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Biomedical subjects

Z M Dong

Publications and source records attributed to Z M Dong.

At least 19 recordsLinked to original sources
PubMed2006

Difference in expression level and localization of DNA polymerase beta among human esophageal cancer focus, adjacent and corresponding normal tissues.

The aim of this paper was to study the expression level and localization of DNA polymerase beta (polbeta) and the difference in those among the human esophageal cancer focus, cancer adjacent and corresponding normal esophageal tissues. These three kinds of tissues were collected from surgically resected tissues in 17 patients with esophageal carcinoma in Linzhou, China. Each of a total of 51 tissue pieces was divided into two aliquots: one aliquot for detection of polbeta expression by in situ hybridization and by immunohistochemistry; another for detection of polbeta expression by RNA dot blot and immunoblotting. In the tissue specimens detected by in situ hybridization and immunohistochemistry, the cancer focus tissue had much stronger polbeta expression signals localized in the scattered heteromorphologic cancer cells. The cancer adjacent tissue exhibited slightly stronger polbeta signals mainly localized in the epithelial proliferating cells and the corresponding normal tissue displayed weak polbeta signals basically located in the epithelial basal cells. The difference in expression level of polbeta among the three kinds of tissues detected by RNA dot blot and immunoblotting was similar to the above results. Further, the truncated POLB could be demonstrated in both cancer focus and cancer adjacent tissues, but could not be found in the corresponding normal tissue in immunoblotting. The results suggest that the overexpression of polbeta with truncated form may be a potential biomarker for early diagnosis of human esophageal carcinoma.

Cytoplasm↗
PubMed2000

Prominent role of P-selectin in the development of advanced atherosclerosis in ApoE-deficient mice.

BACKGROUND: Adhesive interactions between leukocytes and endothelial cells are characteristic of the development of atherosclerotic lesions, but the receptors involved remain to be defined. P-selectin is an adhesion receptor expressed on activated endothelial cells or platelets and was shown to be involved in fatty streak formation in LDL receptor-deficient mice on an atherogenic diet. The main purpose of this study is to examine the role of P-selectin in the spontaneous development of advanced atherosclerosis in apoE-deficient mice. METHODDS AND RESULTS: We intercrossed P-selectin-deficient mice with mice lacking apoE and compared lesion development in apoE-deficient mice with P-selectin (apoE(-/-) P(+/+)) and without P-selectin (apoE(-/-) P(-/-)) that were fed normal mouse chow. At 4 months of age, apoE(-/-) P(-/-) mice had 3. 5-fold smaller aortic sinus lesions than apoE(-/-) P(+/+) mice. These were limited to fatty streaks in the apoE(-/-) P(-/-) mice, whereas 70% of apoE(-/-) P(+/+) lesions contained smooth muscle cells. Significantly more of the aortic sinus circumference was covered by lesions in the apoE(-/-) P(+/+) animals. The P-selectin genotype affected macrophage recruitment, because twice as many mononuclear cells were present in the P-selectin-positive lesions. At 15 months, the lesions progressed to the fibrous plaque stage in both genotypes and spread throughout the aorta, but this process was delayed in apoE(-/-) P(-/-) mice. In the aortic sinus, the lesions of the apoE(-/-) P(-/-) mice were 2.6-fold smaller and less calcified. CONCLUSIONS: P-selectin appears to be a key adhesion receptor mediating leukocyte recruitment into lesions and promoting advanced atherosclerosis in apoE-deficient mice.

Animals↗
PubMed1999

Mechanisms for induction of L-selectin loss from T lymphocytes by a cryptococcal polysaccharide, glucuronoxylomannan.

Disseminated cryptococcosis is accompanied by cryptococcal polysaccharides in the serum and the lack of cellular infiltrates in infected tissues. Cryptococcal polysaccharides given intravenously to mice inhibit the influx of T lymphocytes into the sites of cell-mediated immune response. The focus here was to determine whether cryptococcal polysaccharides modulate the expression of molecules, such as L-selectin, that are important in extravasation of T cells. Cryptococcal glucuronoxylomannan (GXM), but not galactoxylomannan or mannoprotein, was found to cause loss of L-selectin from freshly isolated human T cells of both CD4 and CD8 subsets and from Jurkat cells. With the signaling-pathway inhibitors staurosporine (which inhibits protein kinase C) and herbimycin A (which inhibits protein tyrosine kinases), we showed that GXM or the cryptococcal culture filtrate antigen CneF directly induces L-selectin loss from CD4(+) and CD8(+) T cells via a herbimycin A-sensitive pathway(s) presumably involving one or more protein tyrosine kinases but not via a pathway involving protein kinase C. Loss of L-selectin from the T cells before the T cells have a chance to bind to L-selectin ligands on endothelial cells would be expected to prevent T-cell migration into inflamed tissues and/or lymph organs.

Antibodies, Monoclonal↗
PubMed1999

Donor MHC and adhesion molecules in transplant arteriosclerosis.

Transplant-associated arteriosclerosis remains an obstacle to long-term graft survival. To determine the contribution to transplant arteriosclerosis of MHC and adhesion molecules from cells of the donor vasculature, we allografted carotid artery loops from six mutant mouse strains into immunocompetent CBA/CaJ recipients. The donor mice were deficient in either MHC I molecules or MHC II molecules, both MHC I and MHC II molecules, the adhesion molecule P-selectin, intercellular adhesion molecule (ICAM)-1, or both P-selectin and ICAM-1. Donor arteries in which ICAM-1, MHC II, or both MHC I and MHC II were absent showed reductions in neointima formation of 52%, 33%, and 38%, respectively, due primarily to a reduction in smooth muscle cell (SMC) accumulation. In P-selectin-deficient donor arteries, neointima formation did not differ from that in controls. In donor arteries lacking both P-selectin and ICAM-1, the size of the neointima was similar to that in those lacking ICAM-1 alone. In contrast, neointima formation increased by 52% in MHC I-deficient donor arteries. The number of CD4-positive T cells increased by 2.8-fold in MHC I-deficient arteries, and that of alpha-actin-positive SMCs by twofold. These observations indicate that ICAM-1 and MHC II molecules expressed in the donor vessel wall may promote transplant-associated arteriosclerosis. MHC I molecules expressed in the donor may have a protective effect.

Animals↗
PubMed1998

The combined role of P- and E-selectins in atherosclerosis.

P- and E-selectins are adhesion molecules mediating the first step in leukocyte extravasation. Because their function in leukocyte adhesion is overlapping, we hypothesized that there might be a combined effect of these selectins on the development of atherosclerotic lesions. We bred P- and E-selectin-double-deficient mice onto the low-density lipoprotein receptor (LDLR)-deficient background (LDLR-/- P/E-/-) and compared lesion development in these mice to that in mice wild type for both selectins (LDLR-/- P/E+/+). After 8 wk on atherogenic diet, the LDLR-/- P/E-/- mice developed fatty streaks in the aortic sinus that were five times smaller than those in LDLR-/- P/E+/+ mice. The density of macrophages in the fatty streaks was comparable between LDLR-/- P/E+/+ and LDLR-/- P/E-/- mice. After 22 wk on the diet, the lesions spread throughout the aorta but this process was delayed in LDLR-/- P/E-/- mice. At 37 wk on diet, the lesions progressed to the fibrous plaque stage in both genotypes. However, the lesions in the aortic sinus in LDLR-/- P/E-/- mice were 40% smaller and less calcified than those of LDLR-/- P/E +/+ mice. Our results suggest that P- and E-selectins together play an important role in both early and advanced stages of atherosclerotic lesion development.

Animals↗
PubMed1998

Leukocyte-endothelium adhesion molecules in atherosclerosis.

The genetic manipulation of mice has provided an invaluable tool for studying the molecular mechanism(s) involved in atherosclerotic lesion development and maturation. The use of these new animal models has demonstrated that leukocyte-endothelium adhesion receptors play a significant part in promoting monocyte recruitment and consequently lesion growth. The next phase of investigation should test whether the inhibition of these adhesion receptors can reproduce the powerful anti-atherosclerotic effects seen in the adhesion receptor-deficient mice.

Animals↗
PubMed1997

The simultaneous measurement of low rates of CO2 and O2 exchange in biological systems.

An instrument for measuring low rates of biological O2 exchange using an open-flow gas analysis system is described. A novel differential O2 sensor that is capable of measuring as little as 0.4 Pa O2 against a back-ground of ambient air (20,900 Pa O2), yet has a dynamic range of +/- 2000 Pa O2 (i.e., +/- ca. 2% O2) is described. Baseline drift was typically less than 0.025 Pa min-1. The differential O2 sensor was incorporated into a respiratory quotient/photosynthetic quotient analyzer that contained other environmental sensors for atmospheric pressure, absolute O2 and CO2 concentration, temperature of the differential O2 sensor block, and differential pressure between reference and sample streams. Protocols for how these sensors can be used to calibrate the differential O2 sensor and to improve its stability with time are described. Together, the differential O2 sensor, the environmental sensors, and the simple calibration techniques allow for simultaneous, noninvasive, and accurate measurements of O2 and CO2 exchange in tissues with metabolic rates as low as about 0.1 mumol O2 or CO2 h-1. Example data are provided in which O2 differentials of 3 to 41 Pa O2 were measured in an open-flow system.

Animals↗
PubMed1997

A new class of obesity genes encodes leukocyte adhesion receptors.

Obesity is a complex disease, and multiple genes contribute to the trait. The description of five genes (ob, db, tub, Ay, and fat) responsible for distinct syndromes of spontaneous monogenic obesity in mice has advanced our knowledge of the genetics of obesity. However, many other genes involved in the expression of this disease remain to be determined. We report here the identification of an additional class of genes involved in the regulation of adipose tissue mass. These genes encode receptors mediating leukocyte adhesion. Mice deficient in intercellular adhesion molecule-1 became spontaneously obese in old age on normal mouse chow or at a young age when provided with a diet rich in fat. Mice deficient in the counterreceptor for intercellular adhesion molecule-1, the leukocyte integrin alphaMbeta2 (Mac-1), showed a similar obesity phenotype. Since all mice consumed approximately the same amount of food as controls, the leukocyte function appears to be in regulating lipid metabolism and/or energy expenditure. Our results indicate that (i) leukocytes play a role in preventing excess body fat deposition and (ii) defects in leukocyte adhesion receptors can result in obesity.

Aging↗
PubMed1997

Absence of P-selectin delays fatty streak formation in mice.

P-selectin is expressed on activated endothelium and platelets where it can bind monocytes, neutrophils, stimulated T cells, and platelets. Because recruitment of these cells is critical for atherosclerotic lesion development, we examined whether P-selectin might play a role in atherosclerosis. We intercrossed P-selectin-deficient mice with mice lacking the low density lipoprotein receptor (LDLR) because these mice readily develop atherosclerotic lesions on diets rich in saturated fat and cholesterol. The atherogenic diet stimulated leukocyte rolling in the mesenteric venules of LDLR-deficient mice, and the increase in adhesiveness of the vessels was P-selectin-dependent. Most likely due to the reduced leukocyte interaction with the vessel wall, P-selectin-deficient mice on diet for 8-20 wk formed significantly smaller fatty streaks in the cusp region of the aortae than did P-selectin-positive mice. This difference was more prominent in males. At 37 wk on diet, the lesions in the LDLR-deficient animals progressed to the fibrous plaque stage and were distributed throughout the entire aorta; their size or distribution was no longer dependent on P-selectin. Our results show that P-selectin-mediated adhesion is an important factor in the development of early atherosclerotic lesions, and that adhesion molecules such as P-selectin are involved in the complex process of atherosclerosis.

Animals↗
PubMed1997

Cryptococcal polysaccharides bind to CD18 on human neutrophils.

CD18, the beta chain of the beta 2 integrin family of adhesion molecules, is associated with three different alpha chains (CD11a, -b, and -c) and is expressed on the surface of all types of leukocytes. CD18-containing molecules are up-regulated on the surface of neutrophils (polymorphonuclear cells [PMN]) in response to chemotactic agents and are implicated in mediating adhesion to an inflamed endothelium, which is a prerequisite to migration of PMN into infected tissues. In a previous study, we found that a cryptococcal culture filtrate (CneF), when injected into the bloodstream of mice to simulate the antigenemia in cryptococcosis, inhibits PMN accumulation at the site of an inflammatory stimulus. In the present study, we assessed the ability of CneF and its individual components, i.e., glucuronoxylomannan (GXM), galactoxylomannan (GalXM), and mannoprotein (MP), to interact with CD18 on human PMN. CneF labeled with 14C was shown to bind to human PMN in a dose-dependent manner. Pretreatment of PMN with anti-CD18, but not an isotype-matched control monoclonal antibody (MAb) or anti-CD11a MAb, blocked the binding of 14C-labeled CneF to PMN. In addition, CneF, GXM, and GalXM but not MP significantly blocked the binding of the anti-CD18 MAb to CD18 on the surface of unactivated and formyl methionyl leucyl phenylalanine-activated PMN as determined by indirect immunofluorescence staining and flow cytometric analysis. In the same experiments, the cryptococcal polysaccharides did not affect the binding of an anti-CD11a or anti-L-selectin MAb to the surface of PMN at 4 degrees C. The results suggest that CneF and its components GXM and GalXM bind to CD18 on human PMN. Based on our findings, we propose that CD18 is a possible molecular target of cryptococcal polysaccharides and that binding of the polysaccharides to CD18 has the potential to inhibit leukocyte infiltration into inflammatory sites.

Antibodies, Monoclonal↗
PubMed1996

Cryptococcal polysaccharides induce L-selectin shedding and tumor necrosis factor receptor loss from the surface of human neutrophils.

High titers of cryptococcal polysaccharides in the serum and spinal fluid and the lack of cellular infiltrates in the infected tissues are hallmarks of disseminated cryptococcosis. Cryptococcal polysaccharides given intravenously to mice inhibit the influx of leukocytes into sites injected with inflammatory mediators. The purpose of this investigation was to determine if cryptococcal polysaccharides, i.e., glucuronoxylomannan (GXM), galactoxylomannan, and mannoprotein, affect expression of molecules on the surface of neutrophils that are important in extravasation. GXM in the absence of serum was shown to induce human neurophils to shed L-selectin, a molecule needed in the first step of neutrophil movement into tissues. In the presence of serum, GXM caused a further shedding of L-selectin. Shedding of L-selectin was evident by reduced amounts of L-selectin on the neutrophils treated with GXM and by increased levels of soluble L-selectin in the GXM-treated neutrophil supernatants. GXM also stimulated neutrophils to have reduced expression of TNF receptor. In contrast, GXM-treated neutrophils showed increased levels of CD15 and CD11b, and unchanged CD16 expression. In the absence of serum, galactoxylomannan and mannoprotein did not affect L-selectin, TNF receptor, CD15, CD11b, or CD16 on neutrophils but did induce loss of L-selectin in the presence of serum. Our results indicate that cryptococcal polysaccharides, especially GXM, can cause shedding of L-selectin from the surface of neutrophils, and this may prevent neutrophils from attaching to the endothelial cell surfaces. Blockage of this early step in cell migration from the vessels into tissues may be responsible in part for reduced cellular infiltration into infected tissues of individuals with disseminated cryptococcosis.

Antigens, CD↗
PubMed1995

Intravascular cryptococcal culture filtrate (CneF) and its major component, glucuronoxylomannan, are potent inhibitors of leukocyte accumulation.

Disseminated cryptococcosis is characterized by high titers of cryptococcal polysaccharides in serum and minimal cellular infiltrates in infected tissues of patients. The main objective of this study was to determine whether the circulating cryptococcal polysaccharides could contribute to the lack of cellular infiltration into infected tissues. To assess this possibility, a gelatin sponge implantation model was used. We found that intravenous (i.v.) injection of mice with cryptococcal culture filtrate antigen (CneF) inhibited migration of leukocytes (neutrophils, lymphocytes, and monocytes) into the intrasponge sites of acute inflammation induced by CneF, tumor necrosis factor alpha, or formylmethionyl leucyl phenylalanine. In addition, i.v. administration of CneF inhibited leukocyte migration into the intrasponge sites of a cell-mediated immune reaction irrespective of whether the delayed-type hypersensitivity response was to CneF or the mycobacterial antigen purified protein derivative. Glucuronoxylomannan, a major constituent of CneF and a major cryptococcal antigen detected in the sera of patients with disseminated cryptococcosis, when given i.v. to mice, inhibited leukocyte migration into the sponges. Our results suggest that the minimal cellular infiltrates observed in infected tissues of cryptococcosis patients may be due, in part, to the circulating cryptococcal polysaccharide functioning as we have demonstrated in the mouse model. Furthermore, the high titers of cryptococcal antigen in the sera of patients may diminish leukocyte migration in response to stimuli other than Cryptococcus neoformans, a point that may be relevant in AIDS patients with cryptococcosis.

Animals↗
PubMed1995

Effects of the two varieties of Cryptococcus neoformans cells and culture filtrate antigens on neutrophil locomotion.

Cryptococcus neoformans var. gattii (serotype B and C) isolates have a relative predilection for immunocompetent hosts, and C. neoformans var. neoformans (serotype A and D) isolates have a relative predilection for immunocompromised hosts, suggesting that normal host resistance to the former may be relatively inefficient compared with that to the latter variety. In order to assess the possibility that normal cellular host defense is inadequate in protecting against C. neoformans var. gattii, we compared the two varieties of C. neoformans cells and their culture filtrate antigens (CneF) with respect to effects on neutrophil (polymorphonuclear leukocyte [PMN]) locomotion. In a 48-well modified Boyden chamber, the cells and CneF of C. neoformans var. neoformans (serotype A and D) isolates stimulated chemotaxis and chemokinesis of human PMN and activated a complement component(s) in pooled human serum to become a chemoattractant(s) for human PMN. In contrast, the cells and CneF of C. neoformans var. gattii (serotype B and C) isolates did not stimulate chemotaxis or chemokinesis in human PMN but rather inhibited chemokinesis and chemotactic responses of PMN to pooled human serum and formylmethionyl leucyl phenylalanine. Neither of the CneF from the C. neoformans var. gattii isolates was cytotoxic to PMN. Furthermore, with the mouse model, we found that CneF from C. neoformans var. neoformans caused migration of PMN into gelatin sponges implanted in naive and immunized mice, whereas CneF from C. neoformans var. gattii inhibited PMN migration into sponges. Our results, combined with findings of others showing reduced PMN infiltration in lungs of mice infected with C. neoformans var. gattii compared with PMN infiltration in lungs of mice infected with C. neoformans var. neoformans, indicate that the relative inadequacy of normal host resistance mechanisms to prevent infection with C. neoformans var. gattii results, in part, from inhibition of PMN migration to the site of the organism.

Animals↗
PubMed1993

Mobility of human neutrophils in response to Cryptococcus neoformans cells, culture filtrate antigen, and individual components of the antigen.

The mobility of human neutrophils (PMN) in response to encapsulated or nonencapsulated Cryptococcus neoformans cells or cryptococcal culture filtrate (CneF) and its components was studied by using a 48-well modified Boyden chamber. Encapsulated C. neoformans (isolate 184A) cells and CneF-184A stimulated directed migration of human PMN in the absence of serum (direct chemotactic activity) and activated a heat-labile component(s) in fresh human serum to become a chemoattractant(s) for human PMN (indirect chemotactic activity). At a 1:8 dilution (0.25 mg of carbohydrate per ml), CneF-184A displayed chemokinetic activity when assessed with a checkerboard assay. Nonencapsulated C. neoformans isolate 602 cells did not have direct chemotactic activity but did have indirect chemotactic activity. The capsule of C. neoformans is composed predominantly of glucuronoxylomannan (GXM). Purified GXM displayed both direct and indirect chemotactic activity. CneF-184A contains, in addition to GXM, a concanavalin A-binding mannoprotein (MP), whereas CneF-602 contains no GXM but does contain MP. CneF-184A showed direct chemotactic activity and CneF-602 did not. Both CneF-184A and CneF-602 displayed indirect chemotactic activity for human PMN. In addition, purified MP from CneF-184A, like CneF-602, showed only indirect chemotactic activity. These results indicate that GXM contributes to the direct chemotactic activity of PMN observed with the whole encapsulated yeast cells and the unfractionated CneF derived from the encapsulated cells. Both MP and GXM from encapsulated C. neoformans cells mediate indirect chemotactic activity on human PMN.

Antigens, Fungal↗
PubMed1991

Study of immune function of cancer patients influenced by supplemental zinc or selenium-zinc combination.

Since hair Zn and serum Zn are usually decreased in cancer patients, and Zn deficiency may reduce the function of T-cells, granulocytes, and Nk cells, we observed in cancer patients the influences of the Zinc or Selenium-Zinc on DNCB skin delayed hypersensitivity mediated by T cell, and the effects of Zinc on oxidative metabolic function of neutrophils and level of serum interferon that potentiate NK cell activity. The results showed that DNCB skin reaction was strengthened, the oxidative metabolic function of neutrophils and serum interferon level were increased by the drugs. It is reasonable to expect that Zinc or Selenium-Zinc is instrumental in restoring failing immunocompetence of cancer patient.

Erythema↗
PubMed1991

Relationships between Alternaria alternata and oesophageal cancer.

Although it is uncertain whether fungi can produce the mycotoxins that induce oesophageal cancer, the tumorigenicity of fungi isolated from grain in an area of high incidence of oesophageal cancer has been confirmed. Alternaria alternata is a fungus of importance in this respect. The contamination rate with A. alternata in corn from areas of high morbidity from oesophageal cancer is higher than that in low-morbidity areas. Extracts of A. alternata induced reverse mutation in Escherichia coli, unscheduled DNA synthesis in cultured human amnion FL cells, chromosomal aberrations and sister chromatid exchange in human peripheral blood lymphocytes, mutation in V79 cells and transformation of NIH3T3 cells. Alternariol methyl ether, which is an active compound produced by this fungus, also induced transformation of NIH3T3 cells, and the transformed cells grew in soft agar and were tumorigenic in nude mice. Food mildewed by this fungus induced forestomach tumours in rats. Thus, (i) A. alternata is tumorigenic, (ii) it has been isolated from corn in an area of high incidence of oesophageal cancer, and (iii) contamination with A. alternata in the area of high incidence is higher than that in the area of low incidence. We therefore believe that A. alternata is one of the causes of human oesophageal cancer.

Alternaria↗
PubMed1990

Study of the oxidative metabolic function and chemotaxis of neutrophils from patients with cancer influenced by selenium yeast.

The effects of Selenium Yeast (SY) given orally to patients with cancer on the oxidative metabolic function and chemotaxis of neutrophils were studied by Lumino-dependent Chemiluminescence (CL) assay and agarose plates assay, respectively. The results showed that the background CL and the peak value CL of neutrophils from patients with cancer 14 d after taking SY were, on the average, 4 and 1.2 times higher than those before taking SY. The chemotactic index (CI) and chemotactic differential (CD) increased in response to SY supplementation; the differences are statistically significant (p less than 0.01), and no corresponding differences could be seen in the control group (taking yeast).

Adult↗