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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Small bowel and its mesentery contain considerable amounts of lymphoid tissue that can mediate graft-versus-host disease in small bowel transplant (SBT) recipients. Present studies determined the existence of GVHD in a fully allogeneic SBT model and examined the effect of donor pretreatment with ALS in eliminating GVHD. Adult male Lewis (Lew) rats received orthotopic small bowel transplants from untreated (LewxBN)F1 (LBNF1) donors (group 1) or Brown Norway (BN) donors that were untreated (group 2) or pretreated with ALS (days -2 and -1) (group 3). All recipients were treated with cyclosporine 15 mg/kg/day i.m. on days 0-6 postoperatively. Animals were weighed and examined daily for signs of rejection and GVHD. No animals in groups 1 or 3 showed any physical signs of GVHD, but all of those in group 2 had characteristic weight loss, diarrhea, and dermatitis between 4 and 6 weeks postoperatively, from which they all recovered. Histologic examination of skin and spleen at this time confirmed the presence of GVHD. The relative spleen weight [( spleen weight/body weight] x 100) of group 2 animals was also significantly greater than that of unoperated control Lew animals. Spleen cells obtained from group 2 animals at the time of subclinical GVHD, but not cells from group 1 or 3 animals, caused enlargement of popliteal lymph nodes when they were injected into the footpads of Lew rats. This study shows that GVHD can manifest itself in recipients of a fully allogeneic small bowel transplant even when rejection is prevented by effective immunosuppression with CsA. However, combined use of recipient treatment with CsA and pretreatment of donor animals with ALS eliminates all manifestations of GVHD.
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PMID:Graft-versus-host disease in fully allogeneic small bowel transplantation in the rat. 291 75

In this study we examined the effects of acute graft-vs-host disease (aGVHD) on the Brown Norway (BN) rat liver. When clinical signs of the disease appeared, rats were inoculated with fluorescent latex beads and 30 min later nonparenchymal cells were isolated from the liver. The cells were then analyzed via flow cytometry, histochemistry, and electron microscopy. Flow cytometry demonstrated that 58% of the cells from the 80 ml/min elutriation fraction (normally rich in Kupffer cells) of the non-GVHD liver had high fluorescence intensity compared to 8% in rats with aGVHD. Determination of the cellular composition of the various fractions with electron microscopy confirmed flow cytometry observations in that only 9% of the 80 ml/min elutriation fraction of GVHD livers had peroxidase-positive rough ER and the morphological appearance of macrophages as compared to 60% in the non-GVHD liver. The low percentage of fluorescent-positive Kupffer cells in the 80 ml/min elutriation fraction of the GVHD liver is attributed to a massive lymphocytic invasion of the liver and not necessarily to a defect in the mononuclear phagocyte system.
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PMID:Effects of acute graft-vs-host disease on the liver of the brown Norway rat. 347 36

This study was initiated to evaluate the effects of varying the length and site of origin of small-intestine transplants on rejection and on graft-versus-host disease (GVHD). Eighty rats had heterotopic transplants performed with systemic venous drainage of the grafts. The host native bowel was left in situ and no immunosuppressive agents were used. Twenty male Lewis inbred (LEW) rats who received isogenic grafts survived without any evidence of rejection or GVHD. When intestine from Lewis X Brown Norway hybrid rats (LBN) was transplanted into LEW rats, rejection occurred between day 6 and 9 and the time of onset of rejection was not influenced either by the length of transplanted bowel (10 to 80 cm, n = 6 each) or by whether the graft was from the jejunum or the ileum. However, rates of survival for 100 days from rejection were significantly better if 10 cm (100%) or 20 cm (84%) was transplanted than if the grafts were 40 cm or more in length (56%). The LBN recipients of LEW allografts developed GVHD on days 7 through 9, and this response was similarly unrelated to the length or segment of bowel transplanted. However, host survival was quite dependent on graft segment length and site of origin. All animals who received 20 cm or less of proximal bowel survived (with GVHD but no evidence of rejection). While 50% of the animals that received proximal intestinal grafts 40 cm in length survived GVHD, none who received identical-sized grafts from the distal ileum survived (all were dead by day 20). Our data document that the results of small-intestine transplantation is dependent on the length and site of origin of the grafts.
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PMID:The effects of size and site of origin of intestinal grafts on small-bowel transplantation in the rat. 349 43

No predictive serologic marker exists for rejection or graft versus host disease (GVHD) reactions in small intestinal transplantation (SIT). SIT was performed in Lewis (Lew) and Lew X Brown Norway Fl hybrid (LBN) rats in the following combinations: group 1, Lew X Lew; group 2 (isolated rejection), LBN X Lew, and group 3 (isolated GVHD), Lew X LBN. Procoagulant activity (PCA), an index of monocyte immune activation, was measured in the peripheral blood mononuclear cells of graft recipients to assess its value as an immunologic monitor. Histologic findings and PCA were evaluated on days 1, 2, and 3 and every 2 to 3 days after SIT. No pathologic findings of graft or host tissue developed in group 1 (n = 14). Histologic rejection (blunted villi and mononuclear cell infiltration) was seen beginning on day 5 in group 2 (n = 19); early GVHD (loss of nodal and splenic architecture) was first noted on days 5 and 6 in group 3 (n = 17). PCA elevation in SIT was seen to precede histologic evidence of rejection or graft versus host disease in this model and may constitute an important marker for these immunologic events.
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PMID:Immune responses in small intestinal transplantation in the rat: correlation of histopathology and monocyte procoagulant activity. 349 62

Acute graft-versus-host disease (GVHD) was induced in newborn Brown-Norway (BN) and DA rats by i.v. injection of 3 X 10(7) Lewis (L) lymph node cells. Control BN and DA rats received syngeneic cells. Rats were injected i.v. with [methyl-3H]thymidine for 1 h before being killed at 1, 2, 4, 5, 6, 8, 10, 11, 12, 13, and 14 days after the cellular inoculum. A piece of ventral abdominal skin was removed. Autoradiography was used to determine cell proliferative activity (labeling index, LI) in mast cells and fibroblasts of the dermis and basal cells of the epidermis. In addition, the number of mast cells per high-power field was determined for all 4 groups of rats: control DA, GVHD-DA, control BN, and GVHD-BN. Only GVHD-BN rats demonstrated extensive dermatitis. The LI of mast cells, fibroblasts, and basal cells decreased in control rats with increasing age. Although there were differences between DA and BN rats, there was a general pattern of increased proliferation of mast cells at early time points of GVHD followed by a decrease to or below control levels. The number of mast cells per high-power field also increased at early time intervals in both the DA and BN GVHD rats, but decreased significantly at later time points. These data confirm previous studies on chronic GVHD which demonstrated a decrease in the number of mast cells in the skin. Fibroblast LI was decreased at day 1 in both DA and BN GVHD rats. In GVHD-DA, fibroblast LI remained depressed while GVHD-BN demonstrated a second peak in LI at day 10 before declining below control levels. The most prominent basal cell response occurred in GVHD-BN between days 6-14 and is probably indicative of an attempted reparative response associated with GVHD dermatitis in this species. These data demonstrate that the activation of mast cells (proliferation and subsequent degranulation) correlates temporally with cell kinetic alterations occurring in the dermis and epidermis during acute GVHD.
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PMID:Kinetics of mast cell, fibroblast, and epidermal cell proliferation during acute graft-versus-host disease in the neonatal rat. 355 63

In small-bowel transplantation, the transfer of large numbers of donor lymphocytes with the intestinal allograft may provoke a lethal graft-versus-host reaction. The effectiveness of allograft irradiation in vitro as a method of preventing graft-versus-host disease (GVHD) was studied in a rat model of small-bowel transplantation, with the Lewis----Lewis X Brown Norway F1 hybrid strain combination. Cold harvested small-bowel allografts were irradiated immediately prior to heterotopic or orthotopic transplantation. Animals that had received heterotopic allografts irradiated with 0, 250, or 500 rad all died of GVHD after 14.4 +/- 3.0, 15.0 +/- 1.3, and 14.2 +/- 1.9 days, respectively. None of the animals that had received allografts treated with 1000 rad developed clinical or pathologic evidence of GVHD, however, and all survived for more than 6 months (P less than 0.001). Allograft function was studied in animals that underwent orthotopic transplantation. Recipients of nonirradiated orthotopic allografts all died of GVHD after 14.0 +/- 0.7 days, whereas recipients of allografts irradiated with 1000 rad all survived for more than 5 months (P less than 0.001). After 120 days, weight gain (51.8 +/- 11.7%), serum albumin (3.9 +/- 0.7 g/dl), serum triglycerides (67.0 +/- 24.3 mg/dl), CBC, and differential in these animals were not statistically different from those in either age-matched isograft recipients or normal animals, and when the rats were sacrificed, irradiated allografts showed no changes suggestive of radiation injury. These results indicate that irradiation of small-bowel allografts in vitro prevents development of GVHD, and that this can be achieved at a dose which does not cause injury to or malfunction of the allograft.
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PMID:In vitro allograft irradiation prevents graft-versus-host disease in small-bowel transplantation. 387 77

High dose whole body irradiation is commonly included in conditioning regimens for bone marrow transplantation for treatment of patients with hematological malignancies. Interstitial pneumonitis is a major complication after BMT. About one-fourth of all BMT patients die from IP. In about half of these cases, an infectious agent, particularly cytomegalovirus, is involved. When no infectious cause is found, it is classified as idiopathic IP (IIP). Total body irradiation is often associated with the induction of IIP; however, extrapolation of animal data from the experiments presented indicates that this is not the only factor contributing to IIP in man. Brown Norway (BN/Bi) rats were bilaterally irradiated to the lungs with 300 kV X rays at a high dose rate (HDR; 0.8 Gy/min) and at a low dose rate (LDR; 0.05 Gy/min). The dose-response curves found were very steep. In the LDR group, lung function studies were performed. There was a strong correlation between the increase in ventilation rate and the death pattern. The LD50 at 180 days was 13.3 Gy for HDR and 22.7 Gy for LDR. The ratios of LD50/180 at 0.05 Gy/min to that at 0.8 Gy/min is 1.7, which indicates a great repair capacity of the lungs. Extrapolation of animal data to patient data leads to an estimated dose of about 15-16 Gy at a 50% radiation pneumonitis induction for low dose rate TBI. As the absorbed dose in the lungs of BMT patients rarely exceeds 10 Gy, additional factors such as remission-induction chemotherapy, cyclophosphamide, methotrexate, cyclosporin A, graft-versus-host disease, etc., might be involved in the high incidence of IIP in man after BMT.
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PMID:Lung damage following bone marrow transplantation: I. The contribution of irradiation. 388 9

Tolerance, as defined by an inability to produce runt disease and the failure to elicit a normal lymphocyte transfer reaction, was induced in Lewis and Brown Norway rats by the neonatal injection of bone marrow from the opposite strain. When thymus, thoracic duct lymph, or lymph node cells from such tolerant Lewis and Brown Norway rats were cultured together, or were individually cultured with similar cells from an F(1) hybrid of these strains, transformation was suppressed to the levels observed in nonmixed control cultures. In contrast, mixtures of cells involving nontolerant donors demonstrated significant transformation as measured by per cent enlarged cells and thymidine-(3)H uptake. The specificity of the tolerance was confirmed by the presence of transformed cells in mixtures involving cells from a tolerant donor and an unrelated or a partially related third strain of rats. From these results, it is suggested that the mixed lymphocyte reaction may be used as a simple test for tolerance and that it most likely represents an in vitro immune response.
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PMID:The mixed lymphocyte reaction: an in vitro test for tolerance. 565 1

Thoracic duct lymphocytes from neonatally thymectomized Lewis rats fail to produce runt disease in newborn Brown Norway rats when injected with up to ten times the number of normal lymphocytes needed to cause runting. The immunologically deficient lymphocytes appear, however, to confer tolerance, and at least some enlarge and divide when stimulated in vitro with phytohemagglutinin, or xenogeneic or allogeneic cells. Small lymphocytes from thymectomized animals have defective RNA metabolism as judged by a marked impairment in their ability to incorporate uridine-5-H(3) or cytidine-H(3) in vitro.
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PMID:Lymphocytes from thymectomized rats: immunologic, proliferative, and metabolic properties. 591 Jan 97

Heterotopic, vascularized small intestine transplants were performed in inbred strains of rats to investigate the structural, functional, and immunologic consequences of intestinal transplantation with and without immunosuppression with cyclosporine (CyA). Lewis X Brown Norway F1 intestine was rejected by untreated Lewis recipients in 7 to 10 days. Structurally, rejected intestine was characterized by shortened crypts and villi lined by damaged attenuated epithelial cells. Functionally, rejection was associated with impaired epithelial active ion transport as indicated by decreased potential difference and with diminished epithelial barrier function as reflected by decreased transepithelial resistance. Administration of CyA for 7 days prevented clinical rejection and partially prevented the structural and functional defects. Lewis intestine transplanted into Lewis X Brown Norway F1 recipients caused fatal graft versus host disease (GVHD) in 9 to 17 days. Treatment with CyA for 7 days failed to prevent GVHD routinely, but prolonged administration delayed fatal GVHD until CyA was discontinued. Intestine from Lewis "B" rats made deficient of T cells by thymectomy, irradiation, and reconstitution with syngeneic T cell-depleted bone marrow failed to cause GVHD in Lewis recipients. Reconstitution of the "B" rats with T cells before transplantation restored the GVHD response. These results may be relevant in the consideration of clinical small intestinal transplantation.
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PMID:Small intestine transplantation in the rat--immunology and function. 661 97


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