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Biomedical subjects

D Zeng

Publications and source records attributed to D Zeng.

At least 37 records · Page 2Linked to original sources
PubMed1999

Bone marrow NK1.1(-) and NK1.1(+) T cells reciprocally regulate acute graft versus host disease.

Sorted CD4(+) and CD8(+) T cells from the peripheral blood or bone marrow of donor C57BL/6 (H-2(b)) mice were tested for their capacity to induce graft-versus-host disease (GVHD) by injecting the cells, along with stringently T cell-depleted donor marrow cells, into lethally irradiated BALB/c (H-2(d)) host mice. The peripheral blood T cells were at least 30 times more potent than the marrow T cells in inducing lethal GVHD. As NK1.1(+) T cells represented <1% of all T cells in the blood and approximately 30% of T cells in the marrow, the capacity of sorted marrow NK1.1(-) CD4(+) and CD8(+) T cells to induce GVHD was tested. The latter cells had markedly increased potency, and adding back marrow NK1.1(+) T cells suppressed GVHD. The marrow NK1.1(+) T cells secreted high levels of both interferon gamma (IFN-gamma) and interleukin 4 (IL-4), and the NK1.1(-) T cells secreted high levels of IFN-gamma with little IL-4. Marrow NK1.1(+) T cells obtained from IL-4(-/-) rather than wild-type C57BL/6 donors not only failed to prevent GVHD but actually increased its severity. Together, these results demonstrate that GVHD is reciprocally regulated by the NK1.1(-) and NK1.1(+) T cell subsets via their differential production of cytokines.

Animals↗
PubMed1999

cDNA cloning and sequence analysis of hepatitis G virus genome isolated from a Chinese blood donor.

OBJECTIVE: To obtain full-length sequence of a Chinese hepatitis G virus (HGV) strain (HGVch) and investigate the genetic characteristic of HGVch and its identity to other isolates. METHODS: Reverse transcription (RT) and nested-PCR were used to screen HGV RNA positive serum and amplify cDNA fragments. A positive serum without known hepatitis virus markers was selected for isolating HGV RNA template. The HGV genome was divided into 12 overlapping fragments and directly cloned into pGEM-T vector. Sequences were determined by dideoxy terminus-end method of DNA sequencing and then analyzed by computer. RESULTS: The twelve fragments of HGVch cover 9213 nucleotides in length, containing a large open reading frame (ORF) encoding 2873 animo acids polyprotein that began with a methonine residue and ended at termination codon. HGVch is about 86.5%-89.5% identical to other known HGV isolates at the nucleotide level and about 93.9%-96.2% at the deduced animo acid level. CONCLUSION: HGV is a non-A-E hepatitis causal agent, proved to be related with posttransfusion hepatitis in all over the world. Chinese HGV isolate has very close relationship to other isolates from Africa, Europe, Japan, without significant difference across the entire genome. It is suggested that the sequences of HGV isolates are very conservative and the evolution is very slow.

Blood Donors↗
PubMed1999

[The effects of Xuezhikang on neointimal proliferation and C-myc gene expression after angioplasty in rabbits].

OBJECTIVE: To investigate the effects of Xuezhikang (XZhK) on the neointimal proliferation and C-myc gene expression after angioplasty in rabbits. METHODS: Angioplasty for atherosclerotic stenosis of celiac arteries was performed in 30 male white rabbits after being fed with cholesterol-supplemented diet for 8 weeks, which were then randomized to control group, high-cholesterol group and XZhK group. After 4 weeks, the local vessels were collected for morphological observation. C-myc mRNA level was measured with RT-PCR and C-myc protein with immunohistochemical analysis. RESULTS: Morphological observation showed that the neointimal area in the XZhK group were less than the control group (P < 0.05), and that in control group were less than that in the high-cholesterol group (P < 0.05). The levels of C-myc mRNA measured with RT-PCR and the percentage of C-myc protein positive cell by immunohistochemical analysis were lower in the XZhK group than in the control and high-cholesterol group (P < 0.05), The levels in the latter two groups showed no difference (P > 0.05). CONCLUSION: XZhK can inhibit the neointimal proliferation and the expression of C-myc gene after angioplasty in rabbits.

Angioplasty, Balloon↗
PubMed1998

Donor blood monocytes but not T or B cells facilitate long-term allograft survival after total lymphoid irradiation.

BACKGROUND: Previous studies showed that a combination of posttransplant total lymphoid irradiation (TLI), rabbit antithymocyte globulin (ATG), and a single donor blood transfusion induced tolerance to ACI heart allografts in Lewis rats. All three modalities were required to achieve tolerance. The objective of the current study was to determine the subset(s) of cells in the donor blood that facilitated long-term allograft survival. METHODS: Lewis hosts received TLI, ATG, and donor cell infusion after heart transplantation. Graft survival, mixed leukocyte reaction (MLR), and intragraft cytokine mRNA were studied. RESULTS: The intravenous injection of 25 x 10(6) ACI peripheral blood mononuclear cells (PBMC) significantly prolonged graft survival as compared with that of Lewis hosts given TLI and ATG alone. Injection of highly enriched blood T cells or splenic B cells adjusted for the number contained in 25 x 10(6) PBMC failed to induce significant graft prolongation. Unexpectedly, depletion of monocytes (CD11b+ cells) from PBMC resulted in the loss of graft prolongation activity. Enriched populations of monocytes obtained by plastic adherence were more efficient in prolonging graft survival than PBMC on a per cell basis. Hosts with long-term grafts (>100-day survival) showed evidence of immune deviation, because the MLR to ACI stimulator cells was vigorous, but secretion of interferon-gamma in the MLR was markedly reduced. In situ hybridization studies of long-term grafts showed markedly reduced levels of interferon-gamma mRNA as compared with rejecting grafts. CONCLUSION: Infusion of donor monocytes facilitated graft prolongation via immune deviation.

Animals↗
PubMed1998

A dual thrombin receptor system for platelet activation.

Platelet-dependent arterial thrombosis triggers most heart attacks and strokes. Because the coagulation protease thrombin is the most potent activator of platelets, identification of the platelet receptors for thrombin is critical for understanding thrombosis and haemostasis. Protease-activated receptor-1 (PAR1) is important for activation of human platelets by thrombin, but plays no apparent role in mouse platelet activation. PAR3 is a thrombin receptor that is expressed in mouse megakaryocytes. Here we report that thrombin responses in platelets from PAR3-deficient mice were markedly delayed and diminished but not absent. We have also identified PAR4, a new thrombin-activated receptor. PAR4 messenger RNA was detected in mouse megakaryocytes and a PAR4-activating peptide caused secretion and aggregation of PAR3-deficient mouse platelets. Thus PAR3 is necessary for normal thrombin responses in mouse platelets, but a second PAR4-mediated mechanism for thrombin signalling exists. Studies with PAR-activating peptides suggest that PAR4 also functions in human platelets, which implies that an analogous dual-receptor system also operates in humans. The identification of a two-receptor system for platelet activation by thrombin has important implications for the development of antithrombotic therapies.

Amino Acid Sequence↗
PubMed1998

Antibodies to protease-activated receptor 3 inhibit activation of mouse platelets by thrombin.

Recent studies of mice deficient in the thrombin receptor, protease-activated receptor 1 (PAR1), provided definitive evidence for the existence of a second thrombin receptor in mouse platelets. We recently identified a new thrombin receptor designated protease-activated receptor 3 (PAR3). The mRNA encoding a mouse homologue of PAR3 was highly expressed in mouse splenic megakaryocytes, making it a good candidate for the missing mouse platelet thrombin receptor. We now report that PAR3 protein is expressed on the surface of mouse platelets and that PAR3 antibodies partially inhibit activation of mouse platelets by thrombin but not U46619, a thromboxane receptor agonist. These observations suggest that PAR3 contributes to mouse platelet activation by thrombin.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1998

Subsets of transgenic T cells that recognize CD1 induce or prevent murine lupus: role of cytokines.

T cells with T cell receptor (TCR) transgenes that recognized CD1 on syngeneic B cells stimulated B cells to secrete immunoglobulins in vitro. The CD4+, CD8+, or CD4-CD8- T cells from the spleen of the TCR transgenic BALB/c donors induced lupus with anti-double stranded DNA antibodies, proteinuria, and immune complex glomerulonephritis in irradiated BALB/c nude mice reconstituted with nude bone marrow. Injection of purified CD4-CD8- T cells from the marrow of transgenic donors prevented the induction of lupus by the transgenic T cells. Transgenic T cells that induced lupus secreted large amounts of interferon (IFN)-gamma and little interleukin (IL)-4, and those that prevented lupus secreted large amounts of IL-4 and little IFN-gamma or IL-10.

Animals↗
PubMed1998

H2-uptake activity, spectra, reduction potentials, and kinetics of iron release on the surface of iron core from Azotobacter vinelandii bacterial ferritin.

Bacterial ferritin from Azotobacter vinelandii (AvBFo) has a function in H2 uptake. The Fe3+ reduction on the surface of the iron core from AvBFo is accompanied simultaneously by H2 uptake, with a maximum activity of H2 uptake of 450 H2/AvBFo. A reduction potential of -402 mV for iron reduction on the surface of the core is found. A shift to the red the protein absorbance peaks ranging from 280 to 290 nm is observed between pH 5 and 9 under 100% H2 reduction. The reduction potential for iron release becomes negative at a rate of 0.025 mV/Fe2+ released. The kinetics of iron release on the surface of the core is a first-order reaction.

Azotobacter vinelandii↗
PubMed1997

T helper 2-dominant antilymphoma immune response is associated with fatal outcome.

The precise role of the endogenous immune system in modulating cancer development remains unclear. Tumor cells are generally thought to be nonimmunogenic because they are of 'self' origin. However, tumor-reactive lymphocytes can be isolated from patients with many types of cancer. It is unclear what role these lymphocytes play and why they fail to protect the host. Using a murine B-cell leukemia/lymphoma (BCL1) model, we showed the development of a vigorous antitumor T-cell response in the tumor-susceptible host. Specific T-cell responses against BCL1 developed as early as day 4. However, the nature of this nonprotective response is different from the protective response produced in a major histocompatibility complex-matched tumor-resistant host. Susceptible hosts developed a T helper 2 (Th2)-dominant response, whereas resistant hosts developed a Th1-dominant response to BCL1. Cytolytic activity against BCL1 developed in both resistant and susceptible hosts, but in the susceptible host, this response was weaker and delayed compared with that in the resistant host. Thus, tumor susceptibility does not necessarily mean the absence of an antitumor immune response. Rather, the nature of the antitumor immune response is critical in determining clinical outcome.

Animals↗
PubMed1997

Granulocyte colony-stimulating factor reduces the capacity of blood mononuclear cells to induce graft-versus-host disease: impact on blood progenitor cell transplantation.

The feasibility of transplanting peripheral blood mononuclear cells (PBMC) from granulocyte colony-stimulating factor (G-CSF)-treated normal human donors to myeloablated allogeneic hosts has been demonstrated recently. The current work examined the ability of recombinant G-CSF to alter peripheral blood T-cell function and graft-versus-host disease (GVHD) in a murine model of allogeneic G-CSF-mobilized PBMC transplantation. Administration of recombinant G-CSF to C57BL/Ka mice markedly increased the capacity of PBMC to reconstitute lethally irradiated syngeneic hosts. T- and B-lineage lymphocytes were depleted about 10-fold in the bone marrow of the treated mice, and the T-cell yield in the blood was increased about fourfold. The ability of PBMC or purified CD4+ and CD8+ T cells to induce acute lethal GVHD in irradiated BALB/c mice was reduced after the administration of G-CSF. This was associated with decreased secretion of interferon gamma and interleukin-2 (IL-2) and an increased secretion of IL-4. The donor cell inoculum, which was most successful in the rescue of irradiated allogeneic hosts, was the low-density fraction of PBMC from G-CSF-treated mice. These low-density cells were enriched for CD4-CD8-NK1.1+ T cells and secreted about 10-fold more IL-4 than the unfractionated cells from the G-CSF-treated donors.

Animals↗
PubMed1997

Protease-activated receptor 3 is a second thrombin receptor in humans.

Thrombin is a coagulation protease that activates platelets, leukocytes, endothelial and mesenchymal cells at sites of vascular injury, acting partly through an unusual proteolytically activated G-protein-coupled receptor. Knockout of the gene encoding this receptor provided definitive evidence for a second thrombin receptor in mouse platelets and for tissue-specific roles for different thrombin receptors. We now report the cloning and characterization of a new human thrombin receptor, designated protease-activated receptor 3 (PAR3). PAR3 can mediate thrombin-triggered phosphoinositide hydrolysis and is expressed in a variety of tissues, including human bone marrow and mouse megakaryocytes, making it a candidate for the sought-after second platelet thrombin receptor. PAR3 provides a new tool for understanding thrombin signalling and a possible target for therapeutics designed selectively to block thrombotic, inflammatory and proliferative responses to thrombin.

Amino Acid Sequence↗
PubMed1997

[A three-month follow-up study of excimer laser photorefractive keratectomy for myopia].

In order to evaluate the efficacy of photorefractive keratectomy (PRK) in the treatment of myopia, we summed up and analysed the 3-month follow-up data on 145 cases treated in our hospital. Prior to PRK, refractive dioptal was -1.5 to -11.5; visual acuity was less than 0.1 in 137 cases (94%) and less than 0.5 in 8 cases(6%). One month after operation, the mean refractive dioptal was +0.98 +/- 0.88; visual acuity increased to > or = 1.0 in 95 cases (66%) and to > or = 0.5 in 142 cases(98%). Three months after operation, the mean refractive dioptal was -0.13 +/- 1.09; visual acuity increased to > or = 1.0 in 104 cases(72%) and to > or = 0.5 in 135 cases(93%). There was no severe complication noted in all cases. The results demonstrate that PRK is and effective, safe and predictable treatment for myopia.

Adolescent↗
PubMed1997

[Study on a new rheological equation of state for blood].

Blood behaves like a Non-Newtonian fluid under low shear rate. A number of constitutive equations for blood have been proposed in the literature, but yet a general equation which demonstrates all aspects of blood's Non-Newtonian characteristics has not been established. With this problem we analysed the Oldroyd Equation as a possible model for blood. Theory analysis indicated that the phenomena of blood flow under low shear rate, such as shear thinning, stress overshoot and phase delay in periodic flow, can be explained by introducing the equation with four parameters, suggesting it to be an appropriate model for blood. We tested the parameters. Stress versus time curves under rectangular step of shear rate were also tested and the results were compared with those of theory prediction.

Blood Flow Velocity↗
PubMed1996

Role of the thrombin receptor's cytoplasmic tail in intracellular trafficking. Distinct determinants for agonist-triggered versus tonic internalization and intracellular localization.

The G protein-coupled thrombin receptor is activated by an irreversible proteolytic mechanism and, perhaps as a result, exhibits an unusual trafficking pattern in the cell. Naive receptors tonically cycle between the cell surface and a protected intracellular pool, whereas receptors cleaved and activated at the cell surface internalize and move to lysosomes. Toward understanding how these trafficking events are regulated, we examined a series of receptor mutants. A receptor with alanine substitutions at all potential phosphorylation sites in the cytoplasmic tail failed to display agonist-triggered internalization but, like wild type receptor, displayed robust signaling, tonic cycling, and localization to both the cell surface and an intracellular pool. A truncation mutant that lacked most of the cytoplasmic tail also signaled robustly, lacked phosphorylation, and was defective in agonist-triggered internalization. However, in contrast to the specific phosphorylation site mutant, the truncation mutant did not display tonic cycling and localized exclusively to the cell surface. An analysis of a series of truncation mutants localized residues important for receptor trafficking to a 10-amino acid stretch in its cytoplasmic tail. These data suggest that phosphorylation may trigger internalization of activated thrombin receptors but that a second phosphorylation-independent signal mediates tonic internalization of naive receptors. They further suggest that maintenance of the intracellular pool of naive thrombin receptors requires tonic receptor internalization.

Animals↗
PubMed1996

Mechanisms of tolerance to rat heart allografts using posttransplant TLI. Changes in cytokine expression.

Lewis rats were rendered tolerant to ACI heart allografts using a regimen of posttransplant total lymphoid irradiation (TLI), rabbit antithymocyte or antilymphocyte globulin (RATG or RALG), and a single donor blood transfusion. All three treatment modalities were required to induce tolerance. The mechanism of the maintenance of tolerance was investigated by comparing the secretion of cytokines in the MLR, and the expression of cytokine mRNA in the allografts of tolerant and nontolerant Lewis rats. Although, the 3H-thymidine incorporation and secretion of IL-2 was frequently comparable in the MLR from tolerant and nontolerant rats, the secretion of IFN-gamma was markedly reduced in the tolerant rats. This was reflected in a markedly reduced frequency of cells expressing IFN-gamma mRNA in the allografts of tolerant as compared with nontolerant hosts. The frequency of cells expressing IL-2 and IL-10 mRNA was also reduced, but no significant difference was observed for cells with IL-4 mRNA. Spleen cells from nontolerant rats rapidly rejected ACI allografts in irradiated adoptive hosts, but spleen cells from tolerant rats did not. Evaluation of the cytokine mRNA expression at early and late time points in the allografts of adoptive hosts showed a pattern similar to that of the primary hosts. Thus, the tolerant state was associated with a maintenance or elevation of IL-4 expression and a marked reduction of IFN-gamma expression. Previous reports have shown that TLI alone induced this shift in the early recovery phase after irradiation.

Animals↗
PubMed1996

Different patterns of TCR transgene expression in single-positive and double-negative T cells. Evidence for separate pathways of T cell maturation.

Two lines of transgenic mice were established using the TCR alpha (V alpha 4.4-J alpha 24)- and beta (V beta 9-D beta 1.1-J beta 2.1)-chain genes from a cloned CD4-CD8-alpha beta + (double-negative; DN) T cell line from BALB/c mice. The TCR genes were expressed in CD4+CD8- and CD4-CD8+ (single-positive; SP) and double-positive (DP) T cells in the thymus, and in SP T cells in the peripheral lymphoid tissues, and marrow in one transgenic mouse line, and predominantly in DN T cells in the other. Bone marrow precursor cells from only the DN mouse line generated T cells expressing the V beta 9 transgene during tissue culture. V beta 9+ T cells were found in DN but not SP transgenic mice backcrossed to BALB/c nu/nu mice. The results suggest two separate pathways of T cell maturation, one which generates SP T cells in the thymus, and another which generates DN T cells in both the thymus and bone marrow.

Amino Acid Sequence↗
PubMed1996

Failure to find exon 7 polymorphism of the ADH7 gene in Chinese, Japanese, African-Americans, and Caucasians.

Class IV alcohol dehydrogenase (sigma-ADH) activity has been found in high levels in the stomach and esophagus, but not in liver. Gastric ADH activity has been reported to influence blood alcohol levels after oral ethanol ingestion, suggesting that sigma-ADH activity plays a role in first-pass metabolism. It has also been reported that women have lower sigma-ADH activity than men and that Asians have lower sigma-ADH activity than Caucasians and African-Americans. A genetic basis for these gender and ethnic differences in sigma-ADH activity has been postulated. A recent study in a Japanese subject found a point mutation in the codon for amino acid 287 of the ADH7 gene (which encodes sigma-ADH), changing the amino acid from glycine to valine. A polymerase chain reaction-sequencing assay was established to determine the frequency of this polymorphism in the Asian, Caucasian, and African-American populations. The polymorphism was not present in the 21 Asians, 15 Caucasians, and 3 African-Americans we genotyped, suggesting that if this polymorphism exists, its frequency is low in these ethnic groups. It is therefore unlikely to be responsible for the absence of sigma-ADH activity in gastric specimens from Asians.

Adult↗