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)

We have evaluated the in vivo efficacy of anti-CD3-CRM9, a holo-immunotoxin constructed with a diphtheria toxin binding-site mutant. Eighty percent of established human T-cell subcutaneous tumors in nude mice completely regressed following intraperitoneal injection of immunotoxin at a dose set at half the minimum lethal dose assayed in toxin-sensitive animals. Similar regressions produced by a 137Cs source required a dose in excess of 500 cGy. The high degree of in vivo T-cell ablation produced by this immunotoxin is apparently due to maintenance of the toxin translocation function provided by CRM9 and a necessary intracellular routing function supplied by CD3. This immunotoxin may be useful in treating conditions caused by pathologic oligoclonal T-cell expansion such as graft-versus-host disease, autoimmune diseases, and possibly AIDS.
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PMID:In vivo T-cell ablation by a holo-immunotoxin directed at human CD3. 137 81

Diarrhoea and weight loss are found in more than 50% of patients with the acquired immunodeficiency syndrome (AIDS). In some patients the symptoms can be very severe, leading to death even in the absence of opportunistic infections. In 30% of these patients, enteric pathogens cannot be identified, and approximately only half of the identifiable aetiologic agents of diarrhoea in patients infected with the human immunodeficiency virus (HIV) were treatable with antibiotics. Immunoglobulins from bovine colostrum (Lactobin, Biotest, Dreieich, FRG) contain high titers of antibodies against a wide range of bacterial, viral and protozoal pathogens as well as against various bacterial toxins. Lactobin (LIG) is quite resistant to 24-h incubation with gastric juice. In a multi-center pilot study 37 immunodeficiency patients with chronic diarrhoea [29 HIV-infected patients, 2 patients with common variable immunodeficiency (CVID), one unidentified immunodeficiency, five patients with graft versus host disease (GvHD) following bone marrow transplantation] were treated with oral LIG (10 g/day for 10 days). Good therapeutic effects were observed. Out of 31 treatment periods in 29 HIV-infected patients 21 gave good results leading to transient (10 days) or long-lasting (more than 4 weeks) normalisation of the stool frequency. The mean daily stool frequency decreased from 7.4 to 2.2 at the end of the treatment. Eight HIV-infected patients showed no response. The diarrhoea recurred in 12 patients within 4 weeks (32.4%), while 19 patients were free of diarrhoea for at least 4 weeks (51.3%). In 5 patients intestinal cryptosporidiosis disappeared following oral LIG treatment. LIG treatment was also beneficial in 4 out of 5 GvHD patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Treatment of diarrhoea in human immunodeficiency virus-infected patients with immunoglobulins from bovine colostrum. 139 28

In the decade since the early 1980s, the increasing use of immunosuppressive therapy for cancer and autoimmune disease, as well as for organ transplantation, has combined with the acquired immunodeficiency syndrome epidemic to increase greatly the incidence of opportunistic infections and other complications of the gastrointestinal tract. Consequently, barium fluoroscopic and cross-sectional imaging studies tailored to address these problems are no longer uncommon. Although overlap exists, there are radiographic patterns that can direct the diagnosis to an opportunistic infection and sometimes to a specific pathogen. This article describes and illustrates the radiographic findings of gastrointestinal superinfection with Candida albicans, cytomegalovirus, Cryptosporidium spp, herpes simplex virus, Mycobacterium tuberculosis, M avium-intracellulare, and human immunodeficiency virus. Other gastrointestinal tract complications of immunosuppression are discussed, including graft-versus-host disease following bone marrow transplantation, typhlitis, and pseudomembranous colitis.
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PMID:Gastrointestinal tract in the immunocompromised host: opportunistic infections and other complications. 141 Mar 32

Pneumocystis carinii pneumonitis (PCP) can occur in immunocompromised hosts, especially AIDS and cancer patients. Although recent research has focused on PCP in AIDS patients, few studies have described the clinical presentation of PCP in recipients of bone marrow transplantation (BMT). Between 1976 and 1991, of 1454 BMT patients at the University of Minnesota, PCP was documented in only 19. Eighteen of these had not been receiving PCP prophylaxis. Patients presented with a brief period (2-10 days) of symptoms including dyspnea, cough, and fever in greater than 75% of patients, but had only scant abnormal physical findings. Chest X-rays showed bilateral infiltrates in 58% of all patients, though 15% had no or minimal X-ray findings. Bronchoscopic alveolar lavage confirmed the diagnosis most often, but 13% of lavages were negative and required biopsy for the diagnosis. High dose trimethoprim-sulfamethoxazole was the initial treatment for 84% of the patients though 25% of these patients were later switched to pentamidine due to poor response or hypersensitivity reactions. Despite prompt diagnosis and therapy, overall survival was poor, with only 37% of patients surviving pneumonitis. Patients developing PCP less than 6 months post-BMT had greater mortality (89%) versus only 40% in later onset PCP (p less than 0.0001). Despite this better survival in the late-onset PCP cohort, the development of pneumonitis in these patients underscores the necessity for continued PCP prophylaxis beyond 1 year in some patients. Ongoing immunocompromise and need for prophylaxis should be appreciated in patients with graft-versus-host disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pneumocystis carinii pneumonitis following bone marrow transplantation. 142 81

A 16 year old boy underwent allogeneic bone marrow transplantation (BMT) from an human leukocyte antigen (HLA)-identical sibling for severe aplastic anaemia. He was symptomatic for 7 years before transplantation and had received multiple red blood cell and platelet transfusions. Conditioning for BMT consisted of cyclophosphamide, antilymphocyte globulin and total lymphoid irradiation. Engraftment was rapid, there was no evidence of rejection despite the history of multiple blood product transfusions and he did not develop acute or chronic graft versus host disease. He was well for the first 8 months after transplantation but then developed fevers, interstitial pneumonia, herpes simplex infections and cytomegalovirus enteritis. Serological studies revealed antibodies to human immunodeficiency virus (HIV) and he was considered to have acquired immune deficiency syndrome (AIDS). Retrospective analysis of the serum samples showed that he was seronegative for HIV until approximately 10 months before transplantation when his serum became HIV positive. Lymphocyte function studies done after transplantation suggested immunologic recovery at 3 months post-transplant with a brisk though subnormal response to phytohaemagglutinin stimulation. T cell subset analysis performed subsequently showed complete absence of CD4 positive cells indicating immune incompetence which was associated with clinical features of AIDS. Bone marrow transplantation had failed to produce sustained immunologic reconstitution and prevent the progression of HIV to which he ultimately succumbed.
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PMID:Failure of allogeneic bone marrow transplantation to benefit HIV infection. 149 64

The observation that malignant cells express antigens that may be recognized by immunocytes and that immune effector mechanisms have the capability of destroying tumor cells has increased our appreciation of the biology of cancer and its relationship to immune function as well as offered new options for therapeutic intervention. Clinical trials are in progress to evaluate several different approaches to modifying the host's immune response against tumor. One approach is to administer agents that have direct activity against the malignancy. For example, antibody conjugates bring cytotoxic molecules of chemotherapy, radioisotopes, or toxins directly to the tumor. A second approach is to administer agents that modulate the host's own antitumor response such as IFN-alpha and IFN-gamma. Adoptive cellular immunotherapy aimed at isolating and expanding the host's own tumor-specific lymphocytes and inducing activation and proliferation with lymphokines such as IL-2 has shown encouraging results. Even though clinical data are still quite premature, it is reasonable to assume that in the future immunomodulation including the stimulation of immune effector mechanisms to eradicate tumor, the reconstitution of immune deficiency in diseases such as AIDS, the suppression of immune function to avoid graft rejection and GVHD, and the isolation and insertion of genes encoding tumor antigens into recombinant vectors to immunize the host to the tumor antigen will be commonly and successfully employed.
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PMID:The role of the immune system in the pathogenesis of cancer. 154 19

As HIV readily kills CD4 cells in vitro it has been widely assumed that this would account for the declining CD4 counts in vivo. A growing number of reports suggest that the pathogenesis of AIDS is considerably more complex than had been thought. A number of indirect mechanisms for CD4 cell death have been proposed. In this review of alternative theories which could explain the features of AIDS, autoreactivity and genetic restriction to the development of disease are considered the most important. In addition it is suggested that if HIV is able to mimic MHC antigens on the surface of antigen presenting cells then this could stimulate 'allo reactive' T lymphocytes, which would explain the marked similarity of HIV infection to chronic graft versus host disease.
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PMID:The pathogenesis of AIDS: classical and alternative views. 158 22

Evidence is accumulating that susceptibility to disease following HIV infection is genetically restricted. In addition, activation of the immune response appears to play an important role in disease progression. Here, John Habeshaw and colleagues propose that HIV envelope glycoproteins mimic foreign MHC molecules and, in doing so, stimulate alloreactive lymphocytes. This activation may explain the marked clinical and immunological similarities between chronic GVHD and AIDS.
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PMID:Does the HIV envelope induce a chronic graft-versus-host-like disease? 162 48

Intravenous immunoglobulin (IVIgG) has many potential applications in haematology both as antibody replacement therapy and as an immune-modulater in autoimmune disorders. Antibody replacement appears to be of value in the prophylaxis of infection in low-grade B-cell malignancies, in bone marrow transplant recipients and in children with AIDS, although optimal treatment strategies have not been assessed and determining which patients are likely to derive greatest benefit has been problematic. IVIgG appears to be effective in the prevention or amelioration of CMV-related pathology if given frequently and has also dramatically improved the survival of patients with established interstitial pneumonia when used in combination with ganciclovir. Intriguingly, IVIgG appears to moderate the severity of GVHD in adult transplant recipients. IVIgG has short term efficacy in most patients with ITP but, as long term remissions are uncommon, it has become necessary to be more selective in the use of IVIgG in this disorder. The response to IVIgG in other immune-mediated cytopenias is similar with generally transient improvement but also with occasional spectacular cures. The treatment of the acquired haemophilias with IVIgG has yielded in vivo and vitro evidence to support the idiotype-antiidiotype theory of IVIgG immune-modulation and has also demonstrated significant differences in the sensitivity of coagulation factor autoantibodies and alloantibodies to IVIgG therapy. IVIgG has several roles in pregnancy related disorders, including the management of both mother and fetus in ITP during pregnancy, the antenatal and postnatal management of platelet alloimmunisation and also in the management of severe rhesus isoimmunisation. IVIgG is safe and well tolerated. The expense of this therapy should be balanced against the likely gains and the overall costs of alternative approaches.
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PMID:Applications of intravenous immunoglobulin in haematology. 163 7

We propose an estimator of the prevalence of a transient condition among surviving patients using right censored data. The prevalence of opportunistic infection among surviving AIDS patients and the probability of being in tumour response following cancer therapy conditional on being alive are two examples of such functions. In essence these functions describe a major aspect of the quality of life for surviving patients and may be useful when viewed in conjunction with the survival curves themselves. The method is illustrated using data from a randomized trial of bone marrow transplant patients where the prevalence of chronic graft-versus-host disease is of interest. The non-parametric estimator which we have proposed is contrasted with estimators derived from Markov and semi-Markov models.
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PMID:A qualifier Q for the survival function to describe the prevalence of a transient condition. 202 25


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