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

In order to elucidate the functional significance of somatostatin in thyroid C cells, the alterations of immunoreactive somatostatin in the cells were investigated under various experimental conditions, i.e., hypercalcemia, hypocalcemia, and antithyroid drug treatment. Guinea pigs and rabbits, in which almost all C cells reveal the intense immunoreaction for somatostatin in addition to calcitonin, were used as experimental animals. After chronically induced hypercalcemia, somatostatin immunoreactivity conspicuously diminished coinciding with the decrease of calcitonin; somatostatin as well as calcitonin was responsive to induced hypercalcemia. After hypocalcemic tetany induced by injection of Escherichia coli L-asparaginase, C cells exhibited very intense immunoreactions for both calcitonin and somatostatin. After chronic treatment of ethylenethiourea, immunoreaction of somatostatin in C cells was the same as that of calcitonin. That is, when immunoreactivity for calcitonin remained unchanged, immunoreactivity for somatostatin was also intensive. However, when immunoreaction of calcitonin became very weak, the reaction of somatostatin was also weak. Thus, in all experimental conditions examined the alterations of immunoreactive somatostatin in C cells completely coincided with those of calcitonin. It seems likely that somatostatin in thyroid C cells exerts the synergistic effect on calcitonin action.
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PMID:Alterations of immunoreactive somatostatin in thyroid C cells after induced hypercalcemia, hypocalcemia, and antithyroid drug treatment. 258 Apr 61

L-Asparaginase-induced pancreatitis is an uncommon but potentially lethal complication. An 8-year-old girl with acute lymphoblastic leukaemia developed acute pancreatitis following treatment with asparaginase. Clinical and laboratory improvements were evident after treatment with somatostatin, with no complications of pancreatitis. Induction therapy for the leukaemia was able to be continued and complete remission was documented during the course of pancreatitis and somatostatin treatment, suggesting a beneficial role of somatostatin in the management of asparaginase-induced pancreatitis.
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PMID:Somatostatin therapy in L-asparaginase-induced pancreatitis. 790 15

The covalent conjugation of a functionalized poly(ethylene glycol) (PEG) to multiple nucleophilic amine residues results in a heterogeneous mixture of PEG positional isomers. Their physicochemical, biological, and pharmaceutical properties vary with the site of conjugation of PEG. Yields are low because of inefficient conjugation chemistry and production costs high because of complex purification procedures. Our solution to these fundamental problems in PEGylating proteins has been to exploit the latent conjugation selectivity of the two sulfur atoms that are derived from the ubiquitous disulfide bonds of proteins. This approach to PEGylation involves two steps: (1) disulfide reduction to release the two cysteine thiols and (2) re-forming the disulfide by bis-alkylation via a three-carbon bridge to which PEG was covalently attached. During this process, irreversible denaturation of the protein did not occur. Mechanistically, the conjugation is conducted by a sequential, interactive bis-alkylation using alpha,beta-unsaturated beta'-monosulfone functionalized PEG reagents. The combination of (a) maintaining the protein's tertiary structure after disulfide reduction, (b) the mechanism for bis-thiol selectivity of the PEG reagent, and (c) the steric shielding of PEG ensure that only one PEG molecule is conjugated at each disulfide bond. PEG was site-specifically conjugated via a three-carbon bridge to 2 equiv of the tripeptide glutathione, the cyclic peptide hormone somatostatin, the tetrameric protein l-asparaginase, and to the disulfides in interferon alpha-2b (IFN). SDS-PAGE, mass spectral, and NMR analyses were used to confirm conjugation, thiol selectivity, and connectivity. The biological activity of the l-asparaginase did not change after the attachment of four PEG molecules. In the case of IFN, a small reduction in biological activity was seen with the single-bridged IFN (without PEG attached). A significantly larger reduction in biological activity was seen with the three-carbon disulfide single-bridged PEG-IFNs and with the double-bridged IFN (without PEG attached). The reduction of the PEG-IFN's in vitro biological activity was a consequence of the steric shielding caused by PEG, and it was comparable to that seen with all other forms of PEG-IFNs reported. However, when a three-carbon bridge was used to attach PEG, our PEG-IFN's biological activity was found to be independent of the length of the PEG. This property has not previously been described for PEG-IFNs. Our studies therefore suggest that peptides, proteins, enzymes, and antibody fragments can be site-specifically PEGylated across a native disulfide bond using three-carbon bridges without destroying their tertiary structure or abolishing their biological activity. The stoichiometric efficiency of this approach also enables recycling of any unreacted protein. It therefore offers the potential to make PEGylated biopharmaceuticals as cost-effective medicines for global use.
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PMID:Site-specific PEGylation of protein disulfide bonds using a three-carbon bridge. 1722 58

A 10-year-old girl developed L-asparaginase (ASP)-associated pancreatitis during chemotherapy for acute lymphocytic leukemia. Her symptoms showed alleviation with continuous regional arterial infusion of protease inhibitor and systemic somatostatin analog therapy. She had intermittent and marked hypertriglyceridemia, an initial trigger for pancreatitis, probably as a side effect of ASP and steroids. However, we considered the pancreatitis to have developed mainly because of factors other than hypertriglyceridemia as lipoprotein analysis confirmed chylomicron levels to be nearly undetectable. Extremely large chylomicrons contribute directly to the onset of pancreatitis by causing blockage of small vessels. Although it is necessary to examine patients for dyslipidemia developing as a side effect of ASP, therapeutic intervention for hypertriglyceridemia is not considered to prevent the onset of ASP-associated pancreatitis.
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PMID:Minimal contribution of severe hypertriglyceridemia in L-asparaginase-associated pancreatitis developed in a child with acute lymphocytic leukemia. 2759 14

A boy aged 14 years had abdominal pain as the major manifestation, with elevated serum amylase and lipase. Abdominal ultrasound performed early after onset in another hospital showed enlargement of the pancreas and a reduction in echo. Magnetic resonance cholangiopancreatography (MRCP) showed pancreatic duct dilation and an unclear image of the head of the pancreas. Acute pancreatitis was considered. However, his symptoms were not relieved after fasting, fluid infusion, anti-acid therapy, and somatostatin therapy. Then, abdominal CT scan and MRCP found multiple low-density lesions of the pancreas and enlargement of the hilar and retroperitoneal lymph nodes. Exploratory laparotomy found pancreatic edema and multiple hilar nodules with unclear boundaries, and pathological biopsy showed anaplastic large-cell lymphoma. Since the liver, the spleen, bone marrow, and the central nervous system were not involved, he was diagnosed with stage III primary pancreatic lymphoma. After vindesine and dexamethasone were used to reduce tumor load, the patient underwent vindesine-pirarubicin-asparaginase-dexamethasone chemotherapy once and vinorelbine-dexamethasone chemotherapy 8 times. Imaging examination still showed multiple low-density lesions of the pancreas and retroperitoneal lymph node enlargement. His parents discontinued treatment. It is concluded that the rare causes of acute pancreatitis with poor response to conventional treatment should be considered, especially for patients with abdominal lymph node enlargement. Extranodal lymphoma should be considered, and lymph node biopsy should be performed as early as possible to confirm diagnosis. The prognosis of pancreatic lymphoma is associated with clinical stage and pathology.
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PMID:[Pancreatitis as the initial manifestation and abdominal lymph node enlargement in a boy]. 3036 61