Biomedical subjects

C Deng

Publications and source records attributed to C Deng.

At least 37 records · Page 2Linked to original sources

PubMed2001

Post-transplant lymphoproliferative disease in children.

Epstein-Barr virus (EBV)-driven post-transplant lymphoproliferative disease (PTLD) is an important cause of morbidity and mortality following transplantation, and it occurs more frequently in children than in adults. Of 22 (5%) children at our institution who developed tissue-proven PTLD 1-60 months (mean 16.5 months) following organ transplant, 11 died: nine of these 22 patients developed PTLD between 1989 and 1993, and seven (78%) died; the remaining 13 developed PTLD between 1994 and 1998, and four (31%) died (p = 0.08). All nine patients who developed PTLD < 6 months after transplant died, but 11 of 13 patients who manifested disease > or = 6 months after transplant survived (p = 0.0002). Ten of 11 (91%) survivors, but only two of eight (25%) children who died, had serologic evidence of EBV infection at the time of PTLD diagnosis (p = 0.04). EBV seroconversion identified patients at risk for developing PTLD, but also characterized patients with sufficient immune function to survive EBV-related lymphoid proliferation. In situ hybridization for EBER1 mRNA was diagnostically helpful because it detected EBV in tissue sections of all 20 patients with B-cell PTLD, including those with negative serology.

Adolescent↗

PubMed2001

ADY1, a novel gene required for prospore membrane formation at selected spindle poles in Saccharomyces cerevisiae.

ADY1 is identified in a genetic screen for genes on chromosome VIII of Saccharomyces cerevisiae that are required for sporulation. ADY1 is not required for meiotic recombination or meiotic chromosome segregation, but it is required for the formation of four spores inside an ascus. In the absence of ADY1, prospore formation is restricted to mainly one or two spindle poles per cell. Moreover, the two spores in the dyads of the ady1 mutant are predominantly nonsisters, suggesting that the proficiency to form prospores is not randomly distributed to the four spindle poles in the ady1 mutant. Interestingly, the meiosis-specific spindle pole body component Mpc54p, which is known to be required for prospore membrane formation, is localized predominantly to only one or two spindle poles per cell in the ady1 mutant. A partially functional Myc-Pfs1p is localized to the nucleus of mononucleate meiotic cells but not to the spindle pole body or prospore membrane. These results suggest that Pfs1p is specifically required for prospore formation at selected spindle poles, most likely by ensuring the functionality of all four spindle pole bodies of a cell during meiosis II.

Cell Membrane↗

PubMed2001

Unexpected effects of a heterozygous dnmt1 null mutation on age-dependent DNA hypomethylation and autoimmunity.

DNA methylation modifies gene expression. Methylation patterns are established during ontogeny, but they change with aging, usually with a net decrease in methylation. The significance of this change in T cells is unknown, but it could contribute to autoimmunity, senescence, or both. We examined the effects of a null mutation in DNA methyltransferase 1 (Dnmt1), a gene maintaining DNA methylation patterns, on immune aging. Whereas aged control mice developed hypomethylated DNA, autoimmunity, and signs of immune senescence as predicted, the knockout mice surprisingly increased DNA methylation and developed signs of autoimmunity and senescence more slowly. To identify potential mechanisms, we compared transcripts of DNA methyltransferase and methylcytosine binding protein family members in control and knockout mice. MeCP2, a methylcytosine binding protein involved in gene suppression and chromatin inactivation, was the only transcript differentially expressed between old knockout mice and controls, and thus it is a candidate for a gene product mediating these effects.

Aging↗

PubMed2001

Motor deficits in fibroblast growth factor receptor-3 null mutant mice.

Fibroblast growth factor receptor-3 (FGFR-3) regulates aspects of bone development. Mutations in the FGFR-3 gene (Fgfr3) in humans and mice produce vertebral abnormalities and bone deformities. The present study evaluated the behavioural concomitants of the Fgfr3-/- mutation. Fgfr3-/- null mutant mice displayed severe impairments of motor abilities as detected on the rotarod, wire hang and open field tests. Absence of prepulse inhibition of acoustic startle was seen at prepulse levels from 74 to 86 dB. The motor deficits appear to be a direct and predicted consequence of the skeletal kyphosis, scoliosis and long bone overgrowth previously reported in Fgfr3 null mutant mice. The behavioural phenotype displayed by these mutant mice complements their anatomical, physiological and biochemical phenotypes, to complete the characterization of the functional outcome of a single gene mutation. Simple, robust behavioural symptoms, such as poor rotorod performance in Fgfr3 knockout mice, can provide useful surrogate markers to evaluate pharmacological treatments and gene therapies for human genetic diseases.

Animals↗

PubMed2001

Human cytochrome P450 isozymes in metabolism and health effects of gasoline ethers.

To reduce the production of carbon monoxide and other pollutants in motor vehicle exhaust, methyl tert-butyl ether (MTBE*), ethyl tert-butyl ether (ETBE), and tert-amyl methyl ether (TAME) are added to gasoline as oxygenates for more complete combustion. Among them, MTBE is the most widely used. The possible adverse effect of MTBE in humans is a public concern, but the human enzymes responsible for metabolism of these gasoline ethers and the causes or factors for increased sensitivity to MTBE in certain individuals are totally unknown. This information is important to understanding the health effects of MTBE in humans and to assessing the human relevance of pharmacokinetics and toxicity data obtained from animals. In the present study, we demonstrated that human liver is active in metabolizing MTBE to tert-butyl alcohol (TBA), a major circulating metabolite and an exposure marker of MTBE. The activity is localized in the microsomal fraction but not in the cytosol. Formation of TBA in human liver microsomes is NADPH-dependent and is significantly inhibited by carbon monoxide, which inhibits cytochrome P450 (CYP) enzymes. These results provide strong evidence that CYP enzymes play a critical role in the metabolism of MTBE in human livers. Human liver is also active in the oxidative metabolism of 2 other gasoline ethers, ETBE and TAME. We observed a large interindividual variation in metabolizing these gasoline ethers in 15 microsomal samples prepared from normal human livers. The activity level (pmol metabolite/min/mg) ranged from 204 to 2,890 for MTBE; 179 to 3,134 for ETBE; and 271 to 8,532 for TAME. The microsomal activities in metabolizing MTBE, ETBE, and TAME correlated highly with each other (r = 0.91 to 0.96), suggesting that these ethers are metabolized by the same enzyme(s). Correlation analysis of the ether-metabolizing activities with individual CYP enzyme activities in the human liver microsomes showed that the highest degree of correlation was with CYP isoform 2A6 (CYP2A6)+ (r = 0.94 for MTBE, 0.95 for ETBE, and 0.90 for TAME), which is constitutively expressed in human livers and known to be polymorphic. CYP2A6 displayed the highest turnover number in metabolizing gasoline ethers among a battery of human CYP enzymes expressed in human B-lymphoblastoid cells. CYP2A6 coexpressed with human CYP reductase by a baculovirus expression system was also more active than CYP isoform 2E1 (CYP2E1) in the metabolism of MTBE, ETBE, and TAME. Kinetic studies on MTBE metabolism with human liver microsomes (n = 3) exhibited an apparent Michaelis constant (Km) of 28 to 89 microM and a maximum rate of metabolism (Vmax) of 215 to 783 pmol/min/mg. Metabolism of MTBE, ETBE, and TAME by human liver microsomes was inhibited by coumarin, a known substrate of human CYP2A6, in a concentration-dependent manner. Monoclonal antibody against human CYP2A6 caused a significant inhibition (75% to 95%) of the metabolism of MTBE, ETBE, and TAME in human liver microsomes. Taken together, these results clearly indicate that, in human liver, CYP2A6 is a major enzyme responsible for metabolism of MTBE, ETBE, and TAME. Although CYP2E1 metabolizes diethyl ether and was previously suggested to be involved

Air Pollutants↗

PubMed2001

[The relativity study of thrombopoietin and chronic idiopathic thrombocytopenic purpura].

OBJECTIVE: To explore the relationship between thrombopoietin (Tpo) levels and reticulated platelet (RP), blood platelet count (BPC), maturity of megakaryocytes in patients with chronic idiopathic thrombocytopenic purpura (CITP), and the prediction evaluation according to Tpo levels. METHODS: Serum level of Tpo was measured by a sandwich-ELISA procedure, RP by flow cytometry after stained with thizole orange (TO), and maturity of megakaryocytes by laser scanning confocal microscopy (LSCM). RESULTS: The serum level of Tpo was (204.05 +/- 65.70) ng/L in 23 normal controls and (345.46 +/- 222.23) ng/L in 33 patients with CITP, being no significant difference between the two groups (P > 0.05). Compared with controls, serum Tpo levels in 22 aplastic anemia(AA) patients [(1427.62 +/- 468.84) ng/L] and 10 acute myelogenous leukemia (AML) patients [(596.09 +/- 462.95) ng/L] were increased significantly (P < 0.05). The RPC was significantly lower in AA and AML patients (P < 0.05). The RP% was increased significantly in CITP and AML patients (P < 0.05). The Tpo level was higher in CITP patients with no response to glucocorticoid therapy than in those with response (P < 0.05). CONCLUSION: Serum level of Tpo was not increased in patients with CITP. The RP%, RPC and Tpo levels could reflect thrombocytopoiesis and differentiate the causes of thrombocytopenia. The serum level of Tpo could be useful in prediction of the response to therapy in CITP patients.

Adolescent↗

PubMed2001

[Microsatellite polymorphisms at the TNF locus in Hubei Han population].

OBJECTIVE: To investigate the distribution of tumor necrosis factor(TNF) microsatellite polymorphisms in Chinese. METHODS: DNA was extracted from 164 unrelated healthy individuals' EDTA-blood. TNF microsatellite alleles were typed using PCR technique followed by high voltage denaturing PAGE with silver staining at the same time the PCR products were cloned and sequenced. RESULTS: Thirteen alleles and forty kinds of genotypes were detected at the TNFa locus; two alleles and three kinds of genotypes at the TNFa locus. The polymorphism information contents (PIC) were 0.80 and 0.28 respectively no deviation from Hardy-Weinberg equilibrium was observed. Statistical analysis showed that the distribution of TNFa allele frequencies in Chinese Han population was significantly different from that in European Caucasian or in Japanese P<0.01. The result of sequencing revealed that the copy number of dinucleiotide repeats within the same TNF allele was not consistent with that in the reports from western countries. CONCLUSION: There exists ethnic difference in the distribution of TNFa allele. Further investigations will be necessary to define more accurately and clearly the TNFa alleles.

Alleles↗

PubMed2001

[Hypermethylation of the calcitonin gene as molecular genetic marker in detecting minimal residual disease of leukemia].

OBJECTIVE: To explore whether detecting minimal residual disease (MRD) of leukemia with hypermethylation of the calcitonin gene as molecular genetic marker of leukemic clone may predict the prognosis. METHODS: Polymerase chain reaction (PCR) in combination with digestion of DNA with HpaII was used to examine the methylation patterns of the calcitonin gene in 29 cases with acute leukemia and 8 cases with transformation of chronic myeloid leukemia. By using PCR, MRD was longitudinally detected in patients who were positive for hypermethylation of the calcitonin gene as molecular genetic marker. RESULTS: Twenty patients with acute leukemia and transformation of chronic myeloid leukemia had MRD after complete remission. Bone marrow relapse occurred soon when MRD persisted or reappeared. It may predict bone marrow relapse two to eleven months earlier. The patients who were negative for MRD early and remained persistently negative may acquire prolonged survival. CONCLUSION: MRD of leukemia may be monitored by using PCR with hypermethylation of the calcitonin gene as molecular genetic marker for leukemic clone. It may prove useful in predicting the prognosis of leukemia.

Adult↗

PubMed2001

[Investigation on an outbreak of Legionnaires' disease caused by Lboz in a suburb of Beijing].

OBJECTIVE: To demonstrate the infectious rates and incidence rates through epidemiological investigation. METHODS: Serum samples from 203 new soldiers were detected from Lboz by TAT. RESULTS: Infectious rates was 33.00% (67/203), and the incidence rates was 8.87% (18/203) with 2 cases of pneumonic type and 16 cases of pontiac fever type. CONCLUSION: The results suggested that an outbreak of Legionnaires' desease caused by Legionella bozemanii (Lboz) took place in a suburb of Beijing. However the report of the outbreak caused by Lboz had not been found in related references.

China↗

PubMed2001

[The effects of thrombopoietin and interleukin-11 on bone marrow megakaryocytic progenitors in patients with chronic idiopathic thrombocytopenic purpura in vitro].

OBJECTIVE: To observe the effects of recombinant human thrombopoietin (rhTPO) and rhTPO in combination with recombinant human interleukin-11(rhIL-11) on the megakaryocyte (MK) colony growth and maturation in patients with chronic idiopathic thrombocytopenic purpura (CITP) in vitro. METHODS: Bone marrow (BM) mononuclear cells of 21 patients with CITP were cultured in plasma clot culture systems, to which were added rhTPO alone or rhTPO plus rhIL-11 over a range of concentrations. After 14 days, the MK colonies were stained by GP III a Mc Ab(SZ-21) and ABC-Kit and counted. The diameters and areas of the positive cells of GP III a were measured by BM-cell analysis system of MCDS-2010. RESULTS: The diameters and areas of MK in CITP group were significantly lower than that in control group, P < 0.05. The addition of rhTPO to culture systems increased CFU-MK, total colonies and diameters and areas of MK in CITP patients. And this promoting effect was not dose-dependent. The optimal concentration of rhTPO was 10 ng/ml; in the group where 10 ng/ml rhTPO was used in combination with 20 ng/ml rhIL-11, the counts of CFU-MK, total colonies and the measurements of areas and diameters of MK increased significantly, compared with those in the group where rhTPO was used alone. CONCLUSION: There are maturation dysfunctions of MK progenitors in patients with CITP. rhTPO alone or in combination with rhIL-11 can promote the proliferation and maturation of MK progenitors in patients with CITP and, moreover, the combination of the two cytokines has more significant promoting effects, compared to rhTPO alone.

Adolescent↗

PubMed2001

[Vacuolation effect of Helicobacter pylori on gastric epithelial cells].

This study was designed to observe vacuolation effect of Helicobacter pylori on gastric epithelial cells. The H. pylori isolates derived from patients with peptic ulcer, chronic gastritis and gastric cancer were plated on common selective medium and their vacuolation effects on SGC-7901 cells were compared. The percentage of H. pylori(Tox+) strain in clinical isolates from different gastroduodenal diseases had no significant difference. The toxicity of the H. pylori (Tox+) strain from peptic ulcer was significantly higher than that from chronic gasritis.

Adolescent↗

PubMed2001

[Study on hypermethylation of the calcitonin gene in malignant hematological disorders].

OBJECTIVE: To investigate the clinical significance of hypermethylation of the calcitonin (CT) gene in malignant hematological disorders (MHD). METHODS: Polymerase chain reaction (PCR) in combination with digestion of DNA with Hpa II was used to examine the methylation patterns of the CT gene in 73 patients with MHD, 6 healthy people and 24 patients with nonmalignant hematological disorders (NON-MHD). RESULTS: Hypermethylation of the CT gene occurred in 12 of 14 (85.7%) patients with acute lymphoblastic leukemia (ALL), 9 of 15 (60%) acute nonlymphocytic leukemia (ANLL), 8 of 10 (80%) chronic myelogenous leukemia (CML), 5 of 15 (33.3%) malignant lymphoma (ML), 2 of 5 patients with myelodysplastic syndrome (MDS), 1 of 2 malignant histiocytosis (MH), 1 of 3 chronic lymphocytic leukemia (CLL) and 1 of 9 multiple myeloma (MM). However, it did not occur in normal controls and NON-MHD. CONCLUSION: Hypermethylation of CT gene may serve as an important molecular maker for tumorous cell clone and may be useful in diagnosing MHD, monitoring minimal residual disease and predicting prognosis.

Calcitonin↗

PubMed2000

Mice expressing only monosialoganglioside GM3 exhibit lethal audiogenic seizures.

Gangliosides are a family of glycosphingolipids that contain sialic acid. Although they are abundant on neuronal cell membranes, their precise functions and importance in the central nervous system (CNS) remain largely undefined. We have disrupted the gene encoding GD3 synthase (GD3S), a sialyltransferase expressed in the CNS that is responsible for the synthesis of b-series gangliosides. GD3S-/- mice, even with an absence of b-series gangliosides, appear to undergo normal development and have a normal life span. To further restrict the expression of gangliosides, the GD3S mutant mice were crossbred with mice carrying a disrupted GalNAcT gene encoding beta1,4-N-acetylgalactosaminyltransferase. These double mutant mice expressed GM3 as their major ganglioside. In contrast to the single mutant mice, the double mutants displayed a sudden death phenotype and were extremely susceptible to induction of lethal seizures by sound stimulus. These results demonstrate unequivocally that gangliosides play an essential role in the proper functioning of the CNS.

Age Factors↗

PubMed2000

Resistance to apoptosis in HIV-infected CD4+ T lymphocytes is mediated by macrophages: role for Nef and immune activation in viral persistence.

Apoptosis or programmed cell death may play a critical role in AIDS pathogenesis through depletion of both CD4(+) and CD8(+) T lymphocytes. Using a reporter virus, a recombinant HIV infectious clone expressing the green fluorescent protein (GFP), apoptosis was measured in productively infected CD4(+) T lymphocytes, in the presence and absence of autologous macrophages. The presence of macrophages in the culture increased the frequency of nonapoptotic GFP-positive productively infected CD4(+) T lymphocytes. The appearance of nonapoptotic productively infected CD4(+) T lymphocytes in the culture required intercellular contacts between macrophages and PBLs and the expression of the HIV Nef protein. The presence of macrophages did not reduce apoptosis when CD4(+) T lymphocytes were infected with a GFP-tagged virus deleted for the nef gene. TNF-alpha (TNF) expressed on the surface of macrophages prevented apoptosis in nef-expressing, productively infected CD4(+) T lymphocytes. Similarly, following TNF stimulation, apoptosis was diminished in Jurkat T cells transfected with a nef-expressing plasmid. TNF stimulation of nef-expressing Jurkat T cells resulted in NF-kappaB hyperactivation, which has been shown to deliver anti-apoptotic signals. Our results indicate that intercellular contacts with macrophages increase the rate of productively infected nonapoptotic CD4(+) T lymphocytes. The survival of productively infected CD4(+) T lymphocytes requires Nef expression as well as activation by TNF expressed on the surface of macrophages and might participate in the formation and maintenance of viral reservoirs in HIV-infected persons.

Animals↗

PubMed2000

The steroid receptor coactivator SRC-3 (p/CIP/RAC3/AIB1/ACTR/TRAM-1) is required for normal growth, puberty, female reproductive function, and mammary gland development.

Steroid receptor coactivator-3 (SRC-3) is a coactivator of nuclear receptors in the SRC family as assayed in vitro. Here, we show that mouse SRC-3 is expressed in a tissue-specific fashion and distributed mainly in the oocytes, mammary glands, hippocampus, olfactory bulb, smooth muscle, hepatocytes, and vaginal epithelium. Genetic disruption of SRC-3 in mice results in a pleiotropic phenotype showing dwarfism, delayed puberty, reduced female reproductive function, and blunted mammary gland development. Hormonal analysis indicates that SRC-3 plays a role in both the growth hormone regulatory pathway and the production of estrogen, which may explain the observed phenotypes. These results suggest that the physiological role of SRC-3 is different from that of SRC-1 and prove the diversity among coactivator family members.

Animals↗

PubMed2000

Lack of obesity and normal response to fasting and thyroid hormone in mice lacking uncoupling protein-3.

Uncoupling protein-3 (UCP3) is a mitochondrial protein that can diminish the mitochondrial membrane potential. Levels of muscle Ucp3 mRNA are increased by thyroid hormone and fasting. Ucp3 has been proposed to influence metabolic efficiency and is a candidate obesity gene. We have produced a Ucp3 knockout mouse to test these hypotheses. The Ucp3 (-/-) mice had no detectable immunoreactive UCP3 by Western blotting. In mitochondria from the knockout mice, proton leak was greatly reduced in muscle, minimally reduced in brown fat, and not reduced at all in liver. These data suggest that UCP3 accounts for much of the proton leak in skeletal muscle. Despite the lack of UCP3, no consistent phenotypic abnormality was observed. The knockout mice were not obese and had normal serum insulin, triglyceride, and leptin levels, with a tendency toward reduced free fatty acids and glucose. Knockout mice showed a normal circadian rhythm in body temperature and motor activity and had normal body temperature responses to fasting, stress, thyroid hormone, and cold exposure. The base-line metabolic rate and respiratory exchange ratio were the same in knockout and control mice, as were the effects of fasting, a beta3-adrenergic agonist (CL316243), and thyroid hormone on these parameters. The phenotype of Ucp1/Ucp3 double knockout mice was indistinguishable from Ucp1 single knockout mice. These data suggest that Ucp3 is not a major determinant of metabolic rate but, rather, has other functions.

Adipose Tissue, Brown↗

PubMed2000

Organization of intratelencephalic projections to the visual Wulst of the chick.

The avian visual Wulst, said to be the equivalent of the striate cortex in mammals, is the telencephalic visual area of the thalamofugal visual pathway. In this study, by means of retrograde labelling with fluorescent tracers injected into the Wulst regions in the left and right hemispheres, we have investigated the organization of the intratelencephalic projections to the visual Wulst in chicks. After injecting Fluorogold (FG), True blue (TB) or rhodamine into the visual Wulst, fluorescent-labelled neurones were found in the ipsilateral neostriatum frontale, pars lateralis (NFl), the ipsilateral neostriatum intermedium (NI) and the ipsilateral dorso-lateral neostriatum. Labelled neurones were also found in both the ipsilateral and contralateral archistriata. In addition, some neurones in the archistriatum were double-labelled, which indicates that these archistriatal neurones have axon collaterals projecting to the visual Wulst on both sides of the forebrain. Through these intratelencephalic afferents to the visual Wulst, visual information transmitted in the thalamofugal pathway may be modulated by other telencephalic areas. The possible roles of these connections in regulating behaviour are discussed.

Animals↗

PubMed2000

Animal models of myasthenia gravis.

Myasthenia gravis (MG) is an antibody-mediated, autoimmune neuromuscular disease. Animal models of experimental autoimmune myasthenia gravis (EAMG) can be induced in vertebrates by immunization with Torpedo californica acetylcholine receptors (AChR) in complete Freund's adjuvant. The MHC class II genes influence the cellular and humoral immune response to AChR and are involved in the development of clinical EAMG in mice. A dominant epitope within the AChR alpha146-162 region activates MHC class II-restricted CD4 cells and is involved in the production of pathogenic anti-AChR antibodies by B cells. Neonatal or adult tolerance to this T-cell epitope could prevent EAMG. During an immune response to AChR in vivo, multiple TCR genes are used. The CD28-B7 and CD40L-CD40 interaction is required during the primary immune response to AChR. However, CTLA-4 blockade augmented T- and B-cell immune response to AChR and disease. Cytokines IFN-gamma and IL-12 upregulate, while IFN-alpha downregulates, EAMG pathogenesis. However, the Th2 cytokine IL-4 fails to play a significant role in the development of antibody-mediated EAMG. Systemic or mucosal tolerance to AChR or its dominant peptide(s) has prevented EAMG in an antigen-specific manner. Antigen-specific tolerance and downregulation of pathogenic cytokines could achieve effective therapy of EAMG and probably MG.

Animals↗