Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cell-free supernatants of rabbit bone marrow were fractionated, separated, and purified by Ultrogel and Superose chromatography. A single fraction promoted engraftment of allogeneic bone marrow and enduring hemopoietic chimerism across the H-2 barrier in lethally irradiated mice. This "bio-active" fraction, analyzed by reducing SDS-PAGE electrophoresis, and transblotted on PVDF membrane, and purified by reverse-phase HPLC and SDS-PAGE electrophoresis yielded a main prealbumin band that when examined for primary structure by Edman degradation, proved to be rabbit transferrin. This was also attested by highly specific precipitation of the prealbumin band with polyclonal antibodies to rabbit transferrin. Iron-saturated human transferrin, lactotransferrin, and egg transferrin (conalbumin) were assayed in irradiated C57BL/6 mice infused with bone marrow from histoincompatible BALB/c donors. Mice treated with iron-loaded transferrins survive and develop enduring allogeneic chimerism with no discernible signs of graft-versus-host disease. Iron carrier proteins thus provide an unique means of achieving successful engraftment of allogeneic bone marrow in immunologically hostile murine H-2 combinations.
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PMID:Iron carrier proteins facilitate engraftment of allogeneic bone marrow and enduring hemopoietic chimerism in the lethally irradiated host. 201 4

Rabbit bone marrow supernatants were fractionated and purified by Ultrogel and Superose chromatography. A unique fraction promoted engraftment of allogenic bone marrow and enduring hemopoietic chimerism across the histocompatibility (H-2) barrier in lethally irradiated mice. This fraction analysed by reducing SDS-PAGE electrophoresis and transblotted on PVDF membrane or purified by reverse-phase HPLC and SDS-PAGE electrophoresis yielded a main pre-albumin band that was examined for primary structure by Edman degradation. It appeared to be rabbit transferrin. Iron saturated human transferrin, lactotransferrin and egg transferrin (conalbumin) were then tested in irradiated C57B1/6 mice transplanted with bone marrow from histoincompatible BALB/CJ donors. Most mice treated with iron-loaded transferrins survived and developed enduring allogeneic chimerism with no discernible signs of graft-versus-host disease at 10 months posttransplant. Observation of these animals is still carried on. Iron carrier proteins seem to provide a novel unexpected means for achieving a successful engraftment of allogeneic bone marrow in immunologically hostile murine H-2 combinations and may open a new approach in the clinical area.
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PMID:[The effect of iron carrier proteins on the transplantation of H-2 locus-incompatible bone marrow in irradiated mice]. 225 17

A hybridoma (F6C7) was established by fusing NS1 cells with spleen cells of MRL/Mp-+/+ (MRL/+) mice suffering from lpr-GVHD. This F6C7 mAb (IgG2b, kappa) stains a broad spectrum of blood cells at varying intensities in mice and rats. In normal (BALB/c) mice, granulocytes and B cells are highly positive for F6C7-reactive Ag (F6C7-Ag). Thymocytes and peripheral (CD4+ and CD8+) T cells show negative to low intensities. These staining profiles are similar in C57BL/6, AKR/J, C3H/HeJ, and MRL/+ mice. When spleen cells were activated in vitro, a blastic cell population of autoactivated CD4+ and CD8+ T cells showed increased F6C7-Ag expression. Alloactivated CD4+ blastic T cells also showed increased expression of F6C7-Ag, whereas alloactivated CD8+ blastic T cells as well as Con A-activated CD4+ and CD8+ blastic T cells remained at the level of small (nonblastic) cells. These findings suggest that the surface expression of F6C7-Ag is up-regulated in some activation processes of T cells, particularly in autoactivation. Young (2-month-old) MRL/Mp-lpr/lpr (MRL/lpr) mice show staining profiles of F6C7-Ag similar to those of normal mice, except that many more blastic (CD4+ and CD8+) T cells show high F6C7-Ag expression than those of normal mice. A small but significant number of CD4+F6C7-Ag(high) and a much higher number of CD8+F6C7-Ag(high) blastic T cells were observed in the spleen cells of MRL/+ mice suffering from lpr-GVHD. These blastic T cells may exert autoreactivity and participate in the initiation of autoimmune diseases, lymphadenopathy, and lpr-GVHD. Immunoprecipitation and SDS-PAGE revealed that F6C7-Ag is a heterodimer comprised of approximately 78- and 70-kDa molecules without disulfide bonds.
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PMID:Increased cell surface expression of a newly identified heterodimer on activated blastic T cells. 811 79

The effect of serum from orthotopic liver retransplanted rats (re-OLT serum) on graft-versus-host disease (GVHD) was studied in rats. In the re-transplantation model of rat liver, orthotopic liver transplantation (OLT) was carried out in the DA (RT1a) into PVG (RT1c) combination; two days later the DA liver was removed and a new PVG liver implanted into the same recipient (re-OLT). In the in vivo GVHD model, male PVG rats were sublethally irradiated and injected intravenously with 3 x 10(8) DA or BN (RT1n) spleen through the penial vein. Within 1 h of the inoculation, rats of the experimental group were injected with 1 ml of re-OLT serum taken at postoperative day (POD) 7. Rats in the control group received 1 ml of normal PVG serum or syngeneic re-OLT serum (PVG-PVG, PVG-PVG). All PVG rats in the control groups died of GVHD within 21 days after the inoculation of DA or BN spleen lymphocytes. However, when the animals were treated with re-OLT serum, 100% (6/6) of the rats survived more than 60 days, following inoculation with DA lymphocytes but not with BN lymphocytes. The POD 7 re-OLT serum showed a strong inhibition against DA anti-PVG mixed lymphocyte reaction (MLR), although re-OLT serum did not contain soluble DA class I antigens, anti-DA class I or II antibody. The potential GVHD inhibitory factors in re-OLT serum may be two unique immunosuppressive proteins, which have been detected by SDS PAGE and reported previously. We conclude that re-OLT serum has immunosuppressive factors, which, at least in part, prevented the induction of GVHD in rats.
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PMID:The prevention of graft-versus-host disease by the serum of liver retransplanted rats. 910 37

The aim of this study was to establish a simple, convenient and efficient method of producing placental-eluted gamma globulin (PEGG) from human placenta, explore its inhibitory effect on the function of T lymphocyte in vitro and graft-versus-host disease (GVHD) in vivo. PEGG was prepared by elution at acid pH from human placental tissues that were extensively washed. Its effects on T lymphocyte proliferation induced by PHA and mixed lymphocyte reaction (MLR) were analysed by BrdU ELISA, its effect on the CD25 and CD69 expression on T cells was observed by flow cytometry, and the interferon gamma (IFN-gamma) and interleukin-4 (IL-4) quantification in MLR supernatant were assayed by ELISA. A murine GVHD model was established, the effect of PEGG on the manifestation and pathologic change of GVHD and 45-day survival rate were observed. The results showed that considerable level of immunoglobulin could be eluted from placenta at acid PH, of which the main components were IgG checked by SDS-PAGE analysis. In vitro study indicated that PEGG significantly inhibited both the proliferative response of T cells to PHA and the MLR, down-regulated the expression of CD25 and CD69 on T cells stimulated by PHA, and decreased the secretion of IFN-gamma but increased the production of IL-4 in MLR supernatant. In vivo, recipient mice treated with PEGG had a markedly increased survival rate with less histopathological evidence of GVHD. It is concluded that PEGG can inhibit the proliferation and activation of T cells, regulate the direction of T helper cells differentiating towards Th2 type, and effectively prevent GVHD in a murine model. In short, PEGG may be a potent therapeutic agent for GVHD.
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PMID:[Preparation of placental-eluted gamma globulin and its immunosuppressive effect in vitro and in vivo]. 1680 Sep 36

The study was aimed to establish a new method of preparation of human placenta factor (PF) and to determine its physic-chemical properties, as well as effects on lymphocytes in vitro. PF was prepared by ultrafiltration. The contents and molecular weight of all constitutions were determined by Bradford method and SDS-PAGE, respectively. Cyclosporin A (CsA) was served as positive control, normal saline (NS) was used as negative control. PHA-stimulated lymphocyte proliferation and mixed lymphocyte reaction (MLR) were detected with MTT assay. The expression of CD69 on T cells was analyzed by flow cytometry. Cytotoxicity of natural killer (NK) cells against K562 tumor cells was examined with LDH release assay. The results indicated that PF was determined to be a group of low molecular weight polypeptides, consisting of two major components whose molecular weight were 9.187 and 4.794 kD respectively. The contents of PF were 5.7 - 6.9 mg/g fresh placenta. PF had similar suppressive effects on PHA-stimulated lymphocyte proliferation and MLR in vitro as compared with CsA (P > 0.05). Both PF and CsA could downregulate the expression of CD69 on T cells which had been stimulated by PMA plus ionomycin (PF vs CsA, P > 0.05). The cytotoxicity of NK cells against K562 cells in PF group was slightly higher or equivalent as compared with that in NS group (P > 0.05), but the cytotoxicity in CsA group was much lower than that in NS group (P < 0.05). It is concluded that a new method of preparation of PF has been established. This study first demonstrates that PF has strong immunosuppressive effects on T cell in vitro, and suppresses T cell proliferation and activation induced by mitogen and alloantigen. This study indicats that PF has no any inhibitory effects, but even enhances the cytotoxicity of NK cells against K562 tumor cells. These results suggest that PF may have suppressive effects on graft-versus-host disease (GVHD) without diminishing graft-versus-tumor (GVT) effects. Therefore, PF may probably be an ideal and promising agent against GVHD.
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PMID:[Preparation of placenta factor and its immunoregulatory effects on lymphocytes in vitro]. 1760 67

Cord blood transplantation (CBT) is frequently associated with pre-engraftment immune reaction (PIR), which is characterized by high-grade fever that peaks around day 9 of transplantation. PIR mimics hyperacute GVHD or engraftment syndrome; however, it is considered to be of different etiology as it occurs before engraftment. Proteomic patterns have been studied in the fields of transplantation, but no specific marker has been identified. As there are no data to confirm the mechanism of PIR, we used a surface-enhanced laser desorption/ionization time-of-flight mass spectroscopy (SELDI-TOF MS) system to identify a specific marker for PIR. The protein expression profile of serum samples from CBT patients was analyzed with a SELDI-TOF MS system. A protein peak that commonly predominated in PIR was purified by an anion exchange column, isolated by SDS-PAGE, and identified by in-gel trypsin digestion, and mass fingerprinting. A 8.6-kDa protein and 11-kDa protein that increased by 10- to 100-fold in the serum of patients during PIR was identified as anaphylatoxin C4a and serum amyloid A. SELDI-TOF MS system in combination with other proteomic methods could serve as a potential diagnostic tool in discovering biomarkers for PIR after CBT.
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PMID:Identification of molecular markers for pre-engraftment immune reactions after cord blood transplantation by SELDI-TOF MS. 2022 53

Graft versus host disease (GVHD) occurs after bone marrow transplantation and is one of the most important causes of death worldwide. Reviews demonstrated GVHD patients with involvement of various tissues and organs, such as salivary glands. The diagnosis of acute GVHD has been the biopsies and the histopathologic evaluation of tissue from an involved organ. These procedures are invasive. Saliva proteins as possible biomarker for GVHD could facilitate the management and diagnosis accuracy. For support the proposed hypotheses, in this pilot study we collected whole saliva samples from patients with undergoing allogeneic hematopoietic cell transplantation (HCT) and from healthy subjects. Samples were collected prospectively between pre-transplant, thirty days, one hundred and, two hundred days after transplant. The proteomic profile was analyzed using SDS-PAGE and LCMS-ESI-IT-TOF mass spectrometry. The relevant personal data, past medical history were also recorded. The most relevant proteins found exclusively in GVHD patients were: CSF2RB, Protocadherin (Pcdh) Fat 2 precursor, protein capicua homolog isoform CIC-S, MUC16 and RGPD8_HUMAN RANBP2. This study aims to conduct an initial evaluation of the possible presence of such biomarkers in saliva from GVHD patients, and suggested a potential application of proteomics analysis as a alternative method to diagnose GVHD.
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PMID:Could mucin 16 and colony-stimulating factor 2-receptor beta possible graft versus host disease biomarkers? Medical hypotheses. 2823 56