Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0235394 (wasting)
 8,040 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A patient with severe combined immunodeficiency has been given a transplant of thymic epithelium obtained from short-term culture of normal human thymus. 4 wk after transplantation immunoglobulin was detected and the patient now has normal levels of the three main classes. Functional antibodies of four specificities have been detected. An increase in reactivity to allogeneic cells and phytohaemagglutinin has been observed, with an increase in E rosettes; a positive delayed skin test to candida antigen is now present. The patient has shown reversal of wasting and has been free of infection for 7 months since receiving the transplant. It appears that under certain circumstances thymic epithelium reconstitutes both T and B cell functions.
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PMID:Reconstitution of B and T lymphocyte function in severe combined immunodeficiency disease after transplantation with thymic epithelium. 6 46

MRL/lpr (lpr) mice spontaneously develop a lupus-like illness as well as massive lymphadenopathy. Attempts to transfer autoimmunity by adoptive transfer or radiation bone marrow chimeras have been unsuccessful. Since severe combined immunodeficiency (SCID) mice have been engrafted with human and rat xenografts without apparent graft-versus-host disease (GVHD), we subjected SCID mice to low-dose irradiation and reconstituted the mice with spleen cells from young or old lpr mice or with lpr bone marrow. Fourteen out of twenty (70%) of SCID mice engrafted with spleen cells from old lpr mice produced autoantibodies (anti-DNA and anti-Sm) without evidence of the severe lymphoid atrophy previously described for lpr spleen-->+/+ chimeras. SCID mice engrafted with spleen cells from young lpr mice developed acute GVHD and 5/6 (83%) died within 4 weeks post-transfer. Although 8/11 (73%) of lpr-->SCID bone marrow allografts survived for at least 4 months, these mice developed a wasting disease characterized by lymphoid atrophy and fibrosis without the production of autoantibodies. None of the lpr-->SCID grafts resulted in the transfer of double negative T cells or the lymphoproliferative syndrome characteristic of MRL/lpr mice. These findings indicate that SCID mice can be engrafted with splenocytes from old MRL/lpr mice and that B cells continue to secrete autoantibodies for several months in the SCID recipients. This study also demonstrates that, unlike i.p. transplant of xenogeneic cells, acute GVHD is a consistent feature of i.p. transplants of normal allogeneic mononuclear cells into SCID mice.
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PMID:MRL/lpr-->severe combined immunodeficiency mouse allografts produce autoantibodies, acute graft-versus-host disease or a wasting syndrome depending on the source of cells. 145 84

Cryptosporidium parvum causes protracted diarrhoea in immunodeficient hosts. To characterize the role that T and B lymphocytes play in the eradication of the parasite from the intestinal mucosa, the course of infection in mice with severe combined immunodeficiency (SCID) was studied. Twenty-nine SCID and 26 BALB/c adult mice received 10(6) oocysts intragastrically. The course of infection in the two strains was similar until 2 months after inoculation, when moderate numbers of organisms were identified in the villous and crypt mucosa of the ileum and proximal colon of SCID mice. Three months after inoculation, SCID mice developed wasting and progressive intestinal and biliary tract disease. At 5 months, mortality of 72 and 0 per cent, respectively, was observed in the SCID and BALB/c mice. Twenty-four SCID and 26 BALB/c neonatal mice were also inoculated with C. parvum. Cryptosporidiosis occurred in SCID and BALB/c mice within 2 weeks of inoculation. Subsequently, BALB/c, but not SCID mice, eradicated the parasite from their intestinal mucosa. SCID mice developed progressively severe cryptosporidiosis which killed all animals within 7 weeks. Responses mediated by B or T cells, or both, appeared to play a role in eradicating C. parvum from the intestinal mucosa, since SCID mice were more severely affected than BALB/c mice. The different course of infection in adult and neonatal SCID mice indicated that other age-related factors also played a role in containing C. parvum infection.
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PMID:Cryptosporidiosis in adult and neonatal mice with severe combined immunodeficiency. 164 34

A 7-year-old leukemic girl developed pancytopenia following chemotherapy and was given several transfusions of nonirradiated blood. Within 2 weeks she developed a maculopapular rash, fever, abnormal liver function, diarrhea, and wasting. She became septic and died 6 weeks later. Transfusion-associated graft-versus-host disease (GVHD) was suspected clinically. At autopsy, changes diagnostic of GVHD were present in the skin and liver. The remarkable feature of the case was the histopathology of the thymus, which was morphologically "dysplastic," i.e., minute, lymphoid depleted, devoid of a corticomedullary demarcation, and completely lacking in Hassall's corpuscles. These changes were virtually identical to those seen in the thymus of children with severe combined immunodeficiency disease (SCID). There was no evidence of preexisting immune deficiency. There is compelling experimental evidence that GVHD can produce changes in the thymus that are identical to those of "thymic dysplasia." These observations have led to the hypothesis that immunodeficiency associated with GVHD may stem, in part, from injury to thymic epithelium resulting in defective T cell maturation. As a corollary of this hypothesis, it has been suggested that the pathogenesis of some forms of SCID may involve GVHD-associated injury to the thymus by a maternal allograft acquired in utero. This report further documents thymic pathology in human GVHD and discusses these changes in the light of these ideas.
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PMID:Thymic involution with loss of Hassall's corpuscles mimicking thymic dysplasia in a child with transfusion-associated graft-versus-host disease. 186 63

SCID mice injected with coisogenic CD4+/CD45RBhi lymph node T cells from normal donors develop a wasting disease that is due to hyperplasia of the intestinal epithelium. SCID mice injected with purified lymph node CD4+ T cells or CD4+/CD45RBlo T cells do not develop the disease. In addition, mixture of the CD4+/CD45RBlo T cells with equal numbers of CD4+/CD45RBhi T cells inhibits the development of disease. SCID mice that were reconstituted with CD45RBhi T cells with active disease were treated with oral antibiotics and this ameliorated the symptoms, suggesting a role of the gut bacterial flora in the development of disease. Attempts were made to accelerate or inhibit disease by chronically administering cytokines to the mice. Neither IL2 nor IL4 were effective in altering the course of disease development when given in doses known to be effective in other in vivo models. Thus, the regulation of the reactivity seen in these SCID mice may involve as yet unappreciated mechanisms.
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PMID:Induction of wasting disease in SCID mice by the transfer of normal CD4+/CD45RBhi T cells and the regulation of this autoreactivity by CD4+/CD45RBlo T cells. 770 Nov 15

Transfer of specific T lymphocyte subsets isolated from the spleens of healthy donor mice into immunodeficient SCID mice leads to chronic intestinal inflammation with characteristics similar to those of human inflammatory bowel disease (IBD). CD4+, CD45RBhigh cells cause disease, whereas CD4+, CD45RBlow and CD8+, CD45RBhigh cells do not. Despite this difference, we demonstrate that all three T cell populations reconstitute the intraepithelial and lamina propria compartments of both small and large intestines of SCID recipients. Therefore, infiltration of lymphocytes alone is not sufficient for disease development. CD4+ lymphocytes that have trafficked to the SCID intestine exhibit a phenotype characteristic of normal mucosal lymphocytes. This includes high expression of alpha E integrin and CD69, expression of CD8 alpha alpha homodimers in some of the intraepithelial lymphocytes, as well as low expression of CD62L and CD45RB. The phenotype of the infiltrating mucosal cells is indistinguishable, with respect to the cell surface markers tested, regardless of whether the starting donor population is CD45RBhigh or CD45RBlow. Severe inflammation is restricted primarily to the colon despite lymphocyte infiltration throughout the length of the intestine. This suggests that some property of the colon microenvironment contributes to inflammation. Consistent with this, transfer of CD4+, CD45RBhigh cells to SCID mice that have significantly reduced numbers of enteric flora results in attenuation of the wasting and colitis. Fewer numbers of donor lymphocytes are recovered from the intraepithelial and lamina propria compartments of reduced flora SCID mice. We hypothesize that the ability of pathogenic cells to traffic to the intestine and mediate colitis may be driven by T cell reactivity to bacteria or bacterial products.
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PMID:Analysis of intestinal lymphocytes in mouse colitis mediated by transfer of CD4+, CD45RBhigh T cells to SCID recipients. 912 Mar 8

Severe combined immunodeficiency (SCID) mice were inoculated with Hantaan virus strain 76-118 (HTN) or Seoul virus strain SR-11 (SR) of hantaviruses. Susceptibility of SCID mice was compared with those of immunocompetent adult mice, newborn mice and nude mice. SCID mice inoculated with HTN or SR died 32 to 35 days after infection. Unlike newborn mice which also died of hantavirus infection, SCID mice survived longer than newborn mice and showed typical wasting symptoms rather than nervous symptoms. Immunohistochemical staining and virus isolation indicated that both HTN and SR inoculated SCID and SR inoculated nude mice showed systemic infection, but nude mice inoculated with SR survived for longer than 8 weeks after inoculation. Passive transfer of spleen cells from immunocompetent BALB/c mice conferred protection on SCID mice within 2 weeks of HTN infection. Immune mediated pathologic mechanism was examined by transferring the spleen cells to SCID mice inoculated with HTN virus 3 weeks before the cell transfer. The recipient SCID mice showed an increase of serum BUN level coinciding with the appearance of serum antibody to HTN virus, suggesting the immune mediated pathogenicity.
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PMID:Hantavirus infection in SCID mice. 936 32

Transfer of CD45RBhigh CD4+ T cells from normal mice to congenic SCID mice induces wasting disease, a murine model of inflammatory bowel disease. In this model, colonic inflammation is considered to be caused by a disregulated Th1 response, and Th1 cytokines, especially IFN-gamma, have been suggested to play an important role in the pathogenesis of wasting disease. In order to elucidate the potential role of IFN-gamma in the pathogenesis of wasting disease, we transferred CD45RBhigh CD4+ T cells from IFN-gamma knockout (GKO) mice to congenic SCID mice. The recipient mice were absolutely free of symptoms and clinical signs of disease and showed body-weight gain similar to that seen in normal mice. These data demonstrate the essential and non-redundant role of IFN-gamma in the pathogenesis of wasting disease.
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PMID:CD45RBhigh CD4+ T cells from IFN-gamma knockout mice do not induce wasting disease. 937 73

To determine the basis of susceptibility and resistance to human monocytic ehrlichiosis (HME), immunocompetent and immunocompromised mice were infected with Ehrlichia chaffeensis and bacterial loads were measured by PCR and by immunohistochemistry. Immunocompetent (C. B-17 and C57BL/6) mice cleared the bacteria within 10 days, but immunocompromised SCID and SCID/BEIGE mice developed persistent infection in the spleen, liver, peritoneal cavity, brain, lung, and bone marrow and became moribund within 24 days. Both immunocompromised strains lack T and B lymphocytes, but the SCID/BEIGE strain is also deficient in natural killer (NK) cell function. During advanced stages of disease, the infections were associated with wasting, splenomegaly, lymphadenopathy, liver granulomas and necroses, intravascular coagulation, and granulomatous inflammation. Histochemical and immunohistochemical localization studies confirmed the presence of bacteria in tissues, and viable bacteria were cultured from infected animals. The data reveal that T and/or B cells play an essential role during resistance of immunocompetent mice to infection with E. chaffeensis and demonstrate the utility of immunocompromised mice as an experimental model for the study of HME.
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PMID:Infection of the laboratory mouse with the intracellular pathogen Ehrlichia chaffeensis. 967 77

Cryptosporidiosis is a serious disease in malnourished children and in people with malignancies or AIDS. Current rodent models for evaluating drug therapy against cryptosporidiosis have many limitations, including the need for a high inoculum, the absence of symptoms resembling those seen in humans, and the need to maintain exogenous immunosuppression. We have developed a gamma interferon knockout (GKO) mouse model with which to evaluate therapies against C. parvum and have used paromomycin for evaluation of this model. The GKO model offers considerable improvements over other systems, since it requires no additional immunosuppression and adult mice can be infected with as few as 10 oocysts (compared with 10(7) for SCID mice). Infected mice develop profound gastrointestinal dysfunction due to extensive infection and severe mucosal damage involving the entire small intestine. Clinical symptoms, which include depression, anorexia, weight loss, and wasting, result in death within 2 to 4 weeks. The time of death depends on the oocyst challenge dose. Paromomycin modulated parasitological and clinical parameters in highly predictable and significant ways, including prevention of death. In addition, examination of the extensively infected gut provided an important insight into the dynamics between a specific drug treatment, its impact on the extent and the site of parasite distribution, and clinical outcome. These uniform symptoms of weight loss, wasting, and death are powerful new parameters which bring this model closer to the actual disease seen in humans and other susceptible mammalian species.
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PMID:The gamma interferon gene knockout mouse: a highly sensitive model for evaluation of therapeutic agents against Cryptosporidium parvum. 970 83


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