An AvaII PCR/RFLP in an exon of the canine gene for the beta subunit of the amiloride-sensitive sodium channel (SCNN1B).
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Animals↗
Biomedical subjects
T Zhou
Publications and source records attributed to T Zhou.
A NlaIII PCR/RFLP in an intron of the retinitis pigmentosa GTPase regulator gene (RPGR) on the canine X chromosome.
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Alleles↗
Interleukin 9: a candidate gene for asthma.
Asthma is a complex heritable inflammatory disorder of the airways associated with clinical signs of atopy and bronchial hyperresponsiveness. Recent studies localized a major gene for asthma to chromosome 5q31-q33 in humans. Thus, this segment of the genome represents a candidate region for genes that determine susceptibility to bronchial hyperresponsiveness and atopy in animal models. Homologs of candidate genes on human chromosome 5q31-q33 are found in four regions in the mouse genome, two on chromosome 18, and one each on chromosomes 11 and 13. We assessed bronchial responsiveness as a quantitative trait in mice and found it linked to chromosome 13. Interleukin 9 (IL-9) is located in the linked region and was analyzed as a gene candidate. The expression of IL-9 was markedly reduced in bronchial hyporesponsive mice, and the level of expression was determined by sequences within the qualitative trait locus (QTL). These data suggest a role for IL-9 in the complex pathogenesis of bronchial hyperresponsiveness as a risk factor for asthma.
Animals↗
Tryptophan fluorescence reports nucleotide-induced conformational changes in a domain of the ArsA ATPase.
The ars operon of plasmid R773 encodes an ATP-dependent extrusion pump for arsenite and antimonite in Escherichia coli. The ArsA ATPase is the catalytic subunit of the pump protein, with two nucleotide binding consensus sequences, one in the NH2-terminal half and one in the COOH-terminal half of the protein. A 12-residue consensus sequence (DTAPTGHTIRLL) has been identified in ArsA homologs from eubacteria, archebacteria, fungi, plants, and animals. ArsA enzymes were constructed containing single tryptophan residues at either end of this conserved sequence. The emission spectrum of the fluorescence of the tryptophan on the COOH-terminal end (Trp-159) indicated a relatively hydrophilic environment for this residue. An increase in intrinsic tryptophan fluorescence and a blue shift of the maximum emission wavelength were observed upon addition of MgATP, indicating movement of Trp-159 into a relatively less polar environment. No fluorescence response was observed with MgADP, with nonhydrolyzable ATP analogs, or with MgATP by catalytically inactive enyzmes. This suggests that the location Trp-159 is shifted only during hydrolysis of ATP. In contrast, the emission spectrum of Trp-141, located on the NH2-terminal side of the consensus sequence, indicated a relatively nonpolar environment. The maximum emission wavelength red shifted upon addition of MgADP. MgATP slowly produced a response that correlated with product formation, suggesting that the environment of Trp-141 is sensitive only to MgADP binding. Thus, during ATP hydrolysis the COOH-terminal end of the conserved domain moves into a less polar environment, whereas the NH2-terminal end moves into a more hydrophilic environment as product is formed. A hypothesis is presented in which the conserved domain of ArsA and homologs is an energy transduction domain involved in transmission of the energy of ATP hydrolysis to biological functions such as transport.
Adenosine Diphosphate↗
Increased lymphocyte apoptosis in Fas ligand transgenic mice.
Fas ligand (fasL) transgenic (Tg) mice were produced by introducing a murine fasL cDNA under the control of a TCR beta-chain enhancer minigene. Higher levels of fasL expression with increased biologic activity were observed in the Tg mice compared with non-Tg mice. Numbers of CD4+ CD8+ T cells in the thymus and T cells in the lymph node and spleen were lower in the fasL Tg mice compared with the non-Tg mice. This is consistent with a reduction in the size of the T cell areas in fasL Tg mice compared with non-Tg mice. Conversely, in fasL Tg mice, there was an increase in the number and size of apoptotic foci associated with phagocytic cells, as determined by in vivo TUNEL (TdT-mediated dUTP nick-end labeling) staining. Stimulation of non-Tg mice in vivo with anti-CD3 Ab for 3 days resulted in greatly increased apoptosis of CD4+ CD8+ thymocytes and lymph node T cells. Surviving thymocytes and T cells of lymph node and spleen expressed Fas at low levels. After similar stimulation of fasL Tg mice, however, a discreet population of surviving cells expressed high levels of Fas, indicating that a novel population of Fas apoptosis-resistant cells develops in these mice. These results indicate that high levels of fasL can result in both increased Fas-mediated apoptosis and the development of T cells that express high levels of Fas, but are resistant to Fas-mediated apoptosis.
Animals↗
Glutathione S-transferase expression in hepatitis B virus-associated human hepatocellular carcinogenesis.
Hepatitis B virus (HBV) and aflatoxin B1 represent the main risk factors for the development of hepatocellular carcinoma (HCC) in areas endemic for liver cancer. The glutathione S-transferases (GSTs) are a family of Phase II detoxification enzymes that catalyze the conjugation of a wide variety of endogenous and exogenous toxins, including aflatoxin B1, with glutathione. This study characterizes the GST isoenzyme composition (alpha, mu, and pi) of both HBV-infected normal hepatic tissues and HCCs. Analysis of matched pairs of hepatic tissue (normal and tumor) from 32 HCC patients indicated that total GST activity was significantly higher in normal tissues than in tumor tissues, although the percentage of samples expressing GST alpha and pi was equivalent. GST mu was detected by Western blot in the normal tissue from 87.5% of the subjects possessing the GST M1 gene but only 28.6% of the corresponding tumor tissues. The GST activity of normal tissue from GST M1 null patients was significantly decreased as compared to that of subjects possessing the GST M1 gene (264.6 and 422.2 nmol/min/mg, respectively; P = 0.005). GST pi appeared to be overexpressed in the normal tissue of GST M1 null patients, a potential compensatory effect. Patients positive for HBV DNA had significantly lower GST activity than those who were HBV negative (302.1 versus 450.0 nmol/min/mg, respectively; P = 0.02). These results suggest that cellular protection within the human liver is compromised by HBV infection and further decreased during hepatocellular tumorigenesis.
Adult↗
Increased acute-phase response and renal amyloidosis in aged CD2-fas-transgenic mice.
We previously demonstrated that increased Fas expression in T cells of aged CD2-fas transgenic (Fas-Tg) CD-1 mice results in an increased immune response and T cell apoptosis. Surprisingly, despite prevention of T cell immune senescence, the average life span of Fas-Tg mice is comparable with that of nontransgenic (non-Tg) mice. Histopathologic evaluation of tissue sections showed that nearly 50% of the aged (>18-mo-old) Fas-Tg mice developed renal amyloid A amyloidosis, whereas no amyloid deposition was observed in aged non-Tg mice. The amyloid A deposition was observed primarily in glomeruli by using immunohistochemical stains and electron microscopy. The full-length amino acid coding sequence of serum amyloid A2 cDNA in CD-1 mice was identical to that of amyloid A amyloidosis-susceptible BALB/c mice. Although there was no significant difference in steady-state serum amyloid A level in the serum of aged non-Tg and Fas-Tg mice, challenging mice with staphylococcal enterotoxin B resulted in significantly higher serum levels of serum amyloid A on day 2 and IL-6 on days 1 and 2 and a higher magnitude of weight loss on day 7 in aged Fas-Tg mice compared with young mice. These parameters, at the indicated time points, were equivalent between young and aged non-Tg mice. Taken together, our data suggest that prevention of T cell senescence in Fas-Tg mice may be a factor in induction of an excessive acute-phase response triggered by T cell activation. The Fas-Tg mice are a novel model for understanding the immunologic mechanisms leading to secondary amyloidosis.
Acute-Phase Reaction↗
Kinetics of Fas-induced apoptosis in thymic organ culture.
Although most thymocytes express high levels of Fas antigen (CD95), the role of Fas in apoptosis signaling during thymocyte maturation has not been defined. Fas apoptosis occurs primarily in the CD4+CD8+ subpopulations of thymocytes. Fas expression and apoptosis function were investigated in the CD4-8-, CD4+8+, and CD4+ and CD8 single positive thymocyte subpopulations by in vivo injection of anti-Fas and in vitro incubation of Fas with thymic organ cultures. Fas was first expressed on CD4-8- thymocytes coincident with expression of IL-2R and CD44. In Fas mutant lpr/lpr mice, defective Fas expression correlated with overproduction of late-stage CD4-8(-)-thymocytes. Fas was highly expressed on CD3dull and CD3bright thymocytes. CD4+8+CD3dull thymocytes were sensitive to Fas apoptosis, whereas more mature CD4+8+CD3bright thymocytes were resistant to Fas apoptosis. Anti-Fas incubation with established thymic organ culture for 24 hr resulted in apoptosis of approximately 25% of thymocytes. Continued incubation of thymic organ culture with anti-Fas resulted in an apoptosis rate of 25% of CD4+CD8+ thymocytes per day for the first 3 days of culture. Continued culture for further time points up to 6 days did not result in further apoptosis of the CD4+CD8+ thymocytes. These results suggest that CD4-CD8-CD44+ IL-2R+ thymocytes express Fas and there is overpopulation of the subsequent developmental stage of thymocytes in Fas mutant lpr mice. Also, early-stage CD4+8+ thymocytes are susceptible to Fas apoptosis, whereas Fas apoptosis resistance is required after 3 days of thymic organ culture. We conclude that these two populations of thymocytes are susceptible to Fas ligand-mediated apoptosis during T cell development in the thymus.
Animals↗
Cell death and longevity: implications of Fas-mediated apoptosis in T-cell senescence.
Two prominent features of immune senescence are altered T-cell phenotype and reduced T-cell response. We have previously shown that T-cell senescence is greatly reduced in CD2-fas transgenic mice, in which the Fas apoptosis molecule is constantly expressed on T cells. Using a different experimental approach, the relationship between T-cell senescence and apoptosis was analyzed on human peripheral blood mononuclear cells. The results indicate that there was increased apoptosis of CD45RO- (CD45RA+) T cells upon activation. We propose that this could account for the increase in CD45RO+ "memory" T cells with aging in humans. T-cell responsiveness remained high in CD2-fas transgenic aged mice, but there was no increase in overall life span of these mice. Increased T-cell responsiveness was associated with an increased acute-phase response and serum amyloid A deposition in the glomerulus of aged CD2-fas transgenic mice. Therefore, restoration of the T-cell immune function using a CD2-fas transgene produced undesirable side-effects to aged transgenic mice. In addition to its role in activation-induced cell death, Fas-mediated apoptosis may be important in deleting T cells in response to DNA damage. It may also inhibit cell-cycle progression by cleaving various kinases and DNA repair enzymes. We observed that cell lines derived from human premature aging diseases have a higher sensitivity to Fas-mediated apoptosis. The implications of these observations are discussed.
Acute-Phase Reaction↗
[Clinical study on treatment of arteriosclerosis obliterans using huangqi tongmai decoction].
OBJECTIVE: To test and verify the effects of Huangqi Tongmai Decoction (HQTMI) regulating blood lipid in treating arteriosclerosis obliterans (ASO). METHODS: Thirty-two cases of ASO was treated with HQTMD for two months. The drug was in water decoction, oral taken. RESULTS: Compared with the blood lipid level before treatment, the high density lipoprotein of cholesterol (HDL-C) was increased, the low density lipoprotein of cholesterol (LDL-C), atherogenic index (AI) was decreased (P < 0.01). The serum total cholesterol (TC), triglyceride (TG), very low density lipoprotein of cholesterol (VLDL), apolipoprotein A1 (apoA1), apolipoprotein B100 (apoB100) were all changed (P < 0.05). apoA1/apoB100 ratio increased. CONCLUSION: HQTMD could regulate blood lipid. This method was effective in treating ASO.
Adult↗
[Study on the inclusion compound of phyllostachysin A and DMF].
The crystal structure of inclusion compound phyllostachysin A[1] and DMF, C20H26O6.C3H7ON, was determined by X-ray diffraction. A colorless block crystal with dimensions of 0.6 x 0.6 x 0.8 mm was used for analysis. It shows orthorhombic, and it's space group is P2(1)2(1)2(1) with a = 10.895(3), b = 13.237(2), c = 15.373(3) A, V = 2217.0(3) A3 Z = 4, Dc = 1.302 g cm-3. Direct method was applyed to determine the structure, and the parameters were refined by least square method. The final Rf factor is 0.060 and Rw = 0.083. The result shows that the crystal is formed by Phyllostachysin A and DMF by inclusion interaction.
Antineoplastic Agents, Phytogenic↗
[Study on the degradation kinetics of spiramycin in acid and alkaline solutions].
Physical and chemical characteristics of spiramycin (SPM) were reviewed in this paper. The degradation rule and kinetics of SPM in acid and alkaline solutions were studied, and the kinetic parameters were calculated. The experimental results showed that the stable range of SPM in water is at pH 4.0~10.0 Degradation occurred seriously at pH<4.0 and pH> 10.0, especially at pH< 2.8 and pH> 12.8. For this reason, the yield of SPM is greatly affected. The solubility in water was also studied by using reference data. The thermodynamical parameters were calculated. The results showed that the solution of SPM in water is exothermic. The solubility decreases as temperature rises.
Acids↗
[Cloning of BRCA1 cDNA and detection of BRCA1 mRNA expression in breast cancer cells].
The fragment of BRCA1 cDNA obtained by reverse transcription and polymerase chain reaction(RT-PCR) was inserted into plasmid pUC118 and demonstrated by DNA sequencing. Nucleotide sequence analysis demonstrated that the cloned cDNA for BRCA1 includes zinc finger domain. Two differences in nucleotides were found as compared with the sequence published. One occurs at nucleotide number 409 where Creplaced by A (Asp-->Glu). Another difference occurs at nucleotide number 879 where A replaced by T (samesense mutation). In order to further study the relationship-between BRCA1 function and breast cancer, the probe was prepared from the recombinant plasmid and then hybridized to total RNAs from 6 cases of breast cancer. Compared with normal cells, the expression level of BRCA1 mRNA was normal in 4, decreased markedly in 1, and in one patient there was no any expression of BRCA1 mRNA at all. The results suggested that the expression of BRCA1 mRNA was relatively low in some breast cancer cells.
Amino Acid Sequence↗
Isoniazid-induced hepatic necrosis and steatosis in rabbits: absence of effect of gender.
Isoniazid, a highly effective drug for the chemoprophylaxis and treatment of tuberculosis, is associated with severe hepatotoxicity in 1-2% of individuals. In a rabbit model of isoniazid-induced hepatotoxicity, we have measured hepatic necrosis (quantitated by elevation of plasma argininosuccinic acid lyase (ASAL) activity), hepatic steatosis (quantitated by elevation of hepatic triglyceride content), and elevation in plasma triglyceride concentration in 15 rabbits. Eight of 15 rabbits were male, and 14 of 15 were rapid acetylators of sulfamethazine. Administration of isoniazid to rabbits resulted in a 27-fold increase in plasma ASAL activities, a 7.5-fold increase in hepatic triglyceride content, and a 13-fold increase in plasma triglyceride levels. This study demonstrated no effect of gender on these three pathological changes that occur in this model of isoniazid-induced hepatotoxicity in rabbits.
Animals↗
Significance of P-selectin expression in human glomerulonephritis.
OBJECTIVE: To examine the relationship between P-selectin expression and human glomerulonephritis. METHODS: P-selectin expression was investigated in renal biopsies of glomerulonephritis patients (n = 133) by immunohistochemical and in situ hybridization analyses. They were divided into three groups based on the degrees of cells proliferation or sclerosis. Group I: histological lesions in glomeruli are mild (n = 23); Group II: glomerular cells proliferation is prominent (n = 91); Group III: glomerular sclerosis is severe (n = 19). The Kruskal-Wallis test, Chisquare test and Spearman's correlation were used in our study. RESULTS: In normal controls, renal P-selectin expression was negative (n = 10). In glomerulonephritis, the up-regulated P-selectin expression on tubular epithelium was significantly higher than that on glomeruli and interstitium (P < 0.01). P-selectin was expressed predominantly on platelets in glomeruli, and glomerular P-selectin expression was more significantly up-regulated in Group II than in Group I or Group III (P < 0.05; and P < 0.01, respectively). There were strong correlations between the degree of tubulointerstitial lesions and the expression of P-selectin on tubular epithelium or within interstitium (rs = 0.395 and rs = 0.337, P < 0.01). Furthermore, P-selectin messenger RNA (mRNA) signals were also detected in the cytoplasm of glomerulus, tubular epithelial cells, interstitium and vascular endothelium. CONCLUSIONS: P-selectin might mediate intraglomerular platelets aggregation, activation and leukocyte accumulation in the early stages of human proliferative glomerulonephritis. The up-regulation of P-selectin in interstitium was associated with interstitial fibrosis and tubular atrophy and may contribute to the progression of glomerulonephritis.
Adult↗
[Experimental study of the mechanism on blood supply to delayed separated skin flap by ultrasonic Doppler].
In order to investigate the mechanism of blood supply to the delayed separated skin flap and the time and criteria for its transfer, 5 small-sized Banna pigs were selected to produce 14 skin flaps. In the experimental group the skin flap on one side was made from the middle of the back having an extra-thin steel sheet intervened between the flap and the soft tissue of the back whereas the flap on the opposite side without a steel sheet intervened was served as the self-control. The skin flaps were examined 3,7,10 and 20 days after the operation and 3,7 and 10 days after transfer, respectively, by (1) gross observation; (2) ultrasonic Doppler; (3) superficial skin temperature measurement and; (4) histomorphological examination. In the experimental group the survival rate of the flap was 100 percent whereas in the control group all of the flaps had necrosis from 30 to 50 percent after the flap being transfered. In the experimental group, the echo sound from the arterial blood flow from ultrasonic Doppler was heard at the pedicle 7 days after the operation, and as time elapsed, the echo sound spread distally, whereas in the controls no echo sound could be heard over the skin flap. There was significant difference statistically between the experimental and control groups in the temperature of the flaps while the flaps were being transferred (P < 0.01). The external diameters of the blood vessels in the central area of the skin flap were larger in the experimental group, 0.8 to 1.2 mm in comparison to 0.4 mm.
Animals↗
Inhibition of superantigen-induced proinflammatory cytokine production and inflammatory arthritis in MRL-lpr/lpr mice by a transcriptional inhibitor of TNF-alpha.
We have used fas-defective MRL-lpr/lpr mice to study the effects of the staphylococcal enterotoxin superantigens on the development of autoimmune, inflammatory joint disease in animals that are susceptible to the development of rheumatoid arthritis-like disease. We show that systematic administration by a single i.p. injection of staphylococcal enterotoxin B (SEB; 10 micrograms/mouse) caused a mild, inflammatory arthritis +30 days postchallenge in the knee joints of young (< 2-mo-old) MRL-lpr/lpr mice, but not aged-matched MRL +/+ mice. In aged (> 8-mo-old) MRL-lpr/lpr mice, but not in aged MRL +/+ mice, SEB caused a severe, inflammatory arthritis, as assessed histologically, and systemic autoimmune disease, including glomerulonephritis and autoantibody production. Furthermore, in aged MRL-lpr/lpr mice, SEB but not heat-denatured SEB caused acute weight loss and elevated levels of serum proinflammatory cytokines. Compared with highly purified peritoneal macrophages obtained from either aged MRL +/+, young MRL-lpr/lpr, or young MRL +/+, peritoneal macrophages obtained from aged MRL-lpr/lpr mice constitutively expressed 2- to 10-fold greater levels of TNF-alpha, IL-1 beta, IL-6, and IL-10, and produced elevated amounts of these cytokines when treated in vitro with SEB. SEB-challenged aged MRL-lpr/lpr mice treated with anti-TNF mAb (100 micrograms/mouse; every other day), anti-V beta 8 TCR mAb (250 micrograms/mouse; every other day), or orally with the novel TNF-alpha inhibitor MDL 201,449A (9-[(1R, 3R)-trans-cyclopentan-3-ol] adenine; 25 mg/kg/day) exhibited reduced inflammatory arthritis, autoantibody formation, and serum TNF-alpha levels, but not IL-10 levels, after +30 days of treatment. These data suggest that SEB is an extremely potent macrophage-activating factor in vitro and in vivo, enhancing several aspects of autoimmune disease in MRL-lpr/lpr mice, and that anti-TNF therapies may have potential use in inflammatory arthritis.
Aging↗
Pressure-Temperature Phase Diagram of the Spin-Peierls Compound CuGeO3.
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Journal Article↗