Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The catabolism of two gastric neuropeptides, the C-terminal decapeptide of gastrin releasing peptide-27 (GRP10) and substance P (SP), by membrane-bound peptidases of the porcine gastric corpus and by porcine endopeptidase-24.11 ("enkephalinase") has been investigated. GRP10 was catabolized by gastric muscle peptidases (specific activity 1.8 nmol min-1 mg-1 protein) by hydrolysis of the His8-Leu9 bond and catabolism was inhibited by phosphoramidon (I50 approx. 10(-8) M), a specific inhibitor of endopeptidase-24.11. The same bond in GRP10 was cleaved by purified endopeptidase-24.11, and hydrolysis was equally sensitive to inhibition by phosphoramidon. SP was catabolized by gastric muscle peptidases (specific activity 1.7 nmol min-1 mg-1 protein) by hydrolysis of the Gln6-Phe7, Phe7-Phe8 and Gly9-Leu10 bonds, which is identical to the cleavage of SP by purified endopeptidase-24.11. The C-terminal cleavage of GRP10 and SP would inactivate the peptides. It is concluded that a membrane-bound peptidase in the stomach wall catabolizes and inactivates GRP10 and SP and that, in its specificity and sensitivity to phosphoramidon, this peptidase resembles endopeptidase-24.11.
 ...
PMID:Catabolism of gastrin releasing peptide and substance P by gastric membrane-bound peptidases. 241 13

Forty-two breast carcinomas were studied with different markers for detecting neuroendocrine differentiation. The Bodian and Grimelius silver stains were applied, as well as immunostaining for neurone specific enolase (NSE), chromogranin, prealbumin and a battery of hormones. All cases were studied by electron microscopy as well. The material included 29 infiltrating ductal carcinomas, 10 infiltrating lobular carcinomas and 3 tubular carcinomas. Immunostaining for hormones was obtained in 11 cases (gastrin and PP (4 cases each), leu-enkephalin (3 cases), substance P (2 cases), beta-endorphin (2 cases), ACTH (1 case) and bombesin (1 case). Three cases revealed immunostaining for more than one hormone. Sixteen cases were positively stained with rabbit anti-NSE (Dako Corporation) and included all the 11 cases with proven immunoreactivity for hormones. 20 cases were positively stained with sheep anti-NSE and only 8 of the 11 cases with immunoreactivity for hormones were included. Immunostaining for prealbumin was observed in only 1 case and chromogranin in only 5 cases. All cases were unstained with the Bodian stain, whereas 3 cases showed a positive argyrophilic reaction with the Grimelius technique. Ultrastructural studies revealed typical small membrane-bound electron dense granules in cytoplasm in 4 cases, all among the 11 cases with immunoreactivity for hormones. We conclude that immunostaining with rabbit anti-NSE is the best screening method for detecting breast carcinomas with neuroendocrine differentiation.
 ...
PMID:A study of different markers for neuroendocrine differentiation in breast carcinomas. 243 99

Antibodies to a membrane-bound antigen, localized to the canalicular structures of the parietal cell, are found in most sera of patients with chronic atrophic gastritis and pernicious anemia. In the present study immunoglobulins containing parietal cell antibodies were found to inhibit the activity of H+,K+-adenosine triphosphatase (EC 3.6.1.36) in a tubulovesicular membrane preparation from porcine gastric mucosa. The degree of inhibition correlated to the titer of parietal cell antibodies as assessed by an enzyme-linked immunosorbent assay. The specificity of the enzymatic inhibition was confirmed by the lack of effect of parietal cell antibodies on membrane-bound esterase. A possible interaction of parietal cell antibodies with gastrin binding at the receptor level was investigated in a radioreceptor assay employing 125I-gastrin 1 and gastric mucosal cell suspension from the guinea pig. No blocking capacity was found with immunoglobulins from patients with pernicious anemia as compared with immunoglobulins from healthy controls. The results thus demonstrate a direct inhibitory effect of parietal cell antibodies on the acid producing H+,K+-adenosine triphosphatase of the parietal cell, but also a lack of interaction with the gastrin receptor, and indicate that in the development of hypo/achylia H+,K+-adenosine triphosphatase autoantibodies could have a major pathogenic role.
 ...
PMID:Parietal cell antibodies in pernicious anemia inhibit H+, K+-adenosine triphosphatase, the proton pump of the stomach. 254 Oct 40

Cholecystokinin (CCK) binding sites were solubilized from pig cerebral cortical membranes with digitonin (2%, w/v) in the presence of Na+ (120 mM) and Mg2+ (5 mM). Scatchard plot transformation of equilibrium binding data obtained with 125I-CCK-8S gave an apparent dissociation constant (Kd) of 0.6 nM, comparable to that obtained in membranes in the presence of these cations. Hill coefficients close to unity suggested the presence of a single population of receptor sites. Competitive inhibition studies with pentagastrin, gastrin(1-17)S and the CCKA receptor antagonist L-364,718 indicated that the solubilized receptor sites were of the B-type (CCKB), with the same pharmacological profile as that observed in membranes. Optimal specific binding of 125I-CCK-8S to membrane-bound and solubilized receptors was obtained in the presence of divalent cations. Both the membrane-bound and the solubilized receptor activity were attenuated by guanylyl-imidodiphosphate (Gpp(NH)p) indicating that the brain CCKB receptors are coupled to G proteins.
 ...
PMID:Solubilization and characterisation of the cholecystokininB binding site from pig cerebral cortex. 258 45

An 8-cm mass in the tail of the pancreas was resected from a 40-year-old man with polyarteritis nodosa. The tumor cells contained abundant, finely granular, eosinophilic cytoplasm arranged in a gyriform pattern that suggested the tumor was an oncocytoma of the endocrine pancreas. Electron microscopy confirmed that the tumor was an oncocytoma by demonstrating tumor cell cytoplasm packed with mitochondria. Ultrastructural and immunocytochemical studies confirmed the neuroendocrine nature of the tumor by demonstrating dense-core, membrane-bound structures consistent with neurosecretory granules and neuron-specific enolase immunoreactivity. No immunoreactivity for insulin, glucagon, gastrin, somatostatin, or pancreatic polypeptide was found. No human chorionic gonadotropin alpha-chain immunoreactivity was detected. The patient is well without evidence of tumor five years after operation. The apparently benign behavior of the pancreatic endocrine oncocytoma reported here is in contrast to the malignant nature of another case reported recently.
 ...
PMID:Benign oncocytic endocrine tumor of the pancreas in a patient with polyarteritis nodosa. 288 5

A case of pancreatic tumor in a six-year-old girl is presented. The tumor had histologic characteristics of acinar cell carcinoma with endocrine component. Grossly, it was encapsulated and attached to the tail of the pancreas, measuring 8 cm in the greatest diameter. Histologically, the tumor was composed of medium-sized tumor cells, with mild pleomorphism showing mainly acinar structures. Many of these tumor cell contained fine granules that were periodic acid-Schiff positive, diastase resistant, and positive with dimethylaminobenzaldehyde nitrite strain for tryptophan, and some contained granules that were positive with Grimelius stain and positive with peroxidase-antiperoxidase technic for gastrin. Electron microscopy revealed two types of membrane-bound granules in the tumor cells. The larger granules measured 400-700 nm in diameter and appeared to be zymogen granules, while the smaller ones measured 100-200 nm in diameter and appeared to be neuroendocrine granules. Some cells contained both granules. The postoperative course of the patient was excellent, and she was alive and well 13 years after operation. This may be the second reported case of acinar-endocrine cell tumor of the pancreas.
 ...
PMID:Carcinoma of the pancreas with endocrine component in childhood. A case report. 396 47

Twenty unselected breast carcinomas were examined for argyrophilia by the Sevier-Munger stain and for dense-core secretory granules by electron microscopy. All cases were examined for lactalbumin and five cases were also studied for gastrin, insulin, calcitonin, somatostatin, glucagon, ACTH, prolactin, and pancreatic polypeptide by an immunoperoxidase technique; two cases were further analyzed for lactalbumin by ultrastructural immunoperoxidase stain. Focal or diffuse argyrophilia was present in ten cases. Intracytoplasmic lactalbumin was present in seven of these cases, but immunoperoxidase staining for the neuroendocrine hormones was negative. Fine structural examination demonstrated varying numbers of 95 to 450-nm-diameter, round, membrane-bound, dense-core secretory granules in 13 cases. Nine of the granule-containing cases were also argyrophilic, and seven of these contained intracytoplasmic lactalbumin. Both the argyrophilia and the dense-core secretory granules thus correlated with the presence of intracytoplasmic lactalbumin. None of the 20 patients had clinical evidence of carcinoid syndrome or showed evidence of other hormone secretion. Argyrophilia and granular lactalbumin staining in a somewhat similar pattern was found in pregnant and lactating breast controls. Argyrophilia and ultrastructural dense-core granules are common in breast carcinomas and might represent lactational differentiation. These findings do not indicate the presence of a carcinoid tumor because in most of these tumors the secretory granules appear to contain milk protein secretory product rather than neuroendocrine polypeptides, and most argyrophilic tumors do not morphologically or clinically resemble carcinoid tumors.
 ...
PMID:Argyrophilic breast carcinomas: evidence of lactational differentiation. 618 Jun 51

We present the cytologic, immunohistochemical, flow cytometric and ultrastructural findings of a case of invasive ductal carcinoma of the breast with features of neuroendocrine differentiation occurring in an 83-year-old male. Fine needle aspiration (FNA) cytology of the patient's tumor demonstrated a markedly cellular specimen to discohesive tumor cells, present primarily singly, with occasional loose groups. The cells were relatively large, with pleomorphic, eccentrically placed, round to oval nuclei. The cytoplasm was abundant and contained prominent red granules (Papanicolaou stain) that were also argyrophilic. Immunohistochemical studies performed on the aspirate and the subsequently excised malignant breast tissue revealed positive staining for neuron-specific enolase, chromogranin A, synaptophysin and gastrin. Also, the majority of the tumor stained positive with antibodies to both estrogen and progesterone hormone receptors. DNA flow cytometry demonstrated an aneuploid stemline population with a DNA index of 1.73 and an S-phase fraction of 4.5%. Electron microscopy was performed on the FNA material, and numerous variable-sized, membrane-bound, dense-core granules diffusely scattered within the cytoplasm of the neoplastic cells were identified. The specific cytologic features of this tumor, along with the immunocytochemical and ultrastructural features, can aid the pathologist in rendering an accurate FNA diagnosis of this specific subtype of breast carcinoma.
 ...
PMID:Fine needle aspiration cytology of a male breast carcinoma exhibiting neuroendocrine differentiation. Report of a case with immunohistochemical, flow cytometric and ultrastructural analysis. 763 60

The cases of three patients with primary carcinoid tumor of the testis were reported. The patients were 41, 44, and 83 years of age. At initial examination, all three had testicular masses with or without associated pain, and none had the carcinoid syndrome. The tumors measured 4.3 cm, 3.0 cm, and 6.5 cm in dimension. All three tumors manifested classic histologic features of carcinoid tumors. The neoplastic cells exhibited argyrophilia, and all were immunoreactive to chromogranin, serotonin, neuron-specific enolase, and cytokeratin. Two tumors had positive test results for gastrin and one had positive test results for substance P and vasoactive intestinal polypeptide. No tumors reacted with somatostatin, insulin, pancreatic polypeptide, or placental alkaline phosphatase. Intracytoplasmic, membrane-bound, round-to-elliptical pleomorphic granules were identified by ultrastructural analysis in all cases. DNA flow cytometric analysis revealed a low degree (near-diploid) DNA aneuploidy in all cases, with a DNA index of 1.15 in two tumors and 1.3 in the third tumor. The three patients are alive and well 11 years, 7 years, and 6 months, respectively, after diagnosis. A total of 57 cases of this entity, including the 3 reported here, have been reported. Of these, 43 were pure carcinoid, and 14 were associated with teratoma; 6 (11.6%) patients developed metastases. Tumor size and the presence of carcinoid syndrome have been found to correlate with metastatic potential. Neither tumor necrosis nor local tumor invasion (into vessels, tunica albuginea, etc.) correlated with adverse prognosis. Carcinoid tumor of the testis is a rare indolent neoplasm with potential for distant metastases.
 ...
PMID:Primary carcinoid tumor of testis. Immunohistochemical, ultrastructural, and DNA flow cytometric study of three cases with a review of the literature. 768 60

Incorporation of di-fatty acylglycerol moieties at the N-terminus of human little-gastrin-(2-17) leads to self-aggregation of the resulting lipo-gastrins into stable, most probably fluid vesicles. Net intervesicular transfer of the lipo-gastrins to phosphatidyl-choline model bilayers occurs at high rates whereby the chain length of the gastrin lipid moiety was found to affect the transfer rate more decisively than the nature of the acceptor vesicle. Similarly, the bioactivity of the lipo-gastrins is again affected by the nature of the lipid moiety suggesting differentiated interdigitation with the natural bilayer components and thus, different two-dimensional migration rates to the target receptors. Embedment of the lipo-gastrins in phosphatidylcholine bilayers at high lipid/gastrin ratios as mimicry of the cell membrane bound state does not result in onset of ordered structure, but leads to full exposure of the gastrin in essentially randomly coiled form at the water/lipid interface. This may result from the artificial N-terminal anchorage of the gastrin molecules to the bilayers, but also from the relatively tight packing of the phosphatidylcholine vesicles. Nevertheless, this observation might suggest that in the present case membrane-induced conformation and orientation may not represent a pre-requisite for the hormone receptor binding process. However, the results of this study clearly confirm even for the non-amphiphilic hormone gastrin a membrane-bound pathway for receptor recognition and occupancy.
 ...
PMID:Peptide hormone-membrane interactions. Intervesicular transfer of lipophilic gastrin derivatives to artificial membranes and their bioactivities. 843 55


1 2 Next >>