Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The endocrine cell populations of pancreatic islets in encephalomyocarditis (EMC)-virus infected mice were assessed quanititatively by immunofluorescence using specific antisera against 4 islet hormones. A marked reduction of the volume of insulin-containing (B-) cells (up to one tenth of control values) was observed at all stages studied in the hyperglycaemic mice. This was accompanied by the inversion of the normal ratio between B- and non B-cells. The volume of the latter cell types was also modified at different time points after infection: glucagon-cells were augmented 14 days after infection; PP-cells were decreased 2--3 days and 21 days after infection; somatostatin-cells decreased to one-fourth of control values in hyperglycaemic animals 21 days after infection. The latter results suggest that non B-cells are also involved in islet reaction to virus infection.
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PMID:Virus-induced diabetes in mice: a quantitative evaluation of islet cell population by immunofluorescence technique. 21 98

Substance P (sP) and Somatostatin (SOM), so as other neuropeptides can modulate neurologic and immunologic functions. sP has been described to enhance both in vitro and in vivo immunoglobulin synthesis. On the contrary, SOM has an inhibitory effect on the same activity. The modulating effect is more evident on IgA isotype. Hypergammaglobulinemia and in particular high levels of IgA is a common finding in pediatric AIDS and an imbalance among regulatory effects of neuropeptides might be suggested. In order to evaluate the plasma levels of sP in pediatric AIDS we studied 15 children with HIV infection (status P2), 10 seronegative children born to HIV positive mothers and 10 healthy children of the same age. All the HIV positive children had high plasma levels of IgG and IgA. The plasma level of sP was extremely higher in HIV positive children while no significant difference was found between seronegative children born to HIV positive mothers and healthy children. SOM was decreased in HIV positive children when compared to control groups but a significant difference was not reached. It might be supposed that HIV infection, through a dysregulation among neuropeptides interferes on immune functions and in particular on IgA synthesis. On the other hand it might be suggested that the imbalance between sP and SOM depends on the viral infection of immune cells since it has been demonstrated that SOM and other neuropeptide are synthesized by lymphoid tissue. Further studied relevance of neuropeptide disorders in pediatric AIDS.
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PMID:[Changed levels of substance P and somatostatin in HIV-positive children]. 128 55

Human cytomegalovirus (HCMV) was recently demonstrated in the pancreas of about half the patients with type 2 diabetes mellitus in the absence of mumps, rubella or Coxsackie B virus. The present study addresses the question as to whether type 2 diabetes with an HCMV-positive pancreas differs from those with HCMV-negative pancreases with respect to age, sex, treatment, duration of disease, volume densities of B-cells and D-cells, mRNA levels of insulin and somatostatin, islet amyloid peptide deposits and major histocompatibility complex (MHC) class I and class II gene transcription, and protein expression. HCMV-positive type 2 diabetic patients showed a tendency towards a shorter duration of disease and significantly increased levels of MHC class II on RNA. In addition, expression of MHC class II product (HLA-DR) was identified in duct epithelial cells and/or islet cells in 9 diabetic pancreases and in 2 non-diabetic glands. No MHC class I expression could be detected. No other clinical differences between HCMV-positive and HCMV-negative glands were found. All 10 HCMV-positive diabetics showed a strong expression of MHC class II mRNA in the pancreas. By immunocytochemistry, 4 of 10 demonstrated expression on the islets; three of ten also expressed MHC DR beta on ductal cells. This finding might be related to the viral infection, as only 2 of the 9 HCMV-negative patients were HLA-DR beta positive and none of the non-diabetic controls showed increased levels of MHC class II mRNA. These data suggest that HCMV infection in the pancreas is associated with type 2 diabetes. However, no conclusions as to a role of this virus in the aetiopathology of type 2 diabetes can be drawn at present.
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PMID:Human cytomegalovirus in the pancreas of patients with type 2 diabetes: is there a relation to clinical features, mRNA and protein expression of insulin, somatostatin, and MHC class II? 136 Jul 19

Hybrid cell lines derived from neonatal rat dorsal root ganglia neurons fused with the mouse neuroblastoma N18Tg2 exhibit sensory neuron-like properties not displayed by the parental neuroblastoma. These properties include an inward (depolarizing) current with a conductance increase in response to activation of a bradykinin receptor, an inward (depolarizing) current with a conductance increase in response to the sensory excitotoxin capsaicin, the expression of sensory neuropeptides (substance P, CGRP and somatostatin), the expression of phosphatidylinositol-anchored molecules including adhesion molecules of the immunoglobulin superfamily that can be regulated in serum-free culture by nerve growth factor (N-CAM, F-3 and Thy-1), and low permissivity to herpes simplex virus infection. These lines thus provide appropriate models for the study of mechanisms involved in nociceptor activation and the regulation of expression of sensory-neuron specific markers including neuropeptides.
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PMID:Novel cell lines display properties of nociceptive sensory neurons. 197 43

The selective destruction of the pancreatic islet beta cells in type 1 diabetes mellitus is thought to be mediated by a cellular autoimmune process, possibly triggered by virus infection in genetically susceptible individuals. Because of the potentially important role of cell-cell adhesion in the immune response, we investigated whether cytokine products of mononuclear cells, or virus infection, induced the expression of intercellular adhesion molecule 1 (ICAM-1) on human endocrine islet cells. By flow cytofluorimetry, control islet cells did not express detectable ICAM-1. However, after a 72-hr exposure of islets to interferon gamma (IFN-gamma) and/or tumor necrosis factor alpha (TNF-alpha) (each at 250 units/ml), ICAM-1 was induced on greater than 85% of islet cells. IFN-gamma was 50% more potent than TNF-alpha; together, their effects were additive. Class I major histocompatibility complex (MHC) protein expression, detected on control islet cells, was also stimulated by IFN-gamma and/or TNF-alpha. In contrast, infection with reovirus type 3 did not induce ICAM-1 on islet cells, although it stimulated the expression of class I MHC proteins. By double-label indirect immunofluorescence microscopy, ICAM-1 expression was identified on both beta (insulin-secreting) and delta (somatostatin-secreting) islet cells. Monoclonal antibody to ICAM-1 precipitated protein of Mr 97,000 from [35S]methionine-labeled islets exposed to IFN-gamma and TNF-alpha, but not from control islets. RNA blot analysis revealed a major species of 3.3 kilobases and a minor species of 2.2 kilobases induced in islets exposed to the cytokines. These findings have implications for the molecular mechanisms of beta-cell destruction in type 1 diabetes, in that expression of ICAM-1 by beta cells may facilitate adhesion of antigen-targeted immune cells.
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PMID:Intercellular adhesion molecule 1 is induced on isolated endocrine islet cells by cytokines but not by reovirus infection. 249 83

Despite the fact that heterogeneity of diabetes in man has become more and more evident in recent years, its pancreatic pathology is still represented by two distinct entities, roughly corresponding to the classic juvenile-onset and maturity-onset types of the disease. In juvenile-onset, insulin-dependent diabetes, the pancreatic islets show severe and pathognomonic changes. B cells are greatly reduced in number already at clinical onset. Contrary to classic opinion they do not always disappear in the years to follow. Insulitis, a common finding in the pancreas of recent onset juvenile diabetic subjects, is compatible with a viral infection as well as with an autoimmune reaction as the cause of B cell destruction. In the pancreas of juvenile-onset diabetic subjects the islets, which in the past have been regarded as atrophic and inactive, are actually composed of cells containing glucagon and somatostatin. There is also a profound distortion of islet organization, and many endocrine cells are scattered as single cells in the exocrine tissue. These findings may well account for the abnormal secretory behavior of the glucagon-secreting A cells in insulin-dependent juvenile-onset diabetes. In maturity-onset, noninsulin-dependent diabetes, the pancreatic pathology is extremely variable and not pathognomonic. A numeric reduction of the B cells can be demonstrated in many maturity-onset diabetic subjects, but this reduction is much more moderate than in insulin-dependent juvenile-onset diabetic subjects and does not account for the disease. The same amount of B cell reduction can be found in many elderly subjects without clinical evidence of diabetes. In many maturity-onset diabetic subjects, the cytologic characteristics of the B cells suggest a decreased responsiveness to the stimulus of hyperglycemia. Islet fibrosis and hyalinosis (amyloidosis), although common, cannot explain this secretory dysfunction. The exact site of the defect in the B cells of maturity-onset diabetic subjects remains to be defined. Further investigations are necessary to assess the role of disturbed intraislet intercellular relationships in the pathogenesis of late-onset diabetes. The dual pattern of islet pathology in diabetes in man does not preclude a more profound heterogeneity in the etiology and pathogenesis of the disease.
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PMID:The pancreatic islets in diabetes. 700 84

Motor and cognitive impairment is common in human immunodeficiency virus disease in humans and simian immunodeficiency virus (SIV) disease in rhesus monkeys. We have examined peptide neurotransmitter expression in the frontal cortex of SIV-infected rhesus monkeys to identify alterations in cortical neurons that might explain this impairment. A 2-fold higher number of preprosomatostatin (SRIF) mRNA-positive interneurons was observed in layer IV of frontal cortex in two separate cohorts of SIV-infected animals compared to uninfected controls. Increased SRIF mRNA expression in layer IV was independent of clinical signs of immunodeficiency disease and was associated with both motor and cognitive impairment. Altered SRIF mRNA expression in deeper cortical layers was associated specifically with motor impairment. Increased SRIF mRNA expression occurred without detectable changes in cortical cell density. These data suggest two mechanisms for cortical dysfunction associated with lentivirus infection. Increased SRIF mRNA expression in layer IV may be due to altered patterns of activity in cortical afferents that project to layer IV, while increased SRIF mRNA expression in deeper cortical layers could reflect susceptibility to locally generated mediators in response to primate lentivirus infection of the brain. Altered function of somatostatinergic interneurons may contribute to primate lentivirus-induced encephalopathy.
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PMID:An early increase in somatostatin mRNA expression in the frontal cortex of rhesus monkeys infected with simian immunodeficiency virus. 787 85

The use of primary beta-cells in biochemical and molecular research is limited by the availability of pancreatic endocrine tissue. Numerous investigators have attempted to establish an insulin-secreting cell line that retains normal regulation of insulin secretion. Different approaches have been used, including induction of pancreatic tumors by irradiation or viral infection, immortalization of beta-cells in vitro, and development of transgenic mice with targeted expression of a recombinant oncogene in the beta-cell. Few of these attempts have proven successful, because cell differentiation and proliferation capacities are mutually exclusive. The most widely used insulin-secreting cell lines are RIN, HIT, beta TC, MIN6 and INS-1 cells. These cells contain mainly insulin and small amounts of glucagon and somatostatin. RIN cells, except for the subclone RIN-38, are not glucose-responsive. HIT cells and beta TC cells secrete insulin in response to glucose, but their dose-response curve is markedly shifted to the left MIN6, INS-1 and a newly available subclone of beta TC cells (beta TC-6 F7) are reported to retain normal regulation of glucose-induced insulin secretion. Although the behaviour of none of these cell lines perfectly mimics primary beta-cell physiology, they are extremely valuable tools for the study of molecular events underlying beta-cell function and dysfunction. In addition, insulin-secreting cell lines represent a potential source of transplantable tissue to overcome the limited availability of primary islets for this procedure.
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PMID:Insulin-secreting cell lines: classification, characteristics and potential applications. 869 99

Progressive central nervous system dysfunction analogous to the AIDS dementia complex (ADC) seen in adults (HIV-1-associated progressive encephalopathy or HIV-1 encephalopathy) commonly occurs in HIV-1-infected children. The cause appears to be directly or indirectly related to HIV-1, rather than to other opportunistic pathogens. The exact mechanism(s) by which the virus affects brain function is not known. To determine whether the virus might modify brain function via an alteration in cortical neurons, we examined peptide neurotransmitter expression in the frontal cortex of HIV-1-infected cases with clinical HIV-1 encephalopathy relative to pathologic HIV-1 encephalitis. In situ hybridization was used to determine the level of peptide neurotransmitter expression of somatostatin in the frontal cortex of cases with and without HIV-1 encephalopathy and/or HIV-1 encephalitis. A 2-fold higher number of preprosomatostatin mRNA-positive interneurons was present in layer IV of cases with HIV-1 encephalitis compared with cases without HIV-1 encephalitis. In cases with PE, this neuronal alteration was 4- to 5-fold higher than in cases without PE, and was present in subcortical white matter in addition to layer IV. In cases having both PE and HIV-1 encephalitis, and in cases with HIV-1 encephalitis alone, these neuronal alterations in layer IV and/or subcortical white matter related to disseminated microglial nodules, even when these potentially viral-infected cells were negative for HIV-1 p24 antigen, a marker of productive viral infection. An alteration in preprosomatostatin mRNA-expressing cells occurring with HIV-1 encephalitis may be at least one mechanism that contributes to HIV-1 encephalopathy. When compared with other cortical laminae, layer IV receives most of its synaptic input from the mediodorsal nucleus of the thalamus. Neurons in the subcortical white matter project to the thalamus. The thalamus has been shown to have high amounts of viral antigen and increased metabolic activity in patients with AIDS. An alteration in preprosomatostatin mRNA-expressing cells may play a role in HIV-1 encephalopathy.
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PMID:A neuronal and neuroanatomical correlate of HIV-1 encephalopathy relative to HIV-1 encephalitis in HIV-1-infected children. 929 39

Rabies virus (RABV) infection is characterized by the rapid neuronal spread of RABV into the CNS before a protective immune response is raised. Therefore, a typical feature of RABV infection is the paucity of inflammatory reactions in the brain. Here we examined whether the induction of immunosuppressive neuropeptides, in particular CGRP, may contribute to the ability of RABV to evade immune responses. RABV infection of mice caused a strong induction of calcitonin gene-related peptide (CGRP) in neurons and fibres in the neocortex as well as in the dentate gyrus and CA1 region of the hippocampus although RABV did not infect neurons in which CGRP expression was upregulated. Neuropeptide Y (NPY) or vasoactive intestinal peptide (VIP) expressing neurons also were not infected by RABV. In contrast, somatostatin neurons were infected by RABV. There was evidence for an RABV-induced increase of VIP and somatostatin but not of NPY. To test how CGRP expression is related to TNFalpha-induced enhancement of CNS innate and adaptive immunity during RABV infection, we used recombinant RABVs that contained either an active (SPBN-TNFalpha(+)) or an inactive (SPBN-TNFalpha(-)) TNFalpha gene. As compared to SPBN-TNFalpha(-), infection with SPBN-TNFalpha(+) attenuated the induction of CGRP but simultaneously enhanced induction of the invariant chain of MHC II, microglial activation and T cell infiltration. In conclusion, distinct neuropeptidergic neurons in the brain are remarkably spared from RABV infection suggesting a pivotal role of neuropeptides during CNS virus infection. Given the inhibitory effect of CGRP on antigen presentation, we propose that the strong RABV-induced upregulation of CGRP in the brain may contribute to the mechanism by which RABV escapes immune detection. Targeting the expression of neuropeptides, in particular CGRP, that are induced during RABV infection may open a new avenue for therapeutic intervention in human rabies.
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PMID:Role of virus-induced neuropeptides in the brain in the pathogenesis of rabies. 1863 68


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