Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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 presence of immunoreactivity to the neuronal phosphoprotein B-50 and the peptides bombesin, calcitonin gene-related peptide, galanin, neurotensin, neuropeptide Y, somatostatin, substance P, and vasoactive intestinal polypeptide was examined in biopsy specimens from the duodenum and rectum of human immunodeficiency virus (HIV)-seropositive and HIV-seronegative male homosexual patients. The distribution of B-50 and the peptides was correlated with HIV serology, number of CD4+ lymphocytes, and the presence of HIV in biopsy culture. There was a very low incidence of enteric pathogens in both groups of patients. It was found that HIV-seropositive patients had a greater incidence of abnormal patterns of immunoreactivity (reduced intensity and/or density of innervation) in enteric nerves and enteroendocrine cells than HIV-seronegative patients. A reduction of substance P immunoreactivity was significantly correlated with reduced CD4+ lymphocyte count and HIV status; a similar trend was also seen for somatostatin and vasoactive intestinal polypeptide. Using B-50 as a marker, it was found that both groups of patients had altered patterns of immunoreactivity in rectal nerves. The findings of this study suggest that some of the clinical symptoms associated with HIV infection may be caused by a specific HIV enteropathy that influences enteric nerve and/or enteroendocrine cell function by altering the density of peptide immunoreactivity.
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PMID:Peptides in the gastrointestinal tract in human immunodeficiency virus infection. The GI/HIV Study Group of the University of Calgary. 153 25

The mucosal concentrations of seven regulatory peptides and the density properties and integrity of their storage granules have been studied in mucosal biopsies from the human jejunum in eight gastrointestinal disease states and compared with normal controls. In diseases with associated mucosal inflammation (coeliac disease, Crohn's disease with jejunal involvement, postinfective tropical malabsorption, and common variable immunodeficiency) there was a selective increase in fragility of the gastric inhibitory polypeptide (GIP) and somatostatin storage granules. The gastrin, motilin, enteroglucagon, secretin, and vasoactive intestinal polypeptide granules had normal properties in these conditions. In diseases in which diarrhoea occurred in the absence of changes in jejunal mucosal histology (irritable bowel syndrome, pancreatic insufficiency, jejuno-ileal bypass for morbid obesity, and purgative abuse) there were no abnormalities of the storage granules. Increased mucosal concentrations of all peptides except vasoactive intestinal polypeptide (VIP) were found in coeliac disease and selective increases of VIP found in Crohn's disease, motilin in the irritable bowel syndrome and gastrin and GIP in pancreatic insufficiency. It is suggested that the storage granule abnormalities in the diseases with abnormal mucosal histology are secondary to the inflammatory changes.
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PMID:Gastrointestinal regulatory peptide storage granule abnormalities in jejunal mucosal diseases. 614 62

The long-acting somatostatin analog octreotide (SMS 201-995) possesses immunosuppressive properties and has been successfully used for the management of human immunodeficiency virus (HIV)-associated diarrhea, a condition commonly observed in the absence of known enteric pathogens. Since HIV type 1 (HIV-1) replication can occur in both CD4+ and CD8+ lymphocytes, we hypothesized that this benefit might be due to local effects on HIV-1 replication in these two T-cell subsets. As a model, we studied the effects of two synthetic molecules, SRIH 1-14 and SRIH 1-28, closely related to naturally occurring forms of somatostatin, as well as SMS 201-995 on HIV-1 replication in CD4+ and CD8+ cells derived from peripheral blood mononuclear cells (PBMC). We found that HIV-1 replication was inhibited in CD8+ cells but enhanced in infected CD4+ lymphocytes, as measured by p24 antigen levels in culture fluids. These differential effects were drug concentration dependent. We also observed that somatostatin inhibited the mitogen-induced proliferative responsiveness of both cell types. These effects on both HIV-1 replication and cell proliferation were independent of somatostatin gene expression, since somatostatin mRNAs were not detected in mitogen-stimulated PBMC, as determined by reverse transcription-PCR.
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PMID:Differential effect of the immunomodulatory hormone somatostatin on replication of human immunodeficiency virus type 1 in CD4+ and CD8+ T lymphocytes. 769 28

Prior to the onset of immunodeficiency disease, neurochemical and neuropathological events associated with motor and/or cognitive impairment can be identified in rhesus monkeys infected with simian immunodeficiency virus (SIV). These are astrocytosis, up-regulation of mRNA encoding the neuropeptide somatostatin (SRIF) and an increased expression of MHC Class II antigen. End-stage immunodeficiency disease has been associated with robust viral expression in the CNS frequently observed as multinucleated giant cell formation. SIV encephalitis has not been observed in animals whose only clinical signs of SIV disease were motor and/or cognitive impairment. These data suggest that neuronal dysfunction discernable as altered neuropeptide expression in cortical neurons precedes frank structural damage to the CNS in SIV encephalopathy. This model is consistent with the mechanism of neuropathogenesis in human HIV encephalopathy that can be partially inferred from neurochemical and neuropathological examination of autopsy material in HIV disease.
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PMID:Neuronal substrates for SIV encephalopathy. 787 94

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

1. One of the metabolic features of acquired immunodeficiency syndrome is increased tissue glucose uptake documented by euglycaemic-hyperinsulinaemic clamp studies, suggesting increased insulin sensitivity. However, these results may also be related to the confounding effect of increased non-insulin-mediated glucose uptake in acquired immunodeficiency syndrome, which will result in an erroneously presumed increased insulin sensitivity. To study the contribution of non-insulin-mediated glucose uptake to total tissue glucose uptake in acquired immunodeficiency syndrome, we conducted a hypoinsulinaemic clamp study in clinically stable human immunodeficiency virus-infected (Centers for Disease Control class IV) men (n = 7) and healthy subjects (n = 5). Glucose uptake was measured by a primed, continuous infusion of [3-3H]glucose in the postabsorptive state and during somatostatin-induced insulinopenia at euglycaemic (approximately 5.3 mmol/l) and hyperglycaemic (approximately 11 mmol/l) glucose concentrations. 2. Basal glucose concentration (patients, 5.2 +/- 0.1 mmol/l; control subjects, 5.3 +/- 0.1 mmol/l) and basal glucose tissue uptake (patients, 15.9 +/- 0.5 mumol min-1 kg-1 fat-free mass; control subjects, 15.2 +/- 0.4 mumol min-1 kg-1 fat-free mass) were not different between the two groups. 3. Euglycaemic glucose uptake during somatostatin infusion, reflecting non-insulin-mediated glucose uptake, decreased to 82 +/- 3% in patients and 78 +/- 2% in control subjects (not significant). Under hyperglycaemic (approximately 11 mmol/l) conditions with sustained insulinopenia, no differences in glucose uptake existed between the two groups (patients, 16.8 +/- 0.6 mumol min-1 kg-1 fat-free mass; control subjects, 16.1+/- 0.3 mumol min-1 kg-1 fat-free mass).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Non-insulin-mediated glucose uptake in human immunodeficiency virus-infected men. 809 7

Current evidence indicates that the neuroendocrine system is the highest regulator of immune/inflammatory reactions. Prolactin and growth hormone stimulate the production of leukocytes, including lymphocytes, and maintain immunocompetence. The hypothalamus-pituitary-adrenal axis constitutes the most powerful circuit regulating the immune system. The neuropeptides constituting this axis, namely corticotrophin releasing factor, adrenocorticotrophic hormone, alpha-melanocyte stimulating hormone, and beta-endorphin are powerful immunoregulators, which have a direct regulatory effect on lymphoid cells, regulating immune reactions by the stimulation of immunoregulatory hormones (glucocorticoids) and also by acting on the central nervous system which in turn generates immunoregulatory nerve impulses. Peptidergic nerves are major regulators of the inflammatory response. Substance P and calcitonin gene-related peptide are pro-inflammatory mediators and somatostatin is anti-inflammatory. The neuroendocrine regulation of the inflammatory response is of major significance from the point of view of immune homeostasis. Malfunction of this circuit leads to disease and often is life-threatening. The immune system emits signals towards the neuroendocrine system by cytokine mediators which reach significant blood levels (cytokine-hormones) during systemic immune/inflammatory reactions. Interleukin-1, -6, and TNF-alpha are the major cytokine hormones mediating the acute phase response. These cytokines induce profound neuroendocrine and metabolic changes by interacting with the central nervous system and with many other organs and tissues in the body. Corticotrophin releasing factor functions under these conditions as a major co-ordinator of the response and is responsible for activating the ACTH-adrenal axis for regulating fever and for other CNS effects leading to a sympathetic outflow. Increased ACTH secretion leads to glucocorticoid production. alpha-melanocyte stimulating hormone functions under these conditions as a cytokine antagonist and an anti-pyretic hormone. The sympathetic outflow, in conjunction with increased adrenal activity. leads to the elevation of catecholamines in the bloodstream and in tissues. Current evidence suggests that neuroimmune mechanisms are essential in normal physiology, such as tissue turnover, involution, atrophy, intestinal function, and reproduction. Host defence against infection, trauma and shock relies heavily on the neuroimmunoregulatory network. Moreover, abnormalities of neuroimmunoregulation contribute to the aetiology of autoimmune disease, chronic inflammatory disease, immunodeficiency, allergy, and asthma. Finally, neuroimmune mechanisms play an important role in regeneration and healing.
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PMID:The immune effects of neuropeptides. 891 48

Recent studies have suggested that neuronal populations that contain glutamate receptors are vulnerable to damage mediated by the human immunodeficiency virus 1 (HIV-1). Somatostatin-immunoreactive neurons contain, among other elements, glutamate receptors, and might therefore be susceptible to HIV-mediated damage. In order to test this hypothesis, we compared patterns of somatostatin immunoreactivity in the cortex and subcortex of autopsied AIDS cases with and without HIV encephalitis (HIVE). Somatostatin immunoreactivity in the frontal cortex interneurons, hippocampal pyramidal and nonpyramidal cells, and globus pallidus was significantly reduced in HIVE. Radioimmunoassay demonstrated a comparable decrease in somatostatin levels in the neocortex of HIVE cases. The decrease in somatostatin immunoreactivity in the neocortex was inversely correlated with the severity of HIVE and global cognitive performance, but not with the extent of the astroglial reaction. These findings indicate that somatostatin-immunoreactive neurons in the cortex are susceptible to damage mediated by HIV and that deficient functioning of this neuronal population might contribute to the cognitive dysfunction observed in AIDS patients.
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PMID:Neurodegeneration of somatostatin-immunoreactive neurons in HIV encephalitis. 910 Jun 66

Mice infected with the LP-BM5 murine leukemia virus (MuLV) develop an immune deficiency syndrome together with an encephalopathy characterized by impairments in spatial learning and memory. These cognitive deficits are evident before the appearance of neuron loss and lymphoid cell invasion of the brain. Nonetheless, a prominent gliosis and a variety of neurochemical changes precede the development of cognitive deficits. The neurochemical abnormalities include significant decreases in striatal Met-enkephalin and substance P (but not somatostatin), increases in concentrations of quinolinic acid and platelet-activating factor, and alterations in brain fyn kinase. At this stage of the infection, some of these neurochemical changes can be reversed by glutamate receptor antagonists, cytokine inhibitors, and anti-retroviral agents. In later stages of the infection, however, the infected mice develop irreversible neuronal loss, invasion of hematopoietic cells, and increased viral burden in the CNS. In addition, motor-neuron dysfunction (hindlimb paralysis, weakness, and ataxia) and seizures are sometimes observed during the late stages of infection. Thus, the LP-BM5 MuLV-infected mouse is a useful model for studying the chronology of neurodegenerative changes, ranging from reversible neuron dysfunction to irreversible neuron loss, that are associated with retrovirus-induced immunodeficiency.
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PMID:The encephalopathy associated with murine acquired immunodeficiency syndrome. 962 8

BACKGROUND: gastric abnormalities are a common feature in patients with primary antibody deficiency. The most important problem is the high incidence of stomach cancer found in these patients. Chronic atrophic gastritis with pernicious anemia is also a common finding that predisposes to gastric adenocarcinoma. The aim of the present study was to identify factors predictive of high risk for developing gastric cancer in patients with primary antibody deficiency. PATIENTS AND METHODS: we studied gastric hormones (gastrin, somatostatin and gastrin-releasing peptide, GRP) in 47 patients (23 children and 24 adults) with primary antibody deficiency. In accordance with the World Health Organization (WHO) classification, patients were diagnosed as having X-linked agammaglobulinemia (Bruton disease) in 13 cases, common variable immunodeficiency in 28, and hypogammaglobulinemia with hyperIgM in 6. Gastric biopsy was performed in 22 patients (16 children and 6 adults). Hormone determinations were carried out by radioimmunoassay. RESULTS: baseline serum gastrin levels were normal or increased compared with controls, but the response to stimulation with a hyperproteic diet was delayed in 18 patients and lower than in controls in 7. In 4 adult patients, all with pernicious anemia, gastric biopsy revealed chronic atrophic gastritis involving the stomach corpus and antrum (type B gastritis). The absence of a normal response of gastrin secretion to stimulation with a hyperproteic diet may be explained by this finding. Serum somatostatin and GRP levels were higher than in controls. No correlations were found between these findings and patient age, type of immunodeficiency or duration of clinical manifestations.
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PMID:Study of gastrointestinal polypeptides controlling gastric acid secretion in patients with primary antibody deficiency. 1021 2


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