Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

National death-rates from ischaemic heart-disease are significantly correlated with population frequencies of histocompatibility antigen HLA-8 and haplotype 1-8. Serum-cholesterol levels may also be correlated with population frequencies of HLA-8. Inexplicably high death-rates from ischaemic heart-disease and high levels of serum-cholesterol in Finland may be due to the combined effects of HLA-8 and W15. It is suggested that HLA-8 (and possibly W15) are linked to genes which predispose to hypercholesterolaemia and ischaemic heart-disease. These findings provide some support for i-munogenetic hypotheses for vascular disease in man.
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PMID:Ischaemic heart-disease: possible genetic markers. 5 53

Nineteen insulin dependent diabetics with onset at 30 years of age or less and duration of diabetes of greater than 25 years were divided into two groups on the basis of the presence or absence of clinically evident vascular disease. The patients without vascular disease were characterised by a later mean age of onset, lower fasting growth hormone concentration, and a lower frequency of the unusual HLA pattern B8 without A1 compared to the diabetics with vascular complications. The level of blood glucose control assessed over the last 15 years, insulin antibody titres, plasma glucagon levels and plasma cholesterol did not differ between the two groups. Residual beta cell activity was found in only one of the 19 patients. Although this study does not exclude an effect of the degree of blood glucose control or persistence of beta cell function in the early stages of diabetes on the subsequent development of vascular disease, it suggests that genetic factors, age of onset and plasma growth hormone levels may be more important.
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PMID:Hormonal profile, blood sugar control and HLA patterns in long-term insulin dependent diabetes with and without vascular disease. 36 9

Multiple infections and severe neutropenia were found in a previously healthy 29 year old man with no history of similar syndromes in the family, drug ingestion or exposure to environmental toxins. There was no evidence at the time of presentation of diseases previously associated with agranulocytosis (e.g., neoplasia, thyrotoxicosis, chronic infection, collagen-vascular disease or leukoagglutinating antibody). His serum contained a nonagglutinating, complement-dependent, cytotoxic antibody, however, reactive with peripheral blood granulocytes from 35 per cent of normal donors. The neutropenia was not affected by steroids but resolved promptly after splenectomy. Microscopic examination of the spleen revealed ingestion of polymorphonuclear leukocytes by splenic macrophages. Family studies indicated that the target antigen was non-HLA and that the antibody was not absorbed by lymphocytes or platelets. We conclude that the agranulocytosis was autoimmune in origin and suggest that similar myeloid-specific immune responses could influence granulocyte tranfusion and bone marrow transplantation by alloimmune "rejection" that would not be avoided by matching only for HLA specificities.
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PMID:Acquired agranulocytosis with granulocyte specific cytotoxic autoantibody. 44 60

Autoimmune vasculitis represents a disease characterized by focal inflammation within arteries at multiple sites in the vasculature. Therapeutic interventions in this disease are empirical and often unsuccessful, and the mechanisms of immune injury are not well-defined. The direct transfer of recombinant genes and their expression in the arterial wall provides an opportunity to explore the pathogenesis and treatment of vascular disease. In this report, an animal model for vasculitis has been developed. Inflammation has been elicited by direct gene transfer of a foreign class I major histocompatibility complex gene, HLA-B7, to specific sites in porcine arteries. Transfer and expression of this recombinant gene was confirmed by a polymerase chain reaction and immunohistochemistry, and cytolytic T cells specific for HLA-B7 were detected. These findings demonstrate that expression of a recombinant gene in the vessel wall can induce a focal immune response and suggest that vessel damage induced by cell-mediated immune injury can initiate vasculitis.
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PMID:Transduction of a foreign histocompatibility gene into the arterial wall induces vasculitis. 159 26

We undertook a study to determine the incidence of hypopyon, as well as the most common anterior uveitis entities with which hypopyon is associated. A total of 216 patients with anterior uveitis were studied. The uveitis was acute in 155. Of the 155 patients, 11 (7.1%) had hypopyon. Nine of the 11 patients with hypopyon were positive for HLA B27. Of these nine, two had Reiter's syndrome and one had ankylosing spondylitis; the other six had no confirmed systemic disease. Of the two patients with hypopyon who were HLA B27-negative, one had mixed connective-tissue vascular disease, and one had idiopathic anterior uveitis. Of the 155 patients with acute anterior uveitis, 62 were HLA B27-positive. Thus, the incidence of hypopyon uveitis among HLA B27-positive patients was 14.5% (nine of 62 patients), whereas the incidence among HLA B27-negative patients was only 2.2% (two of 93 patients). These results suggest that HLA B27-related anterior uveitis is the most common cause of hypopyon uveitis, and that most patients with anterior uveitis associated with hypopyon will test positive for HLA B27. Although these results reflect a referral population, they should be of benefit in the treatment of patients with anterior uveitis.
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PMID:Anterior uveitis and hypopyon. 162 8

This review summarizes aspects of the phenotypic expression, natural history, recognition, pathogenesis, and heterogeneous nature of maturity-onset diabetes of the young (MODY), which is inherited in an autosomal-dominant pattern. There are differences in metabolic, hormonal, and vascular abnormalities in different ethnic groups and even among White pedigrees. In MODY patients with low insulin responses, there are delayed and decreased insulin and C-peptide secretory responses to glucose from childhood or adolescence even before glucose intolerance appears, which may represent the basic genetic defect. When followed for decades, nondiabetic siblings have normal insulin responses. The fasting hyperglycemia of some MODY patients has been treated successfully with sulfonylureas for up to 30 yr. In a few patients, after years or decades of diabetes, the insulin and C-peptide responses to glucose are so low that they resemble those of early insulin-dependent diabetes mellitus. The progression of the insulin secretory defect over time distinguishes between these two types of diabetes. In contrast are patients from families who have very high insulin responses to glucose, despite glucose intolerance and fasting hyperglycemia similar to that seen in patients with low insulin responses. In many of these patients, there is in vivo and in vitro evidence of insulin resistance. Whatever its mechanism, the compensatory insulin responses to nutrients must be insufficient to maintain normal carbohydrate tolerance. This suggests that diabetes occurs only in those patients who have an additional islet cell defect, i.e., insufficient beta-cell reserve and secretory capacity. In a few MODY pedigrees with high insulin responses to glucose and lack of evidence of insulin resistance, a structurally abnormal mutant insulin molecule that is biologically ineffective is secreted. No associations have been found between specific HLA antigens and MODY in White, Black, and Asian pedigrees. Linkage studies of the insulin gene, insulin-receptor gene, erythrocyte/HepG2 glucose-transporter locus, and apolipoprotein B locus have shown no association with MODY. Vascular disease may be as prevalent as in conventional non-insulin-dependent diabetes mellitus. Because of autosomal-dominant transmission and penetrance at a young age, MODY is a good model for further investigations of etiologic and pathogenetic factors in non-insulin-dependent diabetes mellitus, including the use of genetic linkage strategies to identify diabetogenic genes.
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PMID:Scope and heterogeneous nature of MODY. 240 17

This review summarized aspects of the widening scope, phenotypic expression, natural history, recognition, pathogeneses, and heterogenous nature of maturity-onset diabetes of the young (MODY), an autosomal dominant inherited subtype of NIDDM, which can be recognized at a young age. There are differences in metabolic, hormonal, and vascular abnormalities in different ethnic groups and even among Caucasian pedigrees. In MODY patients with low insulin responses, there is a delayed and decreased insulin and C-peptide secretory response to glucose from childhood or adolescence, even before glucose intolerance appears; it may represent the basic genetic defect. The nondiabetic siblings have had normal insulin responses for decades. The fasting hyperglycemia of some MODY has been treated successfully with sulfonylureas for more than 30 years. In a few, after years or decades of diabetes, the insulin and C-peptide responses to glucose are so low that they may resemble those of early Type I diabetes. The rate of progression of the insulin secretory defect over time does distinguish between these two types of diabetes. In contrast are patients from families who have very high insulin responses to glucose despite glucose intolerance and fasting hyperglycemia similar to those seen in patients with low insulin responses. In many of these patients, there is in vivo and in vitro evidence of insulin resistance. Whatever its mechanism, the compensatory insulin responses to nutrients must be insufficient to maintain normal carbohydrate tolerance. This suggests that diabetes occurs only in those patients who have an additional islet cell defect, i.e., insufficient beta cell reserve and secretory capacity. In a few MODY pedigrees with high insulin responses to glucose and lack of evidence of insulin resistance, an insulin is secreted which is a structurally abnormal, mutant insulin molecule that is biologically ineffective. No associations have been found between specific HLA antigens and MODY in Caucasian, black, and Asian pedigrees. Linkage studies of the insulin gene, the insulin receptor gene, the erythrocyte/Hep G2 glucose transporter locus, and the apolipoprotein B locus have shown no association with MODY. Vascular disease may be as prevalent as in conventional NIDDM. Because of autosomal dominant transmission and penetrance at a young age, MODY is a good model for further investigations of etiologic and pathogenetic factors in NIDDM, including the use of genetic linkage strategies to identify diabetogenic genes.
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PMID:Maturity-onset diabetes of the young (MODY). 268 21

In random bred species including dog and man, a marrow graft from a donor genetically identical for the major histocompatibility complex is followed by significant graft-versus-host disease (GVHD) in 30% to 50% of the recipients despite the administration of postgrafting immunosuppression. Controlled trials comparing the immunosuppressive drugs methotrexate or cyclosporine have shown no differences in long-term survival, although cyclosporine reduces the incidence of mucositis and is associated with somewhat earlier engraftment. Observations in the canine model indicating efficacy of combining a brief course of methotrexate with the cyclosporine regimen are now being confirmed in patients with early results indicating a reduction in GVHD and an improved survival. In both species failure to administer immunosuppression after grafting is associated with a high incidence of acute GVHD and an adverse effect on survival. Removal of donor T cells from the marrow inoculum reduces the incidence of acute GVHD but at the risk of a higher likelihood of subsequent graft failure and maybe even leukemic recurrence. Results of studies in canine and human chimeras agree with murine data indicating a principal role for T cells in the pathogenic mechanism of GVHD. Chimera lymphocytes (of donor origin) from dogs and patients with acute GVHD show proliferative responses to previously stored host cells, and lymphocytes cytotoxic to host target cells are seen in patients with GVHD. Observations indicate a direct, rather than an indirect, role for T cells in GVHD. "Specific" suppressor cells may be responsible for maintaining stable graft-host tolerance while "nonspecific" suppressor cells may play a role in the impaired immune defenses in patients with chronic GVHD. Chronic GVHD, which resembles systemic collagen vascular disease, occurs in approximately 40% of HLA-identical recipients, particularly following acute GVHD and is more frequent in older patients. Efforts to treat both acute and chronic GVHD with prednisone, antithymocyte globulin, cyclosporine and azathioprine are only unpredictably effective. Data in dogs pointed out the feasibility of transplants from partially matched related donors or matched unrelated donors, an approach that is now being pursued in human patients. Marrow grafts from HLA-partially matched family members resulted in a higher incidence of acute GVHD. There was no difference in acute GVHD comparing class I to class II antigen differences and long term survival was influenced by patient age and disease status rather than HLA incompatibility.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Graft-versus-host disease after marrow transplantation. 354 Sep 90

The heterogeneity within Type II diabetes (NIDDM) and within Maturity-Onset type Diabetes of Young people (MODY), a subset of NIDDM which is inherited in an autosomal dominant fashion, is discussed. Aspects of the definition and phenotypic expression of MODY are reviewed. Within NIDDM there are differences in patterns of inheritance between subgroups. HLA antigen associations are not found in most NIDDM populations but exist in three specific population groups with Type II diabetes. Within NIDDM and within MODY there are differences in the magnitude of insulin responses to glucose, differences in target tissue responsiveness to insulin in vivo, and differences in receptor and post-receptor effects of insulin. Structurally abnormal variant and biologically defective insulin molecules have been found in some Type II diabetic patients and in members of certain MODY families. The presence or absence of obesity may mark heterogeneous groups of Type II diabetic patients, in addition to the importance of obesity in uncovering an insulin secretory defect by causing insulin resistance. There is heterogeneity in susceptibility to vascular disease within NIDDM and MODY. The natural history of carbohydrate metabolism and of insulin secretory responses to glucose in early Type I diabetes and in MODY with low insulin secretory responses are illustrated and similarities and dissimilarities compared and contrasted. Failure to recognize young patients with MODY may contribute to incorrect diagnosis, management, and assignment of prognosis of this form of diabetes in the young by many practicing physicians. The recognition that Type I or insulin-dependent diabetes (IDDM) and Type II or noninsulin-dependent (NIDDM) differ from each other not only phenotypically but also in etiology and pathogenesis led the National Diabetes Data Group (NDDG) to devise the present nomenclature and classification of diabetes mellitus. These were adopted by the World Health Organization. As suggested by the NDDG report, the classification should be reexamined periodically to reflect improved understanding of the disease, to stimulate further research, and to be of help to practicing physicians.
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PMID:Heterogeneity within type II and MODY diabetes. 389 67

In dog and in man a marrow graft from a donor genetically identical for the major histocompatibility complex is followed by significant graft-versus-host disease (GvHD) in approximately one-half of the recipients, despite the administration of post-grafting immunosuppressive therapy. Controlled trials comparing post-grafting therapy using methotrexate or cyclosporine have shown no difference in long-term survival, although cyclosporine reduces the incidence of mucositis and is associated with somewhat earlier engraftment. Observations in the canine model indicating efficacy of a combination of a brief course of methotrexate with the cyclosporine regimen are now being tested in patients, with early results indicating a reduction in GvHD and an improved survival. In both species, failure to administer immunosuppression after grafting is associated with a high incidence of acute GvHD and an adverse effect on survival. Removal of donor T cells from the marrow inoculum may reduce the incidence of acute GvHD but at the price of a higher likelihood of subsequent graft failure. Studies of canine and human chimeras are in agreement with murine data indicating a principal role for T cells in the pathogenic mechanism of GvHD. Chimera lymphocytes (of donor origin) from dogs and patients with acute GvHD proliferate in response to previously stored host cells, and lymphocytes cytotoxic to host target cells are seen in patients with GvHD. Our observations indicate a direct, rather than an indirect, role for T cells since lymphocytes from donors sensitized to chimeric skin grafts can cause lethal GvHD when infused into stable chimeric recipients. "Specific" suppressor cells may play a role in maintaining stable graft-host tolerance while "nonspecific" suppressor cells may be responsible for the impaired immune defenses in patients with chronic GvHD. Chronic GvHD, which resembles systemic collagen vascular disease, occurs in approximately 40% of matched recipients, particularly following acute GvHD, and is more frequent in older patients. Efforts to treat both acute and chronic GvHD with steroids, antithymocyte globulin, cyclosporine and azathioprine are only partially and unpredictably effective. Data in dogs pointed out the feasibility of transplants from partially matched related donors or matched unrelated donors, an approach that is now being actively pursued in human patients. Marrow transplants from HLA-partially matched family members resulted in a higher incidence of acute GvHD.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Graft-versus-host disease in dog and man: the Seattle experience. 391 May 58


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