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Biomedical subjects

D Xu

Publications and source records attributed to D Xu.

430 records · Page 24Linked to original sources
PubMedDate not supplied

Expression of adenylyl cyclase V/VI mRNA and protein is upregulated in cyanotic infant human myocardium.

We have previously demonstrated that both basal and isoproterenol-stimulated activities of myocardial adenylyl cyclase were greater in cyanotic patients with tetralogy of Fallet (TOF) than those in acyanotic patients. However, it was not determined whether increased enzyme activity was related to a similar increase in adenylyl cyclase protein and mRNA expression. In the current study, we examined the mRNA and protein expression of cardiac adenylyl cyclase, types V and VI, in cyanotic and acyanotic patients with TOF. Ribonuclease protection assays and immunoblotting were performed on myocardial specimens obtained from cyanotic patients with TOF and acyanotic patients with TOF or ventricular septal defect. We demonstrated that in both cyanotic and acyanotic patients, there was more type V adenylyl cyclase mRNA than type VI. Types V and VI cardiac adenylyl cyclase mRNA were significantly increased in myocardium of the cyanotic group compared to the acyanotic group. Protein expression of both V and VI adenylyl cyclases was correspondingly upregulated in cyanotic patients compared to acyanotic patients. Our results indicate that gene and protein expression of cardiac adenylyl cyclases, types V and VI, is increased in the cyanotic myocardium. These results suggest that chronic hypoxemia may regulate the expression of adenylyl cyclase enzymes.

Adenylyl Cyclases↗
PubMedDate not supplied

Calcitonin gene-related peptide (CGRP) in normotensive and spontaneously hypertensive rats.

With the techniques of specific radioimmunoassay and gel filtration it was found that CGRP was distributed in various tissues of normotensive (WKY) and spontaneously hypertensive rats (SHR) with the highest concentration in the lumbar spinal cord (1197 +/- 94.8 pg/mg tissue) and the lowest in the auricle (15.0 +/- 2.1 pg/mg tissue). In comparison with WKY, CGRP concentration in the plasma was decreased and in the abdominal aorta and hypothalamus was increased in SHR. Gel filtration revealed only one major CGRP molecular form in the tissues. In addition, CGRP reduced the mean arterial pressure (MAP) in SHR in a dose-dependent manner. These data suggest that CGRP may play an important role in the pathogenesis of hypertension and its possible therapy.

Animals↗
PubMedDate not supplied

Inquiring into indicators and origin of catastrophic events at stratigraphic boundaries.

Since 1982, numerous indicators of catastrophic events have been observed at the main stratigraphic boundaries in China during the Phanerozoic, i.e. Precambrian-Cambrian, Permian-Triassic, Cretaceous-Tertiary as well as Ordovician-Silurian and Devonian-Carboniferous boundaries. These markers are boundary clay layer, microspherules, high Ir anomaly, mass extinction of organisms and impact of meteorite. We support the hypothesis of the extraterrestrial origin of catastrophic events and suggest that the events at different stratigraphic boundaries might be different in features and processes.

Aluminum Silicates↗
PubMedDate not supplied

Immunological evaluation of combination therapy with tacrolimus and sirolimus on long-term allograft survival in nonhuman primates.

UNLABELLED: We reported that a 60-day course of combination therapy with tacrolimus and sirolimus induced long-term survival of renal allograft after withdrawal of immunosuppressants in Vervet monkeys. In the present study, the mechanism of drug-induced allograft survival was evaluated via Th1/Th2 cytokines, apoptosis and MLC activity in primates. MATERIALS AND METHODS: Cytokines were evaluated by ELISA. MLR and CTL assays were performed by incorporation of 72 hours (3)H-TdR and 4 hours (51)Cr release assay. RESULTS: A 60-day course of tacrolimus with sirolimus resulted in long-term survival of kidney allografts. (67% > 100 days) without intermittent acute rejection. Low sensitivity to MLR was seen in long-term renal allograft survival among monkeys treated with tacrolimus and sirolimus. Increased levels of CD3(+)CD8(+), CD3(+)/CD56(+) NKT cells and CD86(+)CD8(-)CD11(+) dendritic cells were observed. A population of high expression of CD4(+)FasL(+) was detected. In addition, the concentrations of IL-2 and IFN-gamma from long-term allograft surviving monkeys was not significantly increased, rather a late phase dominance of Th2, IL-4, IL-10, and TGF-beta was found correlated with long-term survival of recipients. In conclusion, the mechanism of tacrolimus and sirolimus induced long-term allograft survival in primates relates to up-regulated FasL expression, NKT cells and dendritic cells, with downregulation of MLR sensitivity. It is also associated with late-dominant expression of Th2 cytokines.

Animals↗
PubMedDate not supplied

Elemental diet-induced immune suppression is caused by both bacterial and dietary factors.

Because it is unclear whether elemental diet-induced immune suppression is an indirect effect caused by the translocating bacteria or is directly caused by the elemental diet, we tested whether prevention of diet-induced bacterial translocation or disruption of the gut microflora ecology would prevent diet-induced impaired lymphocyte function in a rat elemental diet model. Prevention of diet-induced bacterial translocation was accomplished by the addition of cellulose fiber or oral antibiotics (penicillin and streptomycin) to the elemental diet feeding regimen. Control groups consisted of rat food-fed and elemental diet-fed (4.25% amino acids; 28% glucose) rats. Immune function was quantitated by measuring the mitogen-induced blastogenic response of peripheral blood or splenic mononuclear cells to the mitogens concanavalin A and phytohemagglutinin. Bacterial translocation from the gut to the mesenteric lymph node and cecal bacterial population levels were measured in all groups. Although the incidence of elemental diet-induced bacterial translocation was reduced from 100% to 25% (p < .01) by the addition of dietary fiber, fiber did not prevent diet-induced impaired lymphocyte function. Because fiber supplementation of the elemental diet did not completely prevent diet-induced intestinal bacterial overgrowth or bacterial translocation, the experiment was repeated in antibiotic-decontaminated rats. Antibiotic decontamination completely prevented diet-induced intestinal bacterial overgrowth and bacterial translocation. Although antibiotic decontamination reduced the magnitude of lymphocyte mitogen suppression (p < .05), it was not fully effective in reversing the diet-induced lymphocyte suppression. These results indicate that elemental diet-induced lymphocyte blastogenic suppression is related to both bacterial and dietary factors.

Animals↗
PubMedDate not supplied

The modulatory role of gut hormones in elemental diet and intravenous total parenteral nutrition-induced bacterial translocation in rats.

We have previously shown that parenteral and certain elemental diets promote bacterial translocation and that this diet-induced bacterial translocation can be prevented by the provision of bulk-forming dietary fiber. The goal of the current study was to test the hypothesis that fiber's protective effect on diet-induced bacterial translocation was mediated by trophic gut hormones. This hypothesis was tested by using bombesin (which stimulates gut hormone release) or the somatostatin analog Sandostatin (which inhibits gut hormone release) to modulate gut hormone release in rats receiving rat food, intravenous total parenteral nutrition, or an elemental diet. Both bombesin and fiber were effective in preventing elemental diet-induced bacterial translocation, whereas octreotide acetate abrogated the protective effect of fiber. Bombesin was also effective in limiting bacterial translocation in parenterally fed rats. Although both enteral (elemental diet) and parenteral diet-induced bacterial translocation were associated with cecal bacterial overgrowth, loss of small-bowel weight, and loss of mucosal protein content, none of these factors seemed to be primarily responsible for bacterial translocation. Because bombesin decreased the incidence of villous injury in the elemental diet-fed rats and decreased the incidence of villous injury and prevented loss of intestinal barrier function to horseradish peroxidase in the parenterally fed rats, it is possible that bombesin exerted its protective effect by limiting mucosal injury and preserving barrier function.

Animals↗
PubMedDate not supplied

Elemental diet-induced bacterial translocation associated with systemic and intestinal immune suppression.

BACKGROUND: Elemental diets can lead to a loss of intestinal barrier function, promote bacterial translocation, and impair host immune defenses. The purpose of this study was to determine the effects of i.v. and orally administered total parenteral nutrition (TPN) solution on systemic and intestinal immunity and to establish whether supplemental cellulose fiber could improve the impaired immune response. METHODS: The incidence of bacterial translocation and immune function was quantitated by measuring organ weights, immune cell population levels, and the mitogenic response of lymphocytes from the spleen, mesenteric lymph nodes and Peyer's patches of rats receiving parenteral or enteral TPN solution, with and without fiber supplementation. RESULTS: Parenteral and enterally administered TPN solution promoted bacterial translocation to the mesenteric lymph nodes, reduced immune cell population levels, and decreased the lymphocyte mitogenic response to T- and B-cell mitogens. Supplemental cellulose fiber reduced the incidence of diet-induced bacterial translocation from 84% to 31% (p < .01) and improved immune cell function. To more closely examine the relationship between bacterial translocation and impaired lymphocyte mitogenic activity, rats receiving TPN orally or i.v. were separated into two groups based on whether or not bacterial translocation occurred. Rats in which fiber prevented bacterial translocation had normal mitogenic responses, whereas the sub-group of rats in which fiber failed to prevent bacterial translocation had profound decreases in their lymphocyte mitogenic responses. CONCLUSIONS: Both parenteral and enteral elemental diets induced bacterial translocation and impaired systemic and intestinal immune function. Fiber supplementation was effective in reducing elemental diet-induced bacterial translocation and significantly prevented diet-induced impairment of lymphocyte function.

Administration, Oral↗
PubMedDate not supplied

Biological and receptor-binding activities of human interleukin-2 mutated at residues 20Asp, 125Cys or 127Ser.

We have used site-directed mutagenesis to analyse structure-function relationships of the human Interleukin-2 molecule. The mutations introduced targetted residue 20Asp, within the N-terminal A helix, as well as residues 125Cys and 127Ser in the C-terminal D helix. The results presented here demonstrate that destabilizing the C-terminus alpha helix through introduction of Pro residues in either positions 125 or 127 reduced the biological activity of IL-2 by a factor of 10 that was correlated with a decreased ability to bind the receptor. A number of substitutions in position 20 have an even more drastic effect on biological activity and receptor binding. However, specific substitutions such as 20Asn and 20Leu displayed a differential effect on human or mouse IL-2 receptors. Furthermore, 20Leu IL-2 was found to behave as a partial antagonist of natural IL-2 when tested on murine cells.

Animals↗