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Biomedical subjects

G Huang

Publications and source records attributed to G Huang.

At least 73 records · Page 4Linked to original sources

Genetic reconstitution of systemic lupus erythematosus immunopathology with polycongenic murine strains.

We previously produced three congenic strains carrying lupus susceptibility genes (Sle1-Sle3) from the lupus-prone NZM2410 mouse on the C57BL/6 background and characterized their component phenotypes. Sle1 mediates the loss of tolerance to nuclear antigens; Sle2 lowers the activation threshold of B cells; and Sle3 mediates a dysregulation of CD4(+) T cells. We have now created a collection of bi- and tricongenic strains with these intervals and assessed the autoimmune phenotypes they elicit in various combinations. Our results indicate that Sle1 is key for the development of fatal lupus. The combination of Sle1 with Sle2, Sle3, or the BXSB-derived autoimmune accelerating gene yaa results in the development of systemic autoimmunity with variably penetrant severe glomerulonephritis culminating in kidney failure. In contrast, two locus combinations of Sle2, Sle3, and yaa failed to mediate fatal disease. These results indicate that the loss of tolerance to chromatin mediated by Sle1 is essential for disease pathogenesis and identify the pathway occupied by Sle1 as a strategic target for therapeutic intervention in systemic lupus erythematosus. The coexpression of Sle1, Sle2, and Sle3 as a B6-triple congenic results in severe systemic autoimmunity and fully penetrant, fatal glomerulonephritis. These results demonstrate the fulfillment of the genetic equivalent of Koch's postulate, where susceptibility loci in a lupus-prone strain have been identified by a genome scan, isolated and functionally characterized by congenic dissection, and finally shown to mediate full disease expression when recombined in a normal genome.

Animals↗

[Bone mineral density characteristics at the femoral neck and Ward's triangle for Chinese women].

The incidence of hip fracture is not as high in Chinese women compared to women from Western countries, though they usually have low bone mineral density(BMD) and get osteopenia easily. In this study, reference data(white women) supplied by the manufacturer of Hologic was compared with data obtained from healthy women in Changsha, Hunan, P.R.C. One thousand four hundred and eighty-eight Chinese women aged 15 to 95 years were randomly recruited. Measurements of BMD were taken at the hip by the dual energy x-ray absorptiometry(QDR 4,500A, Hologic Inc., USA). The BMD was somewhat lower than reference curves at all ages and all sites. But at the femoral neck and Ward's triangle, Chinese women reached their peak BMD 5 to 10 years later than the reference group, and had a lower BMD rate of decrease for about 35 years after peak BMD was reached. Whether the differences(i.e., longer time to peak BMD and a lower BMD decrease rate at the neck and Ward's triangle after the peak BMD reached) will result in a protection from hip fractures for Chinese women needs to be studied in the future.

Absorptiometry, Photon↗

Lymphotoxin-alpha-dependent spleen microenvironment supports the generation of memory B cells and is required for their subsequent antigen-induced activation.

Lymphotoxin alpha-deficient (LTalpha-/-) mice show dramatically reduced IgG responses after either primary or secondary immunizations with sheep red blood cells (SRBC). When splenocytes from SRBC-primed wild-type donor mice were infused into irradiated naive wild-type recipient mice, they generated a robust memory IgG response, but not when infused into LTalpha-/- recipients, indicating that the microenvironment that develops in LTalpha-/- mice is incompetent to support the activation of this memory response. When irradiated wild-type mice were reconstituted with splenocytes from primed LTalpha-/- donors and then challenged with the same immunizing Ag, no memory response was observed, indicating further that memory cells could not be generated in the LTalpha-/- environment. To address which lymphocyte subsets were impaired in the LTalpha-/- mice, we performed reconstitution experiments using a hapten/carrier system and T cells and B cells from different primed donors. There was no detectable defect in either the generation or expression of memory T cells from LTalpha-/- donors. In contrast, B cells were not primed for memory in the microenvironment of LTalpha-/- mice. Additionally, primed wild-type memory B cells could not express a memory IgG response in the LTalpha-/- microenvironment. Thus, splenic white pulp structure, which depends on the expression of LTalpha for its development and maintenance, is needed to support the generation of memory B cells and to permit existing memory B cells to express an isotype switched memory Ig response following antigenic challenge.

Animals↗

Antigen persistence is required for somatic mutation and affinity maturation of immunoglobulin.

Whether germinal centers (GC) with follicular dendritic cell (FDC) clusters are the essential sites for affinity maturation of immunoglobulin is still controversial. To re-evaluate the role of GC / FDC in affinity maturation and somatic mutation in a defined antigen system, lymphotoxin-alpha(- / -) and TNF receptor I(- / -) mice, lacking GC / FDC, were immunized with (4-hydroxy-3-nitrophenyl) acetyl-sheep RBC (NP-SRBC). In contrast to soluble hapten-carrier systems, NP-SRBC allows us to compare affinity maturation in the presence or absence of adjuvant. These mice showed a dramatically impaired ability to generate high-affinity IgG to NP, but retained the ability to produce low-affinity anti-NP IgG when NP-SRBC was used in the absence of adjuvant. In contrast to wild-type mice, somatic mutation of the expressed IgG heavy chain gene was rarely detected in these GC / FDC-deficient mice. This suggests that GC / FDC are essential for affinity maturation. Trapping antigen-specific B cells inside the T cell zone of TNFRI(- / -) mice may prolong the interaction between T and B cells, which allows class switching but no further affinity maturation of IgG. Interestingly, GC / FDC-deficient mice could be induced to generate high-affinity, somatically mutated IgG antibodies by immunization with the same amount of NP-SRBC antigen emulsified in incomplete Freund's adjuvant or repeated immunization with the antigen alone. Thus, these data support a model in which prolonged availability of antigen is required for somatic mutation and affinity maturation, and FDC or adjuvants facilitate such processes by slowly releasing antigens.

Animals↗

Rapid amplification and cloning of Tn5 flanking fragments by inverse PCR.

A simple approach is described to efficiently amplify DNA sequences flanking transposon Tn5 insertions. The method involves: (i) digestion with a restriction enzyme that cuts within Tn5; (ii) self-ligation under conditions favouring the production of monomeric circles; (iii) four parallel PCR reactions using primers designed to amplify left or right flanking sequences, and to distinguish target amplicons from non-specific products. This reveals the number of Tn5 insertions and the size of flanking genomic restriction fragments, without Southern blot analysis. The amplified product contains restriction sites that facilitate cohesive-end cloning. This rapid method is demonstrated using Tn5 and Tn5-Mob tagged DNA sequences involved in albicidin biosynthesis in Xanthomonas albilineans. It is generally applicable for efficient recovery of DNA sequences flanking transposon Tn5 derivatives in insertional mutagenesis studies.

Anti-Bacterial Agents↗

Dynamics of coupled gap solitons in diatomic lattices with cubic and quartic nonlinearities

The dynamics of coupled gap solitons in diatomic lattices with cubic and quartic nonlinearities is considered analytically based on an extended quasidiscreteness approach. For various mass differences (and thus different gap widths of the phonon spectrum), the coupled gap solitons are shown to display very rich dynamical behavior and their properties are strongly dependent on the force-constant ratio K(2)(3)/(K2K4), where K(j)(j=1,2,3) are the force constants for the quadratic, cubic, and quartic parts of the intersite interaction potential, respectively. Several previous theoretical approaches for studying gap soliton dynamics in diatomic lattices are recovered in our scheme, and the relations between these methods are elucidated in a systematic way.

Journal Article↗

Study on the physiology and degradation of dye with immobilized algae.

Immobilization of chlorella (pyrenoidosa) with calcium alginate was carried out. Both algal growth and physiological activity increased after immobilization. Algal size and initial density have little influence on cell growth and physiological activity. Algal cell division inside the support was restricted without bubbling air containing 2% CO2. Individual algal cell increased and algal distribution inside the support was not homogeneous, indicating that within the support the resistance of mass transfer of CO2 was the limiting factor for the growth and cell division of immobilized algae. After bubbling 2% CO2, algal growth, the cell division considerably increased and individual cell size restored normally. Study of the degradation of dye (direct brown NM) by immobilized algae was better than that of free algae. Bubbling air containing 2% CO2 in the culture solution was more favorable for increasing decolorization rate. Preliminary study of co-immobilization of algae plus bacterium illustrated that the addition of bacterium increased the anabolic activity of algae, thus increased the decolorization capacity if immobilized algae for dye.

Alginates↗

Mutagenicity of methyl tertiary butyl ether.

Methyl tertiary butyl ether (MTBE), the main component of oxygenated gasoline, is added to gasoline as an octane enhancer to reduce automotive emissions. We evaluated the mutagenicity of domestic MTBE using the Ames test, unscheduled DNA synthesis (UDS) assay, and NIH/3T3 cell micronucleus test. MTBE did not show any mutagenic potential in the Ames assay (TA98, TA100 strains) with or without rat liver-derived metabolic activation system (S-9). In rat primary hepatocyte UDS assay, a dose-response relationship was observed, which meant that MTBE might damage normal DNA and induce unscheduled DNA synthesis. MTBE did not show positive results in the NIH/3T3 cell micronucleus test. It could be concluded that MTBE has some degree of mutagenicity.

3T3 Cells↗

Correlation between bone mineral density and sexual hormones in healthy Chinese women.

Osteoporosis is a common disease in women, but not in men. It is usually induced by the deficiency of estrogen after menopause. The lumbar spine is most often affected. We examined 74 healthy Chinese women in whom we measured serum estradiol (E2), estriol (E3), and total testosterone (TTT) by radioimmunoassay (RIA). The bone mineral density (BMD) of the total lumbar spine in the anterior (TLS-A) and lateral (TLS-L) position, the region of interest (ROI) of lateral spine (M-IALS), the forearm, and the total hip (TH) were scanned by a dual-energy X-ray absorptiometer. We found that (1) E2 and all BMD determinations declined significantly after menopause (p < 0.05 for all), except the BMD of TH; (2) the BMD of TLS-L, TH, and forearm correlated significantly with E2 (r = 0.2986, p < 0.05), E3 (r = 0.3380, p < 0.05), and TTT (r = 0.2867, p < 0.05), respectively, by partial correlation analysis. In conclusion, BMD at different sites of the skeleton correlated with the level of different sex hormones. It seems that BMD at different sites of the body is controlled by different sex hormones. Whether this phenomenon should be considered in the choice of hormone replacement therapy, or in improving the BMD diagnostic standard, needs further study.

Adult↗

[Effects of heparin on the growth, extracellular matrix and matrix metalloproteinase gene expression in rat hepatic stellate cells].

OBJECTIVE: To study the effects of heparin on the growth, extracellular matrix and matrix metalloproteinase (MMP) gene expression in rat hepatic stellate cells (HSC). METHODS: Activated HSC was treated by heparin or fetal calf serum without heparin. The cell growth was evaluated by actual cell count and BrdU-labelled immunocytochemical stain. The gene expressions of type I and IV procollagen, fibronectin, MMP-2 and membrane type matrix metalloproteinase (MT-MMP) were investigated by immunocytochemical stain and digoxigenin-labeled in situ hybridization technique, respectively. In addition, the gelatinase activity of MMP-2 was examined by zymography. RESULTS: Heparin could obviously reduce HSC growth, inhibit the synthesis of type I procollagen and fibronectin protein, and the gene expressions of type I procollagen, fibronectin and MT-MMP. The expressions of type IV procollagen, MMP-2 and MMP-2 activity were not affected by heparin. CONCLUSION: The results demonstrate that heparin can inhibit HSC proliferation, down-regulate interstitial collagen synthesis and inhibit MT-MMP gene expression.

Animals↗

Change of apoptotic status in the human colorectal adenoma-carcinoma sequences and its correlation with carcinogenesis and prognosis.

OBJECTIVE: To assess apoptotic status during the development of colorectal cancer and its prognostic value. METHODS: The apoptotic frequency of 168 fresh adenocarcinoma specimens and primary cultured cells at 2, 12, 24 and 48 hours (9 normal mucosa, 4 adenomas and 9 adenocarcinomas) were measured by flow cytometry (FCM). Apoptotic indices (AI) in situ for 25 adenomas and 77 adenocarcinomas were visualized by TdT-mediated dUTP nick end labeling (TUNEL), Ki-s5 labeling indices (KI), bcl-2, bax, waf1 and p53 were immunostained with ABC method. RESULTS: The culture-related apoptosis at 24-48 hours in vitro was obviously decreased in cultured tumor cells when compared with mucosa cells. Spontaneous apoptosis in situ occurred more frequently in tumor with aneuploid type at late stage. There was positive relationship between apoptosis and proliferative activity, determined by both TUNEL and FCM methods. The well-differentiated or early stage lesions with intensive bcl-2/bax expression were significantly more likely to have low AI. p53 accumulation and waf1 depression were mainly related to KI, whereas bax and waf1 overexpression led to a comparatively higher AI/KI ratio. bcl-2 and KI were found to be independent risk factors. CONCLUSIONS: The data suggest that the depressed susceptibility to inductive apoptosis may contribute to the initial phase of tumorigenesis, and spontaneous apoptosis in vivo may serve as a marker of tumor progression. The bcl-2 and KI may be valuable in predicting prognosis in colorectal cancer.

Adenocarcinoma↗

[A new look at the mechanism of cholera endemicity caused by Vibrio cholerae biotype eltor].

OBJECTIVE: Cholera caused by Vibrio cholerae biotype eltor (EVC) is an endemic disease, subsiding in winter and reappearing in spring and summer. Investigating the state of EVC during the intermittent time is of crucial importance in controlling this disease. METHODS: Different factors mimicking the internal and external environmental conditions of the host, including human and fish bile, bacterial phages and antibiotics were used experimentally to induce variation in EVC. EVC variants were isolated from the stool of diarrhea patients and river water in old endemic areas during the winter. The variants obtained were tested with gene probe hybridization, DNA restriction enzyme mapping, immunoenzyme staining and animal passaging. RESULTS: Due to the loss of cell walls, 3 kinds of EVC variants were obtained during induction: the L-form variant, with a complete loss of cell walls; the nonagglutinating variants, with the loss of surface O-antigen; the phage-resistant variants, with the loss of phage receptors. Similar variants were found in field isolation. This variation was proved to be phenotypic, with no change in genetic material: it was reversible and appeared in a seasonal pattern, which coincided with the endemicity of this disease. Passage in animal enhanced this reversion. In compensation for the loss of cell walls, cell membranes were greatly thickened, increasing the ability of the variants to survive during the unfavorable winter conditions. CONCLUSIONS: EVC varied in a seasonal pattern, coincident with the endemicity of this disease. The compensatory thickening of the cell membranes protects the EVC variants to survive the winter.

Cholera↗

[Apoptosis and apoptosis-related gene expression in nasopharyngeal carcinoma].

OBJECTIVE: To study apoptosis and expression of apoptosis-related genes in nasopharyngeal carcinoma(NPC). METHODS: Paraffin-embedded tissue blocks from 73 cases of NPC and 20 cases of chronic nasopharyngitis were used in this study. Using terminal deoxynucleotidyl transferase mediated dUTP biotin nick end labeling (Tunel) and immunohisytochemistry S-P method, the apoptotic rate (AR) and expression of p16 and bcl-2 protein were examined. RESULTS: Few apoptotic cells were found in NPC, the AR significantly lower than that of chronic nasopharyngitis (P < 0.01). The frequency of expression of p16 and bcl-2 in NPC was 28.8% (21/73) and 81.2% (59/73), respectively, while that in chronic nasopharyngitis was 90% (18/20) and 15% (3/20), respectively. In NPC, expression of p16 was positively correlated, while bcl-2 negatively correlated with the AR (P < 0.01). According to 3-year follow up, the survival rate was higher in NPC patients with AR > 2.0 and negative bcl-2 expression, whereas that was higher in patients with positive expression of p16. CONCLUSION: Apoptosis is inhibited in NPC which may be related to p16 and bcl-2 gene dysregulation. Apoptosis correlates with prognosis in NPC patients.

Adolescent↗

[Study on role of metallothionein in anticancer effect of copper green on treatment of experimental hepatocarcinoma in mice].

OBJECTIVE: To study the role of metallothionein (MT) in the anticancer effect of copper green on experimental hepatoma (H22) in mice. METHODS: Atomic absorbency spectrometry (AAS), silver saturation method and histochemistry method were used to study the content and distribution of copper and MT in liver and tumor tissues. RESULTS: (1) Both copper and MT contents in liver tissue of the copper treated group were significantly higher than that of the control group (P < 0.001 in both). (2) Copper content in tumor tissue of the treated group was higher whereas MT content was markedly lower than that of the control group (P < 0.001). (3) Histochemical examination showed that in the copper treated group, both copper and MT existed simultaneously in plasma and nuclei of liver cells, while in the tumor tissue, rich in copper but few or negative in MT existed. CONCLUSION: (1) In liver tissue, large amount of MT is coupled with copper which is helpful to protect liver from the damage of copper. (2) The decrease of MT in tissue of tumor could be beneficial for copper to exert full effect in killing tumor cell.

Animals↗

[Relationship between serum insulin, C-peptide in hypertension and syndrome differentiation-typing in TCM].

OBJECTIVE: To study the relationship between insulin-resistance (IR), hyperinsulinemia and TCM Syndrome Differentiation-typing. METHODS: The serum insulin, C-peptide level of the four Syndrome-types of hypertension (30 cases each type) and the control group (30 cases) were determined. RESULTS: The serum insulin level in hypertension patients were significantly higher than that of control group, and there were obvious difference among the four types of Syndrome. The following order was: The abundant phlegm-dampness type > exuberant Liver-Fire type > both Yin-Yang deficiency type > Yin deficiency and Yang-Excess type > control type. CONCLUSIONS: The Excess Syndrome was severe and deficiency Syndrome was mild in hyperinsulinemia. The pattern of change was in accordance with etiology and pathogenesis of TCM. It has the guiding significance to the clinical practice and research of TCM and integrated TCM-WM.

Aged↗

[Control genes of chondrocyte apoptosis in osteoarthritic articular cartilage].

OBJECTIVE: To investigate the expression of bax and bcl-2 in normal human articular chondrocytes and in osteoarthritic articular cartilage. METHODS: The samples of articular cartilage were obtained from 9 patients and 6 normal subjects. Bax and bcl-2 mRNA were detected by reverse transcriptase/polymerase chain reaction (RT-PCR) and their expression proteins were analyzed immunohistochemically. TUNEL technique was used to study apoptosis in situ. RESULTS: Bax and bcl-2 mRNA was detectable in chondrocytes of both osteoarthritic and normal cartilage. Bax mRNA of chondrocytes from patients with osteoarthritis (OA) was overexpressed compared with the normal controls (P < 0.01), and OA cartilage chondrocyte also expressed more bcl-2 mRNA than the controls (P < 0.05). There was no statistically significant difference of bax/bcl-2 between the two groups. Immunohistochemical staining demonstrated the same level of bax and bcl-2 proteins as their mRNA. A greater proportion of apoptotic chondrocytes were found in the OA cartilage than that in normal controls (4% - 14% versus 0 - 2%). CONCLUSIONS: Our results suggested that chondrocyte apoptosis was co-regulated by both bax and bcl-2. The ratio of bax to bcl-2 may contribute not only to the lower percentage of apoptotic chondrocytes, but also to the chronic pathologic process in OA.

Adult↗

[The investigation on the safety and immunogenicity of inactived hepatitis A vaccine AVAXIM].

OBJECTIVES: To investigate the safety and immunogenicity of AVAXIM in children and adults. METHODS: One hundred and twenty-one children aged 6 - 12 years and 108 adults with negative HAV antibody, were inoculated by 0, 6 month procedure with inactivated HAV vaccine produced by Pasteur Merieux Connaught (AVAXIM 160 antigen unit). RESULTS: The positive rates of anti-HAV IgG among children group and adult group were 98.15% and 94.17% respectively after one month of first inoculation, and became 100% and 97.22% after one month of second inoculation. The antibody positive rate was higher in children than in adults, but did not show statistical significance (P < 0.05). The side effects of AVAXIM inoculation were mild, mainly local pain with occurrences 1.7% - 2.8% in both groups. No serious systemic and local reactions were noticed. CONCLUSION: AVAXIM had good safety and immunogenicity, seen not only in adults, but also in children.

Adult↗

[Relationship between CYP1A1, GSTM1 genetic polymorphisms and susceptibility to esophageal squamous cell carcinoma].

OBJECTIVE: To investigate the association between susceptibility of esophageal squamous cell carcinoma and the genetic polymorphisms of CYP1A1 and GSTM1. METHODS: Subjects were comprised of 107 esophageal cancer patients and 111 healthy controls. Genotyping of both CYP1A1 and GSTM1 were performed in cancer tissues of all 107 patients and peripheral blood leukocytes taken from the controls by polymerase chain reaction. RESULTS: There were no significant differences in the frequency distribution of CYP1A1 polymorphisms between esophageal cancer patients and healthy controls although the frequency of CYP1A1 with at least one allele of Val showed slightly higher in individuals with esophageal cancer. However, significant difference was observed in the frequency of GSTM1-nulled individuals with esophageal cancer comparing with the controls (P < 0.05). When subjects were categorized by both CYP1A1 genotype and GSTM1 genotype, GSTM1 (-) became markedly expressed in patients with CYP1A1 (I/I) than in the corresponding controls (67% versus 40%, P < 0.01). The frequency of CYP1A1 genotype with at least one allele of Val (I/V and V/V) was also statistically higher in patients with GSTM1 (+), comparing to the corresponding controls (64% versus 41%, P < 0.05). CONCLUSIONS: It was suggested that: genetic polymorphisms of CYP1A1 and GSTM1 were susceptible to esophageal cancer; individuals who are GSTM1-null have an increased risk of developing esophageal cancer; individuals with combined CYP1A1 (I/I) and GSTM1 (-) or with combined CYP1A1 (I/V, V/V) and GSTM1 (+) were more susceptible, when comparing to those with combined CYP1A1 (I/I) and GSTM1 (+).

Adult↗