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)

We have studied the concentration of various gastrointestinal peptides in a crude porcine secretin (Boots) preparation and pure natural porcine secretin (GIH, Kabi) preparation. Boots secretin was found to contain 140.3 ng secretin, 1.27 ng human pancreatic polypeptide (hPP), 1.03 ng gastrin, 137.4 ng cholecystokinin (CCK), 241 microU insulin, 1.86 ng vasoactive intestinal polypeptide (VIP), 2.22 ng glucagon and 6.60 ng somatostatin (SRIF) per Crick Harper unit Boots secretin. Sephadex gel filtration demonstrated that the immunoreactivity was due to the hormone per se. GIH secretin contained 240 ng secretin per clinical unit (CU) and less than detectable concentrations of hPP, gastrin, CCK, insulin, VIP, glucagon and SRIF. To determine the clinical significance of having contaminating peptides in Boots secretin, we investigated the effect(s) in 4 subjects. Determined in a highly gastrin-specific assay, the mean plasma gastrin response to Boots secretin administration was slightly, but not significantly greater than the GIH secretin response at 1 and 2.5 minutes. However, in some subjects false positive elevations in plasma gastrin immunoreactivity occurred when some commercially available kit gastrin assays were employed. After intravenous injection of Boots secretin, mean plasma hPP levels rose significantly more than after GIH secretin administration. The mean peak plasma insulin level after GIH secretin administration was significantly higher than after Boots secretin. Neither secretin preparation caused a change in plasma glucose, glucagon and SRIF levels. From these results, it is suggested that GIH secretin be used as the preparation of choice in provocative testing for diagnosing gastrinoma or deficiencies of exocrine pancreatic function.
 ...
PMID:Stimulation of human pancreatic polypeptide and gastrin by Boots and GIH secretin: in vitro and in vivo studies. 355 22

The aim of this study was to investigate the consequence of Helicobacter pylori eradication on gastric mucosa and antral G and D-cells. Forty children, aged 5-17 years with Helicobacter pylori infection were assessed. Helicobacter pylori was detected by a urease test and identified by serological and microbiological methods. Twenty children were again assessed after the therapy (the combination of colloid bismuth subcitrate, amoxycillin and metronidazole). Gastroscopic examination was performed and at least six bioptic specimens were taken from the antrum, body and fundus. Tissue samples, processed with the paraffin method and stained with hematoxyllin and eosin, were assessed. Monoclonal antiserum Gastrin PAP kit 516 and somatostatin PAP kit 512 (DAKO) in the peroxidase-antiperoxidase technique (PAP) have been used to detect G and D-cells. Helicobacter pylori in the gastric mucosa was demonstrated with the Giemsa method. The results show the coincidence of Helicobacter pylori infection and the count of antral G and D-cells and active chronic gastritis in children. After the treatment Helicobacter pylori was eradicated in 70% of children. In 34% of these cases the eradication was followed by a diminution of activity of gastric antral mucosa inflammation and in 20% of these children the resolution of the inflammatory infiltration in the gastric mucosa was seen. A decrease of the antral G and D-cells count and also a diminution of G/D index in these cases were observed.
 ...
PMID:Morphological and immunohistochemical examinations of the dynamic changes of gastric mucosa associated with the treatment of helicobacter pylori infection in children. 877 26

We examined the potential of radiolabeled somatostatin analogs, 125I-Tyr-3-octreotide (125I-octreotide), (111)In-DTPA(diethylenetriaminepentaacetatic acid)-D-Phe-1-octreotide (111In-octreotide), and 188Re-octreotide for targeting small-cell lung cancer (SCLC) in a mouse model. Tyr-3-octreotide was labeled with 125I by the chloramine T method, and (111)In-octreotide was obtained as a kit, while 188Re was eluted from a 188W/188Re generator, and octreotide was directly labeled with 188Re by reducing disulfide bonds. The 125I-, 111In-, and 188Re-octreotides were injected i.v. into athymic mice bearing NCI-H69 tumors, and the biodistributions were determined at 15 min, and 2, 4, 8, and 24 h. Tumor uptakes were 0.5+/-0.2, 0.3+/-0.1, 0.3+/-0.1 %ID/g, and tumor-to-blood ratios were 1.8, 11.9, 1.2 at 8 h for 125I-, 111In-, and 188Re-octreotides, respectively. Accumulations of 111In-octreotide in normal tissues were lower than those of 125I- and 188Re-octreotides. 188Re-octreotide can be used to localize SCLC lesions as efficiently as radioiodinated octreotide. However, 111In-octreotide was the most suitable agent to obtain high tumor-to-normal tissue contrast for localizing SCLC.
 ...
PMID:Localization of small-cell lung cancer xenografts with iodine-125-, indium-111-, and rhenium-188-somatostatin analogs. 887 64

Conditions are described for the preparation of 188Re-RC-160, a radiolabeled synthetic peptide derived from an analogue of somatostatin, using a lyophilized labeling kit containing RC-160 (200 micrograms) and stannous tartrate to which is added carrier-free 188Re (beta, Emax, 2.12 MeV; gamma, 155 keV, 10%; T1/2 = 16.7 h). The kits have been radiolabeled with > 2960 MBq (80 mCi) with a high labeling efficiency and no need for subsequent purification. Radiolabeling results in one major peak when analyzed by reverse-phase (RP) HPLC. Presumptive radiolysis was detected at 2.5 h post-labeling; however, a convenient method is described for stabilizing the kits against radiolysis by the post-labeling addition of ascorbic acid.
 ...
PMID:Preparation of 188Re-RC-160 somatostatin analog: a peptide for local/regional radiotherapy. 911 51

Islet transplantation is a potential treatment for diabetes mellitus and porcine pancreata may provide a readily available source of islets. The size, number and distribution of islets within the pancreas may influence the choice of age of donor for xenotransplantation. Samples (n = 3 per age group) from the dorsal and ventral pancreas of 5-, 12- and 24-week-old hybrid pigs were fixed in formal saline, processed in paraffin wax and stained with an avidin/biotin immunohistochemical kit for insulin, glucagon, somatostatin and pancreatic polypeptide. The arrangement of endocrine cells within the pancreata were studied and mean diameter of beta-cell groups were measured (from insulin stained sections) in 1 mm2 grid areas (n = 10 per section) and collated into groups according to size. Percentage volume density of beta-cells in relation to the whole pancreas was calculated and also the distribution of beta-cell groups, according to their size, within the total beta-cell mass. There were differences in the frequency and arrangement of endocrine cells within islets at the different ages studied. beta-Cell groups < 50 microm in diameter occupied 70 to 80% of the total beta-cell mass at 5 weeks but, as the age of the pig increased, larger cell groups were more abundant. However, the percentage volume density of beta-cells within the total pancreas did not change as the pancreas matured. This study shows that the endocrine porcine pancreas was maturing and its structure changed between the ages of 5 and 24 weeks. The relevance of these findings may have implications on the isolation and function of islets if young pigs are to be used as donors for transplantation as a treatment for diabetes mellitus.
 ...
PMID:The distribution of porcine pancreatic beta-cells at ages 5, 12 and 24 weeks. 1043 90

Contrary to common belief, organometallic compounds exhibit remarkable stability in aerobic and even diluted aqueous solutions. Technetium-sestamibi (Cardiolite) is one of the most prominent examples of this class of compounds routinely used in nuclear medicine. This review summarises the recent progress in labelling of biomolecules with organometallic complexes for diagnostic and therapeutic application in radiopharmacy and exemplifies in detail developments focussing on organometallic technetium- and rhenium-tricarbonyl technologies. The value of such technologies has been recognised and they have become a valuable alternative to common labelling methodologies. An increasing number of groups have started to employ an organometallic precursor for the purpose of radioactive labelling of various classes of biomolecules, and the advantages and limitations of this new technique are compared with those of other labelling methods. The synthetic access to appropriate precursors via double-ligand exchange or aqueous carbonyl kit preparation for routine application is described. Strategies and examples for the design of appropriate bifunctional chelating agents for the Tc/Re-tricarbonyl core are given. The functionalization of biomolecules such as tracers for the central nervous system (dopaminergic and serotonergic), tumour affine peptides (somatostatin receptors, neuroreceptors) and tumour binding single-chain antibody fragments is summarised. Where possible and appropriate, the in vitro and in vivo results in respect of these examples are compared with those obtained with classical (99m)Tc/(188)Re(V)- and (111)In-labelled analogues. The preclinical results show the in many ways superior characteristics of organometallic labelling techniques.
 ...
PMID:Current use and future potential of organometallic radiopharmaceuticals. 1239 72

Transcriptional profiling (TP) offers a powerful approach to identify genes activated during memory formation and, by inference, the molecular pathways involved. Trace eyeblink conditioning is well suited for the study of regional gene expression because it requires the hippocampus, whereas the highly parallel task, delay conditioning, does not. First, we determined when gene expression was most regulated during trace conditioning. Rats were exposed to 200 trials per day of paired and unpaired stimuli each day for 4 days. Changes in gene expression were most apparent 24 h after exposure to 200 trials. Therefore, we profiled gene expression in the hippocampus 24 h after 200 trials of trace eyeblink conditioning, on multiple arrays using additional animals. Of 1,186 genes on the filter array, seven genes met the statistical criteria and were also validated by real-time polymerase chain reaction. These genes were growth hormone (GH), c-kit receptor tyrosine kinase (c-kit), glutamate receptor, metabotropic 5 (mGluR5), nerve growth factor-beta (NGF-beta), Jun oncogene (c-Jun), transmembrane receptor Unc5H1 (UNC5H1), and transmembrane receptor Unc5H2 (UNC5H2). All these genes, except for GH, were downregulated in response to trace conditioning. GH was upregulated; therefore, we also validated the downregulation of the GH inhibitor, somatostatin (SST), even though it just failed to meet criteria on the arrays. By during situ hybridization, GH was expressed throughout the cell layers of the hippocampus in response to trace conditioning. None of the genes regulated in trace eyeblink conditioning were similarly affected by delay conditioning, a task that does not require the hippocampus. These findings demonstrate that transcriptional profiling can exhibit a repertoire of genes sensitive to the formation of hippocampal-dependent associative memories.
 ...
PMID:Transcriptional profiling reveals regulated genes in the hippocampus during memory formation. 1254 33

Ghrelin is one of the peptides involved into GH-release, binding to specific GHS receptors on hypothalamus and pituitary. The ghrelin peptide and ghrelin mRNA have been detected in several regions of hypothalamus, in normal pituitary, as well as in various types of pituitary adenoma, with different levels of expression in different tumour types. We decided to determine the expression of ghrelin in somatotroph adenomas. Human pituitary somatotroph adenoma tissues were obtained at the time of transsphenoidal surgery from 3 acromegalic patients and studied for ghrelin mRNA expression. Before surgery each patient received a somatostatin analogue treatment at doses 20 mg, 30 mg, 30 mg at 30 days intervals. 20 mg of each tissue sample was used for the isolation of total cellular RNA. The reverse transcription and real-time PCR were performed according to Korbonits et al. method. The reverse transcription of total RNA to cDNA was performed using Super Script TM Rnase H RT kit according to manufacturer protocol. We wished to determine the number of copies of ghrelin gene within the single cell. We used the beta-actin, and the GAPDH genes as a reference molecules for standard curve calculation. Ghrelin mRNA was not detected in any examined tissues. We postulate that the absence of the ghrelin gene transcript is mainly due to the treatment with somatostatin analogues administered preoperatively, which could have suppressed the ghrelin gene transcription.
 ...
PMID:The evaluation of ghrelin mRNA expression in human somatotroph adenomas. 1664 73

In humans, circulating GH levels are increased in catabolic states and suppressed in obesity. In both extremes, normalization of the metabolic environment normalizes GH release, leading to the conclusion that changes in metabolic hormones and/or metabolites promote changes in GH synthesis and release. Metabolic regulation of GH secretion can be mediated centrally by modulation of hypothalamic GHRH and somatostatin input to the pituitary and/or by direct regulation of pituitary somatotrope function. Although data are available showing glucocorticoids, free fatty acids (FFA), IGF-I, and insulin have direct effects on rat somatotrope function, little information is available regarding the direct pituitary effects of these metabolic factors in primates. Therefore, this study examined the effects of glucocorticoids (dexamethasone (0.1-100 nM) and hydrocortisone (10 nM)), FFA (oleic and linoleic acid, 100 and 400 microM each), IGF-I (0.5-50 nM), and insulin (0.5-50 nM) on GH release and GH, GHRH-receptor (GHRH-R) and ghrelin-receptor (GHS-R) mRNA levels, in primary pituitary cell cultures of baboons (Papio anubis) after 24 h treatment. A commercial ELISA kit was used to determine the amount of GH released into the media, while quantitative real-time reverse transcription-PCR was used to determine mRNA levels. To design species-specific primers for baboon GH, GHRH-R, GHS-R, insulin receptor (INSR), IGF-I receptor (IGF-IR), pituitary-specific transcription factor-1 (Pit-1), and cyclophilin A (used as a housekeeping gene) cDNA, sequence data for each baboon transcript were obtained and this data were submitted to Genbank. Glucocorticoids, FFA, insulin and IGF-I treatment did not significantly alter the expression of Pit-1, a transcription factor essential for normal somatotrope development and function. However, as previously reported in the rat, glucocorticoids increased, while FFA, IGF-I and insulin decreased GH release in baboon pituitary cell cultures, where changes in GH release were reflected by comparable changes in GH mRNA levels. In addition, glucocorticoids increased, while FFA, IGF-I and insulin decreased the expression of the GH stimulatory receptors, GHRH-R and GHS-R, without significantly altering cyclophilin A mRNA levels. A role of insulin/INSR pathway, independent of IGF-I, in regulating pituitary function is supported by the fact that (1) IGF-I and insulin significantly suppressed somatotrope function at doses (0.5 and 5 nM respectively) not anticipated to activate their respective receptors, and (2) the baboon pituitary expresses INSR mRNA at levels comparable to or greater than that of tissues commonly considered as insulin sensitive (i.e. liver, skeletal muscle, and fat). Taken together, these results demonstrate that metabolic factors can directly modulate primate somatotrope function through regulating GH synthesis and release, as well as mediating the expression of receptors important in central (GHRH) and systemic (ghrelin) regulation of GH secretion.
 ...
PMID:Examination of the direct effects of metabolic factors on somatotrope function in a non-human primate model, Papio anubis. 1690 21

Because of its monodenticity, 6-hydrazinopyridine-3-carboxylic acid (HYNIC) is of interest as a bifunctional chelator for labeling peptide with (99m)Tc. Here, we confirm the formation of hydrazone in HYNIC-conjugated peptide. The preparative HPLC was used to purify the HYNIC conjugated somatostatin-based peptide and the result showed two peaks, even after two consecutive purifications. Analysis of these peaks by mass spectrometry indicated the presence of hydrazone, produced during preparation conjugate. Further, we have shown that presence of hydrazone really does not matter because under (99m)Tc-labeling conditions, hydrazone is hydrolyzed back to HYNIC that then chelates (99m)Tc. A HYNIC-peptide conjugate freeze-dried kit was also prepared in a mildly acidic or neutral condition with a final pH of 6-7. The kit was then labeled by (99m)Tc and incubated in 100 degrees C for 10min, and a labeling yield of >95% was obtained.
 ...
PMID:Confirmation of hydrazone formation in HYNIC-peptide conjugate preparation, and its hydrolysis during labeling with (99m)Tc. 1746 77


1 2 3 Next >>