Biomedical subjects

Akira Ohtsuru

Publications and source records attributed to Akira Ohtsuru.

At least 37 records · Page 2Linked to original sources

PubMed2004

A rapid and simple detection method for the BRAF(T1796A) mutation in fine-needle aspirated thyroid carcinoma cells.

Fine-needle aspiration biopsy (FNAB) samples from thyroid tumor tissues were analyzed for the presence of the BRAF(T1796A) mutation by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) analysis. This assay utilized a specific mismatched primer and has proved to be a relatively simple, accurate, and highly sensitive method. The analysis of 130 aspirated samples from thyroid tumors (18 follicular adenomas, 72 papillary carcinomas [PTCs], 8 follicular carcinomas, 2 undifferentiated carcinomas, 1 medullary carcinoma, 2 malignant lymphomas, and 27 adenomatous goiters) revealed BRAF(T1796A) mutations in 37 (51.4%) of 72 PTCs, supporting the usefulness of this method. We examined BRAF(T1796A) in 21 patients with thyroid tumors using leftover cells in the needle at the preoperative FNAB. BRAF(T1796A) was detected in 4 patients, of which 3 cases were diagnosed as positive and 1 case as suspicious by cytologic examination. Furthermore, BRAF(T1796A) mutations were found to occur more often in tumors of 3 cm or larger in size. Our results indicate that the preoperative determination of the presence of a BRAF(T1796A) mutation by conventional PCR-RFLP may be potentially useful in the diagnosis of the most common thyroid malignancies.

Adenine↗

PubMed2004

Enhanced expression of interleukin-8 and activation of nuclear factor kappa-B in endoscopy-negative gastroesophageal reflux disease.

OBJECTIVE: Interleukin-8 (IL-8) mediates neutrophil trafficking via its receptors. Recent studies have shown that IL-8 is likely involved in the development and progression of erosive reflux esophagitis (RE), yet little is known about its implication in endoscopy-negative gastroesophageal reflux disease (GERD). The purpose of this study was to determine IL-8 messenger ribonucleic acid (mRNA) expression levels in endoscopy-negative GERD, along with assessment of nuclear factor kappaB (NF-kappaB) activation, which upregulates IL-8 expression. METHODS: We studied 31 patients with endoscopy-negative GERD, 15 patients with erosive RE, and 15 asymptomatic controls. Paired biopsy samples were taken from the esophagus 3 cm above the gastroesophageal junction; one biopsy was snap-frozen for measurement of IL-8 mRNA levels by real-time quantitative polymerase chain reaction, and another was formalin-fixed for histopathological evaluation. In nine endoscopy-negative GERD patients, the IL-8 mRNA expression levels were measured before and 8 wk after treatment with lansoprazole. We also sampled additional specimens for NF-kappaB-DNA binding assay and immunohistochemical analyses of NF-kappaB p65 and p50 subunits, IL-8 and specific IL-8 receptor, CXCR-1. RESULTS: The relative IL-8 mRNA expression levels were significantly higher in esophageal mucosa of patients with endoscopy-negative GERD than those of the controls. The presence of basal zone hyperplasia and intraepithelial neutrophils, histopathological hallmarks of GERD, were associated with higher levels of IL-8 mRNA. Lansoprazole treatment significantly reduced the IL-8 mRNA expression levels. The esophageal epithelium of patients with GERD showed intense immunoreactivity for IL-8, and expressed CXCR-1 antigen. We found NF-kappaB activation in esophageal mucosa in GERD patients and the NF-kappaB subunits were localized predominantly in the nuclei of IL-8-expressing cells. CONCLUSIONS: Our results demonstrate enhanced mucosal expression of IL-8 in incipient GERD even without mucosal breaks. NF-kappaB activation may be implicated in the pathogenesis in GERD.

Adult↗

PubMed2004

Inhibition of nuclear factor-kappaB cascade potentiates the effect of a combination treatment of anaplastic thyroid cancer cells.

Nuclear transcription factor-kappaB (NF-kappaB) is a transcriptional complex that is rapidly activated in the course of an immediate early response of cells after exposure to different stresses including ionizing radiation (IR). To overcome the limitation of radiation therapy for thyroid cancers, we studied the response of the NF-kappaB cascade to IR in cultured normal human thyroid cells and various thyroid cancer cell lines. Exposure to IR resulted in a dose-dependent increase of DNA-binding activity of p65 and p50 subunits in all types of thyroid cells. Specific inhibitors of NF-kappaB or phosphorylation deficient mutant inhibitory protein IkappaBalpha reduced thyroid cancer cell survival after exposure to IR and enhanced IR-induced cell death in a model undifferentiated thyroid cancer cell line. Tumors harboring mutant IkappaBalpha implanted into nude mice exhibited delayed growth rate and increased radiosensitivity. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling and annexinV-propidium iodide staining revealed the increase of radiation-induced apoptosis in the cells with inhibited NF-kappaB signaling. Our results indicate that radiosensitivity of transformed thyroid cells is due in part to elevated basal activity and rapid induction of the active form of NF-kappaB. We therefore suggest that inhibition of NF-kappaB could be an effective modality for radiation therapy of advanced human thyroid cancers.

Animals↗

PubMed2004

Low frequency of BRAFT1796A mutations in childhood thyroid carcinomas.

A high prevalence of the activating BRAF mutation, BRAF(T1796A), is observed in adult papillary thyroid carcinomas (PTCs). The prognosis of childhood PTCs is generally fairly good despite the fact that distant metastases are often documented in these cases. To investigate the differences between the characteristics of childhood and adult PTCs, we analyzed both BRAF(T1796A) and RAS mutations in 31 Japanese and 48 post-Chernobyl Ukrainian thyroid carcinomas. In the 31 Japanese childhood cases, BRAF(T1796A) was found in only one instance (3.2%), and no RAS mutations were detected. In the Ukrainian subjects, of the 15 childhood and the 33 adolescent and young adult PTCs examined, the BRAF(T1796A) mutation was found in zero and eight cases, respectively, and RAS mutations were found in two of the young adult cases. In addition, 17 of the 48 Ukrainian cases showed expression of the RET tyrosine kinase region, indicating the existence of RET/PTC rearrangements. Unlike adult PTCs, we could detect no positive association between BRAF(T1796A) mutations and clinical parameters in the childhood carcinomas, suggesting that a low prevalence of BRAF(T1796A) is a common feature of PTCs in children regardless of radiation exposure levels. The differences in the prevalence of BRAF(T1796A) mutations between childhood and adult cases of PTC may well reflect inherent differences in the clinical features of these cancers between the two age groups.

Adolescent↗

PubMed2004

High brachial-ankle pulse wave velocity is an independent predictor of the presence of coronary artery disease in men.

Pulse wave velocity (PWV) is an index of arterial stiffness, and a simple device for measuring brachial-ankle PWV (baPWV) has recently been developed. However, the clinical application of baPWV in patients with coronary artery disease (CAD) remains to be fully evaluated. This cross-sectional study was conducted to evaluate whether a higher baPWV predicts the presence of CAD. The baPWV was measured in 123 patients (77 males, 46 females; 63.5+/-11.8 years) who were undergoing coronary angiography. CAD was defined as >50% diameter stenosis. Hemodynamic data and cardiovascular risk factors were examined according to the presence or absence of CAD. Patients with CAD were significantly older across both sexes. The presence of hypertension and chest pain, but not baPWV, was correlated with CAD in females. The baPWV, and the presence of diabetes, hyperlipidemia, and chest pain were related to the presence of CAD in males. Multivariate logistic regression analysis in male patients showed that baPWV, diabetes, hyperlipidemia, and chest pain were independent risk factors for the presence of CAD. Furthermore, high baPWV in males with or without chest pain had a positive predictive value of 81.8% and 71.7% for the presence of CAD, respectively. In conclusion, high baPWV was shown to be a good independent predictor for the presence of CAD in men.

Adult↗

PubMed2004

Thyroglobulin-pulsed human monocyte-derived dendritic cells induce CD4+ T cell activation.

Although thyroglobulin (Tg) would be expected to act as a tumor-associated antigen that might be exploitable by immunotherapy against thyroid cancers, it remains unclear how to effectively enhance the immune response to Tg in human since it is a self-component glycoprotein. We therefore tested whether and how human peripheral blood (PB) monocyte-derived dendritic cells (DCs) pulsed with human (h)Tg would induce activation of hTg-specific T cells. We found that immature DCs (iDCs) exhibited a higher endocytic capacity for fluorescein isothiocyanate-conjugated hTg than did mature DCs (mDCs). Although freshly isolated T cells responded poorly to mDCs, hTg-primed T cells responded much more strongly to hTg pulsed mDCs, which selectively induced IFN-gamma-secreting T cells. These results suggest that hTg-pulsed mDCs enhance the responses of Tg-specific T cells, raising the possibility that vaccination with hTg-pulsed mDCs may be an effective approach as immunotherapy to potentiate thyroid cancer specific therapy.

CD4-Positive T-Lymphocytes↗

PubMed2004

[Gastrectomy].

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Anastomosis, Roux-en-Y↗

PubMed2003

Novel tumorigenic rearrangement, Delta rfp/ret, in a papillary thyroid carcinoma from externally irradiated patient.

Molecular analysis of cDNA derived from a papillary thyroid carcinoma (PTC) (follicular variant of papillary thyroid carcinoma on histology) which developed in an externally irradiated patient 4 years after exposure identified a portion of the 5' region, exons 1-3, of the rfp gene juxtaposed upstream of the fragment encoding the tyrosine kinase (TK) domain of the ret gene. The fusion gene, termed Delta rfp/ret, was the result of a balanced chromosomal translocation t(6;10) (p21.3;q11.2) confirmed by interphase FISH painting, with breakpoints occurring in introns 3 and 11 of the rfp and ret genes, respectively. Both Delta rfp/ret and reciprocal ret/rfp chimeric introns had small deletions around breakpoints consistent with presumed misrepair of a radiation-induced double-strand DNA break underlying the rearrangement. No extensive sequence homology was found between the fragments flanking the breakpoints. The fusion protein retained the propensity to form oligomers likely to be mediated by a coiled-coil of the RFP polypeptide as assessed by a yeast two-hybrid system. NIH 3T3 fibroblasts stably transfected with a mammalian expression vector encoding full-length Delta RFP/RET readily gave rise to the tumors in athymic mice suggestive of high transforming potential of the fusion protein. Thus, the Delta rfp/ret rearrangement may be involved in a causative manner in cancerogenesis and provides additional evidence of the role of activated ret oncogene in the development of a subset of papillary thyroid carcinoma.

3T3 Cells↗

PubMed2003

Expression of Tie-2 and angiopoietin-1 and -2 in early phase of ulcer healing.

BACKGROUND: Angiogenesis is an important process in tissue development and wound healing. The Tie-2 receptor tyrosine kinases and ligands, angiopoietin (Ang)-1 and -2 have been postulated to play key roles in vascular development. The purpose of this study was to evaluate the expression of Tie-2 and Ang-1 and -2 in an acetic acid-induced gastric ulcer healing process in rats. METHODS: Gastric specimens were obtained at 0 (control), 1, 3, 5, 7, and 14 days after ulcer induction for reverse transcription polymerase chain reaction (RT-PCR), Western blot analysis, and immunohistochemical analysis. RESULTS: Expression of Tie-2 and Ang-1 and -2 mRNAs was detected in normal gastric tissue and ulcerative tissues by RT-PCR. Western blot analysis revealed that Tie-2 expression reached a maximum on the third to fifth days. Expression of Ang-1 and -2 peaked on the first day. Ang-1 expression gradually became weaker in 2 weeks, whereas Ang-2 expression returned to normal in a few days. Immunohistochemically, Tie-2 was expressed constitutively in the endothelial cells of pre-existing vessels of the gastric wall, and Tie-2 expression was increased in the new capillaries of the ulcer base. CONCLUSIONS: These findings suggest that Tie-2 and Ang-1 and -2 play an important role in angiogenesis in the early phase of ulcer healing.

Angiogenesis Inducing Agents↗

PubMed2003

Insulin-like growth factor-I enhances transforming growth factor-beta-induced extracellular matrix protein production through the P38/activating transcription factor-2 signaling pathway in keloid fibroblasts.

Keloids are benign dermal tumors, characterized by invasive growth of fibroblasts and concomitant increased biosynthesis of extracellular matrix components, with unclear etiology. We previously demonstrated that keloid fibroblasts overexpress insulin-like growth factor-I receptor. In investigating the role of insulin-like growth factor-I receptor overexpression, insulin-like growth factor-I and transforming growth factor-beta interaction was examined in relation to extracellular matrix protein production in cultured human and mouse fibroblasts. Western blotting revealed that collagen type I was expressed in keloid and normal fibroblasts, and its expression was increased by transforming growth factor-beta stimulation more significantly in keloid rather than in normal fibroblasts. Insulin-like growth factor-I and transforming growth factor-beta1 costimulation markedly increased extracellular matrix proteins (collagen type I, fibronectin, and plasminogen activator inhibitor-1) compared with cultures with transforming growth factor-beta1 alone. Insulin-like growth factor-I treatment alone had no stimulatory effect. Real-time reverse transcription-polymerase chain reaction confirmed parallel collagen type I messenger RNA level changes. Luciferase assays were conducted to investigate intracellular signaling pathways in this synergistic stimulation using a mouse fibroblast cell line. Transforming growth factor-beta1 (1 or 10 ng per ml) increased the specific signaling activity approximately 10-fold, whereas the increase with insulin-like growth factor-I (100 ng per ml) was less than 2-fold compared with basal activity; however, the combination of transforming growth factor-beta1 and insulin-like growth factor-I resulted in an approximately 25-fold increase. Insulin-like growth factor-I markedly enhanced transforming growth factor-beta-induced phosphorylation of p38 mitogen-activated protein kinase and activating transcription factor-2. Luciferase assay showed that this synergistic effect was attenuated by the p38 mitogen-activated protein kinase specific inhibitor SB203580 or phosphatidylinositol 3-kinase inhibitor wortmannin, but not by the mitogen-activated protein kinase/extracellular-signal-regulated protein kinase kinase inhibitor PD98059. These results indicate that insulin-like growth factor-I enhances transforming growth factor-beta-induced keloid formation through transforming growth factor-beta postreceptor signal cross-talk, mainly via the p38 mitogen-activated protein kinase/activating transcription factor-2 pathway.

3T3 Cells↗

PubMed2003

Expression of parathyroid hormone (PTH)-related peptide (PthrP) and PTH/PTHrP receptor in osteoclast-like giant cells.

Osteoclast-like giant cells (OCGC), which resemble osteoclasts at both the morphologic and immunohistochemical levels, develop in neoplastic tissue. In bone marrow, parathyroid hormone (PTH)-related peptide (PTHrP) can induce osteoclast differentiation by stimulating osteoclast progenitors through the PTH/PTHrP receptor (PPR). To evaluate the possible involvement of PTHrP in OCGC formation in tumors, we analyzed both PTHrP and PPR expression by immunohistochemistry in giant cell tumor of bone (GCTB) and anaplastic thyroid cancer (ATC) containing OCGC. In all cases of either GCTB (n = 5) or ATC (n = 4), intense stainingfor PTHrP was found in OCGC, but only faintly in mononuclear cells. PPR expression in OCGC was also demonstrated in 3 cases of GCTB and 2 cases of ATC. Double staining for PPR and proliferating cell nuclear antigen (PCNA) revealed that PPR was mainly expressed by PCNA-negative mononuclear cells and OCGC in these tumors. This suggests that OCGC might be derived from non-proliferating mononuclear cells by PTHrP stimulation via PPR. Furthermore, the profiles of PTHrP and PPR expression in OCGC were compared with those in the neoplastic GC found in malignancy (n = 6), osteoclasts in bone with osteoarthritis (n = 5), reactive GC, including Langhans-type and foreign body-type in pulmonary tuberculosis (n = 8), and ruptured epidermal cyst (n = 14) in order to clarify whether their distribution pattern was unique to OCGC. In all cases of malignancy, expression of both PTHrP and PPR was observed ubiquitously in neoplastic GC and mononuclear cells regardless of PCNA immunoreactivity. In contrast, in osteoclasts and reactive GC, PTHrP immunoreactivity was seen in all cases and in 7 of 22 cases, respectively, but no PPR expression was observed in either. In situ hybridization confirmed PTHrP expression at the transcriptional level in OCGC and neoplastic GC, but not in osteoclasts. Thus, although PTHrP expression was commonly observed in various types of multinucleated giant cells, their immunohistochemical profiles for PPR were distinct. We conclude that PPR might play a role during OCGC formation in GCTB and ATC.

Carcinoma↗

PubMed2003

The selective tyrosine kinase inhibitor, STI571, inhibits growth of anaplastic thyroid cancer cells.

To establish a molecular targeting therapy for anaplastic thyroid carcinomas, we studied the effect of the specific tyrosine kinase inhibitor, STI571, on anaplastic thyroid cancer cell lines highly expressing c-ABL ARO (mutated p53) and FRO (undetectable p53). These lines showed marked inhibition of cell growth after treatment with STI571. In contrast, the growth of papillary thyroid cancer cell lines that harbor wild-type p53 and have low levels of c-ABL was not affected by STI571. Fluorescent-activated cell sorting analysis revealed that STI571 treatment increased the fraction of FRO and ARO cells in S and G(2)/M phases, respectively, indicating induction of S and G(2)/M transition arrest. These changes were accompanied by inhibition of c-ABL phosphorylation/activation and increased expression of p21(cip1) in FRO and p27(kip1) in both FRO and ARO cells. Treatment with STI571 also led to reduction of cyclin A, B1, and CDC2 levels. The growth of FRO cells implanted into immunocompromised mice was significantly inhibited by STI571. Taken together, these results suggest that selective suppression of c-ABL activity by STI571 may represent a potential anticancer strategy for p53-mutated undifferentiated thyroid carcinomas.

Animals↗

PubMed2003

Clinical implication of hot spot BRAF mutation, V599E, in papillary thyroid cancers.

Activating mutations in the BRAF kinase gene have recently been reported in human cancers. The aim of the present study was to determine the frequency of BRAF mutations in thyroid cancer and their correlation with clinicopathological parameters. We analyzed exons 11 and 15 of BRAF gene in six human thyroid cancer cell lines and 207 paraffin-embedded thyroid tumor tissues. A missense mutation was found at T1796A (V599E) in exon 15 in four of the six cell lines and 51 of 207 thyroid tumors (24.6%; 0 of 20 follicular adenoma, 0 of 11 follicular carcinoma, 49 of 170 papillary carcinomas, and 2 of 6 undifferentiated carcinomas). Activation of MAPK kinase-MAPK pathway was observed in cell lines harboring BRAF mutation. BRAF mutation-associated enhanced cell growth was suppressed by MAPK kinase inhibitor, U0126. Examination of 126 patients with papillary thyroid cancer showed that BRAF mutation correlated significantly with distant metastasis (P = 0.033) and clinical stage (P = 0.049). Our results indicate that activating mutation of BRAF gene could be a potentially useful marker of prognosis of patients with advanced thyroid cancers.

Adult↗

PubMed2003

Impact of endoscopically minimal involvement on IL-8 mRNA expression in esophageal mucosa of patients with non-erosive reflux disease.

AIM: Little has been known about the pathogenesis of non-erosive reflux disease (NERD). Recent studies have implicated interleukin 8 (IL-8) in the development and progression of gastroesophogeal reflux disease (GERD). The purpose of this study was to determine IL-8 RNA expression levels in NERD patients with or without subtle mucosal changes. METHODS: We studied 26 patients with NERD and 13 asymptomatic controls. Biopsy sample was taken from the esophagus 3 cm above the gastroesophageal junction and snap frozen for measurement of IL-8 mRNA levels by real-time quantitative polymerase chain reaction (PCR). We also examined mRNA expression of IL-8 receptors, CXCR-1 and -2 by reverse transcriptase PCR. The patients were endoscopically classified into grade M (mucosal color changes without visible mucosal break) and N (neither minimal involvement nor mucosal break) of the modified Los Angeles classification. RESULTS: The relative IL-8 mRNA expression levels were significantly higher in esophageal mucosa of NERD patients than those in esophageal mucosa of the controls. There was a significant difference in IL-8 mRNA levels between grades M and N. The CXCR-1 and -2 mRNAs were constitutively expressed in esophageal mucosa. CONCLUSION: Our results suggest that high IL-8 levels in esophageal mucosa may be involved in the pathogenesis of NERD through interaction with its receptors. NERD seems to be composed of a heterogeneous population in terms of not only endoscopically minimal involvement but also immune and inflammatory processes.

Adult↗

PubMed2003

Bax cleavage implicates caspase-dependent H2O2-induced apoptosis of hepatocytes.

Oxidative stress plays an important role in the development of ischemia/reperfusion (I/R)-induced apoptosis of hepatocytes. We aimed to examine the involvement of caspases and calpains in H2O2-induced hepatic cell apoptosis. TUNEL-positive apoptotic cells appeared in parallel with poly(ADP-ribose) polymerase (PARP) cleavage and procaspase-3 proteolysis by H2O2 treatment in a dose-dependent manner (250-1,000 micro M). Bcl-xL and intact Bax expression levels decreased when H2O2 was >250 micro M. The cleaved form of Bax appeared prior to caspase-3 activation, increasing in a dose-dependent manner. A pan-caspase inhibitor, Z-VAD-fmk, completely blocked H2O2-induced procaspase-3 proteolysis and PARP cleavage without changing Bax cleavage, but partially attenuated H2O2-induced apoptosis. Calpeptin, a calpain inhibitor, did not inhibit caspase-3 activation, Bax cleavage or apoptosis. Our results indicate that Bax cleavage is upstream signal of caspase-dependent apoptosis in hepatocytes exposed to H2O2, but not independent upon calpain. Molecular targeting of Bax cleavage may allow the development of strategies to prevent hepatic I/R injury.

Amino Acid Chloromethyl Ketones↗

PubMed2002

Large deletions in mitochondrial DNA in radiation-associated human thyroid tumors.

Paired DNA samples of tumor and normal thyroid tissue from adult patients possibly exposed to radioactive Chernobyl fallout [11 cases of papillary thyroid carcinoma (PTC) and 6 follicular adenomas] and from control samples (9 PTC occurring in Japanese patients) were examined for the relative mitochondrial DNA (mtDNA) content, prevalence and level of common deletion (CD), and large-scale deletions in mtDNA. Elevated relative mtDNA content as estimated by real-time PCR was found in tumor tissue in most cases, but no significant correlation with the level of radioiodine contamination of patients' residency nor with clinicopathological data were found. CD was detected in every DNA specimen from all types of tissue regardless of the presence of oxyphillic cell changes. Elevated level of the CD was predominantly found in tumor tissue of the radiation-associated group but not in sporadic PTC. No correlation was noted with clinicopathological parameters, radioiodine contamination, and relative mtDNA content. The quantity of large-scale deletions in mtDNA was elevated in most tumor tissues, especially in the radiation-associated group and tended to correlate with the level of radiopollutant in PTC. In contrast to sporadic PTC, highly significant-positive correlation between the presence of large scale mtDNA deletions and relative mtDNA content was found in radiation-associated tumors (P = 0.001 and P = 0.019 in PTC and follicular adenoma, respectively). Normal tissue displayed the inverse tendency. No association with level of the CD was found in either group of cases. Concordant increase of both relative mtDNA content and number of mtDNA deletions was detected more often in radiation-associated PTC than in sporadic PTC. Thus, simultaneous determination of the number of large-scale mtDNA deletions and relative mtDNA content may be useful to elucidate molecular distinctive features of radiation-associated thyroid tumors.

Adenoma↗

PubMed2002

Role of c-Fyn in FGF-2-mediated tube-like structure formation by murine brain capillary endothelial cells.

Tube formation of endothelial cells is an important step of angiogenesis. However, little is known about the molecular mechanisms underlying growth factor-mediated tube formation by endothelial cells. FGF-2 stimulates tube formation by a murine brain capillary endothelial cell line, IBE cells, when cultured on collagen gels (differentiation-associated culture condition), whereas cells proliferate and migrate without forming tube on fibronectin-coated surface (proliferation/migration-associated condition). To elucidate FGF-2-mediated signal transduction pathways leading to tube formation by endothelial cells, we focused on the contribution of Src family kinases. Src family kinase inhibitor PP2 attenuated FGF-2-induced tube formation. Stable expression of kinase-inactive c-Src in IBE cells demonstrated no dominant negative effect on FGF-2-induced tube formation. In vitro kinase assay revealed that c-Fyn was activated by FGF-2 only in cells cultured on collagen gels. Three independent cell lines, expressing kinase-inactive c-Fyn, all exhibited attenuation of FGF-2-mediated tube formation. However, FGF-2-mediated proliferation or migration was not clearly perturbed in these cells. These results show the first time that c-Fyn plays a pivotal role in tube formation by endothelial cells.

Animals↗

PubMed2002

Preventive effects of parathyroid hormone-related peptide on stress-induced gastric hypercontraction in the rat.

BACKGROUND AND AIMS: Parathyroid hormone-related peptide (PTHrP) appears to be a potent smooth muscle relaxant, but there has been no study of its effects on gastric motility in vivo. The purposes of this study were to evaluate the effects of external PTHrP on stress-induced gastric motility in vivo and on the expression of PTHrP and PTH/PTHrP receptors in the rat stomach. METHODS: Stress-induced hypercontraction was evoked by restraint water immersion (RWI). Gastric motility was evaluated with a strain gauge force transducer, and the effects of external PTHrP-(1-34) (10 micro i.p.) on gastric motility were examined. Expressions of PTHrP and PTH/PTHrP receptor mRNA were evaluated by RNase protection assay. RESULTS: External PTHrP significantly suppressed abnormal contraction and mucosal lesions upon RWI stress. Upon RWI stress, the expression of PTHrP mRNA decreased, but that of PTH/PTHrP receptor mRNA was enhanced reciprocally. The PTH/PTHrP receptor was localized in smooth muscle cells of the muscle layers immunohistochemically. CONCLUSIONS: These findings suggest that smooth muscle contractile activity is modified by the autocrine/paracrine mechanism of PTHrP in the rat stomach and that the external PTHrP prevents stress-induced hypercontraction and mucosal lesions.

Animals↗