Biomedical subjects

J A Laissue

Publications and source records attributed to J A Laissue.

At least 55 records · Page 3Linked to original sources

PubMed1996

Inhibition of submandibular and lacrimal gland infiltration in nonobese diabetic mice by transgenic expression of soluble TNF-receptor p55.

Besides a prominent mononuclear cell infiltration of the islets of Langerhans, nonobese diabetic (NOD) mice also show massive cellular infiltrates of the submandibular and lacrimal glands concomitant with histological signs of tissue damage. To obtain insights into the mechanisms operative during the initiation and progression of tissue damage, we followed by in situ hybridization the appearance of cells containing mRNA of the gene encoding the proinflammatory cytokine TNF-alpha in the cellular infiltrates. Cells expressing TNF-alpha are mainly located in infiltrates, are absent in nonaffected glands, and are preferentially found among CD4 T cells. Secretion of TNF-alpha by gland-infiltrating cells was confirmed by an ELISPOT procedure. Direct evidence for an instrumental role of TNF-alpha in initiation and progression of submandibular and lacrimal gland infiltration is provided by the observed significant reduction in the extent of infiltration in nonobese diabetic mice transgenic for a soluble TNF receptor p55 fused to the Fc part of human IgG3. This protection from infiltration is paralleled by decreased expression of the adhesion molecules ICAM-1 and VCAM-1 in submandibular and lacrimal glands. These data suggest a central role of TNF-alpha in the initiation and progression of autoimmune tissue destruction of salivary glands and indicate beneficial effects of soluble TNF receptors in the treatment of organ-specific autoimmune diseases.

Animals↗

PubMed1996

Somatostatin and vasoactive intestinal peptide receptors in human mesenchymal tumors: in vitro identification.

Somatostatin and vasoactive intestinal peptide (VIP) have been shown to be of diagnostic and therapeutic interest in several types of human epithelial tumors expressing the respective receptor. The present study evaluates the presence of somatostatin and VIP receptors in 64 primary or metastatic human mesenchymal tumors. In vitro receptor autoradiography on cryostat sections was performed using 125I-labeled [Tyr3]-octreotide as well as 125I-labeled [Leu8,D-Trp22,Try25]-somatostatin-28 as radioligands for somatostatin receptors and 125I-labeled VIP as radioligand for VIP receptors. Somatostatin receptors were identified in bone and vascular/perivascular tumors (3 of 3 osteosarcomas, 1 of 1 giant cell tumor, 2 of 2 angiosarcomas, and 4 of 4 hemangiopericytomas), in 2 of 2 synovial sarcomas, in 2 of 5 histiocytomas, and in several muscle cell tumors (1 of 2 leiomyomas, 2 of 4 leiomyosarcomas, and 3 of 5 rhabdomyosarcomas) but were absent in 4 liposarcomas, 3 mesotheliomas, 3 chondrosarcomas, 10 Ewing sarcomas, 11 schwannomas, and 5 Wilms' tumors. VIP receptors were identified in 3 of 3 differentiated liposarcomas, 2 of 2 angiosarcomas, 4 of 4 hemangiopericytomas, 2 of 2 synovial sarcomas, 3 of 3 mesotheliomas, 5 of 5 Wilms tumors, as well as in 2 of 5 histiocytomas, 1 of 2 leiomyomas, 2 of 4 leiomyosarcomas, 3 of 3 intermediately differentiated rhabdomyosarcomas, and 1 of 3 osteosarcomas but not in chondrosarcomas, Ewing sarcomas, schwannomas, or undifferentiated rhabdomyosarcomas. The receptors were located on neoplastic cells. The somatostatin receptors were of high affinity and of high specificity for biologically active somatostatin analogues with high affinity for somatostatin-14 and somatostatin-28 as well as for octreotide, thus representing the sst2 subtype; in a few cases of tumors having somatostatin receptors with low affinity for octreotide, in situ hybridization techniques identified preferentially sst1 mRNA. These data suggest that human mesenchymal tumors may be targets for somatostatin and/or VIP receptor in vivo imaging; they may also be potential targets for somatostatin or VIP analogue therapy.

Adolescent↗

PubMed1996

Differential in situ expression of the genes encoding the chemokines MCP-1 and RANTES in human inflammatory bowel disease.

Two chemotactic cytokines, monocyte chemoattractant protein-1 (MCP-1) and RANTES, possibly contribute to the recruitment and activation of leukocytes in inflamed tissues. The expression of these cytokine genes was evaluated in tissue sections from resected bowel segments of 14 patients with inflammatory bowel disease (IBD) and seven control patients by use of 35S-labelled antisense RNA probes. MCP-1 and RANTES transcripts were generally increased in the intestinal mucosa of patients with IBD, compared with controls. Whereas MCP-1 gene expression in the mucosa was restricted to the lamina propria, the gene coding for RANTES was expressed in intraepithelial lymphocytes and in the subepithelial lamina propria. Furthermore, MCP-1 mRNA, but not RANTES mRNA, was abundant in vessel-associated cells, such as endothelial cells, medial smooth muscle cells, and intraluminal cells; in smooth muscle cells of the intestinal tunica muscularis; and in cells of the myenteric plexus. Compared with controls, a significant increase of MCP-1-expressing cells was observed in tissue specimens from patients with IBD, in endothelial cells of venules, and in cells present in the lumen of intestinal vessels. Conversely, the expression of MCP-1 mRNA in smooth muscle cells and myenteric plexus cells appeared to be comparable in control and diseased intestines. The increased number of MCP-1 and RANTES mRNA-expressing cells in mucosa from patients with IBD suggests that these cytokines play a role in the pathogenesis of mucosal inflammation. Furthermore, the expression of the MCP-1 gene in vessel-associated cells may indicate its involvement in mechanisms regulating the adhesion of blood monocytes to endothelial cells.

Adult↗

PubMed1996

Somatostatin receptors and their subtypes in human tumors and in peritumoral vessels.

Somatostatin receptors are expressed by a large variety of human tumors. In vitro receptor autoradiographic studies have shown that these tumors can express more than one somatostatin receptor subtype. Whereas the majority of tumors bind octreotide with high affinity, some, i.e., prostate tumors, bind octreotide with low affinity only. The discovery of five somatostatin receptor subtypes, sst1-5, by gene cloning has increased our understanding of somatostatin receptor structure and function. Using in situ hybridization techniques, we found that various human tumors, identified as somatostatin receptor-positive in binding studies, expressed sst2 mRNA in the majority of cases, whereas sst1 and sst3 were less frequent. Often, all three sst were expressed simultaneously. In another recent in situ hybridization study, primary prostate cancers were shown to preferentially express sst1, rather than sst2 or sst3. Moreover, a high incidence of sst5 was found in growth hormone (GH)-producing pituitary adenomas and, to a lesser extent, in active pituitary adenomas; gastroenteropancreatic (GEP) tumors showed all possible combinations, but with a predominance of sst2. Overall, the presence of sst2 mRNA and/or sst5 generally correlated with the presence of octreotide-binding sites, but with exceptions. These results indicate the highly variable abundance of sst mRNAs in individual somatostatin receptor-containing tumors. Somatostatin receptors were not only found in tumoural tissue, but also in the peritumoral vascular system. This was particularly well studied in colorectal carcinomas, where the peritumoral veins were shown to express in all cases a high density of somatostatin receptors, probably of the sst2 type, binding octreotide with high affinity. Therefore, the host peritumoral vascular system may be a possible target of somatostatin action in tumor development. Somatostatin may act locally on tumor growth through two different mechanisms dependent on local somatostatin receptor expression: through direct action on tumor cells or through action on peritumoral vessels, which may alter the hemodynamics of the tumoral blood circulation.

Blood Vessels↗

PubMed1996

Local up-regulation of neuropeptide receptors in host blood vessels around human colorectal cancers.

BACKGROUND & AIMS: Neuropeptide receptors, expressed at high density by neoplastic cells, can be instrumental for diagnosis and therapy. However, little is known about neuropeptides and neuropeptide receptors in the tumor bed. The aim of this study was to study the expression of two neuropeptide receptors in peritumoral blood vessels. METHODS: Somatostatin and substance P receptors were measured using in vitro receptor autoradiography in well-defined submucosal and subserosal vessels located in the immediate surroundings of human colorectal carcinomas or in normal colon taken at increasing distances from the tumor. RESULTS: Both receptors were 3-5-fold overexpressed in the host veins within a 2-cm-wide area surrounding human primary colorectal carcinomas compared with veins located at 5-10-cm distance in normal gut tissue. The expression of peritumoral vascular somatostatin receptor and substance P receptor appears independent of receptor expression in the tumor, of tumor stage, and of the grade of local inflammation. CONCLUSIONS: These biochemical alterations of veins in the immediate vicinity of tumors represent a novel tumor-related site of expression for the two receptors and may point to a new biological principle of host-tumor interaction. Thus, vascular regulatory mechanisms in the tumor bed may be important for tumor development and metastasis and may be used as a target for tumor therapy.

Aged↗

PubMed1996

Abortive mitoses and nuclear DNA fragmentation in CD30+ large cells of Hodgkin's disease.

This study was undertaken to better comprehend the reasons for the scarcity of Hodgkin and Reed-Sternberg (H-RS) cells in Hodgkin's disease (HD) despite their expression of "proliferation-associated antigens". To this end, we assessed the relative frequency of mitotic phases and nuclear damage (detected by in situ end-labeling of DNA strand breaks) in CD30+ large cells of nodular sclerosis and mixed cellularity HD. Our results show that a) most CD30+ cells in HD exhibit abortive mitoses, with a highly significant arrest at the metaphase-ana/telophase transition, and b) many of these elements, i.e. mainly H-RS cells, show fragmentation of nuclear DNA, suggesting imminent or actual death. Percentages of CD30+ cells that entered mitosis and those with DNA strand breaks were of a similar order of magnitude and correlated significantly in a linear fashion. These findings are consistent with the concept that cell deletion is the major cause of the paucity of H-RS cells in HD.

Adolescent↗

PubMed1996

Monocyte chemoattractant protein-1 gene expression in prostatic hyperplasia and prostate adenocarcinoma.

Human monocyte chemoattractant protein-1 (MCP-1) has been shown to act as a chemokine in the recruitment of monocyte/macrophages during inflammation states. Furthermore, there is increasing evidence that MCP-1 is involved in the recruitment of tumor-associated macrophages. In vivo, one of the major cellular sources of MCP-1 are the smooth muscle cells. As MCP-1 gene expression and/or protein production in these cells is not necessarily correlated with the accumulation of inflammatory cells, there might possibly be additional functions of this cytokine. In the present study, we investigated by use of 35S-labeled antisense RNA probes whether the MCP-1 gene is expressed in tissue specimens of benign prostatic hyperplasia (n = 13) and specimens of prostate carcinoma (n = 8), both of which are characterized by a prominent fibromuscular stroma and inconspicuous inflammatory infiltrates. MCP-1 transcripts were located in stromal smooth muscle cells and, additionally, in basal cells of benign prostatic glands. In prostate carcinoma, the number of MCP-1 mRNA-expressing cells was significantly less than in benign prostatic hyperplasia. MCP-1 transcripts were located in preserved fibromuscular stroma and in basal cells of entrapped non-neoplastic glands but not in carcinomatous cells. Immunohistochemical staining with polyclonal antibodies raised against MCP-1 revealed strong reactivity in the fibromuscular stroma surrounding both benign and malignant glands. MCP-1 gene expression or immunoreactivity for anti-MCP-1 antibodies was not related to the rare, lymphocytic interstitial infiltrates. The results show that 1) in the absence of significant leukocyte accumulation, it is unlikely that MCP-1 exerts chemotactic functions in the prostate and 2) that MCP-1, in contrast to previous findings in a wide variety of other human neoplasms, is not expressed in carcinomatous cells of the prostate.

Adenocarcinoma↗

PubMed1996

Tenascin and type IV collagen expression in liver cell dysplasia and in hepatocellular carcinoma.

The extracellular matrix (ECM) located in and around tumors is different from normal organ stroma, and there is evidence that it is critically involved in carcinogenesis and malignant growth. Whereas an abnormal composition of ECM in hepatocellular carcinomas (HCC's) has previously been demonstrated, not much is known so far with respect to putative HCC precursor lesions. We have, therefore, systematically analyzed the immunohistochemical reactivity for two major ECM components, tenascin and type IV collagen, in three types of liver cell dysplasia (LCD), and compared the findings with patterns observed in HCC's of different types and grades. Tenascin reactivity was generally stronger in HCC's than in cirrhosis. In cirrhotic nodules harboring areas of LCD, tenascin expression was significantly lower in small cell LCD than in large cell LCD. Type IV collagen reactivity in and around HCC's decreased as a function of a lower differentiation grade. In both groups of cirrhosis, i.e. with or without HCC, cirrhotic nodules occupied by the small cell variant of LCD exhibited a significantly lower type IV collagen reactivity than those with large cell LCD or simple regenerative cells. Taken together these findings suggest that, similar to adenomatous hyperplasia, small cell LCD is characterized by an abnormal tenascin and type IV collagen expression, thus reflecting the defective ECM pattern observed in HCC's.

Carcinoma, Hepatocellular↗

PubMed1996

Copper/zinc and manganese superoxide dismutases in alcoholic liver disease: immunohistochemical quantitation.

Alcohol damage to the liver can, among other factors, be mediated through the action of toxic oxygen radicals generated by ethanol. Major antioxidants in the liver are copper/zinc and manganese superoxide dismutases (Cu/Zn- and Mn-SODs). In order to test whether SODs may be differentially expressed in alcoholic liver disease (ALD), biopsies from 45 patients with ALD were analyzed for qualitative and quantitative immunoreactivity of Cu/Zn- and Mn-SOD in hepatocytes. The overall amount of Cu/Zn-SOD reactivity was significantly lower in ALD than in control biopsies, whereas no difference was found for Mn-SOD. Staining for both enzymes was decreased in ballooned hepatocytes. Low Cu/Zn-SOD was correlated with advanced lattice-like perisinusoidal fibrosis. In hepatocytes forming cirrhotic nodules, SOD reactivity was similar to that of control cells. The results suggest that SODs may be differentially regulated in ALD, and that Mn-SOD, an inducible enzyme, may be involved in recovery and cell protection in ALD.

Adult↗

PubMed1995

Metastatic hormone-refractory prostatic adenocarcinoma expresses somatostatin receptors and is visualized in vivo by [111In]-labeled DTPA-D-[Phe1]-octreotide scintigraphy.

Thirty-one patients with metastatic hormone-refractory prostatic adenocarcinoma were investigated scintigraphically with the 111In-labeled somatostatin analogue [DTPA-D-Phe1]-octreotide (OctreoScan) and with 99mTc-labeled HDP. In vitro somatostatin receptor autoradiography was performed on biopsies obtained from eight patients with hormone-refractory prostatic adenocarcinoma. In 30 of 31 patients (94%), at least one metastasis was positive at OctreoScan scintigraphy. Of the 346 lesions detected with 99mTc-labeled HDP bone scintigraphy, 128 were visualized with the OctreoScan technique, thus accounting for a 37% detection rate. Two uptakes on OctreoScan could not be identified on bone scintigraphy and were, thus, assessed as false positive. The biopsies of the eight patients disclosed a low density of receptors, localized on the tumor cells, as demonstrated with receptor autoradiography. Two patients with untreated metastatic prostatic adenocarcinoma were investigated in vivo before the start of endocrine therapy. However, none of the lesions detected by bone scintigraphy in these patients could be visualized with the OctreoScan technique. Positron emission tomography using [11C] methionine showed a decreased uptake in a metastatic index lesion in a patient treated with octreotide. It is concluded that hormone-refractory prostatic adenocarcinoma expresses somatostain receptors both in vitro and in vivo. The results obtained form the basis for the development of a new tool for in vivo characterization and of a new treatment strategy in patients with hormone-refractory prostatic adenocarcinoma.

Adenocarcinoma↗

PubMed1995

Paradoxical effects of bleomycin and heavy water (D2O) in mice.

Bleomycin (BLM) lacks many side effects of other cytostatic drugs. Pulmonary toxicity is the major dose-limiting effect of BLM. This is based in part on generation of free radicals. It is conceivable that deuterium in body fluids lessens the production of free radicals, thus preventing or diminishing the morphologic expression of pulmonary BLM toxicity. We therefore studied the effect of moderate deuteration of body fluids on BLM-induced lung damage in BALB/c-mice. In addition to conventional histopathological methods, we used a vertical sectioning design for stereological estimation of pulmonary volumes and surface areas. BLM (low/medium/high dose: 25/50/75 IU/kg body weight) was injected i.p. once a week for 6 weeks. Half the mice drank deuterated water before, during and after BLM treatment. Three weeks after the last injection, the lungs were fixed by airway instillation. Deuterated animals treated with BLM lacked signs of irreversible BLM-induced pulmonary damage. Conversely, focal sub-pleural fibrosis and fibrosing alveolitis were present in BLM-treated mice drinking tap water. Deuterated mice had stereological values for almost all lung parameters that were lower than in non-deuterated mice. The organ-specific advantage of deuteration was offset by marked enhancement of systemic toxicity of BLM. We conclude that (1) moderate concentrations of deuterium may prevent the development of fibrosing alveolitis in BLM-treated mice, possibly by reducing proliferation of alveolar fibroblasts, and, less probably, by impairing generation or enhancing capture of free radicals; (2) the toxicity of BLM was enhanced by ingestion of deuterium, resulting in morphological liver alterations and increased mortality.

Animals↗

PubMed1995

Subacute neuropathological effects of microplanar beams of x-rays from a synchrotron wiggler.

Microplanar beam radiation therapy has been proposed to treat brain tumors by using a series of rapid exposures to an array of parallel x-ray beams, each beam having uniform microscopic thickness and macroscopic breadth (i.e., microplanar). Thirty-six rats were exposed head-on either to an upright 4-mm-high, 20- or 37-microns-wide beam or to a horizontal 7-mm-wide, 42-microns-high beam of mostly 32- to 126-keV, minimally divergent x-rays from the X17 wiggler at the National Synchrotron Light Source at Brookhaven National Laboratory. Parallel slices of the head, separated at either 75 or 200 microns on center, were exposed sequentially at 310-650 grays (Gy) per second until each skin-entrance absorbed dose reached 312, 625, 1250, 2500, 5000, or 10,000 Gy. The rats were euthanized 2 weeks or 1 month later. Two rats with 10,000-Gy-entrance slices developed brain tissue necrosis. All the other 10,000- and 5000-Gy-entrance slices and some of the 2500- and 1250-Gy-entrance slices showed loss of neuronal and astrocytic nuclei and their perikarya. No other kind of brain damage was evident histologically in any rat with entrance absorbed doses < or = 5000 Gy. Brain tissues in and between all the 312- and 625-Gy-entrance slices appeared normal. This unusual resistance to necrosis is central to the rationale of microplanar beam radiation therapy for brain tumors.

Animals↗

PubMed1995

Substance-P receptors in human primary neoplasms: tumoral and vascular localization.

Primary human neoplasms were examined for the presence of substance-P receptors by receptor autoradiography with 125I-labelled Bolton-Hunter substance P. Substance-P receptors were localized and characterized in the neoplastic cells of 9/12 astrocytomas, 10/10 glioblastomas, 10/12 medullary thyroid carcinomas, 8/16 breast carcinomas and 4/5 ganglioneuroblastomas. Conversely, substance-P receptors were not or only rarely identified on non-small-cell carcinomas of the lung (1/16), neuroblastomas (0/8), adenocarcinomas of the colon (1/21) or the pancreas (1/9), or on malignant lymphomas (3/18). However, in the great majority of the investigated tumours, substance-P receptors were found on intra- and peritumoral blood vessels. All substance-P receptors detected had the pharmacological characteristics of the neurokinin-I receptor sub-type. In addition, the expression of somatostatin receptors was examined in all the neoplastic tissues mentioned above. Both substance-P and somatostatin receptors were present in astrocytomas and in ganglioneuroblastomas, whereas little or no receptor was found in pancreatic and non-small-cell lung carcinomas. The extent of somatostatin-receptor expression was inversely correlated to that of the substance-P receptors in glioblastomas, neuroblastomas and non-Hodgkin's lymphomas. The tumoral and vascular localization of substance-P receptors in tumours may have clinical implications. The use of radiolabelled substance P for in vivo scintigraphy may supplement the current set of diagnostic tools. Substance-P antagonists might be used in the treatment of tumours, as their binding to vascular receptors may decrease tumoral blood supply and drainage.

Autoradiography↗

PubMed1995

Presence of the bcl-2 protein and apoptosis in non-Hodgkin lymphomas with diffuse growth pattern.

In an attempt to further clarify the role of the apoptosis-counteracting protein bcl-2, non-Hodgkin lymphomas (NHL, n = 170) were examined immunohistochemically, across the boundaries of histologic classification, for the presence of this oncoprotein, in comparison with apoptotic indices (AI) and percentages of Ki-67+ cells (growth fraction). The results of this retrospective study revealed a highly significant inverse relationship ("mirror image") between the proportion of bcl-2+ cells and the AI per case. Both these parameters, although variable, clearly distinguished low- from high-grade-malignancy lymphomas according to the Kiel classification. Cluster analysis detected 2 separate groups of high-grade NHL, one with rather high AI and low percentages of bcl-2+ cells, comprising most anaplastic large-cell lymphomas, the other group with reverse characteristics. We found no correlation between the percentage of bcl-2+ cells per case and overall survival.

Apoptosis↗

PubMed1995

Low versus high cell turnover in diffusely growing non-Hodgkin's lymphomas.

Cell loss, perhaps as important as cell production in determining the size of an expanding cell population, has not usually been registered in quantitative cellular kinetic analyses of neoplastic disorders. The present retrospective study on various types and subtypes of non-Hodgkin's lymphomas (NHLs; n = 170) was designed to test the usefulness of a novel additional parameter, the 'turnover index' (TI), which is the sum per case of the mitotic index and the apoptotic index. Results document that TIs clearly distinguished between categories and subtypes of NHLs according to the Kiel classification. Cluster analysis of TIs plotted against the percentage of Ki-67-positive cells per case revealed that about one-third of the high-grade malignancy lymphomas actually belonged to the low-turnover lymphomas. Overall survival was longer in the low- than in the high-turnover group of lymphomas. Assessment of TIs can, for practical diagnostic purposes, be replaced by counting mitotic figures and apoptotic cells in several high-power fields. The TI concept may help to interpret the kinetics of NHLs in terms of accumulation vs. proliferation of cells.

Adolescent↗

PubMed1995

Multiple actions of somatostatin in neoplastic disease.

The role played by the neuropeptide somatostatin, also known as somatotropin release inhibitory factor (SRIF), in human cancer is not well understood. Recent investigations involving somatostatin receptors in normal and neoplastic human tissues suggest that the action is complex and involves both direct and indirect mechanisms. In this article, Jean-Claude Reubi and Jean Laissue describe the variety of biological mechanisms involved in neoplasia that are associated with somatostatin, and illustrate the therapeutic potential and present limitations of somatostatin analogues.

Animals↗

PubMed1995

Copper/zinc and manganese superoxide dismutase immunoreactivity in hepatic iron overload diseases.

Iron overload to the liver induces hepatic injury, eventually ending up with liver fibrosis or cirrhosis. Pathogenic mechanisms involved in liver damage are only partially known, but there is evidence for an important role of iron-induced reactive oxygen species. We have, therefore, analyzed the immunohistochemical reactivity for two major free radical scavengers, copper/zinc and manganese superoxide dismutase (Cu/Zn- and Mn-SOD's) in three situations of hepatic iron overload, and compared enzyme patterns with grades of iron deposition, grades of fibrosis, and levels of microphotometrically measured type IV collagen immunoreactivity. Cu/Zn- and Mn-SOD reactivity was detectable in hepatocytes with a heavy and a low iron burden, but Cu/Zn-SOD staining was more intense than that of Mn-SOD in the three groups analysed. There was trend for microphotometrically measured type IV collagen levels to increase with the amount of iron, and increased collagen IV was correlated with higher grades of Cu/Zn-SOD, but not of Mn-SOD, reactivity. The findings suggest that the two SOD's may be differentially expressed in states of hepatic iron overload, and that low expression of the inducible radical scavenger, Mn-SOD, may play a role in chronic iron toxicity.

Adult↗

PubMed1994

Vascular somatostatin receptors in synovium from patients with rheumatoid arthritis.

The peripheral nervous system and its neuropeptidergic pathways may play an important role in the pathogenesis and development of rheumatoid arthritis. In the present study, the role of the neuropeptide somatostatin (SRIF), which was recently shown to be implicated in inflammatory diseases of the gastrointestinal tract, was evaluated by measuring the expression of somatostatin receptors in synovium from patients with rheumatoid arthritis. Somatostatin receptors were detected using in vitro receptor autoradiography in the synovium from five patients with active disease. No receptors were found in one case, a successfully treated patient with quiescent disease. The receptors were of high affinity and specific for biologically active somatostatin analogs. Displacement by nanomolar concentrations of somatostatin-14, somatostatin-28, and octreotide was observed, suggesting that most of the receptors identified belong to the SRIF1A subtype. The somatostatin receptors were preferentially located in blood vessels, with specific labeling of the veins but not of the arteries. The whole vessel wall was homogeneously labeled including the smooth muscle cells and probably the endothelium. These data suggest that the synovium in active rheumatoid arthritis expresses a high density of somatostatin receptors. Somatostatin may act through these venous receptors to influence the inflammatory process by induction of vasoconstriction, inhibition of plasma extravasation and cell migration, or inhibition of neovascularization.

Aged↗