CD62-PSGL-1 interactions regulate cytokine chemokine and apoptotic networks in cardiac allograft recipients.
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Animals↗
Biomedical subjects
L Meng
Publications and source records attributed to L Meng.
Cutting edge: membrane lymphotoxin regulates CD8(+) T cell-mediated intestinal allograft rejection.
Blocking the CD28/B7 and/or CD154/CD40 costimulatory pathways promotes long-term allograft survival in many transplant models where CD4(+) T cells are necessary for rejection. When CD8(+) T cells are sufficient to mediate rejection, these approaches fail, resulting in costimulation blockade-resistant rejection. To address this problem we examined the role of lymphotoxin-related molecules in CD8(+) T cell-mediated rejection of murine intestinal allografts. Targeting membrane lymphotoxin by means of a fusion protein, mAb, or genetic mutation inhibited rejection of intestinal allografts by CD8(+) T cells. This effect was associated with decreased monokine induced by IFN-gamma (Mig) and secondary lymphoid chemokine (SLC) gene expression within allografts and spleens respectively. Blocking membrane lymphotoxin did not inhibit rejection mediated by CD4(+) T cells. Combining disruption of membrane lymphotoxin and treatment with CTLA4-Ig inhibited rejection in wild-type mice. These data demonstrate that membrane lymphotoxin is an important regulatory molecule for CD8(+) T cells mediating rejection and suggest a strategy to avoid costimulation blockade-resistant rejection.
Abatacept↗
Vascular endothelial growth factor: acting as an autocrine growth factor for human gastric adenocarcinoma cell MGC803.
Vascular endothelial growth factor (VEGF) is known to be a highly specific mitogen for endothelial cells through two high-affinity tyrosine kinase receptors, VEGFR-1 and VEGFR-2, which are almost specifically expressed in endothelial cells. However, recent findings showed that VEGF receptors may also expressed by nonendothelial cells, especially by tumor cells. To further understand the functional expression of VEGF receptors by nonendothelial cells, our preliminary screening detected the expression of VEGFR-2 in 115 different paraffin-embedded cancer specimens including 35 cases of bladder tumor, 30 cases of breast cancer, 25 cases of intestinal cancer, and 25 cases of lung cancer with immunohistochemistry. The results showed that VEGFR-2 was widely expressed in different tumor tissues. By reverse transcription PCR, NCI-H23, NCI-H460, MGC803, MDA-MB-231, 293, and MCF7 cells were evaluated for the mRNA expression of both VEGF and VEGFR-2. The data indicated that all these tumor cell lines expressed detectable amounts of VEGF mRNA, but only 293, MCF7, and MGC803 cells coexpressed VEGFR-2. Immunoblot analysis also demonstrated the expression of VEGFR-2 at protein level. We further demonstrate that exogenous rhVEGF(165) could stimulate cell growth in MGC803, a tumor cell line derived from gastric adenocarcinoma, in a dose- and time-dependent manner. Furthermore, the antibodies against rhVEGF(165) and VEGFR-2 could block rhVEGF(165)-mediated proliferation of MGC803 cells. These unexpected results provided direct evidence that VEGF may act as an autocrine growth factor to induce the proliferation of gastric adenocarcinoma cells as well as tumor angiogenic cells, thus suggesting a promising tumor therapeutic application based upon the VEGF system.
Adenocarcinoma↗
Induction of bulk and c-myc P2 promoter-specific DNA damage by an anti-topoisomerase II agent salvicine is an early event leading to apoptosis in HL-60 cells.
Salvicine is a novel diterpenoid quinone derivative possessing strong antitumor activities and was demonstrated to stabilize the DNA topoisomerase II (Topo II) cleavage complex in vitro and in vivo. In the present work we investigated the possible mechanism through which disturbance of Topo II by salvicine led to cell death. We found that salvicine induced DNA strand breaks in human promyelocytic leukemia HL-60 cells and DNA damage correlated with cell growth inhibition. DNA damage induced by brief exposure to salvicine could be partially reversed, but early DNA breaks triggered the process of apoptosis. Preferential damage in the P2 promoter region of the oncogene c-myc was detected, whereas no obvious DNA damage was found in the 3' region of the same gene. Furthermore, the expression of some protooncogenes such as c-myc, c-fos and c-jun was examined, showing that salvicine produced a reduction in the transcription rate of c-myc in a dose-dependent manner and a marked induction of c-fos and c-jun expression was observed. It appears possible that DNA damage within such genomic regions is an early event, which could lead to growth inhibition mediated by alterations of the expression of selected proliferation regulatory genes, such as c-myc, c-fos and c-jun, and ultimately cell death.
Antineoplastic Agents, Phytogenic↗
CD8 T cell-mediated rejection of intestinal allografts is resistant to inhibition of the CD40/CD154 costimulatory pathway.
BACKGROUND: Disruption of the CD40/CD154 pathway inhibits rejection in numerous models. The importance of this pathway on intestinal allograft rejection was examined in this study. METHODS: Intestinal grafts from B6C3F1 mice transplanted into C57BL/6 recipients were assessed histologically for rejection. RESULTS: The monoclonal antibody to CD154, MR1, failed to inhibit rejection in wild-type mice. Similarly, CD154-/- recipient mice rejected intestinal allografts. MR1 did inhibit early rejection in CD8-/- mice, but had no effect in CD4-/- recipients. All MR1-treated CD8-/- recipients eventually developed rejection. No benefit was observed when blockade of the CD40/CD154 pathway by MR1 was combined with blockade of the CD28/B7 pathway by mCTLA4Ig. CONCLUSIONS: These data suggest that CD4+ T cells mediating intestinal allograft rejection may be more dependent upon the CD40/CD154 pathway than CD8+ T cells. This finding highlights the importance of identifying agents that suppress CD8+ T cell-mediated rejection.
Animals↗
Mouse-rabbit germinal vesicle transfer reveals that factors regulating oocyte meiotic progression are not species-specific in mammals.
A series of experiments were designed to evaluate the meiotic competence of mouse oocyte germinal vesicle (GV) in rabbit ooplasm. In experiment 1, an isolated mouse GV was transferred into rabbit GV-stage cytoplast by electrofusion. It was shown that 71.8% and 63.3% of the reconstructed oocytes completed the first meiosis as indicated by the first polar body (PB1) emission when cultured in M199 and M199 + PMSG, respectively. Chromosomal analysis showed that 75% of matured oocytes contained the normal 20 mouse chromosomes. When mouse spermatozoa were microinjected into the cytoplasm of oocytes matured in M199 + PMSG and M199, as many as 59.4% and 48% finished the second meiosis as revealed by the second polar body (PB2) emission and a few fertilized eggs developed to the eight-cell stage. In experiment 2, a mouse GV was transferred into rabbit MII-stage cytoplast. Only 13.0-14.3% of the reconstructed oocytes underwent germinal vesicle breakdown (GVBD) and none proceeded past the MI stage. When two mouse GVs were transferred into an enucleated rabbit oocyte, only 8.7% went through GVBD. In experiment 3, a whole zona-free mouse GV oocyte was fused with a rabbit MII cytoplast. The GVBD rates were increased to 51.2% and 49.4% when cultured in M199 + PMSG and M199, respectively, but none reached the MII stage. In experiment 4, a mouse GV was transferred into a partial cytoplasm-removed rabbit MII oocyte in which the second meiotic apparatus was still present. GVBD occurred in nearly all the reconstructed oocytes when one or two GVs were transferred and two or three metaphase plates were observed in ooplasm after culturing in M199 + PMSG for 8 hr. These data suggest that cytoplasmic factors regulating the progression of the first and the second meioses are not species-specific in mammalian oocytes and that these factors are located in the meiotic apparatus and/or its surrounding cytoplasm at MII stage.
Animals↗
Tumor necrosis factor alpha and interleukin 11 secreted by malignant breast epithelial cells inhibit adipocyte differentiation by selectively down-regulating CCAAT/enhancer binding protein alpha and peroxisome proliferator-activated receptor gamma: mechanism of desmoplastic reaction.
The dense layer of fibroblasts that accumulate around malignant breast epithelial cells (i.e., desmoplastic reaction) arises from the breast adipose tissue and provides structural and biochemical support for breast cancer. We report herein a number of epithelial-stromal interactions responsible for desmoplastic reaction in breast cancer using cultured 3T3-L1 murine fibroblasts and human adipose fibroblasts, which can be activated with a mixture of hormones to differentiate to mature adipocytes. Adipocyte differentiation was inhibited by coculturing fibroblasts with various breast cancer cell lines (T47D, MCF-7, SSC202, SSC78, and SSC30) completely or by breast cancer cell conditioned media in a dose-dependent manner; on the other hand, adipocyte differentiation was not inhibited by coculturing with normal human primary mammary epithelial cell conditioned medium. This tumor effect was eliminated using neutralizing antibodies against tumor necrosis factor (TNF)-alpha or interleukin (IL)-11. TNF-alpha and IL-11 levels were 2.5-3 times higher in T47D conditioned medium compared with control medium, and TNF-alpha transcripts were detectable in T47D but not in 3T3-L1 cells in culture, indicating that the malignant epithelial cell is the major site of cytokine production. This was confirmed in vivo in mastectomy specimens, where immunoreactive TNF-alpha and IL-11 were readily detectable in malignant epithelial cells but not in the majority of the surrounding fibroblasts. Adipocyte differentiation is mediated by the expression of a cascade of adipogenic transcription factors, including CCAAT/enhancer binding protein (C/EBP)beta, C/EBPdelta, peroxisome proliferator-activated receptor (PPAR)gamma and C/EBPalpha. C/EBPalpha and PPARgamma are essential for this process. We demonstrated by Northern analysis that exposure of activated 3T3-L1 cells to T47D cell conditioned medium strikingly decreased the levels of PPARgamma and C/EBPalpha transcripts and increased the levels of C/EBPbeta and C/EBPdelta transcripts. In these 3T3-L1 cells, inhibition of differentiation was also confirmed by markedly suppressed levels of aP2 mRNA, which is an adipocyte-specific gene. These in vitro observations were confirmed in sections of human malignant breast tumors, where immunoreactive C/EBPalpha was readily detectable in adipose flbroblasts distant to the tumor but not in intratumoral fibroblasts. Treatment of 3T3-L1 cells with T47D cell conditioned medium or TNF-alpha changed neither the numbers of cells in G0-G1, S, and G2 phases nor the rate of [3H]thymidine incorporation, thus ruling out a proliferative effect of malignant cells on the surrounding fibroblasts. In summary, desmoplastic reaction primarily occurs via the action of cytokines (TNF-alpha and IL-11) secreted by the malignant epithelial cells to inhibit differentiation of adipose fibroblasts to mature adipocytes. This tumor-induced block in adipocyte differentiation is mediated by the selective inhibition of expression of the essential adipogenic transcription factors, i.e., PPARgamma and C/EBPalpha.
3T3 Cells↗
An investigation of soy intake and mammographic characteristics in Hawaii.
This cross-sectional investigation in Hawaii explored the relation between soy foods and mammographic characteristics using two food frequency questionnaires and a computer-assisted density assessment method. Japanese and Chinese women reported significantly greater soy food intake than Caucasian women. Whereas soy intake and the size of the dense areas were not related, soy intake and percent mammographic densities were positively associated. The size of the entire breast and the nondense area (ie the fatty part of the breast) were inversely related to soy intake. These results suggest the hypothesis that soy foods by themselves or as part of an Asian dietary pattern may affect the growth of the female breast before adulthood, but the possible mechanisms of action have to be explored in future studies.
Breast Neoplasms↗
The spindle observation and its relationship with fertilization after intracytoplasmic sperm injection in living human oocytes.
OBJECTIVE: To image spindles in living human oocytes and to examine the relation between spindles and fertilization after ICSI. DESIGN: The LC polscope was used to examine spindles in an observational study of living oocytes. SETTING: Academic IVF clinic. PATIENT(S): Women being treated for infertility. INTERVENTION(S): Oocytes retrieved from patients for infertility treatment were examined before ICSI. Aged, unfertilized oocytes after IVF or ICSI were examined with polscope and confocal microscopes to compare the two methods. MAIN OUTCOME MEASURE(S): Spindle structure in living oocytes and fertilization after ICSI. RESULT(S): Spindles could be imaged in 61.4% of oocytes. More oocytes with spindles than oocytes without spindles fertilized normally after ICSI (61.8% vs. 44.2%). Spindles in most aged oocytes were partially or completely disassembled, and only a few microtubules around the chromosomes or dispersed microtubules in the cytoplasm were observed. Confocal images of immunostained spindles were almost identical to polscope images of spindle birefringence. CONCLUSION(S): Spindles in living human oocytes can be imaged by using the polscope. A birefringent spindle in human oocytes may clinically predict the quality and age of oocytes. This method also can be used to monitor spindle position during ICSI.
Cellular Senescence↗
Limited recovery of meiotic spindles in living human oocytes after cooling-rewarming observed using polarized light microscopy.
BACKGROUND: Spindles are formed from microtubules and are exquisitely sensitive to changes in temperature. An orientation-independent polarized light microscope, the Polscope, can be used to image spindles in living oocytes allowing analysis of spindle kinetics in the living state. This study examined the effects of cooling on spindle disassembly in living human oocytes and spindle recovery after rewarming. METHODS: Oocytes were imaged continuously with the Polscope during cooling and rewarming. The quantity of microtubules in the spindles was measured by its birefringence using the Polscope. RESULTS: Spindles had completely disassembled by 5 min after cooling and recovered by 20 min after rewarming to 37 degrees C if rewarming started soon after the oocyte's temperature dropped to room temperature. However, when oocytes were cooled and kept at 33, 28 or 25 degrees C for 10 min and then warmed, it was found that warming allowed 5/5, 2/5 and 0/5 oocytes of the spindles to recover respectively. CONCLUSIONS: These results indicate that human meiotic spindles are exquisitely sensitive to alterations in temperature. The maintenance of temperature at 37 degrees C during in-vitro manipulation is important for spindle integrity and, therefore, is likely to be important for normal fertilization and subsequent embryo development.
Cold Temperature↗
Developmental ability of human oocytes with or without birefringent spindles imaged by Polscope before insemination.
BACKGROUND: Birefringent spindles imaged with the Polscope can predict fertilization rates after intracytoplasmic sperm injection (ICSI). The present study examined the development of human oocytes with or without birefringent spindles, imaged with the Polscope before ICSI. METHODS: Oocytes were obtained from stimulated ovaries of consenting patients undergoing oocyte retrieval for ICSI. Spindles were imaged with the Polscope combined with a computerized image analysis system. After imaging and ICSI, oocytes with or without spindles were cultured separately for examination of fertilization and embryo development. A total of 1544 oocytes from 136 cycles were examined with the Polscope and inseminated by ICSI. RESULTS: Spindles were imaged in 82% of oocytes. After ICSI, more oocytes (P < 0.05) with spindles (69.4%) fertilized normally, forming 2 pronuclei, than oocytes without spindles (62.9%). At day 3, more oocytes (P < 0.01) with spindles (66.3%) developed to 4-11 cell stages than oocytes without spindles (55.4%). Significantly more (P < 0.001) oocytes with spindles developed to morula and blastocyst by day 5 (51.1 versus 30.3%) and day 6 (53.2 versus 29.3%) compared with oocytes without spindles. CONCLUSIONS: The results indicate that the presence of a birefringent spindle in human oocytes can predict not only higher fertilization rate, but also higher embryo developmental competence.
Adult↗
Ethnic differences in mammographic densities.
BACKGROUND: Breast cancer incidence is considerably lower among Japanese and Chinese women than among Caucasian and Native Hawaiian even in second and third generation migrants. Mammographic densities, which refer to the radiological appearance of the healthy female breast, are related to breast cancer risk. The purpose of this project was to explore the hypothesis that women from ethnic groups at high breast cancer risk are more likely to have high levels of densities than women from low breast cancer risk groups. METHODS: In a cross-sectional design, 514 pre- and post-menopausal women recruited at mammography screening clinics completed a self-administered questionnaire. We used a computer-assisted method to measure the dense and the total areas of the breast and to compute per cent breast density. Student's t-tests and multiple linear regression were applied to examine ethnic differences and to explore determinants of mammographic densities, respectively. RESULTS: The unadjusted mean dense area was 15% smaller in Chinese and Japanese women than in the Caucasian/Hawaiian group. However, because of their smaller breast size, the per cent of the breast occupied by dense tissue in Chinese and Japanese women was 20% higher than in Caucasian women. Body mass index, age, menopausal status, parity, and oestrogen therapy were associated with mammographic densities, but they did not account for all ethnic differences. CONCLUSIONS: Whereas this study detected some ethnic differences in mammographic densities, the importance of dense areas and per cent densities as indicators of breast cancer risk in ethnically diverse populations remains to be clarified.
Adult↗
Mycoplasma infections and different human carcinomas.
AIM: To explore relationships between human carcinomas and mycoplasma infection. METHODS: Monoclonal antibody PD4, which specifically recognizes a distinct protein from mycoplasma hyorhinis, was used to detect mycoplasma infection in different paraffin embedded carcinoma tissues with immunohistochemistry. PCR was applied to amplify the mycoplasma DNA from the positive samples for confirming immunohistochemistry. RESULTS: Fifty of 90 cases (56%) of gastric carcinoma were positive for mycoplasma hyorhinis. In other gastric diseases, the mycoplasma infection ratio was 28% (18/49) in chronic superficial gastritis, 30% (14/46) in gastric ulcer and 37% (18/49) in intestinal metaplasia. The difference is significant with gastric cancer (chi(2) = 12.06, P < 0.05). In colon carcinoma, the mycoplasma infection ratio was 55.1% (32/58),but it was 20.9% (10/49)in adenomarous polyp (chi(2)=13.46, P < 0.005). Gastric and colon cancers with high differentiation had a higher mycoplasma infection ratio than those with low differentiation (P < 0.05). Mycoplasma infection in esophageal cancer, lung cancer, breast cancer and glioma was 50.9% (27/53), 52.6% (31/59), 39.7% (25/63) and 41% (38/91), respectively. The mycoplasma DNA was successfully amplified with the DNA extracted from the cancer tissues that were positive for mycoplasma infection (detected with antibody PD4). CONCLUSION: There was high correlation between mycoplasma infection and different cancers, which suggests the possibility of an association between the two. The mechanism involved in oncogenesis by mycoplasma remains unknown.
Antibodies, Monoclonal↗
Determinants of mammographic densities among women of Asian, Native Hawaiian, and Caucasian ancestry.
This cross-sectional study explored the relation between mammographic densities (a predictor of breast cancer risk), ethnicity, and dietary factors among women in Hawaii. Thirty-nine postmenopausal women with Japanese, Chinese, Caucasian, and Native Hawaiian ancestry who had received a screening mammogram completed a medical, reproductive, and dietary history. Using a computerized method, we determined the total and the dense area of the breast and calculated the ratio between the two. Blood lipids were measured using standard methods. For statistical analysis, we applied analysis of variance and multiple linear regression. Whereas the mean dense area of the breast was one third smaller in Asian than in Caucasian and Native Hawaiian women, the percent of the breast occupied by dense tissue in the Asian women was slightly higher than in the Caucasian/Hawaiian group, possibly a result of the Asian women's smaller breast size. The exploratory analysis indicated inverse relations of body mass index, high-density lipoprotein cholesterol (HDLC), age at menarche, and soy intake with mammographic densities, as well as direct relations of estrogen use and family history with mammographic densities. The results of this study suggest that variations in these factors may be responsible for ethnic differences in mammographic densities and in breast cancer risk.
Asian↗
Intravascular local gene transfer mediated by protein-coated metallic stent.
OBJECTIVE: To assess the feasibility, efficiency and selectivity of adenovirus-mediated gene transfer to local arterial wall by protein-coated metallic stent. METHODS: A replication-defective recombinant adenovirus carrying the Lac Z reporter gene for nuclear-specific beta-galactosidase (Ad-beta gal) was used in this study. The coating for metallic stent was made by immersing it in a gelatin solution containing crosslinker. The coated stents were mounted on a 4.0 or 3.0 mm percutaneous transluminal coronary angioplasty (PTCA) balloon and submersed into a high-titer Ad-beta gal viral stock (2 x 10(10) pfu/ml) for 3 min, and then implanted into the carotid arteries in 4 mini-swines and into the left anterior descending branch of the coronary artery in 2 mini-swines via 8F large lumen guiding catheters. The animals were sacrificed 7 (n = 4), 14 (n = 1) and 21 (n = 1) days after implantation, respectively. The beta-galactosidase expression was assessed by X-gal staining. RESULTS: The results showed that the expression of transgene was detected in all animal. In 1 of carotid artery with an intact intima, the beta-gal expression was limited to endothelial cells. In vessels with denuded endothelium, gene expression was found in the sub-intima, media and adventitia. The transfection efficiency of medial smooth muscle cells was 38.6%. In 2 animals sacrificed 7 days after transfection, a microscopic examination of X-gal-stained samples did not show evidence of transfection in remote organs and arterial segments adjacent to the treated arterial site. CONCLUSIONS: Adenovirus-mediated arterial gene transfer to endothelial, smooth muscle cells and adventitia by protein-coated metallic stent is feasible. The transfection efficiency is higher. The coated stent may act as a good carrier of adenovirus-mediated gene transfer and have a potential to prevent restenosis following PTCA.
Adenoviridae↗
[Determination of rutin and quercetin in mulberry leaves by high performance capillary electrophoresis].
Rutin and quercetin are the main effective components of mulberry leaves with the functions of controlling the increase of fat in serum and controlling the formation of arterio-sclerosis. In this article a high performance capillary electrophoretic(HPCE) method was used to separate and determine rutin and quercetin in mulberry leaves collected from different periods, different places and different kinds in Xinjiang. Electrophoretic conditions were as follows: a capillary tube (75 microns i.d. x 57 cm (effective length, 50 cm)), with 10 mmol/L dihydrogen sodium phosphate-20 mmol/L sodium borate containing 15% methanol as the running buffer (pH 8.62) and an applied voltage of 20 kV, at 25 degrees C, detected at a wavelength of 245 nm. Under the optimum conditions, rutin and querctin were separated successfully from other components within 12 minutes. The corrected peak areas of rutin and quercetin increased linearly with the increase of their concentrations in the range of 4.4 mg/L-28.8 mg/L and 1.8 mg/L-145.8 mg/L respectively. The corresponding regression equations for rutin and quercetin were Y = 71.60 rho + 30.51 (r = 0.9991) and Y = 315.17 rho - 929.70 (r = 0.9949) respectively, and the recoveries were 95.64% and 99.36%. The analytical results demonstrate the method is simple, quick and well reproducible, and can be used as a reliable tool for the quality control of mulberry leaves.
Drugs, Chinese Herbal↗
[The characteristic infrared spectra of N-(2-phenyl-(1,2,3-triazole-formyl)-N'-arylthioueas].
The characteristic infrared spectra of N-(2-phenyl-(1,2,3-triazole-formyl)-N'-aryl)-thioueas have been studied and the changing rules with the change of chemical structure have been discussed. Specially, the effect of the characteristic infrared of long-range radical by different substitute is discussed in detail. Results show that characteristic bands of radical which as far as five radicals away form substitute group are still affected. It is very suggestive meaning for long-range spectra research.
Anti-Infective Agents↗
Changes of reliability and efficiency of micronucleus bioassay in Vicia faba after exposure to metal contamination for several generations.
Mitotic root micronucleus (MCN) frequency in Vicia faba as a bioassay, is primarily based on the extent of the sentinel Vicia response in terms of cytogenetic damage quantitatively or qualitatively to indicate the presence of mutagenic contaminants. This paper describes an investigation designed to assess changes in MCN frequencies of Vicia faba from three generation plants obtained, respectively from a reference site (RS) and a metal-contaminated experimental field (EF) in the bioassay of mutagenic Cd(2+) and NaN(3). The background value, dose-response to Cd(2+) and to NaN(3) in three generation (F(1), F(2) and F(3)) plants of the EF and the initial (F(0)) plants were determined in terms of MCN frequencies. With more generations of growing Vicia plants in the EF, a higher background value of MCN frequency, a lower slope value in the regression equation, a smaller ratio of MCN frequency between the control and treatment in the same generation and larger perturbation values were observed. This denotes that the decreased reliability and efficiency are represented in Vicia plants from the EF if the plants are used as sentinels in the bioassay of mutagenic Cd(2+) and NaN(3). It was concluded that the Vicia MCN bioassay should be used as an endpoint biomarker acceptable in biomonitoring environmental mutagens when the sentinel plants were collected from clean areas. Because no place is absolutely without pollutants, it is suggested that several seed stock centers should be established for providing sentinel Vicia if Vicia MCN bioassay is used as a biomarker to identify the global environmental status.
Journal Article↗