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Biomedical subjects

H L Chang

Publications and source records attributed to H L Chang.

At least 19 recordsLinked to original sources

Effects of garlic compounds diallyl sulfide and diallyl disulfide on arylamine N-acetyltransferase activity in strains of Helicobacter pylori from peptic ulcer patients.

Arylamine N-acctyltransferase (NAT) activities with p-aminobenzoic acid (PABA) and 2-aminofluorene (2-AF) were determined in the bacterium Helicobacter pylori collected from peptic ulcer patients. Two assay systems were performed, one with cellular cytosols, the other with intact cell suspensions. Cytosols or suspensions of H. pylori with or without specific concentrations of diallyl sulfide (DAS) or diallyl disulfide (DADS) co-treatment showed different percentages of 2-AF and PABA acetylation. The data indicated that there was decreased NAT activity associated with increased levels of DAS or DADS in H. pylori cytosols and suspensions. Viability studies on H. pylori demonstrated that DAS or DADS elicited dose-dependent bactericide affects on H. pylori cultures. The data also indicated that DAS and DADS decreased the apparent values of K(m) and Vmax of NAT enzyme from H. pylori in both systems examined. This report is the first demonstration that garlic components can affect H. pylori growth and NAT activity.

Allyl Compounds

Effects of chronic lead exposure on [3H]MK-801 binding in the brain of rat.

We have used quantitative autoradiographic methods to determine the effects of chronic lead exposure on N-methyl-D-aspartate (NMDA) receptors in the brain of female rat. Rats were exposed pre- and post-natally from day 4 +/- 1 post conception with 1000 ppm lead in their drinking water. This treatment continued after weaning. No effects of lead on [3H]MK-801 binding were found at PN 28. However, lead caused a significant increase in [3H]MK-801 binding in the hippocampus including CA1 and CA2, and in the occipital and temporal cortical areas at PN 56 and at PN 112. An increase in binding was also found in the entorhinal cortex and the dentate gyrus at PN 112. Because the NMDA receptor is involved in learning and memory, the lead-induced disruption of NMDA receptors in the hippocampus and cortex may be associated with the cation-induced cognition deficits.

Animals

Dehydroepiandrosterone induces the transforming growth factor-beta production by murine macrophages.

Dehydroepiandrosterone(DHEA), a predominant androgen secreted by the adrenal cortex, and dehydroepiandrosterone sulfate (DHEAS). Its predominant form in serum, were investigated for their role in the regulation of transforming growth factor-beta (TGF beta) production by murine macrophages. Using a bioassay based on the growing inhibition to Mv-1-Lu cells and RT-PCR analysis, the effect of DHEA and DHEAS on the TGF-beta production and gene expression was studied. Results suggested that DHEA at relatively high concentration (10 microM) significantly induced TGF-beta secretion by both peritoneal cells and P388D1 macrophage-like cells. For the cells treated with DHEAS, no significant increase in TGF-beta secretion was found statistically. Result of RT-PCR confirmed the observation that cDNA from the cells pretreated with DHEA generated a significant amount of amplicons but cDNA samples obtained from both control cells and DHEAS-treated cells showed relatively weak signals. In a quantitative RT-PCR analysis, both DHEAS-treated cells and control cells failed to compete with internal standards and failed to produce any detectable amplicons. Dexamethasone, one of the commonly used glucocorticoids, induced an increase in TGF-beta secretion and in mRNA level. Dexamethasone and DHEA failed to show a synergistic effect on the DHEA-induced increase in TGF-beta secretion and gene expression. The biological significance for DHEA to act as a positive stimulator for TGF-beta production and its role in glucocorticoid-mediated immunoregulation needs to be further delineated.

Animals

Specific Th1 cytokine down-regulation associated with primary clinically derived human immunodeficiency virus type 1 Nef gene-induced expression.

HIV-1 infection is associated with a progressive and functional decline in the CD4+ lymphoid Th1 subset. Here, we propose that the HIV nef gene product may function as a specific regulator of Th1 cytokine production. By use of a T cell-specific inducible expression system, we show that upon T cell activation, induced nef expression down-regulated both IL-2 and IFN-gamma production in a dose-dependent manner, whereas IL-4, IL-9, IL-13, IL-8, and TNF-alpha production remained unaffected. In addition to this, independent transfected clones expressing various nef genes, including nef sequences amplified directly from an HIV-1 primary clinical isolate, displayed a similar pattern of cytokine expression. The specific Th1 impairment induced by nef, therefore, seems to be an important and conserved feature of HIV-1 infection and may represent a significant function of this viral gene in AIDS pathogenesis.

Base Sequence

Histopathologic alterations of periodontium in cyclosporin-treated rats. Is the periodontium a target tissue for the drug?

Gingival dimensions and histopathologic alterations in periodontium were examined in rats continuously exposed to cyclosporin-A (CSA). 60 male Sprague-Dawley rats were divided into 2 groups. Rats in the test group daily received CSA in mineral oil by gastric feeding at a dosage of 30 mg/kg body weight for 6 weeks. Rats in the control group received mineral oil only. 10 rats from each group were sacrificed at 2-week intervals. Gingival dimensions were assessed from stone models obtained from the maxillary and mandibular incisal regions. Horizontal, sagittal and frontal tissue sections were obtained from these regions as well. Gingival dimensions in the mandibular and maxillary incisal regions were significantly increased in rats exposed to CSA. Light-microscopic observations revealed a granulation tissue formation at tooth-gingiva interface and an irregular bony surface on dental alveoli in experimental animals. Because both soft and hard tissue of periodontium in experimental rats being significantly effected by CSA compared to control animals, we hypothesized that the periodontium is a target tissue for CSA.

Alveolar Process

Biodegradation of individual and multiple chlorinated aliphatic hydrocarbons by methane-oxidizing cultures.

The microbial degradation of chlorinated and nonchlorinated methanes, ethanes, and ethanes by a mixed methane-oxidizing culture grown under chemostat and batch conditions is evaluated and compared with that by two pure methanotrophic strains: CAC1 (isolated from the mixed culture) and Methylosinus trichosporium OB3b. With the exception of 1,1-dichloroethylene, the transformation capacity (Tc) for each chlorinated aliphatic hydrocarbon was generally found to be in inverse proportion to its chlorine content within each aliphatic group (i.e., methanes, ethanes, and ethenes), whereas similar trends were not observed for degradation rate constants. Tc trends were similar for all methane-oxidizing cultures tested. None of the cultures were able to degrade the fully chlorinated aliphatics such as perchloroethylene and carbon tetrachloride. Of the four cultures tested, the chemostat-grown mixed culture exhibited the highest Tc for trichloroethylene, cis-1,2-dichloroethylene, tetrachloroethane, 1,1,1-trichloroethane, and 1,2-dichloroethane, whereas the pure batch-grown OB3b culture exhibited the highest Tc for all other compounds tested. The product toxicity of chlorinated aliphatic hydrocarbons in a mixture containing multiple compounds was cumulative and predictable when using parameters measured from the degradation of individual compounds. The Tc for each chlorinated aliphatic hydrocarbon in a mixture (Tcmix) and the total Tc for the mixture (sigma Tcmix) are functions of the individual Tc, the initial substrate concentration (S0), and the first-order rate constant (k/Ks) of each compound in the mixture, indicating the importance of identifying the properties and compositions of all potentially degradable compounds in a contaminant mixture.

Bacteria

Cyclosporin A-induced gingival overgrowth in rats: macroscopic and microscopic observations.

Because the existence of cyclosporin A-induced gingival overgrowth in animals has not been well established, a pilot study was undertaken to determine whether such gingival overgrowth could be observed in Sprague-Dawley rats. Thirty-six male rats, age 6 weeks, were randomly divided into two groups. The test group was given 30 mg/kg of body weight of cyclosporin A daily by gastric feeding. The control group was given mineral oil instead. Stone casts of the gingiva in the mandibular incisor region were made biweekly for 6 weeks. The three-dimensional growth pattern-the buccolingual width, the mesiodistal width, and the vertical height of the gingiva-was analyzed on the casts. The animals were killed after the last impression was taken, and tissue sections were made. Stereomicroscopy revealed marked overgrowth of the gingiva in the test rats. All three-dimensional measurements on the stone casts were greater in the test group, beginning 2 weeks after cyclosporin A was given. Histologically the overgrowth of the epithelia and connective tissue was easily confirmed in the buccal and lingual gingiva of the test rats.

Animals

Changes in lymphocyte single strand breakage and liver function of workers exposed to vinyl chloride monomer.

Vinyl chloride monomer (VCM) is a suspected human carcinogen. Its metabolite, chloroethylene epoxide, is able to alkylate the DNA molecule and to produce single strand breakage (SSB). A total of 244 workers from 4 polyvinyl chloride (PVC) manufacturing factories were recruited to assess the SSB of their peripheral lymphocyte DNA. The method of alkaline unwinding and hydroxyapatite chromatography was used to detect and calculate frequencies of SSB. In addition, hepatitis B and C markers and the liver function of the workers were also examined. The worker's cumulative exposures to VCM were retrospectively constructed from the current monitoring data and each worker's job history. Multiple linear regression models were constructed to predict the worker's level of SSB and liver functions based on various exposure indices and variables, such as age, sex, smoking, drinking, and hepatitis markers. The results showed that current smoking and drinking status, and the presence of VCM exposures on the previous day were 3 major determinants of the level of SSB. Among the liver function tests, only gamma-glutamyl transpeptidase (GGT) was associated with current VCM exposures. In contrast, aspartate aminotransferase (AST), alkaline phosphatase (ALP) and alanine aminotransferase (ALT) were mainly affected by the presence of hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus (anti-HCV). We conclude that GGT should be considered to be included in the regular health screening of VCM workers, and that the SSB method may not be suitable for long-term monitoring of cumulative exposure because of the quick DNA repair mechanism in humans.

Adult

Dose-dependent gingival overgrowth induced by cyclosporin in rats.

This study evaluated the effect of dosage on severity of cyclosporin-A (CSA) induced gingival overgrowth. Eighty (80) male Sprague-Dawley rats were randomly distributed into 4 groups. Rats in each group daily received CSA in mineral oil by gastric feeding at dosages of 0 (control), 3, 10, and 30 mg/kg, respectively, for 6 weeks. Stone models of the mandibular incisal region were obtained biweekly and were used for analysis of the gingival dimensions. Animals were sacrificed at the end of week 6 and tissue sections were processed for histopathologic evaluations. Animals were sacrificed at the end of week 6 and tissue sections were processed for histopathologic evaluation Gingival overgrowth including bucco-lingual and mesio-distal width and vertical height were significantly increased with increasing CSA dosage. Furthermore, the gingival dimensions displayed a positive linear relation to dosage and treatment duration. The histopathologic evaluation revealed a granulomatous tissue wedging the tooth-gingival interface in the 3 mg/kg group. This tissue had reached exuberant size in the 10 and 30 mg/kg groups. In summary, the analysis of gingival dimensions the histopathologic evaluation shows a dose-dependent effect on the severity of CSA-induced gingival overgrowth.

Animals

Gingival overgrowth induced by different dosages of cyclosporin in rats.

BACKGROUND: The purpose of the study was to assess the dose effect on the severity of cyclosporin(CSA)-induced gingival overgrowth by an established rat model. METHODS: A total of 60 Sprague-Dawley male rats which weights were about 250 gm were selected and randomly divided into four groups. Three experimental groups of rats were provided different gastric feedings of 3mg, 10mg, 30mg CSA per kilogram body weight, daily; the last group of rats was fed with mineral oil as the control. Stone impression models of the mandibular incisal region were taken and three-dimensional analyses of the overgrown gingiva were made biweekly. RESULTS: In the 30 mg CSA-treated rats, all three-dimensional measurements of the gingiva were observed to be greater than those of the control rats from the second week after CSA administration. In the 10 mg CSA-treated rats, most of gingival measurements were found to be greater from the fourth week after CSA administration. The bucco-lingual width of interdental papilla on the sixth week after CSA administration was the only significant measurement showing a difference between the 3mg treated rats and the control group. CONCLUSIONS: Because of a significant correlation between CSA-induced gingival overgrowth and CSA dosage, the dose effect on the severity of this gingival overgrowth was established in the rat model.

Animals

Relaxant effects of berberine on the rat fundus.

The present study examines the relaxant effect of berberine on the longitudinal muscle of the isolated rat gastric fundus. Our experiments show that berberine reduces the tonic contraction more than the phasic contraction induced by carbachol. In addition, the carbachol induced phasic contraction in Ca+2 -free solution was only inhibited at the highest concentration of berberine. Berberine inhibited the slow phase more than the fast phase in KCl-induced contractions. These results suggest that the major mechanism of berberine consists of an inhibition of calcium entry from extracellular in the second phase induced by both carbachol and KCl. Conversely, prevention of the mobilization of store Ca+2 in the phasic contraction phase induced by carbachol and prevention of the calcium entry from extracellular in first phase elicited by high levels of potassium play only a minor role in the dilatory effect of berberine.

Animals

Increased transforming growth factor beta expression inhibits cell proliferation in vitro, yet increases tumorigenicity and tumor growth of Meth A sarcoma cells.

Several observations correlate increased expression of transforming growth factor (TGF) beta 1 with tumorigenesis, suggesting that expression of this multifunctional growth factor may provide an advantage in tumor formation. However, many tumor cells are inhibited in their proliferation by TGF-beta in vitro, thus suggesting that TGF-beta synthesis could exert an antiproliferative effect on tumor formation. To evaluate the physiological relevance of increased TGF-beta 1 synthesis in such tumor cells which are strongly inhibited in their proliferation by TGF-beta, we chose Meth A sarcoma cells as a model system. We established cell clones overexpressing TGF-beta 1 and determined its effect on tumor formation in mice that are not immunocompromised. Increased expression of biologically active TGF-beta 1 resulted in a profound growth inhibition in the transfected clones and increased adhesiveness in vitro. However, these cells were much more tumorigenic than Meth A cells that did not overexpress TGF-beta 1, as assessed by both tumor incidence and tumor growth. In addition, parental Meth A cells were inhibited in their tumor formation by neutralizing TGF-beta antibodies and stimulated by exogenous TGF-beta. Our results thus provide evidence that increased TGF-beta synthesis provides a major advantage for tumorigenesis, even if the cells are growth inhibited by their endogenous TGF-beta synthesis in culture. These results suggest that, in vivo, direct effects of TGF-beta on the tumor environment, such as increased extracellular matrix formation and cell-matrix interactions, and local suppression of the immune surveillance may provide a growth advantage which overrules any direct antiproliferative effects of TGF-beta, as suggested by the effects in culture.

Animals

[Effect of spermidine on uptake of chloroquine by Plasmodium berghei].

To probe into the effect of spermidine on chloroquine (Chl) uptake by P berghei and its role of Chl-resistance, mice infected with Chl sensitive strain (CS) of P berghei were given Chl 20 mg.kg-1 ig combined with spermidine (Spe) 42 mg.kg-1 ip. It was found that 3 and 16 h after combined administration, Chl quantity uptaken by the parasites was reduced respectively by 59.6% and 53.8% in comparison with that in the Chl group. However, there was no difference in parasitaemia between Chl group (2.3 +/- 1.0) and Chl-Spe group (1.7 +/- 1.0), whereas the untreated control group remained a parasitaemia of 36 +/- 9. The authors deemed that Chl resistance is not merely attributed to the insufficient quantity of Chl in the Chl resistant parasites, the change in the sensitivity to Chl of Chl resistant parasites and the role of Spe in Chl resistance production should also be taken into consideration.

Animals

Lineage switch macrophages can present antigen.

Recent reports of "lineage switching" from a lymphoid to macrophage phenotype have left unresolved the question of whether such cells are functional macrophages or nonfunctional products of differentiation gone awry. This study demonstrates that several "macrophage-like" cell lines derived from v-Ha-ras-transformed pre-B cells have gained the capacity to effectively present antigen in MHC-restricted fashion. Using an assay involving the cocultivation of putative antigen-presenting cells with chicken ovalbumin (cOVA) and a cOVA-specific T-cell hybridoma, "lineage switch" cell lines were found to present antigen as effectively as macrophage-containing peritoneal exudates. Neither the original pre-B-cell precursors nor B-cell lymphomas derived from them present antigen. Thus, we have demonstrated that these "lineage switch" macrophages are capable of antigen presentation, a mature differentiated function. While gaining macrophage characteristics, these cells have also rearranged their kappa light-chain immunoglobulin locus, suggesting that macrophage differentiation and immunoglobulin rearrangement are not mutually exclusive processes. The existence of both lymphoid and myeloid characteristics in a cell fully capable of antigen presentation suggests greater plasticity in hematopoietic lineage commitment than conventionally thought to be the case.

Animals

Seasonal variation in cell cycle during early development of the mouse embryo.

Studies of the cell cycle of mouse embryos before implantation were conducted using Giemsa and DAPI stains. The time of embryo recovery did not affect the success rate of cultures during the winter, but embryos cultured during the summer showed the 'two-cell block' phenomenon at the early two-cell stage, 30-37 h after the injection of human chorionic gonadotrophin. There was no significant difference in the number of embryos collected per mouse between summer and winter, but cleavage from the two-cell to the four-cell stage occurred later in the summer than in the winter. Cell cycle of mouse embryos may therefore show seasonal variation.

Animals

Developmental expression of CD45 alternate exons in murine T cells. Evidence of additional alternate exon use.

The CD45 glycoprotein family exhibits cell line-age-associated structural heterogeneity arising in part from alternate 5' exon shuffling. Previous studies of exons involved in the final glycoprotein structure have provided evidence of alternate exon use for only three exons (Ex-4, 5 and 6). However, our prior data using reverse transcription-polymerase chain reaction (RT-PCR) suggested the presence of at least one additional CD45 alternate exon. By using RT-PCR, Southern blotting with exon-specific or exon splice junction-specific oligonucleotide probes and direct DNA sequencing of RT-PCR products, we demonstrated additional alternate use involving Ex-7. PCR analysis of stage I thymocytes (CD4-CD8-) revealed only faintly detectable bands for two isoforms: one lacking Ex-4, 5, 6 and 7 (a "minus-one" [Ex(-1)] isoform), and a smaller isoform preliminarily characterized as also lacking Ex-8. Stage II thymocytes (CD4+CD8+) prominently expressed both Ex(-1) and zero alternate exon (Ex(0] isoforms, with one exon (Ex(1] and two exon (Ex(2] isoforms also present. Among stage III thymocytes, both CD4+CD8- and CD4-CD8+ cells expressed only Ex(-1) and Ex(0) isoforms. CD45 alternate exon use in resting CD4+ and CD8+ lymph node T cells was divergent, with CD8+ cells additionally expressing an Ex(2) isoform. Among alloreactive T cell clones, band intensity for the Ex(1) isoform in CD4+ BC-3 cells was much less than for resting CD4+ T cells, while the CD8+ CTL clone 8.2.2 exhibited production of the higher alternate exon isoforms, Ex(2) and Ex(3). We conclude that at least four and possibly five alternate exons exist in the CD45 glycoprotein family, with a previously unrecognized isoform lacking Ex-4, 5, 6 and 7 prominently expressed in T cells. Shuffling of CD45 alternate exons appears to occur in an organized and predictable sequence during cellular maturation and activation.

Animals

Characterization of the CD45 molecule on murine intestinal intraepithelial lymphocytes.

The CD45 molecule was analyzed from murine intestinal intraepithelial lymphocytes (IEL). Immunofluorescent staining of CD8+ IEL revealed varying degrees of reactivity with mAb specific for CD45-restricted determinants, some which are typically expressed only by B cells. Immunoprecipitation of CD45 molecules from IEL yielded an array of proteins with apparent (m.w.) ranging from 180,000 to 260,000. The m.w. 260,000 form was restricted to IEL, was distinct from the B220 molecule, and was the only CD45 isoform that expressed the CD45-associated carbohydrate differentiation Ag CT1. Moreover, the CT1 determinant was present on cells of the Thy-1- but not the Thy-1+ IEL subset. Sequential immunoprecipitation studies indicated that expression of the m.w. 260,000 protein was not restricted to CT1+ cells. The protein composition of the m.w. 260,000 CD45 isoform was examined by using the polymerase chain reaction for analysis of CD45 variable exon usage. In contrast to B cells in which the major CD45 mRNA contained all three variable exons (exons 4, 5, and 6), IEL CD45 mRNA contained significant amounts of two-exon, single exon, and zero variable exon forms. Restriction enzyme analysis identified the single exon form as exon 5 and the two-exon form as a mixture of exons 4 and 5 and exons 5 and 6. Metabolic labeling of CD45 in pulse-chase experiments suggested that the generation of this high m.w. protein was caused by post-translational modifications, perhaps glycosylation. Overall, the results indicated that the high m.w. form of CD45 and the addition of the CT1 determinant were generated via IEL-specific post-translational modifications and not by novel alternate exon usage.

Animals