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61.
Adrenomedullin regenerates alveoli and vasculature in elastase-induced pulmonary emphysema in mice 总被引:2,自引:0,他引:2
Murakami S Nagaya N Itoh T Iwase T Fujisato T Nishioka K Hamada K Kangawa K Kimura H 《American journal of respiratory and critical care medicine》2005,172(5):581-589
RATIONALE: Adrenomedullin, a potent vasodilator peptide, regulates cell growth and survival. However, whether adrenomedullin contributes to lung regeneration remains unknown. OBJECTIVES: To investigate whether adrenomedullin influences the kinetics of bone marrow cells, and whether adrenomedullin promotes regeneration of alveoli and vasculature and thereby improves lung structure and function in elastase-induced emphysema in mice. METHODS: Adrenomedullin or vehicle was randomly administered to C57BL/6 mice for 5 days. We counted the numbers of mononuclear cells and stem cell antigen-1-positive cells in circulating blood. After intratracheal injection of elastase or saline, mice were randomized to receive continuous infusion of adrenomedullin or vehicle for 14 days. Functional and histologic analyses were performed 28 days after treatment. RESULTS: Twenty-eight days after elastase injection, destruction of the alveolar walls was observed. However, adrenomedullin infusion significantly inhibited the increase in lung volume, static lung compliance, and mean linear intercept in mice given elastase. Adrenomedullin increased the numbers of mononuclear cells and stem cell antigen-1-positive cells in circulating blood. Adrenomedullin significantly increased the number of bone marrow-derived cells incorporated into the elastase-treated lung. Some of these cells were positive for cytokeratin or von Willebrand factor. Infusion of adrenomedullin after the establishment of emphysema also had beneficial effects on lung structure and function. In vitro, addition of adrenomedullin attenuates elastase-induced cell death in alveolar epithelial cells and endothelial cells. CONCLUSIONS: Adrenomedullin improved elastase-induced emphysema at least in part through mobilization of bone marrow cells and the direct protective effects on alveolar epithelial cells and endothelial cells. 相似文献
62.
Miyasaka K Ohta M Masuda M Kawanami T Matsumoto M Funakoshi A 《Archives of gerontology and geriatrics》1995,21(2):157-165
The gene expressions of cholecystokinin (CCK) in the proximal small intestinal mucosa and CCK-A receptor in the pancreas were examined in male and female young (4-8 months old) and old (26-29 months old) rats. Their concentrations of CCK in the intestine were also compared. In males, but not in females, the mRNA levels of CCK in the intestine and those of the CCK-A receptor in the pancreas were significantly lower in old than young rats. In females, but not in males, the tissue content of CCK in the proximal intestinal mucosa was significantly higher in old rats. The pancreatic wet weight and trypsin activity in the proximal lumen were similar in young and old rats of both sexes. Therefore, changes in the regulations of gene expressions of CCK and the CCK receptor with age differ in male and female rats. 相似文献
63.
Overexpression of adenylate cyclase‐associated protein 2 is a novel prognostic marker in malignant melanoma
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Yohei Masugi Keiji Tanese Katsura Emoto Ken Yamazaki Kathryn Effendi Takeru Funakoshi Mariko Mori Michiie Sakamoto 《Pathology international》2015,65(12):627-634
Malignant melanoma is one of the lethal malignant tumors worldwide. Previously we reported that adenylate cyclase‐associated protein 2 (CAP2), which is a well‐conserved actin regulator, was overexpressed in hepatocellular carcinoma; however, CAP2 expression in other clinical cancers remains unclear. The aim of the current study was to clarify the clinicopathological significance of CAP2 overexpression in malignant melanoma. Immunohistochemical analyses revealed that many melanoma cells exhibited diffuse cytoplasmic expression of CAP2, whereas no normal melanocytes showed detectable immunostaining for CAP2. A high level of CAP2 expression was seen in 14 of 50 melanomas and was significantly correlated with greater tumor thickness and nodular melanoma subtypes. In addition, a high level of CAP2 expression was associated with poor overall survival in univariate and multivariate analyses. For 13 patients, samples of primary and metastatic melanoma tissue were available: four patients exhibited higher levels of CAP2 expression in metastatic tumor compared to the primary site, whereas no patient showed lower levels of CAP2 expression in metastatic melanomas. Our findings show that CAP2 overexpression is a novel prognostic marker in malignant melanoma and that CAP2 expression seems to increase stepwise during tumor progression, suggesting the involvement of CAP2 in the aggressive behavior of malignant melanoma. 相似文献
64.
Yosuke Homma Takashi Shiga Yuiko Hoshina Kenji Numata Michiko Mizobe Yoshiyuki Nakashima Jin Takahashi Tetsuya Inoue Osamu Takahashi Hiraku Funakoshi 《The American journal of emergency medicine》2018,36(4):673-676
Objectives
Acute alcohol intoxication is often treated in emergency departments by intravenous crystalloid fluid (IVF), but it is not clear that this shortens the time to achieving sobriety. The study aim was to investigate the association of IVF infusion and length of stay in the ED.Methods
This single-center retrospective cohort study was conducted in Japan and included patients aged ≥ 20 years of age and treated for acute alcohol intoxication without or with IVF. The primary outcome was the length of the ED stay and the treatments were compared by time-to-event analysis.Results
A total of 106 patients, 42 treated without IVF and 64 with IVF. The baseline characteristics of the two groups were similar. Kaplan–Meier analysis and the generalized Wilcoxon test found no significant difference between the two treatments in the time to ED discharge. The median time was 189 (IQR 160–230) minutes without IVF and 254.5 (203–267 minutes with IVF; p = 0.052). A Cox proportional hazards regression model adjusted for potential confounding variables found that patients treated with IVF were less likely to be discharged earlier than those treated without IVF (HR 0.54, 95% CI: 0.35–0.84, p = 0.006).Conclusions
IVF for treatment of acute alcoholic intoxication prolonged ED length of stay even after adjustment for potential confounders. Patients given IVF for acute alcohol intoxication should be selected with care. 相似文献65.
Akira Sawa Akihiko Shimizu Takeshi Ueyama Yasuhiro Yoshiga Shinsuke Suzuki Naoki Sugi Makoto Oono Toshihide Oomiya Masunori Matsuzaki 《Circulation journal》2008,72(3):384-391
BACKGROUND: To investigate the activation patterns and conduction velocity (CV) in the posterolateral right atrial (RA) wall during typical counterclockwise atrial flutter (AFL) using an electroanatomic mapping system. METHODS AND RESULTS: During typical AFL in 25 patients, the transverse conduction pattern and CV were classified and calculated. The line blocking transverse conduction was defined by the conduction pattern and double potentials recorded during mapping. There were 3 types (including 2 subtypes) of transverse conduction pattern based on the conduction blocks across the posterolateral RA in a line between the superior and inferior venae cava. Trans-cristal conduction activation in a horizontal direction was seen in all but 4 patients. The CV in the gap area was 0.59+/-0.21 m/s. CONCLUSIONS: Three types of transverse conduction pattern were observed during trans-ctristal conduction and the trans-ctristal CV was relatively slower than that in other parts of the RA, except for the isthmus. 相似文献
66.
67.
The effects of a new cholecystokinin (CCK) antagonist (FK 480; 0.1 mg/kg per day given by intragastric administration to rats
for 3 days) on the expression of the CCK and secretin genes, plasma CCK immunoreactivity, and CCK content in the intestinal
mucosa were examined. FK 480 increased the level of CCK mRNA in the intestine to 1.7 times the level in control rats, but
did not affect the level of secretin mRNA. It did not increase plasma CCK immunoreactivity or CCK content in the intestinal
mucosa. These results suggest that the ingested FK 480 directly increased CCK mRNA level in the intestine and produced a dissociation
between the synthesis and release of CCK. 相似文献
68.
Funakoshi Y Shiono H Inoue M Kadota Y Ohta M Matsuda H Okumura M Eimoto T 《Journal of cancer research and clinical oncology》2005,131(5):314-322
Purpose Glucocorticoids exert anti-proliferative effects in various cell types and have long been known to induce apoptosis in thymocytes. Although a few reports have described the regression of human thymoma with glucocorticoid therapy, its effects on neoplastic thymic epithelial cells (TECs) have not been reported. In the present study, we investigated glucocorticoid receptor (GR) expression on neoplastic TECs and the effects of glucocorticoids in vitro on the cell cycle progression of tumor cells.Patients and methods Thymoma specimens were obtained during surgery from 21 patients. Three of the specimens with glucocorticoid therapy were examined using the TdT-mediated dUTP-biotin nick-end labeling method. Primary tumor specimens from ten untreated thymomas were examined for GR expression by immunohistochemistry. Isolated neoplastic TECs from the remaining eight untreated thymomas were examined using immunohistochemistry, flow cytometric and cell cycle analysis.Results GR are expressed on neoplastic TECs as well as on non-neoplastic thymocytes in thymomas, regardless of WHO histological classification. Glucocorticoids caused an accumulation of TEC in G0/G1 phase in all cases examined (n=6), and also induced apoptosis in the three with the lowest levels of Bcl-2 expression.Conclusions Our results indicate that neoplastic TECs express GR and that glucocorticoids directly suppress their in vitro proliferation. 相似文献
69.
Kiyoo Kuroe Yoichi Haga Osamu Funakoshi Ichiro Mizuki Kosuke Kanazawa Yutaka Yoshida 《Journal of gastroenterology》1996,31(2):199-206
We examined whether extraintestinal manifestations of granulomatous enterocolitis in rabbits might be produced by the long-term
administration of muramyl dipeptide which represents the basic fragment of the bacterial cell wall, emulsified with Freund's
incomplete adjuvant. Muramyl dipeptide emulsion was injected submucosally at six sites in the rectum and colon, 10 cm proximal
to the anus, each time with a flexible endoscope. Seven rabbits were injected nine times or more every month, and all were
sacrificed 1 month after the last injection. The histological changes in the colon in the seven rabbits were mononuclear cell
infiltration, epithelioid granulomas, granulomatous lesion, and denuded and regenerative epithelia, although the changes differed
in degree. In five of the seven rabbits, histological examination of the liver showed pericholangitis and periductal fibrosis,
findings analogous to sclerosing cholangitis in patients with inflammatory bowel disease. In four of the seven rabbits, fibrosis
bridging mainly between portal and portal veins, and, in places, between portal and central veins, was seen. Two of the seven
rabbits developed polyarthritis. The histological changes in our model suggest that continuous stimulation with bacterial
cell wall fragments may be involved in the extraintestinal manifestations of chronic intestinal inflammation such as that
seen in inflammatory bowel disease. 相似文献