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Biomedical subjects

D Xu

Publications and source records attributed to D Xu.

At least 181 records · Page 10Linked to original sources

Immunomodulating effects of second-generation calcium channel blockers on experimental heart transplantation.

The administration of second-generation calcium channel blockers (CCBs) to counteract the adverse effects of conventional immunosuppression gains more and more acceptance. Since these newly developed molecules differ in their chemical structure and possess specific pharmacokinetic profiles, we hypothesized that exposure to clinically relevant concentrations may have a significant immunomodulatory potential. The effects of various second-generation CCBs, felodipine, amlodipine, mibefradil and clentiazem, on cardiac allograft survival were therefore evaluated. Inbred male Lewis rats were used as recipients and Brown-Norway rats as donors. After abdominal implantation of the donor heart, allograft recipients were exposed to felodipine (31 microg/kg/day), amlodipine (25 microg/kg/day), mibefradil (3 mg/kg/day) or clentiazem (2.5 mg/kg/day). Other allograft recipients were treated with low-dose cyclosporine (CsA) alone (2 mg/kg/day) or with low-dose CsA combined with amlodipine (25 microg/kg/day), mibefradil (3 mg/kg/day) or clentiazem (2.5 mg/kg/day). All drugs were given daily by gavage. Median survival time of untreated cardiac allografts was 6.5 days. When given alone, not all the second-generation CCBs elicited a positive effect: the dihydropyridines felodipine and amlodipine were ineffective (median survival time was 6.5 and 7.0 days, respectively), the T- and L-type CCB mibefradil had a significant but minor impact (median survival time = 9.0 days, p <0.0015) while the benzothiazepine clentiazem produced the most significant result (median survival time = 16.0 days, p <0.0033). Neither amlodipine nor mibefradil modified the extent of survival provided by low-dose CsA (median survival time = 9.0 days), while clentiazem had a significant positive effect. These data indicate that second-generation CCBs differ in their immunomodulatory potential. These observations of pharmacodynamic specificity appear to be related to differences in their chemical structure as well as their interaction with other sites than the calcium channel.

Adjuvants, Immunologic↗

A proinflammatory role for IL-18 in rheumatoid arthritis.

IL-18 is a novel cytokine with pleiotropic activities critical to the development of T-helper 1 (Th1) responses. We detected IL-18 mRNA and protein within rheumatoid arthritis (RA) synovial tissues in significantly higher levels than in osteoarthritis controls. Similarly, IL-18 receptor expression was detected on synovial lymphocytes and macrophages. Together with IL-12 or IL-15, IL-18 induced significant IFN-gamma production by synovial tissues in vitro. IL-18 independently promoted GM-CSF and nitric oxide production, and it induced significant TNF-alpha synthesis by CD14(+) macrophages in synovial cultures; the latter effect was potentiated by IL-12 or IL-15. TNF-alpha and IFN-gamma synthesis was suppressed by IL-10 and TGF-beta. IL-18 production in primary synovial cultures and purified synovial fibroblasts was, in turn, upregulated by TNF-alpha and IL-1beta, suggesting that monokine expression can feed back to promote Th1 cell development in synovial membrane. Finally, IL-18 administration to collagen/incomplete Freund's adjuvant-immunized DBA/1 mice facilitated the development of an erosive, inflammatory arthritis, suggesting that IL-18 can be proinflammatory in vivo. Together, these data indicate that synergistic combinations of IL-18, IL-12, and IL-15 may be of importance in sustaining both Th1 responses and monokine production in RA.

Animals↗

Attitudes toward the mentally ill in a sample of professionals working in a psychiatric hospital in Beijing (China).

The attitudes of psychiatric doctors and nurses toward the mentally ill in a large urban psychiatric hospital in China were compared using the Community Attitudes toward the Mentally Ill (CAMI). Data indicated that the attitude of professionals differed on 11 of the 40 questions of this instrument. Those questions are divided along 4 dimensions: authoritarianism, benevolence, social restrictiveness and rehabilitation in the community. Results showed that psychiatric doctors have a more liberal and positive attitude toward the mentally ill than psychiatric nurses, especially about their rehabilitation in the community. Factor analysis also indicated that nurses were more likely than doctors to attribute negative characteristics to the mentally ill. Some explanations are proposed to explain these differences.

Adult↗

Modulation of autoimmune disease in the MRL-lpr/lpr mouse by IL-2 and TGF-beta1 gene therapy using attenuated Salmonella typhimurium as gene carrier.

We have investigated the effects of interleukin-2 (IL-2) and transforming growth factor-beta (TGF-beta) gene therapy on the progress of autoimmune disease in MRL-lpr/lpr mice, a murine model of systemic lupus erythematosus (SLE). These mice have uncontrolled proliferation of T cells, an impaired response to T cell mitogen and produce autoantibodies against nuclear antigens, including DNA. Immune complexes formed by these autoantibodies are believed to cause glomerulonephritis and vasculitis in lupus mice and human SLE. Since there is an imbalance of cytokine production in both SLE patients and lupus mice, we examined the effects of cytokine gene therapy on the progression of autoimmune disease in MRL-lpr/lpr mice. The mice were treated orally with a non-pathogenic strain of Salmonella typhimurium bearing the aroA-aroD- mutations and carrying the murine genes encoding IL-2 and TGF-beta. The bacteria synthesise and slowly release the cytokines in vivo. Our results show that, contrary to expectation, TGF-beta gene therapy produced no improvement in pathology and generally had opposite effects to those of IL-2. IL-2 gene therapy restored the defective T cell proliferative response to mitogen and suppressed the autoantibody response, glomerulonephritis and growth of lymphoid tumours.

Animals↗

Intraclonal heterogeneity in the in vitro daunorubicin-induced apoptosis in acute myeloid leukemia.

Leukemic cells from ten patients with acute myeloid leukemia (AML) were sorted on the basis of in vitro daunorubicin (DNR) uptake. The obtained subpopulations with high and low DNR accumulation were compared with regard to induction of apoptosis, expression of bcl-2 and p53. Heterogeneous induction of apoptosis, confined to subpopulations with high DNR uptake, was observed. The size of the DNR-induced apoptotic fraction (4% to 16%) within a given AML blast population was determined by intracellular drug accumulation and was not related to the level of bcl-2 expression. All tested leukemic samples displayed expression of p53 in a growth promoter orientation, i.e. PAb1620-/PAb240+. In two samples, however, subpopulations expressing a growth suppressor orientation of p53, i.e. PAb 1620+/PAb240-, were also present. These subpopulations were confined to high-DNR-uptake fractions and associated with the induction of apoptosis. We conclude that intraclonal heterogeneity in the intracellular drug accumulation and subsequently in DNR-induced apoptosis might allow the selection of inherently drug-resistant AML clones thus contributing to relapse of leukemia.

Acute Disease↗

[Detection of TTV DNA in liver tissue of patients with non A-G hepatitis].

OBJECTIVE: To study the existence of TTV (transfusion-transmitted virus) in liver tissue of patients with non A-G hepatitis. METHODS: 19 cases of paraffin-embedded liver tissues of the patients with non A-G hepatitis were studied by in sity hybridization with Dig-TTV DNA probe. RESULTS: Out of 19 cases, TTV DNA were detected in 6 cases, including 4 cases of acute mild hepatitis (30.80%) and 2 cases of chronic hepatitis (33.33%), respectively. Hybridization signals were detected within the nuclei or cytoplasm of the hepatocytes. The positive cells were scattered in the intralobular areas in acute mild hepatitis and more aggregated in periportal areas in chronic hepatitis. Among the 6 positive cases, 5 had a raised ALT. CONCLUSION: The result showed that the TTV detected in liver tissue of patients with unknown etiology is a novel virus, which belongs to an hepadnavirus.

Adult↗

Treatment of atrophic cholecystitis by regulating the spleen--a report of 50 cases.

Fifty cases of atrophic cholecystitis were treated by regulating of the spleen. Of them, 21 were cured, 18 remarkably effective, and 7 effective. The overall effective rate was 92.0%. As compared with the results of ultrasonography B performed before and after treatment, it was shown that both the longitudinal and transverse inner diameters of the gallbladder increased evidently, and the condition of atrophy improved remarkably after treatment.

Adolescent↗

[The relationship of serum hepatitis B virus DNA load in HBsAg positive pregnant women to the intrauterine infection of newborns].

OBJECTIVE: To study the relationship of serum hepatitis B virus (HBV) DNA load in HBsAg positive pregnant women to intrauterine infection of their newborns. METHODS: Serum HBV DNA were determined by dot-blot hybridization in 185 HBsAg positive pregnant women. Serum HBsAg were tested by ELISA in their newborns within 24 hours after birth. RESULTS: The prevalence of intrauterine HBV infection of the newborns was associated with the HBV DNA level of the mothers. With the increase of serum HBV DNA load, the risk of fetal intrauterine infection was increasing. CONCLUSION: Fetal exposure to high level of maternal HBV DNA is one of the important determinant of intrauterine infection.

DNA, Viral↗

[The role of placenta in hepatitis B virus intrauterine transmission].

OBJECTIVES: To determine the role of placenta in hepatitis B virus (HBV) intrauterine transmission, and to trace the route of transplacental transmission and the timing of HBV infection in uterus. METHODS: We collected 101 term placentas and newborn infants, 24 aborted first-trimester placentas, and 6 induced aborted fetuses and placentas from 131 HBsAg carrying pregnant women. Serologic HBV markers (HBsAg and HBV DNA) of pregnant women and newborns were detected by ELISA and PCR. The HBsAg, HBxAg, HBcAg and HBV DNA in placentas were determined by ABC immunohistochemical staining and in-situ hybridization. RESULTS: The HBV infection rates of placentas from first-trimester, second-trimester to term periods were 4.2%(1/24), 1/6, and 44.6%(45/101), respectively. In one induced aborted fetal liver tissue (19-week of pregnancy), the proteins and DNA of HBV were detected, and its placental villous capillary endothelial cells were also infected. The OR of HBV infection of villous capillary endothelial cells in intrauterine transmission was 18.46(95% CI = 2.83-152.78). CONCLUSIONS: HBV infection of placental capillary endothelial cell is a major risk factor of intrauterine transmission. HBV transplacental transmission route may be placental cell to cell transfer. The intrauterine infection may occur as early as on the 19th week of pregnancy, but the main timing is possibly in the third-trimester of pregnancy.

Endothelium, Vascular↗

[A molecular epidemiology study on risk factors and mechanism of HBV intrauterine transmission].

OBJECTIVE: To clarify the risk factors and mechanism of HBV intrauterine infection by molecular epidemiology method. METHODS: We performed a case-control study. 402 HBsAg-positive pregnant women and their infants were collected as subjects. 15 infants infected by HBV intrauterine transmission were selected as case group and others as controls. Besides, HBsAg titer in 182 maternal sera and HBV DNA concentration in 185 maternal sera were determined. To identify the HBV infection in the placentas, immunohistochemistry stain and HBV DNA hybridization in situ were conducted. The data from both laboratory and epidemiological fields were analysed. RESULTS: The findings indicated that the positiveness of HBeAg in mother's sera (OR = 17.07) and the history of threatened premature labour (OR = 5.44) were the main risk factors. Intrauterine transmission was significantly related to HBsAg titers and HBV DNA concentration in mother's sera (P = 0.01). The results of immunochemistry stain and HBV DNA situ in hybridization in the placentas from 101 full-term pregnancy women showed that HBV infection rates had a decreasing trend (P = 0.0009) from mother's side to fetus's in placenta and there was a significant association between HBV intrauterine transmission and HBV infection in villous capillary endothelial cells in placenta (OR = 18.46, P = 0.0002). CONCLUSION: There might be a "cellular transfer" of HBV infection in the placenta. With regard to the mechanism of HBV intrauterine transmission; there are two transmission routes, namely, hemagenous route and cellular route.

Adult↗

[Different expressions of cyclins and cyclin dependent kinase inhibitor P27 in vascular smooth muscle cells and cardiac myocytes caused by angiotensin II and PDGF stimulation].

OBJECTIVE: To investigate cell cycle distribution of the vascular smooth muscle cells (VSMC) and cardiac myocytes(CM) and different expressions of cyclins and P27 caused by angiotensin II (Ang II) and platelet derived growth factor BB (PDGF-BB). METHODS: Cultured VSMCs or CMs were collected at 24 h after stimulation of Ang II (10(-6) mol/L) and PDGF-BB (20 ng/ml). Cell cycle distribution, cyclins and P27 expression were determined with flow cytometer. RESULTS: Ang II had no effect on P27 expression in both VSMCs and CMs. It did not cause proliferation of both VSMCs and CMs. Although PDGF-BB could significantly increase cyclins expression in both VSMCs and CMs, it could only significantly inhibit P27 expression in VSMCs (1.8 +/- 1.3 vs 48.1 +/- 5.4, P < 0.01) and cause VSMC proliferation, and had no effect on P27 expression in CMs(39.4 +/- 5.6 vs 44.6 +/- 3.6, P > 0.05). CONCLUSION: The progression of VSMC and CM through G1 to S phase might be brought out by the inhibition of P27 during proliferation.

Angiotensin II↗

Investigation of parvovirus B19 in cardiac tissue from patients with congenital heart disease.

OBJECTIVE: To explore the correlation between human parvovirus B19 (HPV-B19) and congenital heart (CHD) and to investigate the teratogenic effect of HPV-B19. METHODS: A case control study was conducted to investigate the embedded autopsy cardiac tissues of 29 cases of CHD and 30 controls without CHD with nest polymerase chain reaction (PCR). Other viruses, including herpes simplex virus (HSV). Toxoplasma gondii (TOX), cytomegalovirus (CMV) and rubella virus (RV) were also studied in 10 cases of each group with corresponding PCR kits. RESULTS: Five of 29 (17.2%) CHD cases were positive for HPV-B19, while all the 30 controls were negative for HPV-B19 (P=0.0237). All cases studied were negative for both HSV and TOX. Three cases in each group were positive for CMV, with presence of HPV-B19 DNA in 2 cases in the CHD group. Only two cases in the CHD group showed positive reaction for RV. CONCLUSIONS: As far as we know, it is the first report of the presence of HPV-B19 in cardiac tissues of CHD patients. The detection rate of HPV-B19 DNA is significantly different between the two groups, inferring that HPV-B19 might be correlated with CHD.

Adolescent↗

[Effects of ventilation and surfactant perturbation on alveolocapillary permeability].

OBJECTIVE: To investigate the effects of large tidal volume ventilation (LTVV) and surfactant dysfunction induced with dioctyl sodium sulphoccinate (DOSS) on alveolocapillary permeability, and on the surface tension of lung tissue extract (LTE). METHODS: The permeability index of tecthnetium-99m labelled human serum albumin (99mTc-HSA) was used to characterize the alveolocapillary permeability after LTVV and surfactant dysfunction permeability index, dynamic respiratory compliance (Cdyn), arterial blood gas (ABG), wet lung weight and surface tension of LTE were measured in four groups of rabbits: (1) controls; (2) LTVV; (3) DOSS; and (4) DOSS + LTVV. RESULTS: Cdyn and ABG were stable throughout the experiment in all groups. The wet lung weight was (1.85 +/- 0.16) g/kg, (2.50 +/- 0.27) g/kg, (1.88 +/- 0.12) g/kg and (2.65 +/- 0.13) g/kg in four groups respectively. It was significantly increased in LTVV and DOSS + LTVV groups compared with controls and DOSS (P < 0.01). The permeability index was 0.10 +/- 0.04, 0.72 +/- 0.14, 0.13 +/- 0.03 and 0.79 +/- 0.17 in four groups respectively. There was a significantly increased permeability index in LTVV and DOSS + LTVV groups compared with controls and DOSS (P < 0.01). There was no difference of surface tension of LTE among all groups. CONCLUSIONS: The results of this study suggest that the increased alveolocapillary permeability, pulmonary edema and lung injury are induced by LTVV rather than DOSS. The mechanisms of HSA transferring alveolocapillary membrane from different directions are different.

Animals↗

[Immunoregulation of Youguiyin, Sijunzitang, Taohong Siwutang in treating patients with deficiency of kidney, spleen and blood stasis syndrome].

OBJECTIVE: To study the different immunoregulatory effects of Youguiyin, Sijunzitang, Taohong Siwutang to patients with deficiency of Kidney, Spleen and blood stasis Syndrome respectively. METHODS: The treated group, 40 patients in each with deficiency of Kidney, Spleen and blood stasis were treated with Youguiyin, Sijunzitang and Taohong Siwutang respectively. Three control groups (20 patients each) were established respectively. Peripheral venous level of complement C3, circulating immunocomplex (CIC), interleukin-2 (IL-2), interferon-gamma (IFN-gamma), lymphocyte transformation rate (LTR), the activity of natural killer (NK) cell, and the phagocytic function of neutrophil were measured before and after treatment. RESULTS: Sijunzitang could reduce the level of CIC (P < 0.01), raise the activity of NK cell and LRT (P < 0.01) of the patients with deficiency of Spleen syndrome; the same did the Youguiyin to that of patients with deficiency of Kidney syndrome. Also, Sijunzitang could increase the level of IL-2 in blood and the phagocytic function of neutrophil (P < 0.05); the Taohong Siwutang could lower the level of CIC to patients with blood stasis syndrome (P < 0.01), increase the activity of NK cells (P < 0.05). CONCLUSION: Youguiyin, Sijunzitang could enhance the immunoregulatory function of the patients with deficiency of Spleen and Kidney, particularly the cellular immune functions, in which the Sijunzitang effect is more complete and significant, while Taohong Siwutang eliminated the effect of CIC in blood better.

Adult↗

[A study on the pathogenicity of acute hepatitis G infection].

OBJECTIVE: To study the infection due to hepatitis G virus (HGV) in liver tissues of patients with acute hepatitis and to investigate its pathogenicity. METHODS: HGV NS5 antigen was detected by using immunohistochemical method in the liver biopsy tissues of patients with acute hepatitis but serologically negative to hepatitis virus antigens from A to E. The clinical and pathological data were also analysed. RESULTS: 37 samples were tested, HGV NS5 antigen was detected in 14 (37.8%). 4 of the 14 were positive for HGV NS5 antigen alone (acute hepatitis G group) and 10 other cases were also positive for HBsAg, hepatitis C virus (HCV) NS3 antigen or EB virus antigen (superinfection group). 7 cases were HBsAg positive alone (acute hepatitis B group) and the remaining 16 cases were negative for all the antigens mentioned above (non-A - G hepatitis group). There was no difference among the 4 groups in the detecting rate of Fas antigen, histological activity index (HAI), serum alanine transferase (ALT) and total bilirubin (TBil). CONCLUSION: It is suggested that HGV appears to play some role in the pathogenesis of acute viral hepatitis and the degree of liver injury in acute hepatitis G may be as severe as that of hepatitis caused by other types of viruses.

Acute Disease↗

[Detection of apoptosis exposed to 10-hydroxycamptothecin in T24 human urinary bladder cancer cells].

OBJECTIVE: To study whether 10-hydroxycamptothecin (HPT) can induce apoptosis in bladder cancer cell and establish methods for detecting apoptotic cells. METHODS: Human urinary bladder cancer cell line (T24) was exposed in vitro to different concentrations of 10-hydroxycamptothein for various lengths of time. Flow cytometry, Hochest 33258 and Hematoxylin staining were used to determine the induction of apoptosis after use of HPT. DNA gel analysis was also carried out to detect DNA fragmentation. RESULTS: Cell shrinage, nuclear fragmentation and condensed chromosomes showed that apoptosis can be induced by HPT within the concentration of 0.01 - 10 microg/ml. The flow cytometry analysis showed that the percentage of apoptotic cells were related to the concentration and the time of induction. T24 cell line exposed to HPT experienced internucleosomal DNA fragmentation by producing a typical ladder pattern on agarose gel electrophoresis. The detection of minimum exposure time for HPT-induced apoptosis in T24 cells showed that 3 hours of exposure to HPT were enough to trigger internucleosomal DNA fragmentation. Compared to Hochest 33258 staining, Hematoxylin staining was more easy, rapid and accurate to detect apoptosis. CONCLUSIONS: The induction of apoptosis exposed to HPT in T24 human urinary bladder cancer cells is a good model for further studying urinary bladder cancer. Hematoxylin staining is a useful method for detecting apoptosis.

Antineoplastic Agents, Phytogenic↗

[Passive personal sampler for exposure to low concentration of volatile organic compounds].

A passive personal sampler has been developed for monitoring volatile organic compounds(VOCs) in ambient air and nonoccupational exposure. The sampler collecting target VOCs is based upon the mechanism of molecular diffusion and absorption onto a single layer of active carbon fibre (ACF) absorbent. After exposure, the ACF is transferred from the sampler into stainless steel tubes for thermal desorption. The desorbed target VOCs is analyzed by capillary GC. Under the condition of facing velocity of 10-260 cm/s, relative humidity of 30%-80%, and temperature of 10-30 C, the sampling rate for benzene, toluene, tetrachloroethylene, p-xylene and styrene is 25.74, 25.16, 25.85, 8.16 and 6.47 ml/min respectively. The analysis on the new passive sampler demonstrated that its relative overall uncertainty for target VOCs was in the range of +/- 25% compared with the active ACF tube sampling method.

Air Pollutants↗