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

Five cases of intestinal microsporidiosis are reported, including one case of a heterosexual female acquired immunodeficiency syndrome (AIDS) patient, three homosexual males, and one bisexual male AIDS patients with detailed description of their clinical course. These five cases underscore the severity of immunodeficiency in patients with microsporidiosis. All patients had multiple opportunistic infections and a CD4 cell count below 100/microliters long before diarrhea developed. This is the first kinetic study of helper T-lymphocytes in cases of microsporidiosis. Diagnosis was made by duodenal biopsies stained with Brown and Brenn or Gram-Weigert technique (confirmed by electron microscopy) and by stool smears stained with a modified trichrome technique. However, the best preparation was plastic sections stained with toluidine blue, which demonstrated both the spores and plasmodia clearly. In our evaluation, Giemsa stain was also acceptable for identification of microsporidian spores in both intestinal biopsies and stool smears, but there was a failure to identify the organism on hematoxylin and eosin, acid-fast, periodic acid-Schiff, and Gomeri's methenamine silver stained preparations. Therapeutic attempts using albendazole, metronidazole, octreotide, and zidovudine (AZT) failed to eradicate microsporidia in these patients.
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PMID:Intestinal microsporidiosis. Report of five cases. 784 80

The demonstration of vasculitis and anti-myeloperoxidase antibodies in the mercuric chloride treated Brown Norway rat provides a useful, though limited, animal model of systemic vasculitis. We describe some preliminary experiments on the effect of transfer of serum from mercuric chloride treated rats and of two forms of immunotherapy: intravenous immunoglobulin and an anti-CD4 antibody. Transfer of serum did not lead to tissue injury and neither of the two forms of therapy proved beneficial in this model.
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PMID:Further characterization of an animal model of systemic vasculitis. 829 2

Cardiac allografts of (Lewis x Brown Norway) F1 rats are rejected by Lewis recipients at 7.5 days after engrafting. When recipients are presensitized with Brown Norway skin grafts at 7 days before engrafting, the cardiac grafts are rejected between 24 and 36 h (accelerated rejection, ACR). We previously demonstrated that the number of thymocytes in recipients showing ACR is decreased to approximately one eighth at 24 h after engrafting, and the thymocytes remaining in the thymus are phenotypically and functionally more mature. In the present study, flow cytometric analysis of the thymocytes in the sensitized recipient at 24 h after engraftment demonstrated that the frequency of single positive cells (CD4+CD8- and CD4-CD8+) was increased and that of double positive cells (CD4+CD8+) was decreased, indicating that immature thymocytes preferentially disappeared during the ACR episode. Thymocytes of the recipients undergoing ACR suffered from extensive apoptosis, characterized by chromatin condensation in the nuclei, cell shrinkage, nuclear collapse, and DNA fragmentation. Serum levels of corticosterone were elevated but were within a similar range among the transplant recipients destined for acute rejection, those undergoing ACR, and isografted controls, suggesting the participation of mediator(s) other than glucocorticoid in the induction of extensive apoptosis in the transplant recipients with ACR. We propose that thymocyte apoptosis is accelerated during the allograft rejection episode.
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PMID:Extensive apoptosis occurring in the thymus during accelerated rejection of cardiac allografts in presensitized rats. 833 6

Necrotizing leucocytoclastic vasculitis is the histopathological hallmark of the small vessel systemic vasculitides (SV), a group of human diseases commonly associated with anti-neutrophil cytoplasm autoantibodies (ANCA). Necrotizing vasculitis is seen in a number of experimental systems, but none of these provide an ideal animal model for human SV. Vasculitis occurs in serum sickness reactions; in murine models of systemic lupus erythematosus; in association with infection, particularly chronic viral infections; and after treatment with certain drugs or inflammatory mediators. 'Spontaneous' vasculitis has been reported in specific mouse strains, especially with ageing, and in some larger species. The size of vessel involved and the type of inflammatory cells predominating are variable in these experimental situations, and none of these models feature antibodies analogous to ANCA. We have recently reported that Brown Norway rats treated with mercuric chloride (HgCl2) develop necrotizing leucocytoclastic vasculitis, especially in the gut, and also develop antibodies to myeloperoxidase (MPO) which recognize similar determinants on MPO to those bound by a subset of ANCA. Transfer of serum from HgCl2-treated rats to naive animals does not induce tissue injury. Preliminary experiments using pooled immunoglobulin or an anti-CD4 monoclonal antibody did not show useful therapeutic benefit from these treatments. HgCl2-induced vasculitis has weaknesses as an animal model of human SV, but is the only experimental model in which anti-MPO autoantibodies have so far been demonstrated, and therefore may be of particular relevance to ANCA-associated SV.
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PMID:Animal models of systemic vasculitis. 838 93

In in vivo allogeneic bone marrow transplantation studies with the Brown Norway (BN) rat as recipient and the WAG/Rij rat as allogeneic donor a significant graft-versus-leukemia (GVL) effect is observed. Studies were performed to investigate whether lymphokine-activated killer (LAK) cells play a role in this GVL effect. Splenocytes from WAG/Rij and BN rats were activated in vitro by recombinant human interleukin-2 (rhIL-2) for 5-6 days. The cytolytic activity of these LAK cells was tested on four rat solid tumor cell lines, i.e. an ureter carcinoma, a rhabdomyosarcoma, and two lung tumors, and on leukemic cells derived from the BN rat acute myelocytic leukemia (BNML) and the WAG/Rij acute lymphocytic leukemia (L4415). The panel of target cells also included the murine cell lines P815 and YAC. Both WAG/Rij and BN LAK cells were not capable of lysing the leukemic cells in contrast to significant cytolytic activity on the rat solid tumor cell lines and P815 and YAC. BNML cells showed to be resistant to lysis by human NK cells. Phenotypical analysis of the rat LAK population revealed a decrease in the CD4/CD8 ratio compared to the unstimulated splenocyte population. Rat LAK cells displayed no antibody-dependent cellular cytotoxicity (ADCC) on the leukemic cells, whereas IL-2-stimulated human peripheral blood cells showed moderate ADCC activity on the leukemic cells. To investigate whether cytokines play a role in lysis of leukemic target cells, graded numbers of LAK cells and leukemic cells were co-cultivated for seven days in an agar-based colony culture system. This resulted in moderate suppression of leukemic colony formation. From the current in vitro studies it appears that the graft-versus-leukemia observed in in vivo allogeneic bone marrow transplantation studies is probably not due to a direct leukemic cell kill by LAK cells.
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PMID:In vitro resistance of the brown Norway rat acute myelocytic leukemia (BNML) to lymphokine-activated killer activity. 848 27

Injection of mercuric chloride into Brown Norway (BN) rats induces a T lymphocyte-dependent autoimmune syndrome. In order to investigate whether modification of adhesion and costimulatory molecules on T lymphocytes may be involved in early T lymphocyte activation by HgCl2, the authors analysed expression of these molecules in peripheral lymph node cells from BN rats at day 4 after injection of HgCl2. Tri-colour flow cytometry was performed for expression analysis within CD45RC-defined subsets of CD4+ and CD8+ cells. Compared to control rats, HgCl2-exposed rats showed increased numbers of lymphocytes, especially of T lymphocyte blast cells. The levels of LFA-1 expression as well as the fractions of ICAM-1 + cells were significantly increased in all CD45RC-defined subsets of CD4+ and CD8+ cells. Within the CD4 + CD45RC10 T lymphocyte population, HgCl2-injected rats showed a highly significant increase in the number of cells expressing OX40, which is a member of the TNF receptor family. Moreover, only CD4 + CD45RC10 blast cells of HgCl2-exposed rats showed decreased expression of CD43, increased expression of CD49d and decreased numbers of CD26 + cells. The results indicate that induction of autoimmunity by HgCl2 in BN rats is associated with altered expression of T lymphocyte costimulatory molecules, predominantly on CD4+ CD45RC10 cells, which may be caused by a direct effect of HgCl2 on these cells, and may precipitate further activation of T and B lymphocytes by HgCl2.
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PMID:Enhanced T lymphocyte expression of LFA-1, ICAM-1, and the TNF receptor family member OX40 in HgCl2-induced systemic autoimmunity. 863 8

LBNF1 heart grafts are rejected in an accelerated manner within 36 h by LEW rats that have been sensitized with Brown Norway rat skin grafts on day -7. Treatment with RIB-5/2, a CD4-nondepleting mAb (10 doses of 5 mg/rat/day, i.v., from day -7 to day +21) abrogated rejection at <36 h and produced indefinite (>200 days) cardiac allograft survival. Transplantation tolerance in this model developed within several weeks, and during the maintenance phase (>100 days) it was associated with diminished host circulating allo-Ab responses and induction of peripheral allospecific T cell unresponsiveness both in vitro and in vivo. Tolerant cells in mAb-treated hosts could disable naive or alloimmune cells, so that they failed to trigger graft rejection. Moreover, donor-specific and organ-nonspecific tolerance could be adoptively transferred by spleen cells alone into new sets of primary (100%) and secondary (>40%) test recipients. CD4+ T cells were instrumental for the induction of such readily transferable tolerance. The first and second generation suppressive regulatory cells were also critical for the inhibition of allograft recognition by normal or even alloimmune cells. Hence, the features of an "infectious" tolerance pathway to minor histocompatibility-mismatched skin grafts, originally described in thymectomized mice, may be applied to the euthymic primed rats rendered tolerant to fully MHC-incompatible vascularized organ allografts. Such reprogramming of host cell-mediated regulatory mechanisms following CD4-targeted therapy adds to our appreciation of the potential utility and applicability of infectious tolerance in transplant recipients treated with a perioperative course of CD4-targeted monotherapy.
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PMID:Induction of "infectious" tolerance to MHC-incompatible cardiac allografts in CD4 monoclonal antibody-treated sensitized rat recipients. 875 13

Smyth line (SL) chickens spontaneously develop a posthatch autoimmune loss of pigment cells (vitiligo) in the feather. Concurrent with the development of Smyth line vitiligo (SLV), mononuclear cell infiltration and altered T cell profiles can be observed in the pulp of developing feathers. To determine whether the development of SLV is preceded by or associated with alterations in blood lymphocyte and leukocyte populations, blood leukocyte profiles were established at various times prior to and throughout the spontaneous development of SLV. The proportions among various blood leukocyte populations (percentage of lymphocytes, monocytes, heterophils, eosinophils, and basophils) were determined by immunofluorescence and flow cytometric analyses. Lymphocyte markers included fluorescence-conjugated monoclonal antibodies to identify T cells (CD3), T helper cells (CD4), cytotoxic T cells (CD8), and B cells (IgM). The proportions among blood lymphocyte populations examined did not differ between SL and MCH-matched parental Brown line (BL) control chickens prior to and throughout the development of SLV. Compared to BL controls, SL chickens had, however, increased proportions of inflammatory leukocytes in the blood, particularly at the time when most hatchmates developed SLV. Examination of leukocyte alterations with respect to first observation of SLV revealed that inflammatory leukocyte levels were elevated early in SLV. Although altered leukocyte profiles in the blood were observed during the development of SLV, blood from SL chickens did not reflect alterations in lymphocyte populations known to occur at the site of melanocyte destruction. The role of inflammatory blood leukocytes in the development of SLV needs to be further investigated.
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PMID:Alterations in blood leukocyte populations in Smyth line chickens with autoimmune vitiligo. 877 29

Flow cytometry has been found to be a useful tool in the clinical monitoring of patients following solid organ transplantation. Despite the easier assessibility of corneal graft acceptance or rejection, flow-cytometric evaluation of peripheral lymphocytes following systemic immunosuppression is important in the evaluation of therapeutic efficacy. The systemic effect of penetrating keratoplasty (PKP) and of immunosuppression with cyclosporin A (CsA), leflunomide (LF), and the nondepleting anti-CD4 antibody, RIB 5/2, on peripheral lymphocytes was investigated in the rat model. Corneal buttons were grafted from Lewis/Brown Norway rats to Lewis recipients. Animals were randomly assigned to the following treatment groups: (1) untreated; (2) CsA, 10 mg/kg; (3) LF, 10 mg/kg; (4) LF, 5 mg/kg; (5) LF, 2.5 mg/kg; (6) LF, 10 mg/kg; combined with CsA, 10 mg/kg; and (7) RIB 5/2, 4 mg/kg, combined with CsA, 1.5 mg/kg. Controls included the following groups: (8) unoperated, CsA-treated at 10 mg/kg; (9) unoperated, LF-treated at 10 mg/kg; (10) unoperated, LF-treated at 10 mg/kg and CsA-treated at 10 mg/kg; (11) unoperated, RIB 5/2-treated at 4 mg/kg and CsA-treated at 1.5 mg/kg; (12) syngeneic grafts; and (13) normal Lewis rats. Cells from blood and spleen samples were enriched using Ficoll density centrifugation, and lymphocytic surface markers CD 3, CD 4, CD 8, and RT 1b (Ia) were analyzed by direct immunofluorescence using flow cytometry. In the untreated allogeneic PKP, a decrease in the percentage of serum CD 3+, CD 4+, CD 8+, and CD 4+ RT 1b+ lymphocytes was apparent from the 5th to the 9th postoperative day. At corneal graft rejection, a normalization of serum CD 3+ and CD 4+ levels occurred, whereas the percentage of serum CD 8+ lymphocytes remained slightly raised. Significantly enhanced decreases in levels of CD 4+ lymphocytes were observed following treatment with CsA, LF, and, particularly, therapy with RIB 5/2 and a subtherapeutic dose of CsA. Concomitant decreases were also apparent following treatment with CsA or LF. In contrast, the combination of RIB 5/2 and CsA (1.5 mg/kg) resulted in a reactive increase in levels of CD 8+ lymphocytes as well as an increased expression of RT 1b by the remaining CD 4+ lymphocytes. The latter alterations corresponded to indefinite acceptance of the corneal grafts, which was observed only in the animals treated with RIB 5/2 and CsA. PKP in the rat model is accompanied by alterations in peripheral lymphocytes. Additional influences are exerted by immunosuppressive therapy, with the most specific and predictable alterations being achieved with anti-CD4 monoclonal antibody therapy.
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PMID:Flow-cytometric analysis of peripheral lymphocytes in the rat following penetrating keratoplasty and immunosuppressive treatment. 880 75

Lethally irradiated Lewis (LEW) rats reconstituted with syngeneic bone marrow and given CsA for a 4-week period, develop, upon withdrawal of CsA, a graft-versus-host-like disease, so-called CsA-induced autoimmunity (CsA-AI). This T cell-mediated autoimmune disease is thymus-dependent; it is generally held that this disease is a consequence of aberrant T cell recovery brought about by CsA. In this study we determined mononuclear cell subsets phenotypically by tri-colour flow cytometry. A strong decrease in recent thymic emigrants (Thy1.1+, TCR alpha beta +) was observed as a consequence of CsA treatment, eventually resulting in decreased absolute peripheral T cell numbers. In these rats no altered CD4:CD8 T cell ratio was observed before onset of CsA-AI; CD4+ and CD8+ cells consisted predominantly of monocytes (CD4dim+, TCR alpha beta-) and natural killer cells (CD8+, TCR alpha beta-), respectively. LEW rats, x-irradiated, syngeneic bone marrow-reconstituted and treated with CsA, showed a marked and persistent, relative expansion of mature CD45RC+, RT6- Th cells. In contrast, Brown-Norway rats treated in a similar fashion, or LEW rats subjected to either CsA treatment or x-irradiation, did not show a comparable expansion of mature CD45RC+, RT6- Th cells, nor did these animals develop CsA-AI. The CD45RC+, RT6- Th cells produced IL-2, and moreover constituted the only Th subset producing IFN-gamma upon stimulation, and therefore were considered as Th1-like effector cells. These results are consistent with the view that a persistent preponderance of Th1 cells and not the mere presence of autoreactive cells determines whether or not clinically manifest CsA-AI will occur.
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PMID:Susceptibility to clinically manifest cyclosporine A (CsA)-induced autoimmune disease is associated with interferon-gamma (IFN-gamma)-producing CD45RC+RT6- T helper cells. 880 39


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