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

Long-term repopulation of the blood-forming organs of dogs, conditioned by wholebody X-irradiation (1200 R midplane dose), was achieved by transfusion of cryopreserved allogeneic blood mononuclear cells (MNC) without causing graft-versus-host-reaction (GVH-R). Donor and recipient dogs were DL-A identical, MLC-negative, no siblings, non-related. The blood stem cells (CFUc) were procured by a 3- to 4-hour continuous-flow leukapheresis. To increase the CFUc concentration in the peripheral blood, dextran sulfate (DS) was administered intravenously beforehand. About 1 x 10(10) MNC, among them about 1 x 10(7) CFUc, were collected and further segregated using a discontinuous albumin density gradient. Less dense cells were to be found in the upper part of the gradient (fraction 2). These cells included most of the CFUc, enriched by a factor of between 275 and 1730 compared to their concentration in the peripheral blood beforehand. After cryopreservation, these cells, when transfused into lethally irradiated dogs, completely repopulated the marrow and lymph nodes, caused no GVH-R and allowed long-term survival. These dogs received no immunosuppressive therapy, either before or after transfusion. More dense MNC were to be found in fraction 3; their transfusion caused a severe GVH-R, followed quickly by death. Fraction 4 was rich in lymphocytes and poor in CFUc. The transfusion of these cells produced a selective plasma-cell hyperplasia of the lymph nodes but failed to repopulate permanently the marrow. The reappearance of the different cell lineages in the marrow and in the peripheral blood after conditioning and transfusion of these cells produced a selective plasma-cell hyperplasia of the lymph nodes but failed to repopulate permanently the marrow. The reappearance of the different cell lineages in the marrow and in the peripheral blood after conditioning and transfusion of the segregated MNC is described in detail.
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PMID:Albumin density gradient purification of canine hemopoietic blood stem cells (HBSC): long-term allogeneic engraftment without GVH-reaction. 3 71

Mice homozygous for the recessive mutation motheaten (me) are deficient in capacity for immune response but show an elevated level of serum immunoglobulins. In comparison to spleen cells from normal sibs, spleen cells from me/me mice have a severely depressed 19S PFC response to SRBC. In the GVH assay, spleen and thymus cells from motheaten donors caused significantly weaker reactions than like cells from normal sibs. Serum electrophoretic patterns of motheaten mice showed increased levels of alpha-, beta-, and gamma-globulins and decreased levels of albumin. Increases in quantities of all major classes of immunoglobulins were found in serum of me/me mice 5 weeks of age and older. Elevation of serum IgM was evident by 3 weeks of age and had reached 25 times the levels in normal sibs by 6 weeks of age. Immunoelectrophoresis and Ouchterlony analysis showed motheaten serum to have both kappa and lambda2 light chains. Evidence of autoimmunity was found in motheaten mice in the granular deposition of IgM and IgG in kidney glomeruli. Motheaten mice, thus, appear to have a severe immune deficiency, but the basic nature of the deficiency is not yet known.
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PMID:Motheaten, an immunodeficient mutant of the mouse. II. Depressed immune competence and elevated serum immunoglobulins. 5 6

Severe respiratory distress appeared in a 14-year-old girl with acute lymphoblastic leukemia 2 months after receiving syngeneic bone marrow transplantation (BMT) with a conditioning regimen of a high-dose of busulfan, etoposide and nimustine. Rapid body-weight gain and edema, especially in eyelids and lower-limbs, were also observed. Without any findings of heart failure nor GVHD, pulmonary edema was recognized on the chest roentgenogram. As soon as the diagnosis of pulmonary edema due to 'capillary leak syndrome' was suspected, the patient was treated with intravenous administration of diuretics, albumin and bolus methylprednisolone in combination of mechanical ventilation. Although the clinical manifestations were improved by the treatment, the disease recurred 5 weeks later. The patient was successfully treated by the same medications, and there has been no recurrence as of the sixth month after discontinuance of the therapy. At present, the mechanism of capillary leak syndrome is still undefined. In this case, however, we speculate that the conditioning regimen for BMT intensified the capillary disturbance initially caused by intensive chemotherapy since remission induction. Furthermore hypoalbuminemia due to severe anorexia might have enhanced the occurrence of the disease.
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PMID:[Recurrent pulmonary edema in a patient with acute lymphoblastic leukemia after syngeneic bone marrow transplantation]. 157 40

Bronchoalveolar lavage (BAL) cytology and immunoglobulin components of lavage fluid were studied during non-bacterial/non-fungal interstitial pneumonitis, bacterial/fungal pneumonia, and Pneumocystis carinii infection. Lavages done before bone marrow transplantation and in asymptomatic phases were used as controls. The total cell recovery was increased during lung processes of any aetiology. Non-bacterial/non-fungal pneumonitis caused a significant increase in the number of lymphocytes; the number of neutrophils increased particularly during bacterial pneumonia. In Pneumocystis carinii pneumonia the typical cell picture was an increased percentage of lymphocytes together with blasts. During acute graft-versus-host disease without respiratory symptoms the cytology in lavage fluids did not differ from the controls. Cytomegalovirus (CMV) isolation was frequently positive in lavage fluids regardless of the presence or absence of pulmonary symptoms, but most of the symptom-free CMV-positive patients did not have any marked changes in BAL cytology. The albumin content of BAL fluid increased during infectious and immunological processes in lungs.
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PMID:Use of bronchoalveolar lavage cytology and determination of protein contents in pulmonary complications of bone marrow transplant recipients. 215 19

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

In order to understand the mechanism of immunosuppression caused by infusion of placental gamma globulin (PGG) in patients with renal allografts, rheumatoid arthritis, and graft-versus-host disease (GVHD) following bone marrow transplantation (BMT), we have examined the effect of PGG in vitro and in a model of the xenogeneic, local graft-versus-host reaction (LGVHR). PGG inhibited lymphocyte proliferation in mixed lymphocyte cultures (MLC) (P less than 0.005) and depressed interleukin-2 (IL-2) levels in such cultures at 72 hours (P less than 0.01). In contrast phytohemagglutinin (PHA)- and pokeweed mitogen (PWM)-induced T and B lymphocyte blastogenesis was not affected by such PGG treatment. PGG neither decreased the [3H] TdR pulse incorporation in unstimulated lymphocytes nor affected cell viability. Cell cycle analysis by flow cytometry showed that PGG reduced the percentage of cells in S and G2, M phases during the MLC, but did not alter cell cycling during PWM-stimulated proliferation. An immunosuppressive effect of PGG on the LGVHR was tested in a model of intracutaneous transplantation of PGG-treated human lymphocytes into cyclophosphamide-immunosuppressed rats. Lymphoprep-separated human tonsillar lymphocytes were incubated with RPMI-1640 buffer containing: (1)PGG, 4 mg/ml, (2) human plasma albumin, 4 mg/ml, (3) mitomycin-C, 25 micrograms/ml, or (4) no additive. Cells of each preparation (3 X 10(7) cells in 0.1 ml) were injected intracutaneously into cyclophosphamide-treated male rats at separate abdominal locations. A fifth site received only the buffer solution. Five days after injection of cells, each rat received [125I]UdR (10 muCi) intraperitoneally and was killed after 5 hours.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Activity of human placental gamma globulin in blocking immune functions in vitro and in abrogating the xenogeneic, local graft-versus-host reaction. 248 43

The authors review the progress made during the last quarter of a century in the fields of hematopoietic cellular proliferation and differentiation in relation to the bone marrow structure and the microenvironment provided by the marrow stroma in which unlimited self-renewal occurs. The marrow is conceived of as an organ in which the stroma originates from local mesenchymal elements which form a vascularized and innervated matrix, seeded later by blood-borne stem cells. Transplantation studies using total-body-irradiated dogs show that stem cells derived from the marrow, as well as those from the blood and from the fetal liver, are able to repopulate a marrow rendered aplastic by irradiation. By grafting equal numbers of GM-CFU from peripheral blood and bone marrow, a faster hemopoietic reconstitution is provided by blood-derived stem cells. The most efficient stem cells in the long range are those derived from fetal liver. Bone marrow and peripheral blood GM-CFU differ in some in vitro characteristics such as radiation sensitivity. These peripheral blood cells are more radiosensitive than those derived from the marrow. Autografting of bone marrow mononuclear cell fractions obtained by velocity sedimentation techniques demonstrates that the fraction of small mononuclear cells holds a repopulating potential similar to that of circulating blood stem cells. The cells collected in fraction 2 of a discontinuous albumin gradient contain most of the blood stem cells and repopulate the marrow without causing GVHD, while cells collected in fractions 3 and 4 contain a minimal amount of stem cells and cause severe GVHD.
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PMID:Bone marrow structure and its possible significance for hematopoietic cell renewal. 286 31

In 31 consecutive patients who received an allogeneic bone marrow transplantation the loss of proteins during the period at risk for acute graft-versus-host disease (aGVHD) was studied in order to determine whether the quantity of protein loss could be used for grading the severity of aGVHD. It was shown that the grade classified on the basis of the severity of skin rash, the quantity of diarrhea and the seriousness of cholestasis, correlated with serum albumin loss, intestinal plasma loss (expressed by the intestinal alpha 1-antitrypsin clearance) and the occurrence of inflammatory cells (leukocytes) in feces. The quantity of albumin lost by intestinal route accounted for only one third of the total albumin loss. To investigate whether the remaining part of it could be explained by capillary leakage elsewhere in the body, leakage of antileukoprotease from the tissue of the respiratory tract into the blood was measured. It was shown that the serum concentration of this proteinase inhibitor correlated with albumin loss. This means that capillary leakage also occurs in the lung during aGVHD. In conclusion, the loss of proteins can be used as a parameter of the severity of aGVHD once the proper diagnosis has been established. It appears that a combination of the current 'familiar' grading system and SAL yields a more objective classification system with a greater prognostic value.
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PMID:Protein loss during acute graft-versus-host disease: diagnostic and clinical significance. 329 72

Prevention of acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation, requires the depletion of mature T-lymphocytes from bone marrow grafts. The optimal degree of T-cell reduction is still an open question. We compared two procedures of T-cell separation in 18 consecutive recipients of genotypically HLA-matched bone marrow, who also received cyclosporin A for 6 months. The first method (A) was based on a discontinuous albumin gradient fractionation and resulted in an average T-lymphocyte content of 50 X 10(5)/kg body weight (n = 9 patients); the second method (B) was based on E-rosette sedimentation and reduced the contamination to 15 X 10(4) grafted T-lymphocytes/kg body weight on the average (n = 9 patients). Thus, approximately 90 and 99% of the original T-lymphocytes were removed from the marrow grafts respectively. Of the seven patients of the first group who were at risk of GVHD (excluding two cases of early death), five developed a minimal-to-moderately severe acute GVHD and in two cases chronic GVHD ensued. Lethal GVHD was not seen. Of group B, all recipients engrafted and none developed GVHD (0/9). The difference in the frequency of GVHD between the two groups was highly significant (P less than 0.0025). These data confirm our preclinical studies. They demonstrate that a one-log T-lymphocyte reduction of the marrow inoculum, when combined with cyclosporin A prophylaxis after major histocompatibility complex (MHC)-matched transplantation, is still associated with a considerable incidence of GVHD, whereas a two-log reduction of T-lymphocytes may provide full protection against acute GVHD.
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PMID:Graft-versus-host disease following transplantation of 'one log' versus 'two log' T-lymphocyte-depleted bone marrow from HLA-identical donors. 333 28

Whole saliva samples and lip biopsies were collected from 12 allogeneic bone marrow transplant recipients who developed extensive chronic graft-versus-host disease (GVHD) and from 10 healthy allogeneic and syngeneic recipients without GVHD. Six of ten biopsies from patients with chronic GVHD had lichenoid stomatitis or sialadenitis, or both, with sialodochitis. Seven of nine biopsies from patients free of chronic GVHD were entirely normal, and two had either mild glandular or mucosal changes. Salivary gland involvement in chronic GVHD was associated with decreased or absent levels of salivary IgA and inorganic phosphate, decreased salivary flow rates, and increased concentrations of salivary sodium, albumin, and IgG. The most striking abnormalities were found in patients with histologic evidence of sialadenitis. In contrast, marrow transplant recipients without chronic GVHD had normal salivary immunoglobulin and electrolyte levels. Secretory IgA deficiency may contribute to the frequent sinobronchial infections observed in patients with chronic GVHD.
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PMID:Disordered salivary immunoglobulin secretion and sodium transport in human chronic graft-versus-host disease. 634 24


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