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Biomedical subjects

C H Chang

Publications and source records attributed to C H Chang.

At least 181 records · Page 10Linked to original sources
PubMed1998

Video-assisted cardiac surgery for intracardiac tumors.

OBJECTIVE: To present our experience in surgical excision of intracardiac tumors in three patients using video-assisted cardiac surgical techniques. METHODS: Three patients received emergency video-assisted cardiac surgery for excision of right atrial or left atrial tumors. These surgeries were performed through right anterior submammary minithoracotomies and guided by video-assisted endoscopic techniques by projected images on a video monitor while under femoro-femoral cardiopulmonary bypass. The myocardium was protected by continuous coronary perfusion with fibrillatory arrest. Conventional instruments were used. RESULTS: All but one of the tumors were excised completely. The bypass time was 88-148 min. The operation time was 3.5-4.4 h. There were no operative deaths. Pathological examination of the tumors showed left atrial myxoma, metastatic left atrial choriocarcinoma, and right atrial lymphoma. One patient died from non-cardiac origin 5 weeks after discharge. Follow-up was completed with the two survivors. Transthoracic echocardiographic examination showed good ventricular function without any residual tumors. They were both in New York Heart Association functional class I or II. They were satisfied with the cosmetic healing of their incisions. CONCLUSION: Video-assisted cardiac surgery is technically feasible and can be performed in surgical excision of intracardiac tumors.

Adult↗
PubMed1998

Design and selection of DMP 850 and DMP 851: the next generation of cyclic urea HIV protease inhibitors.

BACKGROUND: Recent clinical trials have demonstrated that HIV protease inhibitors are useful in the treatment of AIDS. It is necessary, however, to use HIV protease inhibitors in combination with other antiviral agents to inhibit the development of resistance. The daunting ability of the virus to rapidly generate resistant mutants suggests that there is an ongoing need for new HIV protease inhibitors with superior pharmacokinetic and efficacy profiles. In our attempts to design and select improved cyclic urea HIV protease inhibitors, we have simultaneously optimized potency, resistance profile, protein binding and oral bioavailability. RESULTS: We have discovered that nonsymmetrical cyclic ureas containing a 3-aminoindazole P2 group are potent inhibitors of HIV protease with excellent oral bioavailability. Furthermore, the 3-aminoindazole group forms four hydrogen bonds with the enzyme and imparts a good resistance profile. The nonsymmetrical 3-aminoindazoles DMP 850 and DMP 851 were selected as our next generation of cyclic urea HIV protease inhibitors because they achieve 8 h trough blood levels in dog, with a 10 mg/kg dose, at or above the protein-binding-adjusted IC90 value for the worst single mutant--that containing the Ile84-->Val mutation. CONCLUSIONS: In selecting our next generation of cyclic urea HIV protease inhibitors, we established a rigorous set of criteria designed to maximize chances for a sustained antiviral effect in HIV-infected individuals. As DMP 850 and DMP 851 provide plasma levels of free drug that are sufficient to inhibit wild-type HIV and several mutant forms of HIV, they could show improved ability to decrease viral load for clinically significant time periods. The ultimate success of DMP 850 and DMP 851 in clinical trials might depend on achieving or exceeding the oral bioavailability seen in dog.

Animals↗
PubMed1998

Polyamine inhibition of estrogen receptor (ER) DNA-binding and ligand-binding functions.

Polyamines are known to inhibit sequence specific DNA-binding activity of several zinc-finger transcription factors, including estrogen receptor (ER) binding to its cognate estrogen response element (ERE). The mechanism accounting for this disruption of protein-DNA interaction is unknown, although polyamine induction of DNA conformational changes has been suggested. To determine if polyamines can directly impair ER action, we compared the effects of putrescine (Putr), spermidine (Spd), and spermine (Spm) on ER DNA-binding (ER-ERE complex formation), ER ligand-binding (estradiol), ER structure (circular dichroism and sucrose gradient sedimentation), and the capacity of ER to transactivate an ERE-tk-CAT reporter in transient transfection assays. Polyamine concentrations causing 50% inhibition of ER-ERE formation (IC50 values) were found to be 1 mM for Putr, 4 mM for Spd, and 3 mM for Spm. This loss of ER DNA-binding was associated with a direct and irreversible effect on the ER DNA-binding domain (ER-DBD). Additionally, polyamines were observed to inhibit ER ligand-binding with IC50 values of 10 mM for Putr, 2 mM for Spd, and < 0.1 mM for Spm; and this correlated with a measureable change in higher-order ER structure (5S to 3.5S sedimentation) and inhibition of intracellular ER transactivation. These findings suggest that in ER-positive human breast tumors with increased polyamine (especially Spm) content, ER structure and function may be directly altered by tight-ion polyamine complexing that results in loss of ER-mediated gene regulation.

Breast↗
PubMed1998

HLA-DRB1*0701 and DRB1*1401 are associated with genetic susceptibility to psoriasis vulgaris in a Taiwanese population.

We analysed the allelic frequencies of class II human leucocyte antigen (HLA)-DRB1, DQA1, DQB1 and DPB1 by polymerase chain reaction/sequence-specific oligonucleotide probe hybridization typing in 76 Taiwanese psoriasis vulgaris (PSV) patients and 238 Taiwanese non-psoriatic controls. The analysis revealed the following: (i) the DRB1*0701 allele was positively associated with PSV (relative risk, RR = 6.4, corrected P-value, Pc < or = 0.001); (ii) the DRB1*1401 allele was positively associated with type I PSV (age at onset < 40 years) (RR = 3.5, Pc < or = 0.001); (iii) the DQA1*0501 allele was negatively associated with PSV (RR = 0.4, Pc < or = 0.001); (iv) there was no significant association of HLA-DP genes with PSV; and (v) there was a strong association of beta-chain phenylalanine at position 37 (Phe 37) and glutamate or glutamine at position 74 (Glu 74/Gln 74) with PSV (RR = 3.5, Pc < or = 0.001 for the association of Phe 37 with PSV: RR = 2.2, Pc < or = 0.001 for the association of Glu 74/Gln 74 with PSV). The positive association between PSV and the DRB1*0701 allele is consistent with previous reports. The negative association of the DQA1*0501 allele is reported only in Finland, whereas the positive association between PSV and the DRB1*1401 allele has never been described before. Trans-racial studies may shed further light on the association of class II HLA alleles or other closely linked genes with the development of PSV. Phe 37 (a large, non-polar amino acid) and Glu 74/Gln 74 (both negatively charged amino acids) were the polymorphic residues in pockets 9 and 4, respectively, of the beta-chain, which may have increased their affinity for the small non-polar amino acids and basic amino acids of the psoriatic antigen peptide, thereby activating the T lymphocytes. This finding may facilitate the identification of a psoriatic antigen.

Adolescent↗
PubMed1998

Chemical denaturation of ovalbumin abrogates the induction of oral tolerance of mouse reaginic antibody responses.

The effect of chemical denaturation of ovalbumin (OVA) on the induction of oral tolerance of reaginic antibody responses was studied. Both urea-denatured OVA (UD-OVA) and carboxymethylated UD-OVA (CM-OVA) were purified by centrifugation. When compared with OVA and UD-OVA, CM-OVA had the least sensitizing capacity and allergenicity in IgE responses to OVA. BALB/c IgE, IgG1 and IgG antibody responses were suppressed by OVA, but not by UD-OVA or CM-OVA, fed prior to sensitization with OVA, UD-OVA, or CM-OVA in alum, respectively. The priming effect of specific IgG and IgG1 antibody responses was induced by CM-OVA fed prior to sensitization with OVA or CM-OVA. The proliferation of BALB/c spleen cells and their secretion of T helper type 2 (Th2) cytokines interleukin-4 (IL-4) and IL-5 were also orally tolerized by OVA, but not by denatured OVA. Although denatured OVA is hypoallergenic, the present result indicates that denaturation of a soluble protein prevents the induction of oral tolerance of Th2 responses.

Administration, Oral↗
PubMed1998

Heat denaturation of egg-white proteins abrogates the induction of oral tolerance of specific Th2 immune responses in mice.

Human foods are usually prepared by cooking. Boiling of chicken egg-white (EW) led to decreased allergenicity, and abrogated intestinal uptake of immunoreactive ovalbumin (OVA) when fed to mice. Therefore, the effects of oral administration of boiled EW were examined further in BALB/c mice. Specific IgE, IgG1 and IgG antibody responses were suppressed by raw EW, but not by EW boiled for 5 or 60 min, fed prior to sensitization with 10 microg OVA or 1 microg DNP-OVA in alum. Similar results were obtained when mice were sensitized with 10 microg conalbumin, ovomucoid or lysozyme in alum. BALB/c spleen cell proliferation and secretion of Th2 cytokines IL-4 and IL-5 during in vitro stimulation with OVA were also suppressed by feeding raw EW, but not by boiled EW. Although heat denaturation of proteins can minimize allergenicity, the present results suggest that over-cooking of proteins may affect their intestinal antigen processing and thus prevent the induction of oral tolerance.

Animals↗
PubMed1998

Prenatal sonographic characteristics and Doppler blood flow study in a case of a large fetal mediastinal teratoma.

Although fetal mediastinal teratomas may result in respiratory distress in the neonatal period and lead to perinatal mortality, they are rarely diagnosed prenatally. Furthermore, their impact on fetal hemodynamics has never been described. We report a case of a large fetal mediastinal teratoma prenatally visualized at 38 weeks' gestation by both two- and three- dimensional ultrasound. We also describe the associated changes in the Doppler flow velocimetry, namely, a decrease in cardiac output, prolonged acceleration time in the pulmonary artery and an increase in the umbilical artery S/D ratio. The baby was well at the 5-month follow-up after an operation in the neonatal period. From our case, we believe that accurate prenatal diagnosis and assessment by two- and three-dimensional ultrasound as well as Doppler flow velocimetry may contribute to a better perinatal outcome.

Adult↗
PubMed1998

Prenatal diagnosis of otocephaly using two-dimensional and three-dimensional ultrasonography.

We report a case of the prenatal diagnosis of a very rare anomaly, namely isolated otocephaly, using two-dimensional and three-dimensional ultrasound at 24 weeks of gestation. Two-dimensional ultrasound revealed polyhydramnios, absence of a stomach shadow, hypotelorism and a proboscis-like mass. Three-dimensional ultrasound gave a precise demonstration of the striking craniofacial features of otocephaly including agnathia, synotia, microstomia and protuberance of the nose-mouth fusion. The use of three-dimensional ultrasound provided a whole view of the very rare lethal malformation in utero and contributed significantly to prenatal diagnosis.

Abortion, Legal↗
PubMed1998

Mice lacking the transcription factor CIITA--a second look.

We have generated a second line of mice lacking a transcription factor thought to be a critical regulator of MHC class II gene expression, CIITA (for class II transactivator). Our and the previously published lines differ in the deletion that was engineered and by the fact that we removed the neomycin-resistance promoter and structural gene via the cre-loxP recombination system. Characterization of our line led to two new findings. First, a substantial number of cells can express class II molecules in the absence of CIITA, albeit at 5-fold reduced levels, most notably dendritic cells in s.c. lymph nodes; therefore, the CIITA gene cannot be an absolute 'master gene' controlling the expression of class II molecules, as had been thought. Second, in contrast to recent results on human cell lines, CIITA is not critically involved in the IFN-gamma-induced up-regulation of MHC class I genes.

Animals↗
PubMed1998

The epithelium-specific ets transcription factor ESX is associated with mammary gland development and involution.

To study mammary gland expression of the epithelium-restricted Ets factor, ESX, mouse cDNA and genomic sequences were cloned and a approximately 350 bp proximal promoter region with >80% mouse-human homology was identified that mediates ESX induction by serum, heregulin (HRG), or epidermal growth factor (EGF). ESX mRNA expression progressively increases during embryonic mouse development from day 7 and is detectable in virgin mammary glands; it shows little if any change during pregnancy, then declines to barely detectable levels after 3 days of lactation. Similarly, cultured HC11 cells from midpregnant mouse mammary epithelium show an increase in ESX expression upon reaching lactogenic competency (in the presence of EGF or HRG), with a decline to barely detectable levels upon exposure to lactogenic hormones that induce milk protein (beta-casein) expression. In contrast, involuting mouse and rat mammary glands show maximal ESX expression. High ESX levels are also seen in the involuting ventral prostate gland of rats. These findings, including the persistence of up-regulated ESX in fully regressed mammary glands, suggest that ESX expression can be induced by soluble growth factors and is maximally up-regulated in those partially committed epithelial cells destined to survive both the apoptotic and remodeling phases of glandular involution.

Amino Acid Sequence↗
PubMed1998

Expression of bcl-2, p53 and Ki-67 in arsenical skin cancers.

To investigate the regulation of apoptosis and proliferation in arsenic-induced skin cancers, we examined the expression of bcl-2, p53, and Ki-67 using immunohistochemical staining. Thirty patients with Bowen's disease (BD), ten with basal cell carcinoma (BCC), eight with squamous cell carcinoma (SCC) and eleven of perilesional normal skin (PLN) of the non-sun exposure sites from endemic area were examined. The results showed that: 1) bcl-2 was expressed in all of the BCC homogeneously, in none of the SCC, and in 12/30 of the BD focally or homogeneously; 2) p53 was expressed in all of the arsenical skin cancers with a labelling index of 75 +/- 14% of BD, 50 +/- 17% of BCC, 61 +/- 15% of SCC, and also in all of the perilesional normal skin with a labelling index of 55 +/- 24%; 3) Ki-67 was expressed in all of the skin cancers with labelling index of 58 +/- 17% of BD, 12 +/- 7% of BCC, 47 +/- 21% of SCC, and in 9/11 of PLN with a labelling index of 41 +/- 24%. Expression of bcl-2 in BCC or BD is related to the phenotype of germinative basal cell. The constant expression of bcl-2 i early dysplastic cells of BD and the earliest expression of P53 in the basal cells of perilesional normal skin indicate that the initial step of arsenic-induced carcinogenesis is from the basal germinative cells. There is no mutual relationship between bcl-2, p53 or Ki-67 expression in any type of the arsenical skin cancers, but there is a positive correlation between p53 and Ki-67 expression identified in perilesional normal skin. BD had the highest labelling index of p53 and Ki-67.

Aged↗
PubMed1998

Modulation of secretin release by neuropeptides in secretin-producing cells.

Nerve fibers containing bombesin (BB)/gastrin-releasing polypeptide (GRP), pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal polypeptide (VIP), or galanin are known to innervate the mucosa of the upper small intestine. Both BB/GRP and PACAP have been shown to elicit secretin secretion in vivo. We studied whether the above-mentioned neuropeptides can act directly on secretin-producing cells, including the murine neuroendocrine cell line STC-1 and a secretin cell-enriched preparation isolated from rat upper small intestinal mucosa. Secretin release from both cell types was stimulated by various agents known to elicit secretin release and by the neuropeptides BB, GRP, and PACAP, suggesting a comparable response between the two cell preparations. The effects of neuropeptides were further studied in STC-1 cells. BB, GRP, and PACAP stimulated secretin release time and concentration dependently. VIP also stimulated secretin release concentration dependently. Stimulation by BB/GRP or PACAP was accompanied by elevation of inositol-1,4,5-trisphosphate (IP3) or cAMP, respectively. The stimulatory effect of PACAP on secretin release was synergistically enhanced by BB without any synergistic increase in IP3 or cAMP production, suggesting cross talk between different signal transduction pathways downstream of the production of these two second messengers. The L-type Ca2+ channel blocker diltiazem (10 microM) and the Ca2+ chelator EGTA (1 mM) significantly inhibited BB-stimulated secretin release by 64% and 59%, respectively, and inhibited PACAP-stimulated release by 75% and 55%, respectively. The protein kinase A-specific inhibitor Rp-cAMPS (100 microM) also inhibited both BB- and PACAP-stimulated secretin release by 30% and 62%, respectively. Galanin inhibited BB- and PACAP-stimulated secretin release and production of second messengers in a concentration-dependent and pertussis toxin-sensitive manner. These results suggested that the neuropeptides BB/GRP, PACAP, VIP, and galanin can modulate secretin release in secretin-producing cells and that STC-1 cells can serve as a useful model for studying the cellular mechanism of secretin secretion elicited by luminal secretagogues and neuropeptides.

1-Methyl-3-isobutylxanthine↗
PubMed1998

Role of phospholipase A2 isozymes in agonist-mediated signaling in proximal tubular epithelium.

Angiotensin II in proximal tubule epithelium is known to stimulate the release of arachidonic acid after stimulation of phospholipase A2 (PLA2) independent of phospholipase C-mediated signaling. Furthermore, an angiotensin II type 2 receptor subtype has been linked to this signaling cascade. We investigated the regulation and differential stimulation of PLA2s by comparing the PLA2 activities associated with the membranes and cytosol of rabbit renal proximal tubular epithelial cells after stimulation with angiotensin II, epidermal growth factor, and bradykinin. Both fractions demonstrated PLA2 activity that was dithiothreitol insensitive, required micromolar concentrations of Ca2+ for optimal activity, and was inhibited in a dose-dependent manner by an antiserum to a cytosolic PLA2 with a molecular mass of 85 kD. However, membrane-associated PLA2 did not demonstrate significant substrate specificity, whereas 1-steroyl-2-[14C]arachidonylphosphatidyl choline was the preferred substrate for cPLA2. An antiserum generated against mastoparan, a known PLA2 activator, inhibited membrane- but not cytosol-associated PLA2 activity. Membrane fractions showed a broad pH range (7.5 to 8.5) for optimal PLA2 activity, whereas cytosol was maximum at pH 9.5. Angiotensin II stimulated membrane-associated PLA2 activity by 88%, whereas bradykinin and epidermal growth factor inhibited activity by 54% and 41%, respectively. The three agonists stimulated cPLA2. Moreover, angiotensin II-induced activation of membrane-associated PLA2 preceded the activation of cPLA2. These results demonstrate differential localization and regulation of proximal tubular epithelial PLA2 isozymes, which may determine the pattern of subsequent arachidonic acid metabolism by the cytochrome P450 system.

Angiotensin II↗
PubMed1998

Trends in pediatric asthma hospitalization rates: regional and socioeconomic differences.

OBJECTIVE: Asthma hospitalization rates continue to increase nationally for children despite efforts by the National Institutes of Health and specialty organizations to improve outcomes through the dissemination of practice guidelines. To understand the generalizability of national trends to regional populations, we studied childhood hospitalizations over a 10-year period in four northeastern states. DESIGN: Longitudinal analysis of hospitalization rates by patient residence and patient characteristics using state hospital discharge datasets. POPULATION: Age < 18 years residing in Maine, New Hampshire, Vermont, or New York state during the period 1985 to 1994. RESULTS: In multivariate analyses (controlling for age, sex, race/ethnicity, median household income, metropolitan status), we found that New York asthma hospitalization rates increased 3.8% per annum (95% confidence interval: 3.3, 4.2), whereas in New Hampshire, rates decreased 5.8% (95% confidence interval: 7.6, 4.1). Maine and Vermont rates did not change significantly during the study period. Increased asthma hospitalization rates were noted in black and Hispanic populations, in children residing in zip codes with lower median household incomes, and in those living in metropolitan areas. Hospitalization rates for nonasthma causes fell substantially. As a result, the proportion of hospital days attributed to childhood asthma increased in all population groups. CONCLUSIONS: Asthma discharge rates measured by the state of residence or socioeconomic characteristic do not necessarily parallel national trends. None of the current hypotheses offered to explain national trends in asthma hospitalization rates (changes in disease severity, diagnostic substitution, or differences in the supply and character of medical care) can be the sole explanation of these regional trends. Efforts intended to improve asthma outcomes may benefit a greater number of children by redirecting resources toward specific populations identified through state hospital discharge datasets.

Adolescent↗
PubMed1998

Concentration of metal elements in the blood and urine in the patients with cementless total knee arthroplasty.

Titanium (Ti), cobalt (Co) and chromium (Cr) element concentrations in the whole blood and urine specimen in 40 patients with cementless total knee arthroplasty were determined by the electrothermal atomic absorption spectrophotometry. Their ages ranged from 55 to 78 years (mean, 65 years). Twenty of them had loosening of prosthesis and underwent revision surgery, including 4 subjects with Ti-6Al-4V alloy prosthesis and 16 subjects with Co-Cr-Mo alloy prosthesis. The other 20 patients had well-functioning stable prosthesis, including 5 subjects with Ti-6Al-4V alloy prosthesis and 15 subjects with Co-Cr-Mo alloy prosthesis. The mean duration of prostheses implantation in patients with loosened or well-functioning prostheses were 6.5 and 4.0 years, respectively. The control group consisted of 20 age-matched normal subjects who did not undergo any metal implant surgery. Analysis of variance showed that the metal element concentrations in the whole blood, either Co, Cr or Ti, was statistically higher in the patients with loosened prosthesis than the other two groups. However, the metal element concentrations in the urine did not show any difference. The linear regression analysis showed a moderate positive relationship between the metal element concentrations, either Co or Cr elements, in whole blood and urine only in the patients with loosened prostheses. In conclusion, elevated concentration of metal elements may indicate a loosening of prosthesis while the clinical significance of the metal element concentration in the urine needs further investigation.

Aged↗
PubMed1998

Hypophyseal-portal concentrations of growth hormone-releasing factor and somatostatin in conscious pigs: relationship to production of spontaneous growth hormone pulses.

A method of collecting hypophyseal portal blood (HPB) in conscious pigs was used to show the relationship between GRF and somatostatin (SRIF) concentration and peripheral GH response. Six male castrate pigs (approximately 63 kg body weight) had HPB and jugular blood collected individually for an average of 175 min each. Twenty-seven spontaneous GH pulses were detected in the 1050 min of total HPB collection. Of the associations examined, the only significant finding was that GH pulse maxima occurred nonrandomly within periods of SRIF descent (63%; P = 0.005). Although 48% (13/27) of GH pulse maxima were associated with an ascent in portal GRF concentration, these associations were not determined to be nonrandom (P = 0.14). Only 7 of 27 (26%) GH pulse maxima were associated with an ascent in portal GRF concentration and a descent in SRIF concentration occurring simultaneously. A saline infusion given approximately 120 min after beginning blood collection resulted in an increase in SRIF pulse frequency and a decrease in GH-AUC and GRF-AUC. The cause of this saline effect is unknown, but it may have been related to acclimation of the pigs to the blood collection procedure. These data show the complexity of the relationship between SRIF and GRF concentrations and GH secretion and may indicate a close relationship with SRIF in GH pulse generation in the pig. In addition, these data support the hypothesis that, in the pig, mediation of GH release cannot be explained simply by antagonism between GRF and SRIF.

Animals↗
PubMed1998

Korean Nationwide Surveillance of Antimicrobial Resistance of bacteria in 1997.

Antimicrobial-resistant bacteria are known to be prevalent in tertiary-care hospitals in Korea. Twenty hospitals participated to this surveillance to determine the nationwide prevalence of resistance bacteria in 1997. Seven per cent and 26% of Escherichia coli and Klebsiella pneumoniae were resistant to 3rd-generation cephalosporin. Increased resistance rates, 19% of Acinetobacter baumannii to ampicillin/sulbactam, and 17% of Pseudomonas aeruginoa to imipenem, were noted. The resistance rate to fluoroquinolone rose to 24% in E. coli, 56% in A. baumannii and 42% in P. aeruginosa. Mean resistance rates were similar in all hospital groups: about 17% of P. aeruginosa to imipenem, 50% of Haemophilus influenzae to ampicillin, 70% of Staphylococcus aureus to methicillin, and 70% of pneumococci to penicillin. In conclusion, nosocomial pathogens and problem resistant organisms are prevalent in smaller hospitals too, indicating nosocomial spread is a significant cause of the increasing prevalence of resistant bacteria in Korea.

Bacterial Physiological Phenomena↗