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F Fu

Publications and source records attributed to F Fu.

At least 37 records · Page 2Linked to original sources

[Implementing a relatively rigorous algorithm of dynamic EIT problem on the modified FEM model].

We deduced a relatively rigorous algorithm of dynamic EIT problem-general inverse algorithm, and implemented it on the computer FEM model. Images which can show the changing of the resistivity(i.e. dynamic resistivity images) were gained. Also we modified the ordinary FEM model according to the characteristic of the EIT problem and implemented the general inverse algorithm on the modified model. The ill-posed condition of the forward matrix based on the modified model was fairly improved. It can be seen from the results that the general inverse algorithm with modified FEM model is an algorithm better than the back-projection algorithm in terms of object locating, image definition, and the ability of dealing with complex object and noise.

Algorithms↗

Blockade of the CD40-CD40 ligand pathway potentiates the capacity of donor-derived dendritic cell progenitors to induce long-term cardiac allograft survival.

BACKGROUND: Failure of costimulatory molecule-deficient donor dendritic cells (DCs) to induce indefinite allograft acceptance may be a result of the 'late" up-regulation of these molecules on the DCs after interaction with host T cells. Ligation of CD40 on antigen-presenting cells by its cognate ligand CD40L is thought to induce expression of CD80 (B7-1) and CD86 (B7-2). We examined the influence of anti-CD40L monoclonal antibody (mAb) on the capacity of donor-derived DC progenitors to induce long-term allograft survival. METHODS: High purity DC progenitors were grown from B10 (H2b) mouse bone marrow in granulocyte-macrophage colony-stimulating factor and transforming growth factor beta1 (TGFbeta1). Mature DC were propagated in granulocyte-macrophage colony-stimulating factor and interleukin-4. Their phenotype was characterized by flow cytometric analysis and their function by mixed leukocyte reactivity. Anti-donor cytotoxic T lymphocyte activity in grafts and spleens of vascularized heart allograft recipients was also assessed. RESULTS: The TGFbeta3-cultured cells were (1) DEC 205-positive, MHC class II-positive, CD80dim, CD86dim, and CD40dim, (2) poor stimulators of naive allogeneic T-cell proliferation, and (3) able to prolong significantly B10 cardiac allograft survival in C3H (H2k) recipients when given (2 x 10[6] i.v.) 7 days before organ transplantation (median survival time [MST] 26 days vs. 12 days in controls, and 5 days in interleukin-4 DC-treated animals). Their allostimulatory activity was further diminished by addition of anti-CD40L mAb at the start of the mixed leukocyte cultures. Anti-CD40L mAb alone (250 microg/mouse, i.p.; day -7) did not prolong cardiac graft survival (MST 12 days). In contrast, TGFbeta-cultured DCs + anti-CD40L mAb extended graft survival to a MST of 77 days, and inhibited substantially the anti-donor cytotoxic T lymphocyte activity of graft-infiltrating cells and host spleen cells assessed 8 days after transplant. CONCLUSIONS: The CD40-CD40L pathway appears important in regulation of allogeneic DC-T-cell functional interaction in vivo; its blockade increases markedly the potential of costimulatory molecule-deficient DCs of donor origin to induce long-lasting allograft survival.

Animals↗

Augmentation of dendritic cells in murine organ donors by Flt3 ligand alters the balance between transplant tolerance and immunity.

Treatment of mice with the recently cloned hemopoietic growth factor Flt3 ligand (FL; 10 microg/day for 10 days) resulted in a large increase in myeloid lineage cells within the liver. While the number of nonparenchymal cells (NPC) harvested from liver increased about 9-fold, a 90-fold increase was observed in the proportion of CD11c+ dendritic cells (DC) recovered from NPC following overnight (18-h) culture in granulocyte-macrophage CSF. In contrast, only a 50% increase was seen in CD11c+ cells within heart single cell suspensions and in the number of DC obtained from hearts after 18-h culture. Liver NPC and heart cell suspensions freshly isolated from 10-day FL-treated animals exhibited increased T cell allostimulatory capacity compared with controls. Overnight cultured DC from livers of FL-treated animals expressed both higher levels of costimulatory molecules (CD80 and CD86) and allostimulatory activity than those from controls. Heart-derived DC also displayed enhanced stimulatory capacity. Pretreatment of organ donors with FL for either 5 or 10 days before transplant of organs to normal recipients abrogated the spontaneous liver allograft acceptance normally observed and resulted in delayed or acute graft rejection (median survival times, 40 and 12 days, respectively). Heart rejection was significantly accelerated by pretreatment of donors with FL for 5 or 10 days (median survival times, 8 and 7 days, respectively, vs 12 days in controls). These novel findings reveal the potent immunologic adjuvant properties of FL in vivo. They also show that substantial augmentation of the number of potential allostimulatory cells in donor organs before transplantation favors rejection rather than tolerance induction.

Animals↗

Apoptosis within spontaneously accepted mouse liver allografts: evidence for deletion of cytotoxic T cells and implications for tolerance induction.

MHC-mismatched liver grafts are accepted spontaneously between many mouse strains. The underlying mechanism(s) is unclear. In the B10 (H2(b)) to C3H (H2(k)) strain combination used in this study, donor T cells within the liver were rapidly replaced within 2 to 4 days of transplantation with those of the recipient. Freshly isolated liver graft-infiltrating cells harvested on days 4 and 7 exhibited strong CTL responses against donor alloantigens. CTL activity was reduced substantially, however, by day 14, although levels of CTL precursors in the spleen and liver remained high. Examination of the liver allografts by in situ terminal deoxynucleotidyltransferase-catalyzed dUTP-digoxigenin nick end labeling on days 4, 7, and 14 after transplantation revealed prominent apoptotic cells dispersed throughout the nonparenchymal cell population. When acute liver allograft rejection was induced by administration of IL-2 from days 0 to 4 post-transplant (median survival time, 5 days), apoptotic activity (day 4) was reduced substantially, whereas CTL activity was enhanced. Nonparenchymal cells isolated from allografts of unmodified recipients 4, 7, and 14 days after transplantation exhibited significantly higher DNA fragmentation after 18-h culture than cells from liver isografts. Moreover, the level was 4 to 5 times higher than that of cells from IL-2-treated mice (on day 4). These observations suggest that T cell deletion, not regulation, may be responsible for spontaneous liver allograft acceptance. The molecular recognition events that cause apoptosis of infiltrating T cells and why this occurs within liver grafts, but not heart or skin grafts, remain to be elucidated.

Animals↗

Interleukin-2 and interleukin-12 mediate distinct effector mechanisms of liver allograft rejection.

Interleukin-2 (IL-2), interleukin-12 (IL-12) or interleukin-4 (IL-4) were administered postoperatively to otherwise spontaneously accepting mouse liver allograft recipients (C57BL/10-->C3H) to test whether TH1 cytokines are critical mediators of rejection in this model. The induction of rejection at days 5 to 7 by exogenously administered IL-2 and IL-12, but not IL-4, suggests that mouse liver allograft rejection can be induced by TH1 cytokines; however, there appeared to be differences in the mechanism by which these cytokines induce liver rejection. IL-2 administration was accompanied by an increased intragraft infiltration of CD4+ and CD8+ cells and an up-regulation of natural killer (NK), lymphokine-activated killer (LAK), allospecific cytotoxic killer (CTL) activity and perforin mRNA when compared with media-treated controls. In contrast, exogenous IL-12 treatment was associated with a suppression of CTL, NK, and LAK activity compared with controls but an enhanced infiltration of F4/80+ macrophages as determined by immunohistochemistry. Determination of cytokine mRNA profiles by semi-quantitative reverse transcription polymerase chain reaction showed the up-regulation of interferon (IFN)-gamma, IL-4, IL-6, and IL-10 mRNA with IL-2 treatment when compared with media-treated controls. Interestingly, IL-2 mRNA was down-regulated in these animals, suggesting a negative feedback mechanism in IL-2 regulation. IL-12 treatment resulted in the up-regulation of IFN-gamma, IL-6, and IL-10 mRNA, but not IL-2 or IL-4 mRNA. Higher complement-directed cytotoxic antibody titers were seen in IL-12-treated recipients compared with controls, whereas IL-2 treatment showed no apparent differences in antibody titers compared with media treatment. These in vivo observations were mimicked in a mixed leukocyte reaction by supplementing the reaction with IL-2, IL-12, or media. These results suggest that rejection of mouse liver allografts may involve more than one distinct cellular immunological effector mechanism. One is mediated by IL-2 and appears to favor alloreactive CTL, whereas the other pathway is mediated by IL-12/IFN-gamma and involves macrophages and cytotoxic antibodies largely resembling a delayed-type hypersensitivity reaction.

Animals↗

[X-ray photoelectron spectroscopy (XPS) and mass spectrum (MS) study of organic tin compounds II].

Seven new synthetical (Z)-1-[2-(Triarylstannyl) vinyl]-1-cycloheptanols organic tin compounds were studied by X-ray photoelectron spectroscopy and mass spectrum method. The influence of different replacement radical in compounds on the d orbit of tin atom was discussed. The coordinate substance had an effect on the chemical displacement of Ols binding energy. The O-->Sn bond was affected by the different replacement radical. The results of X-ray photoelectron spectroscopy and mass spectrum show that Cl, Br and I had the important action.

Electrons↗

Systemic administration of cellular interleukin-10 can exacerbate cardiac allograft rejection in mice.

Cellular interleukin-10 (cIL-10) has been shown to inhibit cytokine production by T helper type 1 (Th1) cells by blocking antigen presenting cell function. This activity has suggested that IL-10 might be useful in the treatment of transplant rejection. Stimulatory effects of IL-10 however, have also been observed both on T and B cell differentiation. In this study, we examined the influence of recombinant (r) mouse (m) IL-10 on heterotopic vascularized heart allograft survival in the B10(H2b)-->C3H(H2k) strain combination that crosses both major histocompatibility complex (MHC) and non-MHC-histocompatibility antigen (non-MHC-HA) barriers. The influence of IL-10 was also examined in the B10.BR (H2k)--> C3H combination with disparity at only non-MHC-HA loci. Postoperative intraperitoneal administration of IL-10 (100 microg/d, days 0-6) significantly accelerated heart graft rejection both in the B10-->C3H (mean survival time [MST] 7.8+/-0.2 days; control MST 10.6+/-0.6 days; P<0.05) and the B10.BR-->C3H combination (MST 14.3+/-0.5 days; control MST 77.7+/-14.4 days). Ex vivo IL-10 perfusion of donor hearts for either 15 min or 2 hr did not affect subsequent graft survival. Immunologic monitoring of transplanted mice revealed that IL-10 treatment (100 microg/d, i.p., days 0-6) increased both the circulating complement-dependent cytotoxic (CDC) antibody titer and splenic anti-donor cytotoxic T lymphocyte (CTL) activity measured up to 3 weeks posttransplant. These findings indicate that post transplant systemic administration of cIL-10 can promote vascularized allograft rejection, and that this may reflect stimulation both of B and T cell alloimmune responses.

Animals↗

Costimulatory molecule-deficient dendritic cell progenitors (MHC class II+, CD80dim, CD86-) prolong cardiac allograft survival in nonimmunosuppressed recipients.

We have shown previously that granulocyte-macrophage colony-stimulating factor-stimulated mouse bone marrow-derived MHC class II+ dendritic cell (DC) progenitors that are deficient in cell surface expression of the costimulatory molecules B7-1 (CD80) and B7-2 (CD86) can induce alloantigen-specific T-cell anergy in vitro. To test the in vivo relevance of these findings, 2 x 10(6) B10 (H2b) mouse bone marrow-derived DC progenitors (NLDC 145+, MHC class II+, B7-1dim, B7-2-/dim) that induced T-cell hyporesponsiveness in vitro were injected systemically into normal C3H (H2k) recipients. Seven days later, the mice received heterotopic heart transplants from B10 donors. No immunosuppressive treatment was given. Median graft survival time was prolonged significantly from 9.5 to 22 days. Median graft survival time was also increased, although to a lesser extent (16.5 days), in mice that received third-party (BALB/c; H2d) DC progenitors. Ex vivo analysis of host T-cell responses to donor and third-party alloantigens 7 days after the injection of DC progenitors (the time of heart transplant) revealed minimal anti-donor mixed leukocyte reaction and cytotoxic T lymphocyte reactivity. These responses were reduced substantially compared with those of spleen cells from animals pretreated with "mature" granulocyte-macrophage colony-stimulating factor + interleukin-4-stimulated DC (MHC class IIbright, B7-1+, B7-2bright), many of which rejected their heart grafts in an accelerated fashion. Among the injected donor MHC class II+ DC progenitors that migrated to recipient secondary lymphoid tissue were cells that appeared to have up-regulated cell surface B7-1 and B7-2 molecule expression. This observation may explain, at least in part, the temporary or unstable nature of the hyporesponsiveness induced by the DC progenitors in nonimmunosuppressed recipients.

Animals↗

Second-set rejection of mouse liver allografts is dependent on radiation-sensitive nonparenchymal cells of graft bone marrow origin.

Livers are accepted spontaneously when transplanted orthotopically from B10 (H2b) or BALB/c (H2d) to C3H (H2k) mice without host immunosuppression. Presensitization to donor can, however, be induced by skin grafting two weeks prior to liver transplantation, resulting in second-set or "accelerated" liver graft rejection, within 4-5 days. In this study, the role of liver nonparenchymal cells (NPC) in second-set rejection was tested by donor whole-body irradiation and replacement of donor B10 liver NPC with those of either third-party (BALB/c) or recipient strain (C3H) bone marrow. Irradiation alone (9.5 Gy) of normal B10 donors before liver transplantation significantly prolonged graft survival in presensitized C3H recipients. Three months after bone marrow transplantation (BMT), chimeric livers expressing third-party or recipient haplotype, were transplanted orthotopically into unmodified C3H recipients. Graft survival was prolonged significantly compared with livers from normal or syngeneically reconstituted B10 donors. Prolonged survival of chimeric (BALB/c->B10) livers was also evident in C3H mice presensitized to alloantigens expressed on both the liver parenchymal (B10) and third-party NPC (BALB/c) by simultaneous grafting of skin from each donor strain. Determination of graft cytokine mRNA profiles 4 days posttransplant showed that replacement of donor with third-party or recipient strain BM-derived cells was associated with reduced expression of IL-2 and IFN-gamma mRNA compared with that in grafts from syngeneically reconstituted donors. IL-10 transcripts, however, were not significantly affected. The results are consistent with a key role of radiation-sensitive, donor-specific NPC of bone marrow origin in second-set liver rejection in presensitized hosts. In this process, competent donor-strain NPC appear to augment the activity of primed T cells responsible for the second-set rejection.

Animals↗

Impact of donor MHC class I or class II antigen deficiency on first- and second-set rejection of mouse heart or liver allografts.

The influence of donor major histocompatibility complex (MHC) class I- or class II-deficiency on the initiation of first- and second-set rejection of mouse heart and liver allografts was examined. C3H (H-2k) mice received heterotopic cardiac or orthotopic liver grafts from unmodified B10 (H-2b), B6 (H-2b), b2m (H-2b; class I deficient) or AB0 (H-2b; class II deficient) donors. Organ survival was also investigated in C3H recipients that had been presensitized by a normal B10 skin graft 2-3 weeks before heart or liver transplantation. The absence of cell surface MHC class I or class II resulted in significant prolongation of primary cardiac allograft survival. Three of seven (43%) MHC class I-deficient, and two of five (40%) class II-deficient heart grafts were accepted indefinitely (survival time > 100 days). Thus both MHC class I and class II molecules appear to be important for the elicitation of first-set rejection in the heart allograft model. All liver allografts survived > 100 days in normal recipients. In C3H recipients that had been presensitized by a B10 skin graft, however, both heart and liver grafts from AB0 (class II deficient) donors underwent accelerated rejection (median survival time [MST] 3 and 4 days, respectively). In contrast, liver grafts from class I-deficient mice (b2m) were still accepted indefinitely by B10 skin-presensitized C3H recipients, whereas class I-deficient hearts survived significantly longer than those from class II-deficient or normal donors. These data demonstrate that the expression of donor MHC class I, and not class II is crucial in initiating second-set organ allograft rejection. In vitro monitoring revealed that at the time of organ transplant, both splenocytes and serum of the skin-presensitized animals displayed high cytotoxicity against AB0 (class II-deficient) but not against b2m (class I-deficient) targets.

Animals↗

[Sixty years of study on ancient medical history].

The paper includes ten parts, viz. origin of medicine, division of historical periods in Chinese medicine, medical institution, history of preventive medicine, history of medicl disciplines and diseases, history of exchanges among China and foreign countries, history of medical education, history of minority medicine, studies on medical figures, works on Chinese medical history. It summarizes the brilliant achievements in the study of ancient Chinese medical history.

China↗

Growth of donor-derived dendritic cells from the bone marrow of murine liver allograft recipients in response to granulocyte/macrophage colony-stimulating factor.

Allografts of the liver, which has a comparatively heavy leukocyte content compared with other vascularized organs, are accepted permanently across major histocompatibility complex barriers in many murine strain combinations without immunosuppressive therapy. It has been postulated that this inherent tolerogenicity of the liver may be a consequence of the migration and perpetuation within host lymphoid tissues of potentially tolerogenic donor-derived ("chimeric") leukocytes, in particular, the precursors of chimeric dendritic cells (DC). In this study, we have used granulocyte/macrophage colony-stimulating factor to induce the propagation of progenitors that give rise to DC (CD45+, CD11c+, 33D1+, nonlymphoid dendritic cell 145+, major histocompatibility complex class II+, B7-1+) in liquid cultures of murine bone marrow cells. Using this technique, together with immunocytochemical and molecular methods, we show that, in addition to cells expressing female host (C3H) phenotype (H-2Kk+; I-E+; Y chromosome-), a minor population of male donor (B10)-derived cells (H-2Kb+; I-A+; Y chromosome+) can also be grown in 10-d DC cultures from the bone marrow of liver allograft recipients 14 d after transplant. Highly purified nonlymphoid dendritic cell 145+ DC sorted from these bone marrow-derived cell cultures were shown to comprise approximately 1-10% cells of donor origin (Y chromosome+) by polymerase chain reaction analysis. In addition, sorted DC stimulated naive, recipient strain T lymphocytes in primary mixed leukocyte cultures. Evidence was also obtained for the growth of donor-derived cells from the spleen but not the thymus. In contrast, donor cells could not be propagated from the bone marrow or other lymphoid tissues of nonimmunosuppressed C3H mice rejecting cardiac allografts from the same donor strain (B10). These findings provide a basis for the establishment and perpetuation of cell chimerism after organ transplantation.

Animals↗

Cytokine mRNA profiles in mouse orthotopic liver transplantation. Graft rejection is associated with augmented TH1 function.

Although mouse liver allografts are spontaneously accepted without immunosuppression in many strain combinations, rejection can be induced by presensitization with a donor skin graft two weeks prior to transplantation. In this study, the semiquantitative reverse transcription polymerase chain reaction (RTPCR) was used to assess the involvement of T helper (TH) cell subsets in liver allograft acceptance by determining cytokine mRNA in the graft and spleen of recipients with (A) spontaneously accepting allografts (B) rejecting liver allografts after previous skin sensitization, and (C) syngeneic controls. Spontaneously accepted liver allografts showed upregulation of TH1 (IL-2, IFN-gamma) and TH2 (IL-4, IL-10) intragraft cytokine mRNA, which peaked at day 6 and tapered off thereafter, when compared with levels in syngeneic grafts, but both IFN-gamma and IL-10 mRNA persisted up to day 30. This cytokine mRNA profile correlated with the transient intragraft inflammation associated with spontaneously resolving rejection. Presensitized recipients that rejected their grafts revealed marked upregulation of TH1 (IL-2 and IFN-gamma) and TH2 (IL-4, IL-6) intragraft cytokine mRNAs compared with spontaneously accepting recipients, although IL-10 mRNA levels showed no differences between the two groups. The most striking difference was seen in IFN-gamma levels, which correlated well with the preferential deposition of IgG2a antibody isotype in the rejecting compared with the spontaneously accepting liver allograft recipients. These results suggested an association between liver allograft rejection and enhanced TH1 cytokine immune response. The ability to reject liver allografts by the adoptive transfer of splenocytes, but not serum, from a sensitized mouse ruled out preformed antibodies alone as a cause of rejection. However, spleen cytokine mRNA profiles showed no differences or trends in TH1 or TH2 expression in spontaneously accepting versus rejecting recipients, which suggested that the spleen is not a major site of alloreactive immune expansion. These data suggest that spontaneous acceptance of mouse liver allografts is associated with an insufficient intragraft TH1 cytokine response, the cause of which is currently under investigation.

Animals↗

Validity of conventional anthropometric techniques for predicting body composition in healthy Chinese adults.

There is little information on the application of generalized prediction equations to ethnic groups other than Europeans and groups of European descent. The purpose of this study was to crossvalidate conventional equations on a group of 56 Chinese adults. Body density was assessed by underwater weighing and also predicted by equations which use a combination of selected skinfolds-biceps, triceps, pectoral, subscapular, abdominal, suprailiac, thigh and calf. There were significant correlations (P < 0.01) between the various methods of predicting percentage fat. However, analysis of variance revealed significant differences (P < 0.01) between mean values. In the men, the Jackson and Pollock equation underestimated, and the Durnin and Womersley equation overestimated, the percentage fat predicted by underwater weighing. The best predictor site in this group was the medial calf skinfold (r = 0.81), which is not included in either equation. In the women, the best predictor sites were the triceps, suprailiac and thigh. As these sites are also used in the Jackson et al. equation, it is not surprising that there was no difference between the prediction of percentage fat by this equation and underwent weight. It is concluded that the Durnin and Womersley and Jackson and Pollock equations tend to overestimate and underestimate, respectively, the percentage fat in Chinese men. Alternative equations which use the calf skinfold may be more appropriate for this ethnic group. In Chinese women, there appears to be good agreement between Jackson and Pollock and hydrodensitometric estimations of percentage fat.

Adult↗

Presensitization by skin grafting from major histocompatibility complex class I or major histocompatibility complex class II deficient mice identifies class I antigens as inducers of allosensitization.

Livers but not hearts are accepted spontaneously without immunosuppression when transplanted from B10 (KbAbEbDb) to C3H (KkAkEkDk) mice. Both organs however, undergo accelerated rejection in C3H recipients presensitized with B10 skin grafts. In this study, we have investigated further the role of functional cell-surface major histocompatibility complex (MHC class I or class II molecules in allosensitization. Skin from transgenic MHC class I (b2mmlUncbcr; AbEb) or class II (C2DTM, KbDb) gene 'knockout' mice was grafted onto naive recipients 2-3 weeks prior to whole organ transplantation. When C3H hosts were presensitized with skin from C2DTM (class II deficient) mice, they promptly rejected (within 4 days) subsequently transplanted B10 liver or heart allografts. In contrast, presensitization with skin from b2m (beta 2-m mutant; class I deficient) mice did not significantly affect the survival of either organ graft. Maximal sensitization was established by day 14 after skin grafting and persisted for at least 12 weeks. Splenocytes obtained from C3H mice sensitized with skin from B10, B6 (KbAbEbDb), or C2DTM but not from b2m mice exhibited an H-2b-specific cytolytic response when tested in cell-mediated lymphocytotoxicity assays. Sera from C3H mice sensitized with B10 or b2m skin contained high titres of cytotoxic activity specifically against H-2b class I. Taken together, these observations suggest that in the strain combination studied, MHC class I rather than class II molecules play an important role in allosensitization. The results indicate the potential importance of avoiding transplantation of organs into recipients of secondary grafts from donors that share human leucocyte antigen (HLA) class I antigens with the first donor.

Animals↗