Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Graft-versus-host reactions were induced in adult F1 hybrid animals by injecting parental spleen cells. Adenylate cyclase activity was determined in the washed cell particles of the lymphoid tissues. During a time course study of the regional GVH reaction an increase in lymph node weight was apparent at day 2, whereas the adenylate cyclase activity increased at day 4 after the injection. Maximal lymph node hypertrophy and adenylate cyclase activation were observed 8 to 10 days after initiation of the GVH response. Adenylate cyclase stimulation by epinephrine of the GVH response. Adenylate cyclase stimulation by epinephrine and glucagon in experimental preparations was less than in the control. NaF was stimulatory only in the control preparations. Ca-2+ in concentrations up to 8 mM had no inhibitory effects on the control or experimental preparations. The pattern of responses of the experimental preparations to Zn-2+ and Cu-2+ was different than the control; however, in high concentrations both of these cations had marked inhibitory effects. An increase in the adenylate cyclase activity was also direct relationship between the adenylate cyclase activity and the cytolytic activity of spleen cells from mice undergoing systemic GVH reaction. These results can be explained on the basis of alterations in the cell membranes, and it is suggested that such changes play an important role in the pathogenesis of GVH disease.
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PMID:Adenylate cyclase activation in lymphoid tissues during graft-versus-host reaction. 23 44

Twenty-three patients with recent onset Type 1 (insulin-dependent) diabetes in whom residual insulin secreting B cells were present and 12 patients with disease of more prolonged duration (maximum 9 years), 8 of whom had residual B cells, were studied. Aberrant expression of Class II major histocompatibility complex molecules was demonstrated immunohistochemically on insulin secreting B cells in 21 out of 23 patients with recent onset disease and 6 of the patients with more prolonged disease. No such expression was seen on glucagon secreting A cells or somatostatin secreting D cells. Islets where there was marked hyperexpression of Class I major histocompatibility complex molecules on islet endocrine cells were seen in all cases in which residual B cells were present. Ninety-two per cent of insulin containing islets but only 1% of insulin deficient islets exhibited this phenomenon (p less than 0.001, Chi-squared test). There was evidence to suggest that both these abnormalities of major histocompatibility complex expression preceded insulitis within a given islet. They also appeared to be unique to Type 1 diabetes, being absent in pancreases of patients with Type 2 (non-insulin-dependent) diabetes, chronic pancreatitis, cystic fibrosis, graft-versus-host disease and Coxsackie B viral pancreatitis. The development of autoimmunity to B cells in Type 1 diabetes may be a "multistep" process in which abnormalities of major histocompatibility complex expression on islet endocrine cells are crucial events.
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PMID:Aberrant expression of class II major histocompatibility complex molecules by B cells and hyperexpression of class I major histocompatibility complex molecules by insulin containing islets in type 1 (insulin-dependent) diabetes mellitus. 330 84

Patients with graft-versus-host disease (GVHD) develop multiple organ failure (MOF), so systematic management is needed. First, patients should be kept in a clean room. Antibiotics, anti-fungal drugs and gamma-globulins are essential for the prevention and treatment of infections. If patients are hypoxic for the nasal cannula or the mask, continuous positive airway pressure (CPAP) or artificial ventilation must be used. In the treatment of hepatic dysfunction, lactulose, branched chain amino acid, glucagon-insulin, and Prostaglandin E1 (PGE1) are given. If plasma exchanges are ineffective, a bilirubin absorption therapy may remain partially effective. In the treatment of renal failure, diuretics, PGE1 and dopamine are given. Hemofiltration and hemodialysis will be effective. But the effective treatment for post-transfusion GVHD is unavailable, so systematic management of GVHD is no more than allopathic treatment.
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PMID:Systematic management of graft-versus-host disease (GVHD). 792 35

Acute graft-versus-host disease (GVHD) is a life-threatening complication after allogeneic hematopoietic cell transplantation (allo-HCT). Although currently used GVHD treatment regimens target the donor immune system, we explored here an approach that aims at protecting and regenerating Paneth cells (PCs) and intestinal stem cells (ISCs). Glucagon-like-peptide-2 (GLP-2) is an enteroendocrine tissue hormone produced by intestinal L cells. We observed that acute GVHD reduced intestinal GLP-2 levels in mice and patients developing GVHD. Treatment with the GLP-2 agonist, teduglutide, reduced de novo acute GVHD and steroid-refractory GVHD, without compromising graft-versus-leukemia (GVL) effects in multiple mouse models. Mechanistically GLP-2 substitution promoted regeneration of PCs and ISCs, which enhanced production of antimicrobial peptides and caused microbiome changes. GLP-2 expanded intestinal organoids and reduced expression of apoptosis-related genes. Low numbers of L cells in intestinal biopsies and high serum levels of GLP-2 were associated with a higher incidence of nonrelapse mortality in patients undergoing allo-HCT. Our findings indicate that L cells are a target of GVHD and that GLP-2-based treatment of acute GVHD restores intestinal homeostasis via an increase of ISCs and PCs without impairing GVL effects. Teduglutide could become a novel combination partner for immunosuppressive GVHD therapy to be tested in clinical trials.
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PMID:Glucagon-like peptide 2 for intestinal stem cell and Paneth cell repair during graft-versus-host disease in mice and humans. 3254 57