperative-TTP. Two patients underwent vascular surgery, 5 patients coronary artery bypass grafts, and 1 patient resection of myocardial sarcoma. Prior to surgery, all patients except one had normal hemograms and platelet counts, and blood smears showed no schistocytes. Five to 19 days after surgery, all 8 patients developed postoperative TTP, which clinical feature was characterized by unexplained progressive encephalopathy, thrombocytopenia, and microangiopathic hemolytic anemia. In addition, in 3 patients, progressive gangrene of the toes also developed. Four patients achieved complete remission following exchange plasmapheresis and 1 patient spontaneous remission. Due to complicated surgical settings after surgery, recognition of TTP was often delayed and it contributed to death in 3 patients despite treatment with exchange plasmapheresis. In view of occurrence of postoperative TTP following cardiac and vascular surgeries, pathogenic mechanism for postoperative TTP may be explained on the basis of injury of diseased endothelial surface and release of a humoral factor(s) that results in platelet aggregation in the capillaries and arterioles. Our experience with these cases indicates that TTP may occur as a serious complication of cardiac and vascular surgeries, and early recognition of the diagnosis and institution of exchange plasmapheresis are of paramount importance for favorable outcome.

Adult↗
PubMed1996

Microleakage of a 4-methacryloxyethyl trimellitate anhydride bonding agent with amalgams.

Microleakage contributes to deterioration of materials, recurrent decay, growth of microorganisms at the interface, and postoperative tooth sensitivity. This study examined the microleakage between amalgams and tooth surfaces with a cavity liner, a 4-methacryloxyethyl trimellitate anhydride bonding agent (Amalgambond) and six different types of amalgams. Class 1 cavity preparations in extracted human molars were filled with different combinations of liners and amalgams and were stored at 37 degrees C in physiologic saline solution. After 1 week half of each amalgam restoration was removed. Within the same group the same cavity treatment was performed and the same type of amalgam was packed as before. Microleakage was determined after 2000 thermal cycles. Statistical analysis indicated that Amalgambond significantly reduced microleakage of different amalgams compared with the Copalite-lined and unlined controls. No microleakage was detected at the interface between the existing and replacement amalgams.

Dental Amalgam↗
PubMed1996

Review of quantitative standards and guidelines for fungi in indoor air.

Existing quantitative standards/guidelines for fungi in indoor air issued by governmental agencies are based primarily on baseline data (rather than health effects data), and are either absolute (numerical) or relative (indoor/outdoor comparisons) or a combination of the two. The Russian Federation is the only governmental agency that has binding quantitative regulations for bioaerosols. Recommended guidelines have been proposed or sponsored by North American and European governmental agencies and private professional organizations. A considerable number of frequently cited guidelines have been proposed by individuals based either on baseline data or on personal experience. Quantitative standards/guidelines range from less than 100 CFU/m3 to greater than 1000 CFU/m3 (total fungi) as the upper limit for non-contaminated indoor environments. Major issues with existing quantitative standards and guidelines are the lack of connection to human dose/response data, reliance on short term grab samples analyzed only by culture, and the absence of standardized protocols for data collection, analysis, and interpretation. Urgent research needs include the study of human responses to specific fungal agents, development and widespread use of standard protocols using currently available sampling methodologies, and the development of long term, time-discriminating personal samplers that are inexpensive, easy to use, and amenable to straightforward, relevant analysis.

Air Microbiology↗
PubMed1996

Effect of Mycobacterium tuberculosis and its components on macrophages and the release of matrix metalloproteinases.

BACKGROUND: Pulmonary tuberculosis is associated with caseating necrosis, parenchymal lung destruction, and cavity formation. It was hypothesised that tuberculous lung destruction is mediated, at least in part, by the participation of matrix metalloproteinases released by mononuclear phagocytes. METHODS: Cells of the myelomonocytic leukaemia cell line THP-1 were incubated with lipoarabinomannan (LAM), the major antigenic cell wall component, and with Mycobacterium tuberculosis and analysed by Northern blot analysis. Two patients with active cavitary tuberculosis also underwent bronchoalveolar lavage and the cells were analysed by Northern blotting. RESULTS: Incubation of THP-1 cells with LAM resulted in the stimulated release of matrix metalloproteinase-9 (MMP-9), a 92 kDa gelatinase, by 24 hours in a dose-dependent fashion. In addition, Northern analysis revealed that LAM upregulated the gene for MMP-9 by 24 hours, but not the gene for the 72 kDa gelatinase MMP-2. Heat killed M tuberculosis H37Ra also upregulated the MMP-9 gene. Bronchoalveolar lavage of the two patients with active cavitary tuberculosis showed striking upregulation of the MMP-9 gene compared with a normal control using Northern analysis. LAM also upregulated the type I interstitial collagenase (MMP-1) gene by 24 hours in both THP-1 cells and peripheral blood monocytes. CONCLUSIONS: These data suggest that M tuberculosis and its major cell antigenic component, LAM, stimulate the release of MMP-9 and upregulate the expression of genes for MMP-1 and MMP-9. It is possible that M tuberculosis and its components contribute directly to cavity formation by their ability to stimulate macrophages to release matrix metallo-proteinases that digest collagens I-IV, and indirectly by stimulating the release of the cytokines interleukin 1 beta and tumour necrosis factor alpha that induce fibroblasts to amplify the release of matrix metalloproteinases.

Antigens, Bacterial↗
PubMed1996

Relationship of uterine perfusion to outcome of intrauterine insemination.

This prospective study was undertaken to evaluate the prognostic value of uterine perfusion on the day of human chorionic gonadotropin administration in patients who were undergoing intrauterine insemination. Uterine perfusion was evaluated by measuring the pulsatility index of the ascending branch of the uterine arteries on the day of administration of human chorionic gonadotropin. No pregnancy occurred when the pulsatility index of the ascending branch of the uterine arteries was more than 3. The fecundity rate was 18% when the pulsatility index was less than 2 and was 19.8% when the pulsatility index was between 2 and 3 (not significant). The continuing pregnancy rate was 18% when the pulsatility index was less than 2, compared with 12.1% when the pulsatility index was between 2 and 3 (P < 0.05). Our data suggest that the measurement of uterine perfusion on the day of human chorionic gonadotropin administration may have predictive value regarding fecundity and the continuation of pregnancy in intrauterine insemination.

Adult↗
PubMed1996

Early discontinuation of gonadotropin-releasing hormone agonist in controlled ovarian hyperstimulation: a preliminary report.

The purpose of this study was to evaluate the applicability of continuing daily injectable GnRHa, after pituitary desensitization, for the first 4 or 5 days of ovarian stimulation. We proposed a new calculation and estimated that it took as early as 6 to 7 days for pituitary and gonadotropin release to return after cessation of daily administered leuprolide acetate. A modified regimen based on this new calculation, i.e. Daily administered GnRHa continued for the first 4 or 5 days with ovarian stimulation after pituitary desensitization had been achieved was applied to patients undergoing assisted reproductive technology (ART). Thirty-five patients prospectively assigned to use this early discontinuation regimen were analyzed with respect to age, indications, duration of ovarian stimulation, dose of exogenous gonadotropin required, ovarian response and oocytes obtained, rate of fertilization, and rates of pregnancy. There was no spontaneous LH surge occurred. Premature luteinization occurred in one patient. We concluded that, after pituitary desensitization, there was no spontaneous LH surge when daily administered GnRHa continued for 4 or 5 days only with ovarian stimulation. Impacts on the ART outcome required further evaluation in a prospectively randomized study. Based on theoretical estimation, cessation of GnRHa at the beginning of ovarian stimulation might eliminate most, but not all, spontaneous LH surges.

Adult↗
PubMed1996

Coamplification of the ZFX and ZFY genes for sex identification in preimplantation embryos.

Knowledge of the sex of an embryo may be particularly useful for couples who have a high risk of producing offspring with inherited genetic disorders. We present a rapid and reliable nested polymerase chain reaction strategy to simultaneously amplify the ZFX and ZFY genes at the single cell level. Forty single blastomeres isolated from six triploid preembryos were subjected to coamplification of ZFX and ZFY genes. The results obtained from the preembryo were consistent with the assigned genotype. The amplification rate was 80% for ZFX and 84% for ZFY. Our strategy can be applied to preimplantation diagnosis of single gene disorders, and is especially useful for preimplantation diagnosis and prevention of X-linked diseases in in vitro fertilization programs.

Blastocyst↗
PubMed1996

Multivariate analyses of the relationship between umbilical cord length and obstetric outcome.

To investigate the clinical significance of umbilical cord length in human pregnancies, 1087 deliveries at Kaohsiung Chang Gung Memorial Hospital from May 1995 to August 1995 were studied. Our data showed that male fetuses had longer cord length than female and vertex presentation had longer cord length than breech presentation. The cord length and placental weight were significantly related to the birth weight. We found that: 1) only intrauterine growth retardation was associated with the increased risk of fetal distress; 2) secondary arrest of labor and advanced gestational age were correlated with meconium stain; and 3) birth weight and presence of meconium stain were correlated with the secondary arrest (p < 0.05). However, there was no significant correlation between umbilical cord length and fetal well-being. As a result of multivariate analyses, we conclude that the umbilical cord length does not significantly correlate with either maternal age, gestational age (> or = 28 weeks), parity fetal outcome or intrauterine fetal well-being. Birth weight is the only characteristic that is correlated with cord length.

Adult↗
PubMed1996

Second trimester diagnosis of thanatophoric dysplasia.

Thanatophoric dysplasia is one of the most common skeletal dysplasia, with an incidence from 1:6,400 to 1:100,000 births. While the etiology is unknown, either autosomal recessive or polygenic transmission with 0.2% recurrence risk had been suggested. It is a lethal disorder characterized by extremely short ribs, tubular bones and macrocephaly. Death is often secondary to pulmonary hypoplasia caused by the small thoracic cavity. We present a fetus with shortening of four limbs, typical thanatophoric dwarfism, diagnosed by sonography at the 25th week of gestation. The second trimester diagnosis by ultrasound was crucial, because it gave an alternative option of pregnancy termination when the affected fetus was discovered.

Adult↗
PubMed1995

CD8+ T-cells in psoriatic lesions preferentially use T-cell receptors V beta 3 and/or V beta 13.1 genes.

Restricted T-cell receptor V beta gene use in animal models of autoimmune disease has led to the development of strategies to treat autoimmune disease by targeting the T-cell receptors of the pathogenic T-cells. Restricted T-cell receptor gene use has been noted in human autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. We report here the finding of restricted T-cell receptor gene use in psoriasis vulgaris, as well. Our results show an elevated skin (over PBL) expression of V beta 3 and/or V beta 13.1 messages in the CD8+ T-cells in a majority of patients studied. CDR3 sequence analysis on these two V beta s from the skin demonstrated monoclonality or marked oligoclonality. A second biopsy performed 3.5 to 8 months later in four patients, at the same or different lesions, again revealed an elevated V beta 3 and/or V beta 13.1 expression and clonality. Moreover, in three of the four patients, the same TcR V beta CDR3 rearrangement was found in both biopsies, although there was no V beta CDR3 homology noted between patients. In two patients in which V beta 3 and/or V beta 13.1 was not elevated in the CD8+ T-cell population, an increase in V beta 17 gene use and clonality was found. The persistence of V beta 3- and/or V beta 13.1-bearing CD8+ T-cells in lesions that did not undergo resolution suggests their role as effector cells rather than as regulatory cells. The effector function of these CD8+ T-cells is further supported by the clonality of TcR V beta sequence data, which indicates they are recruited and expanded in situ. The V beta s identified in this study are candidate targets for selective immunotherapeutic intervention in psoriasis.

Amino Acid Sequence↗
PubMed1995

The effect of passive smoking and tobacco exposure through breast milk on sudden infant death syndrome.

OBJECTIVE: To examine the relationship between sudden infant death syndrome (SIDS) and smoking during pregnancy; postnatal tobacco smoke exposure from the mother, father, live-in-adults, and day care providers; and postnatal smoke exposure from breast-feeding. DESIGN: Case-control study. SETTING: Five counties in Southern California. PARTICIPANTS: A total of 200 white, African-American, Hispanic, and Asian parents of infants who died of SIDS between 1989 and 1992 were compared with 200 control parents who delivered healthy infants. Case infants were matched to control infants on the basis of birth hospital, birth date, gender, and race. All information was obtained from a detailed telephone interview and validated with medical records. MAIN OUTCOME MEASURES: Risk of SIDS associated with passive smoking by the mother, father, live-in adults, and day care providers; smoking in the same room as the infant; total number of cigarettes smoked by all adults; and maternal smoking during the time period of breast-feeding. RESULTS: Conditional logistic regression resulted in overall adjusted odds ratios (ORs) for SIDS associated with passive smoke from the mother of 2.28, the father of 3.46, other live-in adults of 2.18, and all sources of 3.50 (95% confidence interval, 1.81 to 6.75), while simultaneously adjusting for birth weight, sleep position, prenatal care, medical conditions at birth, breast-feeding, and maternal smoking during pregnancy. A dose-response effect was noted for SIDS associated with increasing numbers of cigarettes, as well as total number of smokers. Breast-feeding was protective for SIDS among nonsmokers (OR = 0.37) but not smokers (OR = 1.38), when adjusting for potential confounders. CONCLUSIONS: Passive smoking in the same room as the infant increases the risk for SIDS. Physicians should educate new and prospective parents about the risk of tobacco smoke exposure during pregnancy and the first year of the infant's life.

Breast Feeding↗
PubMed1995

Lung cancer in nonsmoking women. Histology and survival patterns.

BACKGROUND: Despite the widespread view that important clinical and etiologic differences exist between histologic categories of lung cancer, few studies have examined the accuracy of hospital-reported pathologic diagnoses of lung cancer. METHODS: A review of pathologic material and an assessment of survival patterns were conducted in conjunction with a recently completed case-control study of lung cancer among nonsmoking women in Missouri. Using established protocols, tissue slides from tumors of 482 patients were reviewed by 3 pathologists. RESULTS: Adenocarcinoma was the most common histologic type among former smokers and lifetime nonsmokers. The overall agreement rate between the original and review diagnoses was 65.6%. The positive predictive value ranged from 0.33 for bronchioalveolar carcinomas to 0.84 for adenocarcinomas. Agreement rates for small, medium, and large hospitals were 63.1, 66.6, and 66.2%, respectively. Survival rates were highest for bronchioalveolar carcinoma and lowest for small cell carcinoma. CONCLUSION: Given the importance of lung cancer to public health and the need to examine risk by histologic type, these data indicate that pathologic review of registry-reported lung cancer cases may be an important component of large scale studies of etiology.

Adenocarcinoma↗
PubMed1995

Thymic epithelial neoplasms in transgenic mice expressing SV40 T antigen under the control of an erythroid-specific enhancer.

The beta-globin locus control region is known to be a powerful erythroid-specific enhancer. In an attempt to produce immortalized erythroid percursor cells, transgenic mice have been generated with the simian virus (SV) 40 T antigen gene under the control of the locus control region. As previously reported, transgenic mice did not develop erythroleukaemia, but rather succumbed to insulinomas and poorly differentiated rhabdomyosarcomas. This paper describes additional mice containing this transgene that developed thymomas of the mixed epithelial/lymphocytic type, in which only the epithelial component expressed the T antigen. Epithelial cell lines have been established from these tumours. This system may be useful in future studies on the pathogenesis of thymomas and the function of thymic epithelial cells.

Animals↗