Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An association between the ingestion tryptophan and a syndrome characterized by scleroderma-like skin abnormalities, fasciitis, and eosinophilia has recently been recognized in the United States. We report the clinical and histopathological findings in nine patients and the results of biochemical analyses of tryptophan metabolism in seven patients with this syndrome. Edema of the extremities, frequently accompanied by pruritus, paresthesia, and myalgia, developed in the nine patients (six women and three men; age range, 30 to 66 years) 1 to 18 months after the start of therapy with tryptophan (1.5 to 3.0 g daily) for insomnia, depression, or obesity. Five patients were taking drugs (benzodiazepines) known to inhibit hypothalamic-pituitary-adrenal function, and one had adrenal insufficiency. All had blood eosinophilia in the acute phase of their illness (mean eosinophil count [+/- SD], 3.62 +/- 2.87 X 10(9) cells per liter). All had histopathological changes in the dermis and subcutaneous tissue typical of scleroderma, and seven patients had eosinophils. The fascia was inflamed and fibrotic, and adjacent skeletal muscle often showed perifascicular inflammation. Tryptophan was discontinued in all patients, and eight received prednisone. The cutaneous symptoms improved, but only two patients had complete resolution of their illness. The patients had plasma levels of tryptophan before and after an oral dose of tryptophan that were similar to those in normal subjects. Plasma levels of L-kynurenine and quinolinic acid, which are metabolites of tryptophan, were significantly higher in four patients with active disease than in three patients studied after eosinophilia had resolved or in five normal subjects (P less than 0.001)--findings consistent with the activation of the enzyme indoleamine-2,3-dioxygenase. This illness resembles eosinophilic fasciitis and probably represents one aspect of the recently reported eosinophilia-myalgia syndrome. The development of the syndrome may result from a confluence of several factors, including the ingestion of tryptophan, exposure to agents that activate indoleamine-2,3-dioxygenase, and possibly, impaired function of the hypothalamic-pituitary-adrenal axis.
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PMID:Scleroderma, fasciitis, and eosinophilia associated with the ingestion of tryptophan. 231 25

The combined Collis-Nissen operation has been performed in 353 patients. Forty-five percent had reflux esophagitis without stricture; 20%, peptic stricture; 72%, a sliding hiatal hernia; 17%, a paraesophageal hernia; 21%, previous antireflux operation; 15%, esophageal spasm; 8%, scleroderma; and 32%, marked obesity. There were 4 postoperative deaths (mortality rate, 1.1%). Complications occurred in 28 patients (8%) and included wound infection (2.2%), esophageal or gastroplasty tube leak (1.7%), bleeding (1.1%), splenic injury, gastric atony, and crural repair dehiscence (each less than 1%). Follow-up includes personal interview, esophageal manometry, and standard acid reflux testing. The average length of follow-up for 261 patients (74%) followed at least 12 months is 43.8 months. Fifty-eight percent have been followed at least 36 months; 41%, 48 months; and 29%, 60 months or longer. Subjectively, in these 261 patients, reflux has been eliminated in 75%, is mild in 11%, is moderate in 9%, and is severe in 5%. Eight percent have postthoracotomy pain; 3%, early satiety ("bloats"); and 1%, postvagotomy diarrhea. Seventeen percent require either periodic or regular esophageal dilations for dysphagia. Objectively, intraesophageal pH studies show good reflux control in 91% and poor reflux control in 9%. Twenty-six patients (10%) have required reoperation for recurrent reflux or dysphagia. These results substantiate satisfactory reflux control using the Collis-Nissen operation in patients at risk for recurrence after standard repairs, but also emphasize that, like other antireflux procedures, the Collis-Nissen operation is not without some degree of postoperative adverse symptoms.
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PMID:Continued assessment of the combined Collis-Nissen operation. 291 6

The presence of antithyroid plasma membrane antibodies (ATMA) has been detected in 97% of patients with untreated hyperthyroid Graves' disease, 85% of methimazole treated hyperthyroid Graves' disease, 25% of Hashimoto's thyroiditis and 6.9% of patients with toxic nodular goitre. The ATMA index was negative in all healthy blood donors, in patients with non-toxic nodular goitre, with the thyrocardiac syndrome and with simple obesity. Studies of patients with non-thyroid autoimmune diseases revealed that ATMA is positive in 11% of patients with scleroderma, 17.6% of systemic lupus erythematosus and 16% of rheumatoid arthritis. The amount of immunoglobulin bound to thyroid plasma membranes after pre-incubation with serum from patients with Graves' disease varied from 4.2 to 25.2 pmoles per mg of membrane protein; these values are several times higher than the maximal binding capacity for thyrotrophin which is 1.28 pmole/mg protein. In the majority of the cases studied TSH did not significantly inhibit IgG bound from thyroid plasma membranes. Significant amounts of IgG were displaced by an excess of TSH only in three cases with untreated hyperthyroid Graves' disease.
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PMID:The presence of autoantibodies directed to thyroid plasma membrane antigens in sera of patients with thyroid disorders, estimated by the reaction with labelled protein A. 632 47

We previously reported on an altered immune-endocrine feedback loop via the hypothalamo-pituitary-adrenal (HPA) axis in Obese strain (OS) chickens afflicted with spontaneous autoimmune thyroiditis. These animals are deficient in plasma corticosterone increase after antigenic challenge or application of cytokine-containing conditioned medium of mitogen-stimulated spleen cells (CM). To investigate whether the impaired ability to respond to cytokines with glucocorticoid-increasing factor (GIF) activity, e.g. interleukin 1 (IL 1), is restricted to OS chickens as a model for an organ-specific autoimmune disease, we extended our experiments to another autoimmune-prone animal strain, the chickens of the University of California at Davis line 200 (UCD-200). These animals develop an inherited inflammatory fibrotic disease that closely resembles human progressive systemic sclerosis (scleroderma). Application of GIF-containing CM to UCD-200 chickens leads to a transient increase in glucocorticoid serum levels within 1-2 hours comparable to that of controls. But, while corticosterone levels in the latter returned to normal baseline levels after 4 hours, they were still elevated in autoimmune chickens. Although the peak of the glucocorticoid hormone serum concentrations was equal to that of controls, UCD-200 had to secrete twice as much adrenocorticotropic hormone to achieve this corticosterone serum level due to an apparent hyporesponsiveness of the adrenal gland to this secretagogue. The altered cytokine-induced glucocorticoid secretion is found in early as well as in chronic, sclerotic stages of the disease. Cellular alterations in the peripheral blood of UCD-200 chickens during the prolonged elevated corticosterone section, i.e. between 2-4 hours after CM application, are characterized by a significant decrease in the percentage of CD4+ and CD8+ cells. Furthermore, a significant increase in B cells up to 24 hours with a maximum after 1 hour was found. The proliferative response to the mitogen concanavalin A of peripheral mononuclear cells was inversely correlated to the serum corticosterone level, showing a permanent decrease of 80-90% after 1-4 hours in autoimmune animals. This functional alteration in UCD-200 was accompanied by an 80% decrease in serum interleukin 2 (sIL 2) activity 4 hours after CM application. Twenty-four hours later an eight-fold increase in sIL 2 rebound activity was found, indicating that the inhibitory effect of corticosterone in UCD-200 chickens is not long-lasting.
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PMID:Effects of cytokine application on glucocorticoid secretion in an animal model for systemic scleroderma. 815 53

Previous studies in our laboratory demonstrated an altered immuno-endocrine feedback communication via the hypothalamo-pituitary-adrenal (HPA) axis, which may be an important modulatory factor in the development of spontaneous autoimmune thyroiditis in Obese strain (OS) chickens. These birds show a significantly lower, or even absent, increase in serum glucocorticoid levels in response to an intravenous injection of antigen or conditioned medium (CM) from mitogen-stimulated spleen cells known to contain glucocorticoid-increasing factors (GIFs), notably interleukin-1 (IL-1). The present study was aimed at investigating this feedback regulation in animal models with spontaneous systemic autoimmune diseases, such as the UCD-200 chicken, which serves as a model for human scleroderma, and various murine lupus models. In contrast to OS chickens, UCD-200 chickens displayed a nearly normal plasma corticosterone surge in response to CM, and IL-1 was again identified as the primary GIF in CM. Recombinant IL-1 also induced a drastic increase in plasma corticosterone levels in various strains of normal mice. A similar increase was observed in the bacterial lipopolysaccharide-resistant C3H/HeJ strain, thus excluding the possibility of bacterial endotoxin contamination. However, in young lupus-prone (NZB/W)F1 and MRL/MP-lpr mice, a significantly lower increase in plasma corticosterone levels was observed after injection of recombinant IL-1, suggesting a deficient immuno-endocrine communication via the HPA loop in this instance as well. Detailed studies to identify further cytokines with GIF activity in the avian and murine systems showed that both IL-6 and tumor necrosis factor-alpha could induce increased plasma corticosterone levels in mice, but not in chickens. IL-3, IL-8, transforming growth factor-beta, interferon-gamma and granulocyte-macrophage colony-stimulating factor were devoid of GIF activity in both chickens and mice.
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PMID:Disturbed immuno-endocrine communication via the hypothalamo-pituitary-adrenal axis in autoimmune disease. 821 76

Werner syndrome (WS) is a rare autosomal recessive disease with poor growth, premature aging, scleroderma-like skin changes, endocrine abnormalities, and deficiencies of adipose tissue. Could there be a genetic obesity syndrome which offers an instructive contrast to at least one form of WS? At least one form of WS might result from an enzyme defect that causes hypertriglyceridemia, hyperinsulinism, and hyperglucagonism; the defective enzyme might play a key role in the utilization of tryptophan, riboflavin (vitamin B2), or other vitamins or in the synthesis of prostaglandins that inhibit insulin secretion. At least one form of genetic obesity might result from an enzyme defect that causes hypotriglyceridemia and hyperinsulinism without hyperglucagonism; the defective enzyme might be unable to bind properly to a product that inhibits some step in the process of conversion of free fatty acid (FFA) CoA into ketoacids.
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PMID:Werner syndrome and genetic obesity: speculation. 852 89

Skin grafts were performed to prove the level of genetic diversity in chicken populations of the Obese strain (OS), which develops a spontaneous Hashimoto's-like thyroiditis, and University of California at Davis (UCD) Line-200 chickens, which are hereditarily afflicted with progressive systemic sclerosis (scleroderma). As controls, Cornell C-strain (CS) and inbred, normal White Leghorn CB chickens were included in the genetic monitoring program. At the commencement of this study in 1988, median allograft rejections were observed after 9 to 12 d (range 8 to 14 d) in OS and CS chickens that derived from large flocks at Cornell University, whereas OS sublines of the smaller, more closely-bred colonies at the University of Innsbruck, Austria, showed median allograft rejection after 19 d (range 12 to 35 d). From 1988 to 1993, allograft survival was only slightly prolonged in the OS sublines. However, the results of the skin allotransplantations in inbred UCD-200 chickens revealed two subpopulations in this line. In one subgroup the median of allograft rejection was calculated with 13 d (range 6 to 37 d) in 1989, 30 d (10 to 37 d) in 1990, 21 d (8 to 90 d) in 1991, and 16 d (7 to 26 d) in 1993. In the other subgroup allografts were accepted at rates similar to autografts. In addition, the inbreeding coefficient was calculated for eight male and eight female OSB5B5Cornell (C) and OSB5B5Innsbruck (INN) chickens, respectively, hatched in 1993. On the basis of mating records, the minimal estimate of the inbreeding coefficient was calculated to be 0.0679 in the OSB5B5C and 0.1035 in the OSB5B5INN population. The results demonstrated a higher degree of consanguinity in the smaller population of OSB5B5INN chickens compared to OSB5B5C birds. The later are maintained in larger numbers, therefore, the frequency of matings between related individuals should be lower.
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PMID:Skin allograft survival in chicken strains with spontaneous autoimmune diseases. 877 18

According to our concept, the development of autoimmune disease depends on the presence of two sets of essential genes, one coding for an abnormal autoreactivity of the immune system, the other for a primary susceptibility of the target organ/structure for the immune attack. The final outcome of the disease in a given individual is then fine tuned by modulatory factors, such as diet or hormones. With regard to the latter, the immuno-endocrine interaction via the hypothalamo-pituitary-adrenal (HPA) axis has proven to be of special importance. Investigating the so-called Obese strain (OS) of chickens, an animal model with a spontaneously occurring Hashimoto-like autoimmune thyroiditis, we have first shown an impaired surge of glucocorticoid hormones after stimulation of the HPA axis by antigens or certain cytokines (glucocorticoid-increasing factors--GIFs). More recently, we have found a similar behavior in models with systemic autoimmune diseases, that is, murine lupus erythematosus and avian scleroderma. More detailed studies have, however, proven that the mechanisms underlying this altered immuno-endocrine communication via the HPA axis differs in different models. Finally, recent data point to the possibility that the classical pathways of glucocorticoid-T-cell interactions also take place in the thymus itself, which has been shown to be a site of steroid hormone production.
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PMID:Neuroendocrine-immune disturbances in animal models with spontaneous autoimmune diseases. 962 86

The vascular placental pathology (VPP) is associated with many etiologies. Some are the consequence of a maternal genetic or acquired predisposition. Others are associated with a chronic maternal disease (hypertension, lupus, obesity, diabetes, ...). Finally, some others are associated with placental implantation leading to fetal ischemia (multiple pregnancy, chorioangioma, primiparity, feto-placental hydrops) or to environmental (altitude) or nutritional factors (famine and specific alimentary depressions). We classify these factors into three categories according to the risk level (moderate, significant and elevated). While any of these factors can increase the risk of VPP, no one is sufficiently sensitive or specific in predict inevitable onset of VPP. In most cases VPP results from a combination of two (or more) risk factors. The risk factors of VPP classified as moderate include age (> or = 35 years), increased blood pressure during the second trimester of pregnancy, a new paternity, dietetic factors or environmental factors, smoking and controlled diabetes (class B, C), or inactive systemic diseases. Risk is significantly elevated among obese (BMI > or = 25), primiparous women, women with a past familial history (first degree) of preeclampsia or eclampsia, cocaine use or association of tobacco and caffeine use, increased placental mass (associated with twin pregnancy, fetal hydrops or molar pregnancy), uncontrolled diabetes, lupus, active scleroderma. Risk is considered to be high among patients with chronic hypertension, women with a past history of preeclampsia, diabetes (class D, F, R), patients with active systemic disease or with antiphospholipid antibodies or women with lupus or renal lesions and/or proteinuria as well as chronic kidney disease resulting in proteinuria, hypertension and renal insufficiency. Finally, the risk of VPP is considered to be increased in the presence of acquired thrombophilia. It remains moderate in the presence of isolated genetic thrombophilia, except in forms presenting with multiple genetic mutations or associated with an hyperhomocysteinemia. A "high-risk group" is defined among women with past history of deep venous thromboembolic events outside pregnancy, or with a past history of placental vascular pathology (intra-uterine death, placental abruptio, severe and precocious placental, intra-uterine growth retardation, early and repetitive fetal loss) and who, in addition, present with acquired thrombophilia (antiphospholipid antibodies, thrombocytemia), unique homozygous genetic thrombophilia, amultiple genetic thrombophilia or unique heterozygous genetic thrombophilia associated with hyperhomocysteinemia. Prophylactic treatment of acquired thrombophilia and of the multiple genetic forms or associated with hypercysteinemia is a logical rationale, particularly among women with a past history of placental vascular pathology, or with a past history of venous thromboembolic events. On the contrary, prophylaxis using low-molecular-weight heparin in the event of asymptomatic genetic thrombophilic mutations and for women without a past history of deep venous thromboembolism or vascular placental pathology remains controversial.
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PMID:[Vascular placental pathology in high-risk groups: definition and synopsis]. 1502 87

Autoimmune diseases in human patients only become clinically manifest when the disease process has developed to a stage where functional compensation by the afflicted organ or system is not possible anymore. In order to understand the initial etiologic and pathogenic events that are generally not yet accessible in humans, appropriate animal models are required. In this respect, spontaneously developing models--albeit rare--reflect the situation in humans much more closely than experimentally induced models, including knockout and transgenic mice. The present chapter describes three spontaneous chicken models for human autoimmune diseases, the Obese strain (OS) with a Hashimoto-like autoimmune thyroiditis, the University of California at Davis lines 200 and 206 (UCD-200 and -206) with a scleroderma-like disease, and the amelanotic Smyth line with a vitiligo-like syndrome (SLV). Special emphasis is given to the new opportunities to unravel the genetic basis of these diseases in view of the recently completed sequencing of the chicken genome.
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PMID:Avian models with spontaneous autoimmune diseases. 1714 2


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