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81.
Tomomitsu Tahara Tomoyuki Shibata Masakatsu Nakamura Hiromi Yamashita Daisuke Yoshioka Masaaki Okubo Naoko Maruyama Toshiaki Kamano Yoshio Kamiya Hiroshi Fujita Yoshihito Nakagawa Mitsuo Nagasaka Masami Iwata Kazuya Takahama Makoto Watanabe Hiroshi Nakano Ichiro Hirata Tomiyasu Arisawa 《Clinical and experimental medicine》2009,9(2):125-130
Tryptase acting at protease-activated receptor 2 (PAR2) contributes to the pathogenesis of Inflammatory bowel diseases (IBDs).
DNA methylation has been shown to be an important mechanism in gene silencing. We attempted to clarify the relationship between
the promoter methylation of PAR2 and ulcerative colitis (UC). 84 UC patients enrolled in the study. UC patients were classified
by disease behavior, severity and extent of disease. For rectal inflammatory mucosal specimens from all the patients, and
normal terminal ileum from 23 patients, promoter methylation of PAR2 gene was quantified by digital densitographic analysis
following to methylation-specific polymerase chain reaction (MSP). The mean methylation levels of the PAR2 gene in all 84
subjects was 38.4 ± 19.6%. Although mean methylation levels in rectal inflammatory mucosa, and paired normal terminal ileum
did not vary, methylation levels of PAR2 gene was significantly higher in total colitis than rectal colitis (total colitis
vs. rectal colitis; 42.9 ± 19.6% vs. 34.5 ± 18.9%, P = 0.046). The higher methylation levels were also associated with Steroid-dependent (P = 0.002) and refractory (P = 0.007) UC. Our data suggest that PAR2 methylation status in rectal mucosa correlates with more severe disease phenotypes
of UC. 相似文献
82.
Osugi H Lee S Higashino M Tokuhara T Kaseno S Takada N Takemura M Mizumoto Y Kinoshita H 《Surgical endoscopy》2002,16(10):1478-1482
BACKGROUND: Patients with unresectable malignant gastroesophageal strictures often are troubled with reflux esophagitis after
stent placement. METHODS: A self-expandable metallic stent (SEMS) without an antireflux mechanism was placed in seven patients
with unresectable malignant gastroesophageal strictures (group A), and SEMS with an antireflux mechanism was placed in five
patients (group B). After we obtained monitoring systems, two patients in group A and all the patients in group B underwent
measurement of bilirubin and pH in the esophagus using a 24-h bilirubin and pH monitor. RESULTS: The mean percentage of total
time less than 0.14 for use of the bilirubin absorbance unit was 12.4% in group B and 64.0% in group A. The mean percentage
of total time for a pH less than 4 was 2.9% in group B and 37.8% in group A. CONCLUSION: The placement of SEMS with the antireflux
mechanism can be effective not only for palliation of gastroesophageal stricture, but also for prevention of reflux. 相似文献
83.
We encountered a 75-year-old man who complained of exertional dyspnea. An echocardiographic examination showed aortic regurgitation and a tumor in the left ventricular outflow tract. Under complete extracorporeal circulation, we surgically made an incision of the ascending aorta with a slight thickening of the aortic valve and an enlarged annulus. After excising the aortic valve, an examination of the subvalvular region revealed mitral valve-like tissue extending from the annular region of the right coronary cusp to the ventricular septum, while the chordae tendinae was attached to the septum. This issue was excised, and the aortic valve was replaced with a 27-mm SJM valve. The postoperative course was uneventful, and the patient was discharged in good condition on postoperative day 30. An accessory mitral valve is extremely rare. Since this indication for surgical treatment is associated with congenital heart disease or a left ventricular outflow tract obstruction, most patients are young. Our patient had no associated cardiac anomalies and no pressure gradient attributable to a left ventricular outflow tract obstruction. This accessory mitral valve was discovered during aortic valve replacement surgery. To our knowledge, our patient is the oldest reported with an accessory mitral valve to have undergone a surgical resection. 相似文献
84.
Contrasting effect of estrogen on VEGF induction under different oxygen status and its role in murine ROP 总被引:22,自引:0,他引:22
Miyamoto N Mandai M Takagi H Suzuma I Suzuma K Koyama S Otani A Oh H Honda Y 《Investigative ophthalmology & visual science》2002,43(6):2007-2014
PURPOSE: It has been reported that 17beta-estradiol (E2) may enhance the proliferation of bovine retinal vascular endothelial cells (BRECs) by increasing the expression of VEGFR-2 and VEGF. The hypothesis in the current study was that estrogen may contribute to fetal vascular development and the cessation of exposure to estrogen of premature infants on birth may have an inhibitory effect on retinopathy of prematurity (ROP). Because ROP is thought to develop under relative hypoxia after exposure to high-dose oxygen, this study was conducted to investigate how estrogen modulates hypoxia-induced VEGF in BRECs and mouse ROP. METHODS: Gene expression of VEGF and hypoxia-inducible factor (HIF)-1alpha were studied in BRECs, with or without E2, under normoxia and hypoxia (1% O2). A binding assay was performed to determine whether estrogen interferes with HIF-1-mediated induction of VEGF. In a mouse ROP model, effects of E2 were evaluated by avascular area, subsequent extraretinal neovascularization, and retinal expression of the VEGF gene, by administering E2 during hyperoxia (75% O2) and/or after exposure to room air. RESULTS: Hypoxia-induced VEGF mRNA in BRECs was reduced dose dependently by 1 to 100 nM E2. E2 reduced hypoxia-induced binding of HIF-1 to the VEGF promoter site and reduced the HIF-1alpha mRNA level. In mouse ROP, injection of E2 during hyperoxia increased retinal VEGF mRNA and reduced the retinal avascular area at the end of hyperoxia. E2 treatment during the normoxia that followed reduced VEGF mRNA and extraretinal neovascularization. Treatment with E2 throughout both periods significantly improved retinopathy. CONCLUSIONS: Estrogen may function as a significant modulator of the level of VEGF mRNA under different oxygen conditions and could serve as a prophylactic agent for ROP. 相似文献
85.
Amemiya K Takahashi M Nishida A Matsumura M Hayakawa M Honda Y 《Nippon Ganka Gakkai zasshi》2002,106(4):236-242
PURPOSE: To describe the histological and cytological findings in the epiretinal membrane around a macular hole. CASE: A 24-year-old male patient with retinitis pigmentosa had had night blindness since childhood. A macular hole(Stage 2) in his left eye was noted when he was 18 years old. He visited our department when he was 22 years old. The visual acuity on the left was 0.5 at the first examination and two years later it was 0.2 with enlargement of the macular hole. Pars plana vitrectomy was applied, and we removed the thick yellow epiretinal membrane around the hole. The macular hole was closed, and the visual acuity improved to 0.7. The removed membrane contained many cells including macrophages, Müller cells, glial cells, and fibroblasts. There were many granules that appeared to be xantophyll outside the cell bodies. CONCLUSION: The components of the membrane suggest that the macular hole was caused by vitreous degeneration due to retinitis pigmentosa. 相似文献
86.
Tsuchiya M Fujiwara Y Kanai Y Mizutani M Shimada K Suga O Ueda S Watson JW Nagahisa A 《Pharmacology》2002,66(3):144-152
The anti-emetic effects of a novel tachykinin NK(1) receptor antagonist, ezlopitant ((2S,3S-cis)-2-diphenylmethyl)- N-[(2-methoxy, 5-isopropylphenyl)methyl]-1-azabicyclo- [2.2.2]octan-3-amine), were investigated in ferrets. Ezlopitant inhibited [(3)H]substance P ([(3)H]SP) binding to the human, guinea pig, ferret and gerbil NK(1) receptors (K(i) = 0.2, 0.9. 0.6 and 0.5 nmol/l, respectively), but had no affinity to NK(2) and NK(3) receptors up to 1 micromol/l. Ezlopitant also inhibited SP-induced contraction of guinea pig trachea with a pA(2) value of 7.8, but had no effects on the baseline tension and maximum contractile response. In ferrets, ezlopitant, either orally (0.03-3 mg/kg) or subcutaneously (0.3-3 mg/kg), prevented acute retching and vomiting responses induced by intraperitoneal injection of cisplatin (10 mg/kg). In addition, repeated subcutaneous injection of ezlopitant significantly inhibited delayed retching and vomiting responses that occurred in ferrets treated with the lower dose of cisplatin (5 mg/kg, i.p.). Ezlopitant (0.1-1 mg/kg, s.c.) also produced a dose-dependent inhibition of hindpaw tapping induced by intracerebroventricular injection of [Sar(9),Met(O(2))(11)]SP in gerbils, which is known to be mediated by NK(1) receptors in the brain. These findings indicate that ezlopitant is a potent and selective NK(1) receptor antagonist, and that it inhibits both acute and delayed emetic reactions induced by cisplatin in ferrets via acting on NK(1) receptors in the central nervous system. 相似文献
87.
Shimada K Terai T Igari J Inoue H Nakadate T Oguri T Suwabe A Obata R Ikemoto H Ohno I Okada S Hayashi K Mori T Nakano K Arakawa M Gejyo F Igarashi K Yokouchi H Okada M Ito A Sumitomo M Aoki N Matsushima T Niki Y Kitamura N Suga M Suzuki Y Karasawa Y Tosaka M Nakata K Nakatani T Kohno S Tomono K Miyazaki Y Inagawa H Hirakata Y Aoki S Matsuda J Kudo K Kobayashi N Kinoshita T Konosaki H Nasu M Nagai H Kobayashi H Kawai S Takayasu S Hiramatsu K Nakano T 《The Japanese journal of antibiotics》2002,55(5):537-567
From October 2000 to September 2001, we collected the specimen from 410 patients with lower respiratory tract infections in 16 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various anti-bacterial agents and antibiotics and patients' characteristics. Of 499 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in inflammation, 493 strains were investigated. The breakdown of the isolated bacteria were: Staphylococcus aureus 78, Streptococcus pneumoniae 73, Haemophilus infiuenzae 99, Pseudomonas aeruginosa (non-mucoid) 64, P. aeruginosa (mucoid) 14, Klebsiella pneumoniae 25, Moraxella subgenus Branhamella catarrhalis 21, etc. Of 78 S. aureus strains, those with 4 micrograms/ml or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) occupied 53.8%. Vancomycin and arbekacin had the most potent activities against MRSA as observed in 1999. The frequency of S. pneumoniae exhibiting low sensitivity to penicillin (penicillin-intermediate S. pneumoniae: PISP + penicillin-resistant S. pneumoniae: PRSP) was 38.4% being consistent with that in 1999 (34.7%). PRSP accounted for 11.0% of the total, being more than that in 1999 (3.0%). Carbapenems had strong activities against S. pneumoniae. Especially, panipenem inhibited the growth of all 73 strains at 0.125 microgram/ml. Generally, all drugs had strong activities against H. influenzae with MIC80s of 8 micrograms/ml or less. The drug that had the strongest activity against H. infiuenzae was levofloxacin, which inhibited the growth of 94 of the 99 strains at 0.063 microgram/ml. Tobramycin had a strong activity against P. aeruginosa (both mucoid and non-mucoid) with MIC80 of 1 microgram/ml. The mucoid strain was little isolated (14 strains) but the susceptibilities to all drugs were better than the non-mucoid strain. K. pneumoniae showed good susceptibilities to all drugs except ampicillin and the MIC80S were 2 micrograms/ml or less. Particularly, cefpirome, cefozopran, and levofloxacin had strong bactericidal activities against K. pneumoniae with MIC80s of 0.125 microgram/ml, and cefotiam, second-generation cephems, also had a favorable activity being MIC80 of 0.25 microgram/ml. Also, all drugs generally had strong activities against M. (B.) catarrhalis. MIC80s of all drugs were 2 micrograms/ml or less. The drug having the strongest activity was imipenem and levofloxacin inhibiting all 21 strains at 0.063 microgram/ml. Most of the patients with respiratory infection were aged 70 years or older, accounting for approximately a half of the total (44.4%). As for the incidence by the diseases, bacterial pneumonia and chronic bronchitis were the highest, being noted in 38.0% and 31.7% of all the patients, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. aureus (18.3%) and S. pneumoniae (16.1%). In contrast, H. infiuenzae (20.4%) and P. aeruginosa (both mucoid and non-mucoid: 16.7%) were frequently isolated from the patients with chronic bronchitis. Before the drug administration, the bacteria frequently isolated from all the patients were S. pneumoniae (24.3%) and H. infiuenzae (26.7%). The frequency of isolated S. pneumoniae tended to decrease with the increase in the number of administration days while that of isolated H. infiuenzae did not. The frequency of isolated P. aeruginosa tended to increase with the duration of administration. The isolated bacteria were comparable between the patients already treated with penicillins and cephems. In the patients treated with aminoglycosides, macrolides, and quinolones, P. aeruginosa was most frequently isolated (33.3 to 40.0%). 相似文献
88.
Using subtractive cloning, we identified a 1.4 kb mRNA that was ubiquitously expressed in various tissues; this mRNA was highly up-regulated in amygdala nuclei in mice when morphine was repeatedly administered but not when an opiate-receptor antagonist was co-administered. The mRNA encodes a 23 kDa protein, designated 'addicsin'. This contains two putative PKC-phosphorylation motifs and several hydrophobic regions, and was recovered in a soluble protein fraction of brain lysate. Its primary structure showed 98% identity with that of rat glutamate-transporter-associated protein 3-18 (GTRAP3-18), a putative modulator of neural glutamate-transporter EAAC1. Up-regulation of addicsin expression by morphine may affect glutamate uptake in the amygdala, causing mice to develop morphine tolerance and dependence. 相似文献
89.
Clinicopathologic and immunohistochemical features of surgically resected small cell carcinoma of the esophagus 总被引:5,自引:0,他引:5
Osugi H Takemura M Morimura K Kaneko M Higashino M Takada N Lee S Kinoshita H 《Oncology reports》2002,9(6):1245-1249
Esophageal small cell carcinoma (SmC) is considered an aggressive cancer carrying a poor prognosis, although the rarity of this tumor has impeded statistical evaluation. We reviewed records of 457 esophageal cancer patients treated in our department from 1986 to 2000, comparing clinicopathologic factors and post-treatment outcomes, for 9 patients with SmC, most undergoing esophagectomy including lymphadenectomy, with data from 128 patients with esophageal squamous cell carcinoma (SqC) invading to the muscular layer or beyond. Immunohistochemical features were compared between the SmC and 12 consecutive SqC. All patients studied had localized disease according to preoperative staging. SmC showed more ulcerative and infiltrative growth, and more aggressive lymphatic spread, than SqC. All SmC patients had lymph node metastasis (thoracic nodes, 9 patients: abdominal 6; cervical 1). All SmC specimens but no SqC were immunoreactive for neuron-specific enolase. Two and three SmC specimens were reactive for epithelial membrane antigen and keratin, respectively. Survival of SmC patients after esophagectomy (median, 11 months) was worse than for SqC patients (p=0.013). However, 1 SmC patient remains alive at 76 months. Survival was not related to any clinicopathologic or immunohistochemical features. While SmC shows aggressive behavior and worse outcomes than SqC, combining esophagectomy with chemotherapy or radiotherapy may prolong survival. 相似文献
90.
Watanabe O Haga S Shimizu T Imamura H Kinoshita J Utada Y Okabe T Kimura K Hirano A Kajiwara T Aiba M 《International journal of clinical oncology / Japan Society of Clinical Oncology》2002,7(5):0322-0325
Intravenous digital subtraction angiography (IV-DSA) was performed before and after neoadjuvant chemotherapy (NACT) in five
patients with locally advanced breast cancer, and the efficacy of NACT was evaluated on the basis of the results of IV-DSA
and histopathological examination. Following NACT, the maximum density of tumor enhancement (MAX) in the IV-DSA image decreased
by 61.6% in case 1, 50% in case 2, 58.1% in case 3, 90.8% in case 4, and 97.2% in case 5. In all five patients, the efficacy
of chemotherapy was rated as a partial response in terms of tumor size, while histological efficacy was rated as slightly
effective in cases 1–4 and moderately effective in case 5. The pathological efficacy of NACT was highest in case 5, which
showed the greatest decrease in MAX. These results indicate that variations in MAX reflect clinical efficacy, and, to some
extent, also permit prediction of pathological efficacy.
Received: March 4, 2002 / Accepted: June 10, 2002
Correspondence to:O. Watanabe 相似文献