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J Gogusev

Publications and source records attributed to J Gogusev.

At least 19 recordsLinked to original sources
PubMed2006

Expression of c-KIT oncoprotein in gastrointestinal stromal tumors in adults and children: guideline for diagnosis and treatment.

Gastrointestinal stromal tumors (GISTs) represent a distinct oncogenetic entity that is now center stage in clinical trials of kinase-targeted therapies. These neoplasms express the c-KIT oncoprotein and occur predominantly in adults, more rarely in children. Two selected cases of GIST expressing c-KIT, including one adult patient and a 9-year-old boy are presented. The adult patient was admitted for palpable abdominal mass without other clinical symptoms. On biopsies obtained by scanner-guided procedure, diagnosis of ganglioneurinoma was proposed with the remark that GIST tumor could not be categorically excluded. At surgery, voluminous encapsulated tumor located at the jejunal wall was found and totally excised. The second patient presented with acute upper gastrointestinal hemorrhage associated with several months history of general fatigue and loss of appetite. Computed tomography (CT) and magnetic resonance imaging (MRI) showed a tumoral mass arising from the lesser curvature of the stomach compatible with GIST. Two small metastatic lesions in the liver were also detected. Combined treatment by surgery and systemic therapy by the tyrosine kinase inhibitor imatinib mesylate was applied.

Benzamides↗
PubMed2000

Absence of response to human parathyroid hormone in athymic mice grafted with human parathyroid adenoma, hyperplasia or parathyroid cells maintained in culture.

In athymic mice we have developed a model of long-term human PTH hypersecretion, using xenotransplantation of respectively parathyroid gland fragments obtained from patients with primary (primary) or secondary (secondary) uremic hyperparathyroidism (HPT), and parathyroid cells maintained in culture from patients with secondary uremic HPT. Both grafted parathyroid tissue fragments and cultured cells induced prolonged and marked secretion of human intact PTH (iPTH) in nude mice. Despite extremely high plasma iPTH levels, hypercalcemia or hypophosphatemia was not observed. Moreover, PTH secretion was not significantly modified by low-calcium, high-phosphate diet for 3 weeks. Four mice which had a mean plasma human iPTH level of 237+/-152 pg/ml for more than 9 months and 4 age-matched, sham-grafted control mice with undetectable human iPTH levels underwent bone histomorphometry examination. No difference was found between the two groups with respect to active bone resorption surface or number of osteoclasts/mm2. We hypothesize that the characteristic deficit of T cell function and of cytokine and growth factor production may protect nude mice with chronic hypersecretion of human PTH from hypercalcemia and bone lesions. We suggest that this strain of mice could be used for better understanding the relationship between cytokines and bone turnover.

Adenoma↗
PubMed2000

Apoptosis in parathyroid hyperplasia of patients with primary or secondary uremic hyperparathyroidism.

BACKGROUND: Chronic oversecretion of parathyroid hormone (PTH) is associated with parathyroid hyperplasia, reflecting a disturbed balance between cell proliferation and apoptosis. This study addressed the unsolved issue of apoptosis in hyperparathyroidism. METHODS: Parathyroid glands from 19 patients with primary (1 degrees ) and 11 patients with secondary (2 degrees ) uremic hyperparathyroidism, as well as 13 normal parathyroid glands, were examined. Apoptosis was evaluated by terminal deoxynucleotidyl transferase (Tdt)-mediated dUTP nick end-labeling assay (TUNEL). Because the apoptotic process is regulated by several oncoproteins, the expression of Bcl-2 and Bax was analyzed by immunohistochemistry. RESULTS: The numbers of apoptotic cells in 1 degrees parathyroid adenoma (0.99 +/- 0.03 per 1000 cells, mean +/- SE, P < 0.009) and 2 degrees parathyroid hyperplasia (1.20 +/- 0.54 per 1000 cells, P < 0.005) were significantly higher than in normal parathyroid tissue (0.13 +/- 0. 06 per 1000 cells). Light microscopy examination of hyperplastic parathyroid tissue from a uremic patient showed the presence of nuclei with dense chromatin characteristic of apoptosis. Bcl-2 staining was strong in normal tissues but weak or negative in several sections of 1 degrees and 2 degrees hyperparathyroid tissues, mostly in nodular areas. Bax staining was homogeneous in normal tissue but patchy in several hyperplastic tissues. CONCLUSION: These results suggest that hyperparathyroidism is associated with a compensatory increase in apoptosis, possibly favored by a diminished Bcl-2/Bax ratio. This renders highly improbable the hypothesis that parathyroid hyperplasia is due to a decreased rate of apoptosis.

Apoptosis↗
PubMed2000

Genetic abnormalities detected by comparative genomic hybridization in a human endometriosis-derived cell line.

Comparative genomic hybridization (CGH) was used in parallel with fluorescence in-situ hybridization (FISH) and conventional karyotyping to perform a genome-wide survey of DNA gains and losses in the endometriosis-derived permanent cell line, FbEM-1. The cytogenetic analysis showed a complex karyotype with numerical changes and multiple chromosome aberrations, including the der(1) complement marker exhibiting a large homogenous staining region (HSR). The chromosomal rearrangement interpreted as der(5) t(5;6)(q34;p11) was found in the majority of the metaphases indicating a clonal abnormality. Repeated CGH experiments demonstrated over-representation of chromosomes 1, 2, 3, 5, 6p, 7, 16, 17q, 20, 21q and 22q, while chromosomes 6q, 9, 11p, 12, 13q, 18 and X were under-represented. Using DNA from the original endometriotic tissues, including a peritoneal implant and ovarian endometrioma, CGH analysis revealed loss of DNA copy number on 1p, 22q and chromosome X, while gain was found on chromosomal arms 6p and 17q. FISH analysis confirmed that the gain at 17q includes amplification of the proto-oncogene HER-2/neu in 16% of the FbEM-1 nuclei and in 12% of cells from the primary ovarian endometrioma tissue. These findings demonstrate that FbEM-1 cells share certain molecular cytogenetic features with the original tissue and suggest that chromosomal instability is important in the development of endometriosis.

Cell Line↗
PubMed2000

Potential role of macrophage colony-stimulating factor in the proliferation of DEL cells.

The replication and activation of both vascular smooth muscle cells and macrophages, which have previously entered the arterial wall, are key events in the atherosclerotic process. The importance of macrophage colony-stimulating factor (MCSF) in control of the growth/proliferation of both cell types confers to this compound a central role in the development of vascular lesions. In order to gain insight into the mechanisms of macrophage proliferation, we investigated the effect of MCSF upon the proliferation of DEL cells. DEL cells constitute a monocyte/histiocytic cell line that differentiates along a macrophage lineage following exposure to phorbol ester. DEL cells constitutively express MCSF, and its receptor MCSFR is encoded by c-fms. We examined whether MCSF might play a role in the proliferation of cultured DEL cells. [3H]Thymidine or 5-bromo-2-deoxyuridine (BrdU) incorporation was measured following the addition of recombinant MCSF or L929 cell supernatant (as a source of MCSF) to quiescent DEL cells. In DEL cells, serum-free L929 cell supernatant induced DNA synthesis in a dose-dependent manner, and such an effect could be blunted by pretreatment of L929 cell supernatant with anti-mouse MCSF antibody. In these cells, DNA synthesis could also be triggered in a dose-dependent manner by the addition of recombinant human MCSF (rh MCSF) or thrombin. These findings clearly show that MCSF influences DEL cell proliferation and suggest an autocrine loop activation. They indicate that MCSF plays an important role in the development of vascular lesions, which occur during atherosclerotic progression.

Cell Division↗
PubMed1999

Detection of DNA copy number changes in human endometriosis by comparative genomic hybridization.

Endometriosis is characterized by infertility and pelvic pain in 10-15% of women of reproductive age. The genetic events involved in endometriotic cell expansion remain in large part unknown. To identify genomic changes involved in development of this disease, we examined a panel of 18 selected endometriotic tissues by comparative genomic hybridization (CGH), a molecular cytogenetic method that allows screening of the entire genome for chromosomal gains and/or losses. The study was performed on native, nonamplified DNA extracted from manually dissected endometriotic lesions. Recurrent copy number losses on several chromosomes were detected in 15 of 18 cases. Loss of chromosome 1p and 22q were detected in 50% of the cases. Additional common losses occurred on chromosomes 5p (33%), 6q (27%), 7p(22%), 9q (22%), 16 (22%) as well as on 17q in one case. Gain of DNA sequences were seen at 6q, 7q and 17q in three cases. To validate the CGH data, selective dual-color FISH was performed using probes for the deleted regions on chromosomes 1, 7 and 22 in parallel with the corresponding centromeric probes. Cases showing deletion by CGH all had two signals at 1p36, 7p22.1 and 22q12 in less than 30% of the nuclei in comparison to the double centromeric labels found in more than 85% of the cells. These findings indicate that genes localized to previously undescribed chromosomal regions play a role in development and progression of endometriosis.

Chromosome Aberrations↗
PubMed1999

[Macrophage colony-stimulating factor production and c-fms expression in cultured rat aortic vascular smooth muscle cells].

The resulats of this study are as follows. (1) As measured by a bioassay, a macrophage colony-stimulating activity was detected in the serum-free conditioned medium of rat aortic vascular smooth muscle cells (VSMCs), which could be subdued by the addition of specific anti macrophage colony-stimulating factor (MCSF) antibody. (2) The presence of MCSF receptor was confirmed by immunocytochemistry using a specific anti c-Fms antibody. (3) The presence of mRNAs for MCSF and c-fms (which encoded MCSF receptor) was determined by Northern blot analysis. Their expressions were detectable in quiescent VSMCs and markedly increased after addition of serum. These data demonstrated for the first time the production of MCSF and the presence of MCSF receptor in cultured rat VSMCs. It is suggested that MCSF might modulate VSMCs functions via both autocrine and paracrine mechanisms. Rat VSMCs appear to be a suitable cell model for studying the cell proliferation effect of MCSF.

Animals↗
PubMed1998

Malignant histiocytosis. Histologic, cytochemical, chromosomal, and molecular data with a nosologic discussion.

Although myelomonoblastic leukemia is thought to originate from a malignant transformation of the stem cell of the mononuclear phagocyte system, malignant histiocytosis (MH) is classically assumed to represent a malignant change of the terminal and fixed elements of this system. Indeed, MH is characterized by the proliferation of large, clear, pleomorphic, "histiocytic-like" HLADR and CD30+ cells resulting in a nodal and extranodal disseminated neoplasm affecting preferentially and severely children and young adults. Although there is broad agreement on the clinicopathologic presentation of this condition, there is currently quite a controversy over the T-lymphoid or histiocytic origin of the proliferative cells that results in a nosologic discussion between the anaplastic large cell lymphoma (ALCL) advocates and the MH supporters. This article has dealt mainly with this nosologic discussion and with the contributions provided by the investigations performed on MH permanent cell lines. These in vitro studies have demonstrated that the proliferation is characterized by a unique chromosomal abnormality, the 5q35bp usually associated with a t(2;5) translocation generating a fusion gene NPM/ALK and the subsequent translation of p80 protein. Although it is known that no single chromosomal abnormality is strictly restricted to a cell lineage, this 5q35bp and associated translocations seem today to represent the hallmark for this condition. In view of these chromosomal aberrations, the CD30+ ALCLs represent a heterogeneous group because 15% to 50% express the NPM/ALK fusion gene. In addition, these in vitro investigations have shown that 5q35bp proliferative cells are glass-adherent, can develop an immunodependent phagocytosis, and are able to reduce NBT and produce TNF-alpha. More significantly, they express constitutively the c-fms (the receptor of the macrophage growth factor) and, under TPA stimulation, are able to modulate the expression of this receptor and its ligand, as well as TNF-alpha and IL-1. None of these cell lines express CD3, but several express CD68 and CD71. In contrast, genomic investigations have shown the underlying existence of monoallelic and even biallelic gene rearrangements for TCR beta and IgJH. In view of these discrepancies between the genomic and phenotypic features of these cells, the histogenetic debate should remain open but must take into account these new chromosomal and molecular data.

Adult↗
PubMed1998

Structural analysis of gene marker loci on chromosomes 10 and 11 in primary and secondary uraemic hyperparathyroidism.

BACKGROUND: The genetic molecular anomalies in patients with primary (I degree) and secondary (II degree) hyperparathyroidism (HPTH) are still largely unknown. In particular, the changes underlying monoclonal growth in the parathyroids of patients with II degree HPTH are not well understood. METHODS: We screened genomic DNA from a total of 30 patients with I degree HPTH and 29 patients with II degree uraemic HPTH for possible rearrangements or allelic losses of several gene markers located on chromosome 11p near the PTH gene, namely Ha-ras, IGF-2, WT1, and the PTH gene itself. In addition, two other gene markers, PRAD1 (localized on 11q13) and RET (localized on 10q11) were examined for possible structural alterations. Moreover, we used fluorescence in situ hybridization (FISH) which is another technique to detect numerical alterations of chromosome 11. RESULTS: The results show that one of 13 patients with I degree HPTH (8%) exhibited a rearrangement for the PRAD-1 gene. Loss of heterozygosity of Ha-ras locus was observed in one of 11 uraemic patients with II degree HPTH (9%). Three of 10 patients with I degree HPTH (30%) and one of 7 patients with II degree HPTH (14%) showed an allelic loss of the WT1 gene. No evidence of rearrangement or allelic loss was detected for the IGF-2, PTH or RET genes respectively. Using FISH method, three normal parathyroid gland, six I degree HPTH adenomas and eight II degree HPTH hyperplastic glands from uraemic patients were studied with centromeric probe for chromosome 11. Monosomy 11 was observed in one case of I degree HPTH and in one other case of II degree HPTH. CONCLUSION: Evidence of loss of heterozygosity for several genes located on human chromosome 11p has been found in a series of parathyroid glands from several patients with I degree and II degree uraemic HPTH, corresponding to monosomy of chromosome 11 in some cases.

Adult↗
PubMed1998

Amlodipine inhibition of serum-, thrombin-, or fibroblast growth factor-induced vascular smooth-muscle cell proliferation.

Atherosclerosis, like several other vascular diseases, exhibits structural and functional abnormalities resulting partially from an exaggerated proliferation of vascular smooth-muscle cells (VSMCs). Ca2+ channel blockers, such as amlodipine, have been suggested to retard or even prevent the progression of atherosclerosis. To determine the mechanisms involved in these effects, we investigated the influence of amlodipine on VSMC proliferation by using rat aortic VSMCs in culture. Amlodipine (0.1-10 microM) inhibited serum-, basic fibroblast growth factor (bFGF)-, and thrombin-induced VSMC proliferation and DNA synthesis in a concentration-dependent manner, as demonstrated by cell count and bromodeoxyuridine (BrdU)-incorporation measurements, respectively. Delayed addition of amlodipine after VSMC stimulation showed that the drug exerted its effect early in G1 phase of the cell cycle. This observation was confirmed by the finding that amlodipine did not influence DNA synthesis in VSMCs arrested to the G1/S boundary by hydroxyurea treatment. Consistent with its effects on VSMC growth/proliferation, amlodipine also decreased c-myc, c-fos, and c-jun protooncogene expression induced by serum, thrombin, or bFGF within 1 h after cell activation, as assessed by semiquantitative reverse transcriptase (RT)-polymerase chain reaction (PCR) analysis. The calcium channel agonist Bay K 8644, which counteracted the inhibition by nifedipine of bFGF-, thrombin- or serum-induced DNA synthesis, was ineffective to antagonize the inhibitory effect of amlodipine. The aforementioned effects of amlodipine were of similar amplitude, irrespective of the growth-enhancing agent used. This strongly indicates that amlodipine acts downstream of receptor activation to exert its antiproliferative action, probably early in the G1 phase of the cell cycle. Moreover, the lack of antagonistic effect between amlodipine and Bay K 8644 suggests that, in addition to its L-type Ca2+ channel inhibitory effect, amlodipine inhibits other intracellular signaling pathways. Such an interference of amlodipine with mitogenic signaling pathways might contribute to confer a blood vessel-protecting potential on amlodipine.

Amlodipine↗
PubMed1998

Persistence of Ca2+-sensing receptor expression in functionally active, long-term human parathyroid cell cultures.

An original human parathyroid cell culture model from uremic patients with IIo hyperparathyroidism has been developed, with its main feature being long-term functionally active viability up to 5 months, as assessed by persistent responsiveness to changes of extracellular Ca2+ concentrations ([Ca2+]e). In addition to the inhibitory effect of increasing [Ca2+]e, increasing extracellular phosphate exerted a biphasic effect on parathyroid hormone (PTH) secretion. The presence of the Ca2+-sensing receptor (CaR), on which depends the response to [Ca2+]e and its persistence, has been demonstrated in our culture system both by direct detection and by inhibition of its activity. CaR protein was detected by Western blot analysis with a specific anti-CaR antibody. CaR gene transcripts have been identified by reverse transcription-polymerase chain reaction analysis. mRNA (by in situ hybridization) and protein (by immunocytochemistry) expression were detected for both CaR and PTH. Adding a specific anti-CaR antibody to the medium induced a marked reduction of low [Ca2+]e-stimulated PTH release, which decreased to levels equivalent to those obtained in high [Ca2+]e medium. The described long-term functionality could be due to several factors, including the clustered cell type of culture yielded by our preparation procedure, the growth characteristics of hyperplastic uremic tissue, and the use of a phosphate-rich medium. The present model, because of its long-term functionality, is a unique tool for the exploration of PTH synthesis and secretion and for studies of parathyroid cell growth in vitro.

Animals↗
PubMed1997

Control of vascular smooth-muscle cell growth by macrophage-colony-stimulating factor.

Since in several vascular diseases abnormal vascular smooth-muscle cell (VSMC) proliferation is often associated with the presence of macrophages, we examined whether macrophage-colony-stimulating factor (M-CSF) might play a role in the control of VSMC growth. VSMCs were isolated from rat aorta and maintained in culture. Using a bioassay, a macrophage-colony-stimulating activity was detected in the serum-free supernatant of VSMCs, which could be inhibited by the addition of specific anti-M-CSF antibodies. The presence of M-CSF receptor protein and of M-CSF and M-CSF receptor gene transcripts was demonstrated by immunocytochemistry, using a specific anti-c-Fms antibody and Northern blot analysis respectively. [3H]Thymidine incorporation was measured following the addition to quiescent VSMCs of various dilutions of L929 cell supernatant (as a source of M-CSF) or of recombinant M-CSF. Both exogenous M-CSF and serum-free VSMC conditioned medium promoted DNA synthesis in a concentration-dependent manner, and this effect could be abrogated by the presence of a specific anti-M-CSF antibody. Under similar experimental conditions, L929 cell supernatant modulated proto-oncogene expression, as assessed by Northern blot analysis of c-fos, c-myc, egr-1 and junB. It was further demonstrated that M-CSF could act in synergy with thrombin, platelet-derived growth factor or basic fibroblast growth factor in promoting VSMC DNA synthesis. These results support the hypothesis that M-CSF affects the growth of cultured rat VSMCs through paracrine/autocrine mechanisms. Its effects at both the macrophage and the VSMC level confer to M-CSF a central role in the development of vascular lesions that occurs during atherosclerotic progression.

Actins↗
PubMed1997

Nitric oxide and the renin angiotensin system: contributions to blood pressure in the young rat.

The present study was designed to investigate the effects of chronic administration of the arginine analogue L-Name (50 mg/kg body weight), the angiotensin converting enzyme inhibitor, perindopril (2 mg/kg body weight), and perindopril (2 mg/kg) plus L-Name (50 mg/kg) on blood pressure, plasma renin activity, plasma angiotensinogen, and hepatic angiotensinogen mRNA levels in young and adult rats. The drugs were given daily from birth to day 21 to puppies and for 15 days to adults. Analytical procedures were performed on day 21 for the puppies and at 10 weeks for the adults. In puppies, blood pressure did not change with L-Name, it decreased to 45% of control values (P < 0.001) with perindopril, and decreased to 77% of control values (P < 0.05) with perindopril plus L-Name. In adults, blood pressure increased to 129% of control values (P < 0.02) with L-Name, decreased to 80% of control values (P < 0.05) with perindopril, and did not change with perindopril plus L-Name. Compared with controls, plasma renin activity was unchanged in puppies and adults with L-Name, undetectable in puppies and slightly increased in adults with perindopril, undetectable in puppies and slightly decreased in adults with perindopril plus L-Name. With L-Name, angiotensinogen mRNA levels were unchanged in puppies and slightly increased in adults, while plasma angiotensinogen levels were decreased (P < 0.05) in puppies and increased (P < 0.01) in adults; with perindopril, angiotensinogen mRNA levels were unchanged in puppies and slightly decreased in adults, while plasma angiotensinogen levels were undetectable in puppies and decreased (P < 0.05) in adults; with perindopril plus L-Name, angiotensinogen mRNA levels were unchanged in puppies while plasma angiotensinogen levels were undetectable in puppies and decreased (P < 0.01) in adults. This study suggests that during the early postnatal period (1) nitric oxide does not exert a basal vasodilator tone but contributes to the hypotensive state induced by perindopril, (2) angiotensin II is essential to maintain blood pressure, (3) and angiotensinogen mRNA levels are not influenced by nitric oxide or angiotensin II.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Depressed expression of calcium receptor in parathyroid gland tissue of patients with hyperparathyroidism.

The factors involved in abnormal parathyroid cell secretory function and growth in patients with primary (I degree) and secondary (II degree) hyperparathyroidism are still incompletely understood. We compared the expression of the calcium-sensing receptor (CaR) at the gene message and the protein level in parathyroid tissue obtained from patients with I degree non-uremic or II degree uremic hyperparathyroidism with that in normal parathyroid tissue, using in situ hybridization and immunohistochemistry techniques. The expression of the CaR mRNA and protein was reduced in most cases of I degree adenoma and II degree hyperplasia, compared with strong expression normal parathyroid tissue. In II degree hyperparathyroidism, expression of both receptor mRNA message and protein was often particularly depressed in nodular areas, compared with adjacent non-nodular hyperplasia. Decreased Ca-R expression in adenomatous and hyperplastic parathyroid glands would be compatible with a less efficient control of PTH synthesis and secretion by plasma calcium than in normal parathyroid tissue.

Adult↗
PubMed1996

De novo expression of transforming growth factor-alpha in parathyroid gland tissue of patients with primary or secondary uraemic hyperparathyroidism.

BACKGROUND: The factors involved in abnormal parathyroid cell secretory function and growth in patients with primary and secondary hyperparathyroidism are still incompletely understood. PATIENTS AND METHODS: We studied the expression of transforming growth factor-alpha (TGF-alpha), epidermal growth factor (EGF) and EGF receptor (EGF-R) at the gene message and the protein level in parathyroid tissue obtained from six patients with primary hyperparathyroidism, 15 patients with secondary uraemic hyperparathyroidism and five subjects with normal parathyroid tissue, using in situ hybridization and/or immunostaining technique. RESULTS: We found a consistent expression of TGF-alpha mRNA and protein in parathyroid endocrine cells of all six cases of primary parathyroid adenoma and in nearly all cases of secondary hyperplasia, in contrast to the absence of expression in normal parathyroid tissue. A marked expression of EGF-R mRNA and protein was also found in four of five tissue samples of primary parathyroid adenoma, in 13 of 15 tissue samples of secondary parathyroid hyperplasia and in most samples of normal parathyroid gland tissue. EGF mRNA and protein expression was undetectable in the majority of parathyroid tissue samples examined. CONCLUSION: Since TGF-alpha is known to bind to the EGF-R, the finding of an increased expression of TGF-alpha at the gene message and the protein level, together with a strong expression of EGF-R, in hyperplastic and adenomatous parathyroid glands suggests that this growth factor interacts with its receptor to promote parathyroid cell proliferation, perhaps by an autocrine mechanism.

Adult↗
PubMed1996

Direct effect of erythropoietin on rat vascular smooth-muscle cell via a putative erythropoietin receptor.

BACKGROUND: The treatment of uraemic patients with recombinant human erythropoietin (rHuEpo) often leads to an increase in blood pressure. Indirect and direct effects of the hormone are probably involved. We explored the possibility of a direct action on the vascular smooth muscle cell (VSMC). METHODS: Rat VSMC were isolated from aortas of spontaneously hypertensive rats (SHR) and normotensive control rats (WKY) and maintained in culture. They were exposed to rHuEpo under various experimental conditions, and cells proliferative index was measured by [3H]-thymidine incorporation. Binding studies and Northern blots were performed in an attempt to identify a specific erythropoietin receptor (EpoR). In the latter experiment, Epo-responsive Rauscher Reds cells (Reds cells) were used as a positive control for mRNA EpoR expression. RESULTS: VSMC growth index of SHR was enhanced up to 1.6-fold by rHuEpo concentrations of 16 U/ml or more, in the presence of 1% fetal calf serum. No such stimulation was observed in VSMC of WKY. Binding studies with radiolabelled rHuEpo showed either extremely low or no specific binding of radiolabelled rHuEpo by VSMC. However, Northern blot analysis revealed the expression of EpoR mRNA in VSMC of either rat strain. CONCLUSION: The present report provides preliminary evidence in favour of a direct action of the hormone on vascular smooth muscle via a specific EpoR.

Animals↗