Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0009319 (colitis)
 19,384 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Callithrix jacchus is an outbred New World primate characterized by a naturally occurring bone marrow chimerism, restricted polymorphism at many MHC loci, and unusual susceptibility to viral pathogens, adenocarcinoma, colitis, and, following immunization with myelin antigens, a demyelinating disease of the central nervous system closely resembling human multiple sclerosis. Here we characterize the TCRB repertoire in this species, representing the first such analysis in a New World monkey. Two TCRBC, 13 BJ, 2 BD, and 15 BV genes were identified. Overall, a high degree of similarity with human TCRBV-D-J-C gene sequences was observed, indicating a close phylogenetic relationship. Biased usage in favor of genes from the TCRBC1-BJ1 cluster was present in 77% of sequences, in contrast to preferential usage of BC2-BJ2 genes known to occur in humans and mice. Complementarity-determining region 3 averaged 10 amino acids in length and were diverse. Framework regions of TCRBV genes were extensively conserved. Phylogenetic analysis of TCRBV sequences from different species indicated that TCR genes are highly stable across primates. Thus, a diverse TCRB repertoire is generated in C. jacchus despite the limited polymorphism of class I MHC loci. Extensive homology to human TCR genes, natural chimerism, and susceptibility to inflammatory disorders are characteristics of C. jacchus that create a useful model system for the study of human autoimmunity.
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PMID:Characterization of the TCRB chain repertoire in the New World monkey Callithrix jacchus. 901 60

Extra-intestinal manifestations of inflammatory bowel diseases are frequent and numerous. We report a case of ulcerative colitis associated with multiple sclerosis, ankylosing spondylitis and pyoderma gangrenosum. This observation shows the rare association of ulcerative colitis-multiple sclerosis, and extra-intestinal manifestations of inflammatory colitis are discussed.
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PMID:[Systemic manifestations of hemorrhagic rectocolitis: apropos of a case of hemorrhagic rectocolitis associated with multiple sclerosis]. 909 32

The etiology of inflammatory bowel disease (IBD) is still unknown. However, a satisfactory solution cannot be far away. IBD actually encompasses two diseases, i.e. Crohn's disease (CD) and ulcerous colitis (UC). These diseases resemble each other so closely that they cannot be distinguished even pathologically, but differ from each other sufficiently to regard them as independent entities. Epidemiological observations may be helpful in identifying the true causative factors of this evasive disease. Geographically, the prevalence of the disease has a slope from North to South and, to a lesser degree, from West to East. The Western-Eastern discrepancy can be attributed to a difference in Western life styles. The incidence of the disease has been increasing world-wide of late, but its spread has been slowing down in highly affected countries. Racial and ethnic relations in different populations and immigration studies offer interesting data which can reflect genetic, inherited, environmental and behavioural factors. The disease seems to have a characteristic racial-ethnic distribution: the Jewish population is highly susceptible everywhere, but its prevalence in that population nears that of the domestic society in which they live. In Hungary, the Roma (Gypsies) have a considerably lower prevalence than the average population. This can be attributed to a genetic or environmental influence. According to age, the onset of the disease occurs more often in the second or the third decade of life, but there also is another peak in the 60s. Regarding sexual distribution, there is a slight preponderance of colitis ulcerosa in men and of Crohn's disease in women. It may correspond to the stronger auto-immune affection in the process of Crohn's disease. Environmental factors and behavioural influences also are investigated. Diet, the role of the early ages, smoking habits and the influence of hormonal status and drugs are viewed as useful contributing factors in the manifestation of the disease. Genetic studies show that one-fourth of IBD patients have an affected family member. HLAB27 histocombatibility also plays an important, but not determining role in the development of the disease. Genetic factors seem to have a stronger influence in Crohn's disease than ulcerative colitis. The existence of multiple sclerosis-IBD families may reflect the common genetic background or the similar microbial effect as well. A great number of bacterial and viral factors has been suspected of being infectious factors in IBD, mostly in CD. Mycobacteria, Yersinia, Campylobacter, Clostridium, Clamidias, etc. as well as bacteria and some viruses such as herpes and rotavirus and the primary measles virus. None of them has been proven as a real and exclusively pathogenic factor. Immunological background has an important function in the manifestation of the disease. If an individual has a genetic susceptibility to infections, the down regulation of an inflammation in the bowel wall does not occur in a proper way. This initiates the auto-immune process which is a self-increasing cycle. Extra-intestinal manifestations of IBD are of high importance because they can not only follow intestinal symptoms, but precede them by years. Hepatic and biliary disturbances (primary sclerosing cholangitis), are the most serious complications. Mucocutaneous manifestations can be the first appearance of the main disease (in the mouth). Auto-immune consequences (erythema nodosum) or complications caused even by the therapy can occur. Ocular and musculoskeletal manifestations supposedly have the same genetic background and often precede the intestinal symptoms. Considering the epidemiological, genetic and immunological data, we can conclude that ulcerative colitis and Crohn's disease are heterogeneous disorders of mutifactorial etiology in which hereditary (genetic) and environmental (microbial, behaviour) factors interact to produce the disease.
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PMID:The epidemiology and the pathogenesis of inflammatory bowel disease. 1100 May 58

Vasospasm can have many different causes and can occur in a variety of diseases, including infectious, autoimmune, and ophthalmic diseases, as well as in otherwise healthy subjects. We distinguish between the primary vasospastic syndrome and secondary vasospasm. The term "vasospastic syndrome" summarizes the symptoms of patients having such a diathesis as responding with spasm to stimuli like cold or emotional stress. Secondary vasospasm can occur in a number of autoimmune diseases, such as multiple sclerosis, lupus erythematosus, antiphospholipid syndrome, rheumatoid polyarthritis, giant cell arteritis, Behcet's disease, Buerger's disease and preeclampsia, and also in infectious diseases such as AIDS. Other potential causes for vasospasm are hemorrhages, homocysteinemia, head injury, acute intermittent porphyria, sickle cell disease, anorexia nervosa, Susac syndrome, mitochondriopathies, tumors, colitis ulcerosa, Crohn's disease, arteriosclerosis and drugs. Patients with primary vasospastic syndrome tend to suffer from cold hands, low blood pressure, and even migraine and silent myocardial ischemia. Valuable diagnostic tools for vasospastic diathesis are nailfold capillary microscopy and angiography, but probably the best indicator is an increased plasma level of endothelin-1. The eye is frequently involved in the vasospastic syndrome, and ocular manifestations of vasospasm include alteration of conjunctival vessels, corneal edema, retinal arterial and venous occlusions, choroidal ischemia, amaurosis fugax, AION, and glaucoma. Since the clinical impact of vascular dysregulation has only really been appreciated in the last few years, there has been little research in the according therapeutic field. The role of calcium channel blockers, magnesium, endothelin and glutamate antagonists, and gene therapy are discussed.
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PMID:Vasospasm, its role in the pathogenesis of diseases with particular reference to the eye. 1128 96

This review addresses three related bone marrow failure diseases, the study of which has generated important insights in hematopoiesis, red cell biology, and immune-mediated blood cell injury. In Section I, Dr. Young summarizes the current knowledge of acquired aplastic anemia. In most patients, an autoimmune mechanism has been inferred from positive responses to nontransplant therapies and laboratory data. Cytotoxic T cell attack, with production of type I cytokines, leads to hematopoietic stem cell destruction and ultimately pancytopenia; this underlying mechanism is similar to other human disorders of lymphocyte-mediated, tissue-specific organ destruction (diabetes, multiple sclerosis, uveitis, colitis, etc.). The antigen that incites disease is unknown in aplastic anemia as in other autoimmune diseases; post-hepatitis aplasia is an obvious target for virus discovery. Aplastic anemia can be effectively treated by either stem cell transplantation or immunosuppression. Results of recent trials with antilymphocyte globulins and high dose cyclophosphamide are reviewed. Dr. Abkowitz discusses the diagnosis and clinical approach to patients with acquired pure red cell aplasia, both secondary and idiopathic, in Section II. The pathophysiology of various PRCA syndromes including immunologic inhibition of red cell differentiation, viral infection (especially human parvovirus B19), and myelodysplasia are discussed. An animal model of PRCA (secondary to infection with feline leukemia virus [FeLV], subgroup C) is presented. Understanding the mechanisms by which erythropoiesis is impaired provides for insights into the process of normal red cell differentiation, as well as a rational strategy for patient management. Among the acquired cytopenias paroxysmal nocturnal hemoglobinuria (PNH) is relatively rare; however, it can pose formidable management problems. Since its first recognition as a disease, PNH has been correctly classified as a hemolytic anemia; however, the frequent co-existence of other cytopenias has hinted strongly at a more complex pathogenesis. In Section III, Dr. Luzzatto examines recent progress in this area, with special emphasis on the somatic mutations in the PIG-A gene and resulting phenotypes. Animal models of PNH and the association of PNH with bone marrow failure are also reviewed. Expansion of PNH clones must reflect somatic cell selection, probably as part of an autoimmune process. Outstanding issues in treatment are illustrated through clinical cases of PNH. Biologic inferences from PNH may be relevant to our understanding of more common marrow failure syndromes like myelodysplasia.
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PMID:New Insights into the Pathophysiology of Acquired Cytopenias. 1170 33

Nerve growth factor (NGF), a target-derived factor for survival and maintenance of peripheral and central neurons, has been implicated in inflammatory processes. Mast cells are the principal effector cells in IgE-dependent hypersensitivity reactions, and also play a role in diseases characterised by inflammation, including those of the nervous system like multiple sclerosis. Mast cells are capable of synthesising and responding to NGF, although the occurrence of other members of the NGF family of neurotrophins and their protein forms have not been described. Immunoblot analysis with highly selective neurotrophin antibodies has now been used to show that rat peritoneal mast cells express a higher molecular weight form (73 kDa) of NGF, but not the monomeric (13 kDa) NGF polypeptide. Mast cells also expressed 73 kDa forms of neurotrophin-4 and neurotrophin-3; brain-derived neurotrophic factor was not detected. Medium conditioned by degranulating peritoneal mast cells contained similar high molecular weight forms of NGF and neurotrophin-4 on Western blots, but no neurotrophin-3. Mast cell-derived neurotrophin immunoreactivities were inhibited by the respective peptide antigen, further demonstrating the specificity of the mast cell-derived neurotrophic protein. Mast cell-released proteins supported the survival of cultured chicken embryonic neural crest- and placode-derived sensory neurons; neurotrophic activities were inhibited by neutralising antibodies for NGF and neurotrophin-4, respectively. High molecular isoforms of neurotrophins have been reported to occur in experimental colitis and in the inflamed gut of patients with Crohn's disease and ulcerative colitis, tissue sites rich in mast cells. The data suggest an important role for neurotrophins in the pathophysiology of inflammatory disease.
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PMID:Mast cells differentially express and release active high molecular weight neurotrophins. 1175 74

Among 4380 children born in 1987-1997 of women with a diagnosis of diabetes and alive at the age of one, 10 were registered in the Swedish Cancer Registry before the end of 1998. The odds ratio for having a childhood cancer after maternal diabetes, stratified for year of birth, maternal age, parity, multiple birth, and 500 g birth weight class was 2.25 (95%CI 1.22-4.15). Among 5842 children born during the period 1973-1997 whose mothers had other auto-immune diseases (SLE, rheumatoid arthritis, Crohn, ulcerous colitis, multiple sclerosis or thyroiditis), the number of observed childhood cancers (9) was close to that expected (8.5). Maternal diabetes but not other auto-immune diseases may be a risk factor for childhood cancer.
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PMID:Childhood malignancy and maternal diabetes or other auto-immune disease during pregnancy. 1195 52

A major problem in inflammatory bowel disease (IBD) is the accumulation of highly activated T-helper cells that are refractory to apoptosis induction. Hence, persistent inflammatory lesions are prevalent and are the basis of chronic disease. In IBD upregulation of costimulatory molecules on lamina propria lymphocytes has been described leading to apoptosis resistance. CD44 is a cell adhesion molecule and a signalling receptor that functions as a costimulatory molecule in T-cell activation. Several variant isoforms of CD44 (CD44v) are expressed by alternative splicing of variant exons encoding extracellular regions. Particularly isoforms containing CD44v7 are expressed on T cells and macrophages in T-helper-1 (Th1)-mediated chronic inflammation and autoimmune diseases. In this review recent data on the functional involvement of CD44v7 isoforms in IBD are discussed. In a mouse model of experimental colitis blockade or deletion of CD44v7 protects mice from severe intestinal inflammation by inducing apoptosis in lamina propria mononuclear cells. Recently, we observed that in lamina propria mononuclear cells from the inflamed but not uninflamed mucosa of patients with Crohn's disease, blockade of CD44v7 isoforms also induces apoptosis. The finding that obstruction of CD44v7 isoforms can antagonize Th1-cytokine-dependent immune pathology identifies CD44v7 as a target in the treatment of inflammatory diseases such as IBD, rheumatoid arthritis, multiple sclerosis and other autoimmune diseases in which CD44v7 isoforms are upregulated.
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PMID:Functional involvement of CD44 variant 7 in gut immune response. 1257 24

Glatiramer acetate (GA, Copaxone, Copolymer 1) is an approved drug for the treatment of multiple sclerosis and is highly effective in the suppression of experimental autoimmune encephalomyelitis in various species. The mode of action of GA is by initial strong promiscuous binding to MHC molecules and consequent competition with various myelin antigens for their presentation to T cells. A further aspect of its action is potent induction of specific suppressor cells of the T helper 2 (Th2) type that migrate to the brain and lead to in situ bystander suppression. Furthermore, the GA-specific cells in the brain express the antiinflammatory cytokines IL-10 and transforming growth factor beta, in addition to brain-derived neurotrophic factor, whereas they do not express IFN-gamma. Based on this immunomodulatory mode of action, we explored the potential of GA for two other applications: prevention of graft rejection and amelioration of inflammatory bowel diseases. GA was effective in amelioration of graft rejection in two systems by prolongation of skin graft survival and inhibition of functional deterioration of thyroid grafts, across minor and major histocompatibility barriers. In all transplantation systems GA treatment inhibited the detrimental secretion of Th1 inflammatory cytokines and induced beneficial Th2/3 antiinflammatory response. GA was effective also in combination with low-dose immunosuppressive drugs. Inflammatory bowel diseases are characterized by detrimental imbalanced proinflammatory immune reactivity in the gut. GA significantly suppressed the various manifestations of trinitrobenzene sulfonic acid-induced colitis, including mortality, weight loss, and macroscopic and microscopic colonic damage. GA suppressed local lymphocyte proliferations and tumor necrosis factor alpha detrimental secretion but induced transforming growth factor beta, thus confirming the involvement of Th1 to Th2 shift in GA mode of action.
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PMID:Mechanism of action of glatiramer acetate in multiple sclerosis and its potential for the development of new applications. 1537 92

Inflammatory bowel diseases are characterized by detrimental immune reactivity in the gut and imbalance between proinflammatory and antiinflammatory reactivity. In an attempt to downregulate inflammatory bowel disease, we tested whether the immunomodulator glatiramer acetate (GA; Copaxone, copolymer 1), an approved drug for the treatment of multiple sclerosis, can ameliorate trinitrobenzene sulfonic acid (TNBS)-induced colitis, a murine model that resembles human Crohn's disease. Experimental colitis was induced by rectal instillation of TNBS in 3 mice strains: BALB/c, SJL/J, and (SJL/JXBALB/c)F1, and its severity was evaluated by gross colon injury, histologic damage, body weight, and survival rate. We studied the effect of GA on all these parameters as well as on lymphocyte reactivity manifested by proliferation and secretion of tumor necrosis factor-alpha, and transforming growth factor-beta. GA treatment significantly suppressed the various manifestations of TNBS-induced colitis as demonstrated by substantial reduction in the macroscopic colonic damage, preservation of the microscopic colonic structure, reduced weight loss, and improved long-term survival, in GA treated mice compared with untreated mice. The parenteral route was more effective than the oral route. GA suppressed the proliferation of local mesenteric lymphocytes to syngeneic colon extract and the detrimental tumor necrosis factor-alpha secretion. In addition, it induced a beneficial secretion of transforming growth factor-beta. The ability of GA to effectively modulate the clinical manifestations and the detrimental immune response involved in experimental colitis warrants further studies to determine the clinical efficacy of GA in the treatment of human inflammatory bowel diseases.
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PMID:Therapeutic effect of the immunomodulator glatiramer acetate on trinitrobenzene sulfonic acid-induced experimental colitis. 1567 3


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