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)

The cellular composition of the pancreatic islets of juvenile diabetics was studied, using recently developed immunocytochemical methods. B-cells were identified only in juvenile diabetics with a disease of short duration. In chronic juvenile diabetics, the islets which are classically viewed as "atrophic", were shown to be composed of glucagon- and of somatostatin-cells. Another type of islets which commonly occurs in the pancreas of juvenile diabetics, i.e. the ribbon-like type first described by Cecil in 1911, appeared to be composed almost exclusively of "pancreatic polypeptide" (HPP)-cells. It is suggested that hyperplasia of the HPP-cells in the pancreas of juvenile diabetics results from an atypical type of islet regeneration induced by a severe and prolonged injury to the pancreatic endocrine tissue.
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PMID:Hyperplasia of "pancreatic polypeptide"-cells in the pancreas of juvenile diabetics. 32 79

The survival and cellular and connective organization of intracephalic transplants of developing, freeze-stored rat hippocampal tissue were examined. Blocks of tissue containing the hippocampus and fascia dentata were obtained from late embryonic (E16-E22) and early postnatal rats (P0-P4) and immersed in a tissue culture medium with 10% of the cryoprotective agent DMSO, frozen at a cooling rate of approximately 1 degree C/minute, and stored for 1-226 days in liquid nitrogen. After quick thawing and washing out of the DMSO the tissue blocks were transplanted to the brain of adult rats. From 2 weeks to 3 months later the recipient brains were processed histologically. The cellular and connective organization of the transplants and their interaction with the host brains were analyzed after thionin cell staining, Timm's staining for hippocampal and dentate afferents, immunohistochemical staining for enkephalin-, CCK-, and somatostatin-reactive neurons and afferents, AChE staining for cholinergic afferents, and silver stains for fiber architectonics and tracing of connections by anterograde axonal degeneration. Freeze-storage narrowed the range of donor ages with good transplant survival. The best surviving hippocampal and dentate transplants thus came from 17-21-day-old embryos. There was no correlation between the length of storage and survival. Structurally the transplants of stored tissue were more frequently fragmented than the transplants of fresh tissue when located outside the brain parenchyma in the brain ventricles. This was in accordance with the results of a previous study of grafts of freeze-stored and fresh hippocampal tissue placed in the anterior eye chamber. Despite the decrease in survival and the tendency for fragmentation many well-structured and organotypically organized hippocampal and dentate transplants were recovered corresponding to the donor ages E19-E21. In addition to the main cell types (granule cells and pyramidal cells) the freeze-stored transplants also contained peptidergic nerve cells reacting for CCK, somatostatin, and enkephalin. The organization of the intrinsic nerve connections and the exchange of connections with the host brain were similar for transplants of stored and fresh tissue. Besides the consistent innervation of the hippocampal and dentate transplants by host cholinergic afferents monitored by AChE staining, several appropriately located dentate transplants thus sent mossy fibers to the host CA3. Others received host perforant path projections. A CA3-associated transplant projection to the denervated perforant path zones in the host fascia dentata was also observed.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Intracephalic transplants of freeze-stored rat hippocampal tissue. 378 12

Sugar conjugation of biooactive peptides has been shown to be a powerful tool to modulate peptide pharmacokinetics. In the case of radiolabeled somatostatin analogues developed for in vivo scintigraphy of somatostatin receptor (sst) expressing tumors, it generally led to tracers with predominant renal excretion and low uptake in nontarget organs, and in some cases also with enhanced tumor accumulation. Especially with respect to endoradiotherapeutic applicability of these tracers, however, understanding the structural requirements for minimal kidney accumulation and maximal tumor uptake is important. The aim of this study was therefore the evaluation of the potential of specific glycoside structures in combination with reduced peptide net charge to reduce kidney accumulation without affecting tumor accumulation. Three glyco analogues of radioiodinated Tyr(3)-octreotate (TOCA) with z = 0 were evaluated in a comparative study using [(125)I]Mtr-TOCA (z = +1), the maltotriose-Amadori analogue of [(125)I]TOCA, as a reference, [(125)I]Glucuron-TOCA, the Amadori conjugate with glucuronic acid, and [(125)I]Gluc-S- and [(125)I]Gal-S-TOCA, the coupling products with glucosyl- and mannosyl-mercaptopropionate. In cells transfected with sst(1)-sst(5), all three new analogues show sst-subtype binding profiles similar to I-Mtr-TOCA with high, but somewhat reduced, affinity for sst(2). In contrast, internalization into sst(2)-expressing cells (in % of [(125)I]Tyr(3)-octreotide ([(125)I]TOC)) as well as the EC(50,R) of unlabeled TOC for internalization determined in dual-tracer experiments are substantially enhanced for [(123)I]Gal-S-TOCA and [(123)I]Gluc-S-TOCA (internalization, 190% +/- 12% and 265% +/- 20%, respectively, vs 168% +/- 6% of [(125)I]TOC for [(123)I]Mtr-TOCA; EC(50,R), 2.62 +/- 0.07 and 2.96 +/- 0.14, respectively, vs 1.81 +/- 0.07 for [(123)I]Mtr-TOCA). The tumor accumulation of [(125)I]Gal-S-TOCA and [(125)I]Gluc-S-TOCA in AR42J tumor-bearing nude mice 1 h p.i. is consequently very high (22.6 +/- 2.2 and 26.2 +/- 5.6%ID/g) and comparable to that of [(125)I]Mtr-TOCA (25.1 +/- 4.4%ID/g). [(125)I]Glucuron-TOCA showed lower uptake in sst-expressing tissues than did [(125)I]Mtr-TOCA, but considerably enhanced accumulation in nontarget organs such as liver, intestine, and kidney. Due to increased lipophilicity, hepatic and intestinal uptake 1 and 4 h p.i. of [(125)I]Gal-S-TOCA and [(125)I]Gluc-S-TOCA was also slightly higher than that of [(125)I]Mtr-TOCA. Kidney accumulation, however, was reduced by approximately 50% for both compounds (2.6 +/- 0.3 and 2.2 +/- 0.4, respectively, vs 4.0 +/- 0.7%ID/g at 1 h p.i.). Because no sugar-specific effect was detected in the latter case, it is concluded that general ligand pharmacokinetics and especially kidney accumulation of the tracers investigated are mainly determined by physicochemical characteristics such as lipophilicity, net charge, and also charge distribution ([(125)I]Glucuron-TOCA vs [(125)I]Gal-S- and [(125)I]Gluc-S-TOCA). With respect to receptor targeting, however, the structure of the carbohydrate moiety plays an important role, leading to dramatically enhanced ligand internalization, especially in the case of [(123)I]Gluc-S-TOCA. Taking into account the combined effects of the Gluc-S-moiety both on kidney and on tumor accumulation, this group seems to be a promising synthon for the synthesis of other radiolabeled peptide analogues with improved pharmacokinetics.
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PMID:Modulation of pharmacokinetics of radioiodinated sugar-conjugated somatostatin analogues by variation of peptide net charge and carbohydration chemistry. 1576 98

Lung cancer is nowadays one of the most common malignancies and the leading cause of cancer mortality worldwide. Its early diagnosis and treatment is therefore the target of extensive research. Although radiologic imaging methods, especially CT, are the most widely used, they have well known constraints, including solitary pulmonary nodule characterisation, mediastinal lymph node staging, characterisation of the remaining tissue after chemo- or radiotherapy and early diagnosis of relapse. The main reason for these drawbacks is that radiologic methods primarily rely upon morphologic and anatomic criteria, which usually have little relevance to the biological status of a pulmonary lesion. The radiopharmaceuticals used in nuclear medicine, exploit special pathophysiologic localization mechanisms and provide unique functional information for their target tissues. Thus, many of the above mentioned problems can be elucidated. This is obvious in the published figures of sensitivity and specificity of the radionuclidic methods, which are often superior to those of CT [Table 1: see text]. In this article the main nuclear medicine procedures in the field of lung cancer imaging are reviewed. Emphasis is given in newer developments such as (99m)Tc-sestamibi, labeled somatostatin analogues and positron emission tomography with (18)F-FDG. We especially describe the "weaknesses" of the anatomic-radiologic imaging modalities and how the attending physicians, i.e. the pneumonologists, oncologists and thoracic surgeons can overcome them, by using the functional imaging methods of nuclear medicine.
Hell J Nucl Med
PMID:[Nuclear medicine procedures in lung cancer imaging]. 1584 Dec 89

Multiple endocrine neoplasia syndrome type II-A (MEN-IIA) is a rare endocrinological disorder occurring in 0.04% of the general population. The combination of papillary thyroid carcinoma with MEN-IIA appears even less frequently. We describe the case of a 21-year-old woman with pheochromocytoma of the left adrenal gland, medullary thyroid carcinoma, hyperplasia of the parathyroid glands and papillary thyroid carcinoma. MEN II-A syndrome resulted from de novo mutation of the RET proto-oncogene, which was detected in the DNA of peripheral blood leucocytes. Three months postoperatively calcitonin levels were normal, whilst increased serum thyroglobulin values prompted the need for further investigation. Whole body scanning with (131)I and with (99m)Tc-sestamibi and also US test of cervical lymph nodes, were negative. The synthetic analogue of somatostatin (99m)Tc-depreotide was used for whole body scintigraphy, cervical and thoracic tomographic scanning and revealed anterior cervical, upper mediastinal and right hilar foci of pathological uptake[Fig.1 and Table 1: see text]. These findings were compatible with findings from CT and MRI that followed in order to complete the diagnostic evaluation. The patient underwent surgical resection of the metastatic foci with uneventful postoperative course. Histology showed lymph node metastases originating from the papillary thyroid carcinoma. Ratio values >2 were abnormal (Fig. 2). Computer processing of the corresponding ROIs on healthy tissues produced the following normal values: Th/Arm: 1.874,, Med/Arm: 1.699, Hi/Arm: 1.141 (Fig. 3).
Hell J Nucl Med
PMID:[A patient with MEN-IIA syndrome due to de novo mutation and papillary thyroid carcinoma; the role of 99m Tc-depreotide in diagnosing metastases and brief review of the literature]. 1584 Dec 92

Medullary thyroid carcinoma (MTC) as a neuroendocrine tumour arising from C cells of the thyroid gland secrets hormonal peptides; among them, calcitonine (CT) and carcino-embryonic antigen (CEA). These two peptides are used for the diagnosis and treatment response of MTC cases. In patients with advanced MTC, scintigraphy by [(111)In-DTPA-d-phe1]-octreotide is able to detect somatostatin receptors (SSTR) and thus identify regional lymph nodes and/or distal metastases. In this article, we have studied the use of [(111)In-DTPA-d-phe1]-octreotide in the treatment of patients with advanced MTC, and a positive octreotide scan. Twenty-two patients were studied, 16 with persistent MTC and six with relapsed MTC. All patients' tumours were detected by [(111)In-DTPA-d-phe1]-octreotide-scan to be SSTR positive. All patients were treated with the somatostatin analog (SST-A) octreotide, for 3-21 months. Nine patients were treated only with SST-A (Group A). The remaining 13 patients (Group B) received adjuvant treatment as follows: six patients received chemotherapy (Ch), five patients received both Ch and external radiotherapy (eRT) and two patients received only eRT. Results were as follows: Group B patients as compared to Group A patients had about the same objective and biological response. Patients of Group B had relatively better subjective response (less diarrheas and abdominal cramps) versus Group A patients, although this finding was not significant. Group B patients had a longer mean survival time after treatment as compared to Group A patients: 39 months (with a range of 4-72 months) versus 20 months (with a range of 3-60 months) respectively, (P<0.05). Also Group B patients had longer than Group A patients mean total survival time - measured from the start of the disease: 138 (18-270) versus 97 (13-235) months respectively (P<0.05). Based on the above findings, it is the opinion of the authors that patients with advanced MTC and SSTR tumor expression in vivo as indicated by [(111)In-DTPA-d-phe1]-octreotide scanning, when submitted to treatment with SST-A octreotide and adjuvant Ch and/or eRT treatment may have a better treatment response than if submitted to treatment with SST-A octreotide alone. More cases are being studied by us at the present.
Hell J Nucl Med
PMID:The therapeutic value of SST-A octreotide alone or with adjuvant treatment in patients with advanced medullary thyroid carcinoma and positive (111)In-octreotide scan. 1588 53

Somatostatin-expressing (SS) cells are inhibitory interneurons critical to the regulation of excitability in the cerebral cortex. It has been suggested in several animal models of epilepsy that the activity of these neurons reduces the occurrence and strength of epileptiform activity. The physiological properties of SS cells further support these hypotheses. Freeze lesions of neonatal rats serve as a model of human polymicrogyria, which is often characterized by severe seizures. Here we investigate the effects of neonatal freeze lesions on SS-expressing neurons by measuring their densities in control and lesioned hemispheres at two ages. We found that in late juveniles (P30-P32), SS-expressing neurons were depleted by 20% in areas adjacent to the freeze lesion, but at an earlier developmental age (P14-15), there was no significant loss. Since the deficit in SS-expressing neurons occurs well after the onset of epileptiform activity (P12-P18), we conclude that the death of these interneurons does not initiate hyperexcitability in this model.
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PMID:Developmental changes in somatostatin-positive interneurons in a freeze-lesion model of epilepsy. 1673 97

The solitary pulmonary nodule (SPN) is a relatively common imaging finding, often representing a diagnostic challenge. Radiological appearance, growth rate calculation during follow up and probability of malignancy assessment by the Bayes' theorem are widely used for identifying the nature of a SPN. Molecular imaging by fluoro-18 deoxy glucose positron emission tomography has revolutionised non-invasive diagnosis of lung cancer, but the low-cost, widely available conventional nuclear imaging modalities still remain valid in the field. We present a case of a growing SPN in a middle-aged male smoker. Growth rate assessment by sequential computed tomography scans, over a follow up period of five years, was suggestive of benign histology, while Bayesian analysis warranted histological confirmation of the nodule's nature. Imaging by both labelled somatostatin analogue technetium 99m-depreotide ((99m)Tc-depreotide) and thallium 201-chloride was almost exclusive of malignancy. The nodule was excised and histology showed a pulmonary hamartoma. We briefly discuss the relative role of invasive and non-invasive methods, with emphasis in conventional radionuclide molecular imaging, for the identification of the nature of SPN.
Hell J Nucl Med
PMID:The contribution of conventional nuclear molecular imaging in characterising the nature of a growing solitary pulmonary nodule. Report of a case. 1745 Feb 48

Gastro-entero-pancreatic tumors (GEP) contain, in their majority, somatostatin receptors. In-111-DTPA-phenyl-pentetreotide has been proved to have high affinity for somatostatin receptors subtypes 2, 3 and 5. The aim of the present study was to evaluate the utility of (111)In-DTPA-O somatostatin receptors' scintigraphy (SRS) in the diagnosis of suspected GEP. Thirty-five consecutive patients (17 males and 18 females-mean age 57.9+/-7.6) with GEP as a possible diagnosis were enrolled in the study. The primary diagnosis was diarrheic syndrome susceptive of intestinal carcinoid tumor (24 patients), carcinoid of the rectum (2 patients), adenocarcinoma of the pancreas (2 patients), insulinoma (2 patients), gastrinoma (3 patients) and hepatocellular carcinoma (2 patients). All patients were submitted to computerized tomography (CT) of the thorax and the abdomen and pentetreotide SRS was performed 4 h (total body and SPET acquisition) and 24 h (planar views), post iv injection of 185 MBq of the radiolabeled compound. Results showed: Four of the patients were false positive diagnosed as having inflammatory intestinal disease and gallbladder dilatation. At the time of the evaluation, 14 of the remaining patients were free of disease, concerning secondary involvement. In these cases, CT and SRS studies matched each other, with no pathological lesions and no abnormal accumulation of the radiopharmaceutical respectively. Concerning pathological cases, only one SRS study in a patient with rectum carcinoid was normal, with liver lesions in the CT study. These lesions were considered as subtypes 2, 3 and 5 somatostatin receptors negative. SRS revealed three lesions more than CT. According to these results, sensitivity of SRS study was 93.8% and specificity 86.9%. The authors believe that molecular imaging of somatostatin receptors, is a sensitive method for the evaluation of patients with GEP tumors. However, in cases of intestinal disease, we should be aware of false positive results due to inflammatory processes and the presence of lymphocyte infiltration.
Hell J Nucl Med
PMID:[Indium-111-DTPA-phenyl-pentetreotide somatostatin receptors' scintigraphy in the evaluation of patients with suspected gastro-entero-pancreatic tumors. Comparison with computerized tomography]. 1808 69

Somatostatin receptor scintigraphy (SRS) has been used for the detection of neuroendocrine tumors. Melanoma is a malignant tumor of melanocytes, considered to derive from the neural crest. As the prognosis of melanoma is very poor, early detection of the disease, of recurrences and of distal metastases, is important. The aim of our study was to evaluate the clinical impact of indium-111-diaethyleno triamino pentaacetic acid-d-phe1-octreotide ((111)In-DTPA-octreotide or octreoscan or (111)In-O) in the management of melanoma patients after first diagnosis and first surgery and during three years of follow-up. We have studied 35 patients 20 female and 15 male, with histological proven melanoma. Scintigraphic images with single photon emission tomography gamma-camera (Millenium GE-USA) were performed after the administration of 220MBq (111)In-O. The scintigraphic data were compared to axial computerized tomography (CT). Patients were followed for 3 years after the initial diagnosis and surgery. Our results showed that during the 3 years follow-up period, 26/35 patients had a clinical recurrence. Twenty of them had positive (111)In-O scans with 56 lesions mainly metastatic, while 6 had negative scans. The CT scans showed only 31/56 lesions. In conclusion, SRS with (111)In-O, for diagnosing metastases from malignant melanoma, showed a sensitivity and specificity of 87% and 94% respectively and within the 3 years of follow-up, the stage of melanoma and surgical strategies were modified by 48% and 32%, respectively. Twenty five tumor sites, unsuspected by CT were visualized by (111)In-O.
Hell J Nucl Med
PMID:Iotandium-111 pentetreotide scintigraphy and CT scans after 3 years in the follow-up of patients with malignant melanoma. 1967 68


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