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

A sequential analysis was made of various areas within the lymph nodes and spleen of newborn Brown Norway (BN) rats suffering from graft-versus-host disease (GVHD) subsequent to an allogeneic injection of adult Lewis (L) lymph node cells (experimental). One micron thick autoradiographs were compared between such experimental and control littermates having received the same number of syngeneic adult BN cells. Both experimental and control animals received tritiated deoxythymidine (3HdT) one hour before killing. The autoradiographs revealed a 2.25 and 2.50 times higher thymidine labeling index of lymphocytes in the deep cortex of mesenteric lymph nodes and white pulp of the spleen, respectively, for experimental animals. The experimental effect occurred within one day. The majority of the labeled cells in experimental animals were large lymphoblasts with prominent nucleoli. The labeling index within these areas remained significantly higher than control values until day 8 in the spleen and through day 14 within the lymph nodes. However, differences in labeled cells present in high powered microscopic fields reached a peak on day 3 within compartments in experimental animals but fell significantly below control values by day 9 owing to a pronounced disappearance of both small and large lymphocytes from these areas, and a decreased intensity of individual cell labeling as the reaction progressed. In contradistinction the concentration of labeled cells present in high powered microscopic fields of lymph nodes' medulla became 3.13 times controls by day 4. Most of these labeled cells contained a more basophilic cytoplasm than those found in the deep cortex and some were distinctly plasma cell precursors. In contrast to the deep cortex their concentration remained approximately three times control values until death. The data indicates that the major proliferative events within the spleen and lymph nodes in neonatal rat GVHD are initially restricted to donor cell localization areas of these tissue compartments. Subsequently the GVHD-related events may be attributed to other areas and possibly cell types. Thus any proliferation contributing to splenomegaly in the latter stages of GVHD appears to occur in the red pulp and that contributing to lymph node enlargement a medullary response.
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PMID:3H-deoxythymidine incorporation in graft-versus-host disease in the Norway rat. II. Autoradiographic studies. 1 7

Serum complement (C) and C components were examined during a systemic graft versus host (GVH) reaction in the rat. In our series of experiments (Lewis times Brown Norway) F-1 hybrid rats (60-80g) were given 200 times 10-6 or 400 times 10-6 Lewis spleen cells intravenously. Clinical GVH disease appeared 5-7 days after cell injection. Five of six rats in the experimental groups had a fall in levels of serum C2 (20-76%) and C4 (75-98%). Only one of six rats in the control group had a significant fall in C components. In a subsequent experiment (Fisher 344 times Brown Norway) F-1hybrid rats (60g) were given 400 times 10-6 Fischer 344 spleen cells or 200 times 10-6 Fischer 344 Ficoll-Hypaque separated spleen lymphocytes. Clincal GVH disease in this instance appeared on day 10. As in the previous experiments C2 and C4 fell markedly, 20-60% and 60-8-%, respectively, from baseline titers. The control groups did not have a significant fall in C2 or C4. Further examination showed reduction in C3, C5, C6,AND C8 suggesting a sequential activation of the C system via the classical pathway. We have postulated that the cells undergoing blast transformation may be activating the C system through membrane changes during the GVH reaction. Furthermore, the deficiency of C AND C components during GVH disease may contribute to the increased susceptibility of the host to infection and sepsis.
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PMID:Complement in graft versus host disease: IL Depletion of complement components during a systemic graft versus host reaction in the rat (38499). 23 66

Graft failure in recipients of lymphocyte-depleted allogeneic bone marrow transplants is a major limitation to the success of this approach for preventing acute graft-versus-host disease. In a rat BMT model, we evaluated the effect of cyclosporine dose and schedule of administration on the engraftment of MHC-mismatched bone marrow. Lewis Brown-Norway rat recipients were prepared with myeloablative doses of busulfan (day -2) and cyclophosphamide (day -1) and then transplanted with MHC-mismatched ACI rat BM (day 0) that had been depleted of lymphocytes by counterflow centrifugal elutriation. Beginning on day -1, LBN rats received variable doses of CsA (i.e., 12.5, 10.0, 7.5, 5.0, 2.5, 0.0 mg/kg/day) for various lengths of time after BMT (i.e., 7, 14, 21, or 28 days). While all rats receiving high-dose CsA (i.e., 12.5 or 10.0 mg/kg/day) for 28 days had stable donor-derived hematopoietic reconstitution, rats receiving a daily dose of CsA less than or equal to 5.0 mg/kg/day or CsA for less than or equal to 21 days had a high incidence of graft failure. The data argue that (1) graft resistance can be suppressed by CsA and (2) the effectiveness of CsA for securing engraftment is dependent upon both dose and duration of treatment.
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PMID:Prevention of graft failure by cyclosporine in rats receiving lymphocyte-depleted MHC-mismatched bone marrow. 154 56

To explore the efficacy of ultraviolet B-irradiated donor-specific leukocyte transfusions (UV-DSLT) with short-term cyclosporine to control intestinal allograft rejection, 75 adult Lewis (RT1l) rats underwent total small-intestinal transplantation from Brown-Norway (RT1n) donors. Recipients were randomly divided into ten treatment and control groups utilizing various combinations of donor-specific and third-party (Wistar-Furth, RT1u) leukocyte transfusions (TPLT), with or without transfusion UVB irradiation, and either alone or in combination with short-term cyclosporine administration (5 mg/kg intramuscularly on days -7, 0, 1, and 2 relative to transplantation). Leukocytes (10(8) cells) separated from a spleen cell suspension were infused on day -7. Certain transfused leukocytes were treated with 12,000 joules/m2 of UVB irradiation. Groups were monitored for mean survival time (MST) and cause of death. UV-DSLT alone (MST = 19.8 +/- 4.6) or in combination with cyclosporine (UV-DSLT+CsA, MST = 53.1 +/- 22.5) significantly (P less than 0.003-0.0002, Mantel-Cox) prolonged recipient survival when compared with appropriate controls (i.e., no treatment, MST = 11.2 +/- 3.4; CsA, MST = 17.2 +/- 9.0; UV-TPLT, MST = 12.4 +/- 4.0; and UV-TPLT+CsA, MST = 25.1 +/- 9.7) No significant increase in graft-versus-host disease occurred in any group, with 85% (64/75) of the recipients dying of acute rejection. Conversely, the UV-DSLT+CsA group had a significant increase (9/11; chi-square, P less than 0.0001) in chronic rejection. Because UV-DSLT+CsA improved survival as compared with third-party controls, a limited donor-specific unresponsiveness may have been induced. Furthermore, this treatment produces a consistent, chronic rejection rodent intestinal allograft model.
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PMID:The role of ultraviolet B-irradiated leukocyte transfusions and cyclosporine in intestinal transplantation. 163 41

The effect of rapamycin (RAPA) on both host-versus-graft (HVG) and graft-versus-host (GVH) immune responses was examined in small bowel transplant models using strongly histoincompatible donor-recipient combinations. Normal Wistar Furth (WFu; RT-1u) recipients rejected Buffalo (BUF; RT-1b) small bowel allografts within a mean survival time (MST) of 10.5 +/- 0.5 days. Administration of RAPA (0.8 mg/kg) by continuous intravenous infusion for 14 days via an osmotic pump prolonged graft survival to 25.0 +/- 4.6 days (P = 0.01). In a second strain combination, the 12.5 +/- 2.2 day survival of Brown Norway (BN; RT-1n) small bowel allografts in Lewis (RT-1l) recipients was prolonged to 21.6 +/- 2.0 and 28.5 +/- 2.8 days by 14 days of i.v. RAPA at doses of 0.8 and 1.6 mg/kg, respectively. In this model RAPA is five times more effective than cyclosporine, which at 4.0 mg/kg prolongs BN small bowel allografts in Lewis recipients to 21.6 +/- 6.3. To isolate HVG and GVH immune responses, (BN x Lewis)F1 hybrid rats served as the graft donor or host, respectively. In the HVG model, (BN x Lewis)F1 small bowel allografts, which were rejected by normal Lewis recipients at 12.2 +/- 3.6 days, were prolonged to 40.8 +/- 5.8 days (P = 0.001) by RAPA (0.8 mg/kg x 14 days). In the GVH model, the ability of Lewis small bowel allografts to produce severe GVH disease in untreated (BN x Lewis)F1 recipients at 12.3 +/- 2.8 days was delayed to 21.3 +/- 5.2 days by 0.8 mg/kg RAPA (P = 0.025). Thus, RAPA protects small bowel allografts more effectively against HVG than GVH immune responses.
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PMID:Inhibition of host-versus-graft and graft-versus-host responses after small bowel transplantation in rats by rapamycin. 173 17

For characterization of histopathological changes during pancreas graft rejection, pancreaticoduodenal transplants were performed in three groups: (1) Brown Norway into diabetic Lewis rats without immunosuppression, (2) Brown Norway into diabetic Lewis rats with cyclosporin A, and (3) Lewis into Lewis rats. Diffuse inflammatory infiltration of the acini by mononuclear cells indicated the onset of rejection (stage I). Shortly after acinar infiltration, damage to small and large interlobular excretion ducts occurred. This took the form of florid circumferential inflammation and vacuolar degeneration of epithelium similar to the bile duct damage seen in primary biliary cirrhosis, graft-versus-host disease, and liver allograft rejection (stage II). Thereafter, endothelialitis and destruction of islets were evident, consistent with a more advanced and irreversible stage of rejection (stage III). Acinar inflammation and moderate duct lesions were not prevented by immunosuppression but were delayed. Nonetheless, severe vascular changes and loss of islets were avoided. We conclude that duct lesions are a reliable criterion for pancreas allograft rejection. They are more sensitive than vascular changes and more specific than cellular infiltration of acinar tissue, which may also occur in infection.
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PMID:Histological features of acute pancreatic allograft rejection after pancreaticoduodenal transplantation in the rat. 178 60

This study was undertaken to investigate under which circumstances graft versus host disease occurs following fully allogenic small bowel transplantation in the rat. To facilitate the development of GVHD, Brown-Norway donors were specifically sensitized against the Lewis hosts prior to transplantation. Additionally, the Lewis recipients were immunocompromised before transplantation using splenectomy, cyclosporine, and antilymphocyte serum. No further immunosuppressive therapy was administered after transplantation. When all pretreatment regimens were used, acute lethal GVHD arose in two of nine animals (22%), whereas in two animals (22%) signs of acute GVHD and rejection were observed concurrently. When recipients of sensitized grafts were pretreated with CsA alone, one of eight animals (12.5%) showed signs of GVHD and rejection. All other animals died of acute rejection without clinical signs of acute GVHD. However, histological signs of GVHD were observed frequently in hosts grafted with a sensitized small bowel transplant. These data show that acute lethal GVHD can occur when an immunocompromised host is grafted with a sensitized intestinal transplant.
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PMID:Induction of graft-versus-host disease and rejection by sensitized small bowel allografts. 189 8

Transplantation of a Lewis rat small bowel allograft (SBTx) into Lewis x Brown Norway F1 (LBNF1) hybrid recipients provokes lethal graft-versus-host disease. GVHD in F1 hybrid rats inoculated with large number of parental lymphocytes may be abrogated by prior treatment of F1 hybrids with a sublethal dose (SLD) of the same parental lymphocytes. Therefore, we sought to determine whether this type of immunomodulation would prevent GVHD after SBTx. We examined whether pretreatment of LBNF1 recipients with a SLD of parental lymphocytes, or with a revascularized segment of parental small bowel, might ameliorate GVHD following transplantation of the entire parental small bowel. Nonpretreated LBNF1 recipients died of GVHD after entire Lew SBTx; 95% of LBNF1 recipients pretreated with SLD of Lew lymphocytes and 84% of LBNF1 recipients first transplanted with a segment of Lew small bowel survived GVHD induced by entire Lew SBTx 10 days later. Of LBNF1 recipients pretreated with SLD of Brown Norway lymphocytes or first transplanted with a segment of BN small bowel, none were protected from GVHD induced by entire Lew SBTx 10 days later. We concluded that pretreatment of LBNF1 recipients either with an SLD of parental lymphocytes or with a segment of parental small bowel provides profound protection from the effects of GVHD following transplantation of an entire small bowel of the same parental strain specificity.
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PMID:Resistance to graft-versus-host disease following small bowel transplantation. 198 5

A rat model of multiorgan transplantation (MOTx) including the liver, pancreas, duodenum, and variable segments of small bowel (SB) was used to ascertain whether graft-versus-host disease (GVHD) could be produced by this procedure. Rats receiving an isogeneic multiorgan transplant (MOT) survived more than 150 days. MOTx was then performed in the Lewis to (Lewis x Brown Norway) LBNF1 semiallogeneic combination, ensuring unidirectional GVHD. En bloc transplantation of the liver, pancreas, duodenum, and entire jejunum provoked lethal GVHD in all animals, and the mean time to recipient death (MT) was 16.5 +/- 0.43. When only one-half of the jejunum was included in the MOT, lethal GVHD similarly occurred in 100% of animals and the MT was 18 +/- 0.86. Finally, when only liver, pancreas, and duodenum were transplanted, the incidence of lethal GVHD was reduced to 50% (P less than 0.1). In those rats that died of GVHD, MT was 16 +/- 0.33. Fifty percent of the rats in this group, however, recovered from a milder form of GVHD and survived more than 150 days. These results demonstrate that MOTx induces GVHD and that the lethality of this process correlates with the inclusion of the SB in the graft and thus, with the overall amount of transplanted lymphoid tissue.
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PMID:Graft-versus-host disease after multiorgan transplantation. 205 73

Graft-versus-host disease was studied on the 10th and 14th postoperative days in Lewis x Brown Norway F1 rats (LBN-F1) receiving Lewis accessory heterotopic intestinal allografts. LBN-F1 isograft recipients and LBN-F1 rats were used as controls. The rats were injected with sheep erythrocytes five days before sacrifice. Rats with graft-versus-host disease had progressive loss of the normal architecture of the lymphoid organs. Skin, liver, colon, and salivary glands were infiltrated with immunoblasts and had patchy areas of necrosis. Concurrent with these changes, there were significant, progressive reductions in hemolytic titers, splenocyte plaque-forming counts, viable splenocytes, and the in-vitro splenocyte response to stimulation with concanavalin A. Graft-versus-host disease following intestinal allotransplantation damages the host's lymphoid tissues, producing profound immunosuppression. This finding has implications for clinical intestinal transplantation.
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PMID:Graft-versus-host disease associated with intestinal transplantation in the rat. Host immune function and general histology. 279 6


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