Biomedical subjects

Z Qi

Publications and source records attributed to Z Qi.

At least 91 records · Page 5Linked to original sources

PubMed1997

Activation of alloreactive natural killer cells is resistant to cyclosporine.

BACKGROUND: We have previously shown that cytotoxic T lymphocytes (CTL) with alloreactivity were induced when Wistar Furth (WF; RT1u) rats were immunized with allogeneic Brown Norway (BN; RT1n) cells. In contrast, when BN rats were immunized with WF cells, the allospecific response was confined to alloreactive natural killer (NK) cells, and no CTL activity was observed. In this study, the effect of cyclosporine (CsA) on the activation of alloreactive NK cells in vivo was analyzed. METHODS: Distinct peritoneal effector cells from rats immunized with allogenic cells with or without concomitant CsA and/or interleukin (IL) 2 treatment were tested for specific cytolytic activity. Furthermore, the presumptive role of NK cells in rejection immunity was addressed in a cardiac graft model. RESULTS: The results showed that doses of CsA that completely inhibited the activation of alloreactive CTL, only marginally affected the activation of alloreactive NK cells. We also showed that CsA treatment failed to prolong graft survival in BN recipients of WF hearts. Treatment of BN rats with CsA/IL-2 during immunization with allogeneic WF cells resulted in concomitant induction of alloreactive NK cells and alloreactive CTL. CONCLUSIONS: We have demonstrated that CsA failed to suppress the activation of alloreactive NK cells. Consequently, the cardiac graft survival in the donor-recipient combination known to activate alloreactive NK cells was not significantly prolonged by CsA treatment, emphasizing the involvement of NK cells as effectors in organ rejection. Furthermore, the parallel emergence of alloreactive NK cells and CTL only in the presence of CsA/IL-2 indicated that CsA interfered with alloreactive NK cell-associated suppression of CTL activated by allogeneic tissue.

Animals↗

PubMed1997

Single dose anti-CD4 monoclonal antibody for induction of tolerance to cardiac allograft in high- and low-responder rat strain combinations.

Repeated administration of monoclonal antibodies (mAb) directed against the CD4 lymphocyte receptor may induce specific, long-lasting unresponsiveness to fully MHC-mismatched cardiac allografts in rats without additional immunosuppression. We assessed the effect of a single dose of murine anti-rat depleting anti-CD4 mAb (OX-38) on allograft survival in high- and low-responder rat strain combinations. Isogenic strains of DA (RT1av1), PVG (RT1c), AUG (RT1c), and WF (RT1u) rats were used. Recipients in antibody treated groups were given one dose of 5 mg/kg OX-38 mAb on the day of transplant, a dose which was shown to effectively deplete (or block) circulating CD4+ T cells. Other groups were treated for 10 days with cyclosporin A (CsA) and/or Linomide, a novel immunomodulator, which is the first compound able to fully eliminate the effect of CsA in the rat cardiac allograft model. The DA strain was identified as a low-responder to the allogeneic haplotype RT1c (PVG or AUG), but not to RT1u (WF), and developed true tolerance following RT1c grafting and OX-38 or low-dose CsA (5 mg/kg) induction, as verified by the response to retransplantation of a graft from the same donor strain or a third-party challenge. PVG recipients of DA grafts were characterized by high response and only modest (OX-38; median 9.5 days) or moderate (CsA; 23.5 days) prolongation of graft survival. Contrasting graft survival results were obtained in the low-responder combination, either very early rejection (at 10 days) or permanent graft survival (> 100 days). Linomide challenge affected CsA treatment in the high-responder combination but not tolerance induction in the low-responder combination, or the effect of OX-38. It was concluded that in rat heart transplantation a single-dose anti-CD4 mAb therapy may induce permanent donor-specific unresponsiveness in a low-responder strain combination, and that anti-CD4 mAb seems to be unique among immunosuppressive agents while being resistent to challenge by Linomide.

Adjuvants, Immunologic↗

PubMed1997

Mycophenolate mofetil, azathioprine and cyclophosphamide enhanced efficacy combined with cyclosporine in rat cardiac transplantation.

Anti-proliferative drugs have been used for immunosuppression since the introduction of clinical transplantation. Most transplant centres include azathioprine (Aza) and cyclosporine (CyA) in their standard regimens, despite several controlled studies having failed to confirm the benefit of this combination. Aza is still the most commonly used anti-proliferative drug, although no major differences in immunosuppressive or toxic effects have been shown between Aza and cyclophosphamide (Cph). Cph as an adjunct to CyA has never been tested in a randomized study. Recently, mycophenolate mofetil (MMF) has been developed as the most selective inhibitor of T- and B-cell proliferation and promoted as an adjunct to CyA treatment. In the present study, the additive or synergistic effects of these three anti-proliferative agents in combined treatment with CyA have been investigated using a rat cardiac transplantation model in which the immunomodulator linomide (Lin) was included as a potentiator of rejection. As single drug treatment, CyA, Cph and MMF, but not Aza, exerted a beneficial effect on graft survival. This prolongation of graft survival was abrogated when any one drug was administered together with Lin. The addition of MMF, Aza or Cph to CyA plus Lin treatment improved the graft survival significantly, thus demonstrating each of the anti-proliferative drugs to exert additive or synergistic effects in conjunction with cyclosporine. MMF seemed to be the most effective and least toxic of the drugs tested.

Adjuvants, Immunologic↗

PubMed1997

Complete regression of established murine hepatocellular carcinoma by in vivo tumor necrosis factor alpha gene transfer.

BACKGROUND & AIMS: Although tumor necrosis factor (TNF)-alpha possesses a potent antitumor activity, systemic administration of TNF-alpha causes severe side effects. To circumvent this, the efficacy of tumor cell-targeted TNF-alpha gene therapy was investigated. METHODS: Murine hepatocellular carcinoma (HCC) cells were infected with MNSM-Alb e/p-TNF-alpha retroviruses carrying the murine TNF-alpha gene under the transcriptional control of the murine albumin gene promoter, and antitumor effects induced by TNF-alpha gene transfer were examined in vitro and in vivo. RESULTS: Although MNSM-Alb e/p-TNF-alpha retrovirally infected HCC cells showed the same in vitro cell growth as parental HCC cells, they lost their tumorigenicity when implanted in syngeneic mice and induced tumor immunity against parental HCCs. The retrovirally infected HCC cells also significantly inhibited the tumorigenicity of previously implanted parental HCCs. Furthermore, intratumoral administration of MNSM-Alb e/p-TNF-alpha retroviruses showed the antitumor effect against established HCCs, resulting in significantly prolonged survival periods. Most importantly, intratumoral implantation of MNSM-Alb e/p-TNF-alpha retroviral-producing cells completely abrogated established HCCs in mice. CONCLUSIONS: These results indicate the potential efficacy of transferring the TNF-alpha gene via retroviral vectors directly into tumors for gene therapy against HCCs.

Animals↗

PubMed1997

Adenovirus-mediated expression of the secreted form of basic fibroblast growth factor (FGF-2) induces cellular proliferation and angiogenesis in vivo.

Blood supply through collateral arteries is of critical importance in occlusive arterial diseases such as coronary atherosclerosis. Induction of angiogenic growth factor within either the narrowing arteries or jeopardized myocardium may promote angiogenesis in vivo, leading to salvage of ischemic myocardium. We constructed a replication-defective adenovirus (AdCAsFGF-2) coding for human basic fibroblast growth factor (FGF)-2 that is modified, so that its secretion will be facilitated, by tagging a signal sequence derived from FGF-4. A large quantity of FGF-2 was detected in both the cell lysate and culture medium of COS cells infected with AdCAsFGF-2, indicating that FGF-2 was secreted at least partly from the infected cells. The conditioned medium from the infected COS cells stimulated DNA synthesis in and induced cellular proliferation of arterial smooth muscle cells. These effects were eliminated by adenovirus-mediated overexpression of a dominant-negative truncated FGF-receptor type 1. Implantation of a gel of basement membrane proteins containing fibroblasts infected with AdCAsFGF-2 into the ventral subcutaneous space of mice induced extensive cellular proliferation and the formation of functional arterioles. Cells surrounding the vessels were positively immunostained with antibodies recognizing either smooth muscle-specific alpha-actin or factor VIII antigen as a marker for endothelium. These results suggest that AdCAsFGF-2 may be useful for delivering functional FGF-2 into tissues and may lead to therapeutic angiogenesis in vivo.

Actins↗

PubMed1997

[Gene frequency of HPA among Hunan population of Han nationality].

We used allele specific primer PCR (ASP-PCR) method to detect the genotype of five major HPA systems among Hunan population of Han nationality. The results showed: The gene frequency of PLA1 was 81.00% and 85.87% for Kob, 71.00% for Baka, 91.00% for Pena, 90.67% for Brb which provided the basis for further clinical application of HPA.

Adult↗

PubMed1997

[Efficacy of dihydroartemisinin in treatment of 37 malaria cases].

Dihydroartemisinin is an efficacious derivative of artemisinin which can be taken orally in treatment of malaria with less side reactions. Thirty-seven cases with malaria were treated with this drug in Beijing and in Ruili City, Yunnan Province. Out of them, 25 cases suffered from falciparum malaria with an average parasitemia of 73,218/microliter and 12 from vivax malaria with an average parasitemia of 4,950/microliter. The dosage was 60 mg daily or 2 mg/kg for paediatric patients for 7 successive days with the first dose doubled. All the patients were clinically cured after treatment. Fever subsided 22-72 hours after the beginning of treatment in falciparum malaria patients with an average fever clearance time of 36.24 +/- 15.30 hours and their parasite clearance time was 24-72 hours with an average parasite clearance time of 44.80 +/- 19.09 hours. One of them had recrudescence 19 days after the disappearance of parasites, hence the recrudescence rate of falciparum malaria was 4.8%. Five early cerebral cases in this series were completely cured after the treatment. All the 12 cases with vivax malaria were also clinically cured after treatment, but 1 case had relapse 35 days after treatment. This patient was completely cured with another course of dihydroartemisinin combined with primaquine. All patients tolerated well the oral administration of dihydroartemisinin and no significant side reactions were seen.

Adolescent↗

PubMed1997

[Simultaneous coronary artery bypass grafting with other cardiovascular surgical procedures].

To improve the effect and reduce the mortality of the simultaneous coronary artery bypass grafting (CABG) with other cardiovascular surgical procedures, from Nov, 1984 to July, 1996, 51 patients underwent such operation. Among them 45 patients had valvular heart diseases, 4 postinfarction ventricular septal defect and ventricular aneurysm, and 1 myxoma of left atrium and abdominal aortal aneurysm. The operative mortality was 5.85% (3/51), and 3 patients died. Cardiovascular surgical patients of over 50 years or with angina pectorsi and ECG confirmed myocardiac ischemia should undergo coronary angiography routinely. If main coronary artery branches stenosis occupied over 50%, CABG must be performed. During the operation revasculariztion should be made as full as possible to enhance myocardiac protection and reduce the ascending aortic cross-clamping time.

Adolescent↗

PubMed1997

[Effects of HE particles on medicinal plant Agastache rugosus (Fisch. et Mey.) O. Ktze].

The biological effect of HE particles on the seeds of Agastache rugosus was probed in experiments on board a retrievable satellite. The result shows that the germination rate of the seeds pierced by HE particles radiation appears rather low. The seeds hit by HE particles (piercing radiation or not) start to germinate two days earlier than those in the control group, and the first leaf emerges four to five days earlier than that in the control group. The resultant seedlings grow markedly faster. Variations take place in the nuclear types of chromosome. The yield of essential oils becomes slightly higher. No marked changes have been observed in the major chemical components of these oils.

Chromosomes↗

PubMed1997

[An analysis of radiation risk for manned space flight in low-earth orbits with medium inclination].

The radiation risk for manned space flight in the orbit with altitude <500km and inclination 40 degrees-50 degrees was analyzed. The doses of several anomalously large solar proton events (SPE) were estimated from the measured doses during the SPE where the spectral parameters were known. The result shows that the radiation risk is not serious for the mission with above orbital parameters.

Cosmic Radiation↗

PubMed1997

[Herbological study of 4 Chinese herbs in Ardisia and "yiedihong"].

Herbological study are given to the original plants of "Zijinniu", "Pingdimu", "Xiaoqing", "Duanjiaosanlang" and "Yiedihong" recorded in the herbal books. The research shows that they are not the same plant with different names. Also, "Yiedihong" doesn't belong to Ardisia.

Ardisia↗

PubMed1997

[Hepatitis B virus DNA detection by means of polymerase chain reaction in patients with chronic hepatitis and hepatocellular carcinoma].

HBV immunological detection and HBV DNA detection by polymerse chain reaction (PCR) or molecular hybridization with 32P labeled probe were done in 61 patients with chronic hepatitis (CH) and 47 patients with hepatocellular carcinoma (HCC) to investigate the relationship between HBV replication and serum markers. The HBV DNA was detected in 90.50% of CH patients and 50.00% of HCC patients with HBsAg, HBeAg and anti-HBc positive; in 45.40% of CH patients and 7.14% of HCC patients with HBsAg, anti-HBe and anti-HBc positive; in 60.00% of CH patients and 40.00% of HCC patients with HBsAg and negative HBeAg, anti-HBe positive; in 20.00% of CH patients and 22.22% of HCC patients with HBsAg negative and anti-HBe or anti-HBe or anti-HBs positive; in 0 of CH or HCC patients lack of HBV serum markers. Our data suggested that the most active HBV replication was correlated to the presence of both HBsAg and HBeAg, there were some extent of HBV replication in CH or HCC patients with positive HBsAg, the inhibition of HBV replication was related to anti-HBe, the less active HBV replication was seen in HCC patients when compared with CH patients.

Carcinoma, Hepatocellular↗

PubMed1997

[Experimental study on free grafting of fat particles].

Forty-eight rats were used to study the change in fat tissue after grafting. In the experimental group, the fat tissue to be grafted was treated with insulin. Evaluation was made by graft measurement, ink injection, light microscopic and electronic microscopic observations. The results showed that the volume of the grafted fat decreased obviously and there was no significant difference between the experimental and the control groups in the change of volume of the grafted fat tissue. At the early stage of grafting, the grafted fat showed ischemia. The adipocytes released lipid and dedifferentiated to preadipocytes. After revascularization, the preadipocytes began to absorb lipid and became mature adipocytes. The structure of the grafted fat was almost normal at 6 months after grafting. The formation of the cytoskeletal filament, found by ultrastructural study, was closely related with the synthesis of lipid.

Abdominal Muscles↗

PubMed1997

[Studies on purging leukemic cells by photosensitizer PSD-007 laser photoradiation in vitro].

The sensitivity to photosensitization mediated by the hematoporphyrin photosensitizer PSD-007 of acute promyelocytic leukemic cell line (HL-60) was compared with normal human hemopoietic progenitor cells. The results showed that the leukemic cells were more sensitive. After being treated with 10 micrograms.ml-1 PSD-007 followed by 2J.cm-2 copper vapor laser light irradiation, the clonogenic leukemic (HL-60) cells were reduced 98%, but the survival rate of human granulocyte-macrophage colony-forming units (CFU-GM) was 40 +/- 8%. Mixing of normal human marrow cells with leukemic (HL-60) cells (ratio 100:1) did not interfere with elimination of tumor cells. The ultrastructure changes of HL-60 cells treated by laser photoradiation was observed under the trans-electronic microscope. The mitochondria, endoplasmic reticulum and cell membrane were involved. This means that the cell biomembrane is the main target to be attacked. It is considered that PSD-007-laser photoradiation therapy is efficient for killing leukemic cells.

Adult↗

PubMed1996

Thalidomide prolonged graft survival in a rat cardiac transplant model but had no inhibitory effect on lymphocyte function in vitro.

The effects of thalidomide on in vitro interleukin 2 (IL-2) production and thymidine uptake by human peripheral blood lymphocytes or rat splenocytes were investigated. Phytohaemagglutinin-stimulated human lymphocytes were incubated in the presence of thalidomide added at culture initiation. No immunosuppressive effect of thalidomide was observed in these experiments. Primary human mixed lymphocyte cultures treated with thalidomide for 6 days were also unaffected. A microsomal rabbit liver homogenate was prepared for metabolizing thalidomide. Stimulated lymphocytes secreted significantly more IL-2 in the presence of microsomal-treated thalidomide than did controls. The effect of thalidomide was then studied either as single therapy or in combination with cyclosporin A (CyA) in a rat allograft cardiac transplantation model. In addition, T cell subsets were analysed by flow cytometry in untransplanted rats treated with thalidomide. Treatment was given as induction therapy from the day of transplantation until day 9. Graft survival in rats treated with thalidomide was significantly prolonged compared to the untreated group. No difference in graft survival was detected between rats treated with thalidomide or CyA only. Graft survival was found to be slightly prolonged in rats given thalidomide and CyA in combination compared to rats treated with CyA alone. In untransplanted rats given thalidomide a decrease of CD4 positive T cells was detected on days 3 and 5. The T helper/cytotoxic-suppressor cell ratio was significantly diminished but, after 1 week of treatment, values for T cell subsets had almost returned to baseline levels. No inhibitory effect was obtained when phytohaemagglutinin-stimulated rat splenocytes were cultured with metabolized thalidomide. In summary, the ability of thalidomide to improve allograft survival in a solid organ transplant model was verified. The occurrence of thalidomide-induced changes in T cell subset ratios was demonstrated. In in vitro studies, however, there was no decrease but an increase in IL-2 production, and no change in thymidine uptake. The mechanism responsible for the immunosuppressive effect of thalidomide remains to be elucidated.

Animals↗

PubMed1996

Moderate additive immunosuppressive effect of thalidomide combined with cyclosporin A in rat cardiac transplantation.

Thalidomide is an immunomodulating agent shown to prolong graft survival in experimental skin, renal, cardiac and bone marrow transplantation. The main purpose of the present study was to investigate the possible additive effect of combining thalidomide with cyclosporin A (CyA). Members of our group have previously created a basis for such studies by demonstrating the ability of Linomide to abolish the effect of CyA. The additional effect of combined treatment with a second drug is thereby more readily evaluated, compared with using subtherapeutic dose levels to induce early rejection. Cardiac grafting was performed in three rat strain combinations (BN to WF, DA to Lew, and BN to Lew). Rats were given no treatment, or thalidomide, CyA and/or Linomide in single, double or triple drug therapy. Except for a consistent beneficial effect of CyA as single drug treatment, graft survival varied depending on the rat strain combination used. In the DA to Lew combination, the expected effects of Linomide were seen, and thalidomide was shown to prolong graft survival significantly (P = 0.004) when added to CyA and Linomide. However, there was no effect of thalidomide when given alone. In WF recipients of BN hearts, thalidomide tended to prolong graft survival (P = 0.07), and surprisingly Linomide manifested a marked immunosuppressive effect (P = 0.0002) and did not counteract the effect of CyA. When transplanting BN grafts to Lew recipients, Linomide reduced significantly but did not abolish completely the effect of CyA. Neither Linomide nor thalidomide had any beneficial impact on graft survival on their own. To sum up, thalidomide was shown to have a minimal or moderate immunosuppressive effect additive to that of CyA. The effects of the two immunomodulating drugs, thalidomide and Linomide, varied depending on the rat strain combination used, and were similar with respect to prolongation of graft survival when used as single drug treatment in BN to WF grafting, a fact which may indicate them to have a similar mechanism of action, both having been shown to exert similar effects on levels of tumour necrosis factor alpha.

Adjuvants, Immunologic↗

PubMed1996

Bioavailability of cyclosporine in rats after intragastric administration: a comparative study of the L2-phase and two other lipid-based vehicles.

The purpose of this study was to evaluate formulations based on surface active dietary lipids only as oral vehicles for cyclosporine. The absolute bioavailability of cyclosporine from two new lipid vehicles was determined in rats after intragastric administration and compared to that of Sandimmun oral solution, which contains non-ionic surface active substances in addition to dietary lipids. In the new vehicles, cyclosporine was dissolved in two different mixtures of glycerides from long-chained fatty acids. One mixture forms an L2-phase, an oil with very low interfacial tension towards water, and was administered both as the oily L2-phase and as a predispersed emulsion formulation. The other mixture forms a liquid crystalline phase and was administered only as an aqueous dispersion. The mean bioavailability of cyclosporine from Sandimmun was 8% while it was 34% from the L2-phase, 38% from the predispersed L2-phase and 27% from the dispersed liquid crystalline phase. The coefficients of variation in area under the blood concentration curve after administration of the two formulations based on the L2-phase were quite low (31% for the L2-phase and 24% for the predispersed L2-phase) and comparable to that after intravenous administration (24%), while the dispersed liquid crystalline phase gave a higher variability (91%), comparable to that of Sandimmun oral solution (101%). The low variabilities found with the two L2-phase vehicles suggest that this formulation is "self-emulsifying' in the gastrointestinal tract. Since the L2-phase is based on dietary lipids only, it is expected to be well tolerated and could prove to be a good vehicle for long-term clinical use of oral cyclosporine.

Administration, Oral↗

PubMed1996

Determination of the steady state tissue distribution of midazolam in the rat.

The aim of this study was to determine the steady state tissue:blood (Kb), tissue:plasma (Kp), and tissue:plasma water (Ku) partition coefficients of midazolam in all major organs and tissues in the rat, after development of a gas chromatographic assay. The Kp in 12 tissues ranged between 1.3 (in muscle) and 9.0 (in fat). Ku ranged correspondingly between 16 and 115.

Animals↗