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Biomedical subjects

T Nishida

Publications and source records attributed to T Nishida.

At least 91 records · Page 5Linked to original sources

Characterization of total occlusions with intracoronary ultrasound: the importance of the duration of occlusion.

OBJECTIVE: To assess the impact of the occlusion duration on the characteristics of coronary occlusive plaques. BACKGROUND: The percutaneous recanalization of chronic total coronary occlusions is a technically demanding and yet often unsuccessful procedure due to unfavorable morphological changes described by histology but not well defined in vivo. METHODS: Thirty-five consecutive total occlusions of > or = 1 month duration in previously untreated native coronary arteries were studied using intracoronary ultrasound following dilatation with a 1.5 mm balloon. Plaque characteristics of lesions with an occlusive duration of > or = 3 months (old occlusions) and those of < 3 months (recent occlusions) were then compared. The ultrasound cross-section where there was maximal plaque accumulation at the site of occlusion was analyzed for its qualitative and quantitative characteristics. The lesion remodeling index was defined as the vessel area at occlusion divided by the vessel area at a proximal reference. RESULTS: The old occlusion group comprised 11 lesions whereas 16 lesions were found in the recent occlusion group; the occlusion duration was undetermined in the remaining 8 lesions, and the mean occlusion duration was found to be 4.9 +/- 4.3 months, over a range of 1 36 months. The baseline clinical and angiographic characteristics were similar in the 2 groups. The lesion remodeling index was found to be significantly lower in older occlusions than in the more recent occlusions (0.75 +/- 0.14 vs. 1. 06 +/- 0.25; p = 0.007) and the duration of the occlusion also correlated with the length of calcified segment as determined by ultrasound (p = 0.040), and with a smaller angiographic proximal reference diameter (p = 0.043). CONCLUSION: Long-standing occlusions undergo lesion shrinkage and exhibit more extensive calcification.

Adult↗

Role of the small GTP-binding protein rho in epithelial cell migration in the rabbit cornea.

PURPOSE: To determine the role of the small guanosine triphosphate (GTP)-binding protein Rho in the migration of corneal epithelial cells. METHODS: The presence of the Rho target proteins Rho-associated coiled coil-containing protein kinase (ROCK)-1 and ROCK-2 in rabbit cornea was examined by immunohistochemical analysis, and that of the corresponding mRNAs in rabbit corneal epithelial cells was determined by reverse transcription-polymerase chain reaction analysis. The effects of various agents on epithelial cell migration were investigated by measuring the length of the migration path in rabbit corneal blocks in culture. RESULTS: Both ROCK-1 and ROCK-2 were detected in the rabbit corneal epithelium at both protein and mRNA levels. The Rho activator lysophosphatidic acid (LPA) stimulated corneal epithelial migration in a dose-dependent manner, whereas exoenzyme C3, a Rho inhibitor, inhibited epithelial migration also in a dose-dependent manner. The stimulatory effect of LPA on corneal epithelial migration was prevented by exoenzyme C3. Both cytochalasin B, an inhibitor of actin filament assembly, and ML-7, an inhibitor of myosin light chain kinase, also prevented LPA stimulation of epithelial migration. CONCLUSIONS: These results suggest that Rho mediates corneal epithelial migration in response to external stimuli by regulating the organization of the actin cytoskeleton.

Actins↗

Assessment of the functional significance of coronary lesions using a monorail catheter.

Myocardial fractional flow reserve (FFR) < 0.75 is a reliable index of a functionally severe coronary stenosis. FFR is best assessed by a sensor-tipped pressure monitoring guidewire (PW). The purpose of this study was to assess whether a multifunctional probing catheter (MFP), a 3 French dual-lumen monorail catheter, can be used to accurately measure intracoronary pressure and FFR. In 35 lesions (35 patients; learning group), we calculated FFR by both PW (FFRPW) and MFP (FFRMFP). Using ROC analysis, the FFRMFP value of 0.65 had the highest sensitivity with the FFRPW < 0.75. FFRMFP cut-off (0.65) was tested in 40 patients (testing group). In all cases, lumen diameter was documented by an intracoronary ultrasound examination. In the learning group, the FFRPW was 0.82 +/- 0.17 and FFRMFP was 0.70 +/- 0.23 (r = 0.88; p < 0.001). The FFRMFP cut-off value (0.65) correctly predicted the FFRPW in 37/40 cases in the testing group. In the 3 discordant cases, FFR was critical (< 0.65) by MFP and normal (> 0.75) by PW. In all these cases, minimal lumen cross-sectional area was < 2.8 mm2. When FFRMFP is > 0.65, FFRPW is always > 0.75. These data demonstrate that even with larger cross-sectional area than a pressure wire, the MFP catheter can easily and reliably be used to assess the functional severity of coronary stenosis.

Cardiac Catheterization↗

Stimulatory effect of pseudomonal elastase on collagen degradation by cultured keratocytes.

PURPOSE: The pathobiology of corneal ulceration induced by Pseudomonas aeruginosa was investigated by characterization of the pseudomonal pathogenic factors responsible for degradation of the collagen matrix. METHODS: Three-dimensional gels of type I collagen containing (or not) rabbit keratocytes were incubated in the presence of either culture supernatant of P. aeruginosa strain PAO1 or pseudomonal pathogenic factors (elastase, lipopolysaccharide, or exotoxin A), and the extent of collagen degradation was assessed after 24 hours by measurement of released hydroxyproline. Activation of matrix metalloproteinases (MMPs) produced by keratocytes was also examined by gelatin zymography and immunoblot analysis. RESULTS: In the absence of keratocytes, the PAO1-conditioned medium increased the extent of collagen degradation. The conditioned medium also promoted keratocyte-mediated collagen degradation. Of the pseudomonal pathogenic factors examined, only elastase degraded collagen directly as well as stimulated keratocyte-mediated collagen degradation. Culture supernatant of elastase-deficient P. aeruginosa (lasR or lasB) mutants had no effect on collagen degradation in the absence or presence of keratocytes. Elastase also induced the conversion of the inactive precursors of MMP-1, -2, -3, and -9 produced by keratocytes to the active forms of the enzymes. CONCLUSIONS: These results suggest that pseudomonal elastase both degrades type I collagen directly and promotes collagen degradation mediated by keratocytes, the latter effect being likely attributable, at least in part, to the activation of proMMPS:

ADP Ribose Transferases↗

[Clinical study on renal trauma].

A total of 64 patients with renal trauma were treated at the Department of Urology, St. Marianna University School of Medicine, from January 1988 to December 1996. Patients were between 3 and 66 years old (mean 28.2); 56 (87.5%) of them were male and 8 (12.5%) were female. The main cause of injury was a traffic accident in 33 cases (51.6%). According to the Classification of Renal Injury by the Japanese Association for the Surgery of Trauma in Japan, there were 27 cases (42.2%) of Type I (subcapsular injury), 12 cases (18.8%) of Type II (superficial injury), 16 cases (25.0%) of Type III (Deep injury), 6 cases (9.4%) of Type IV (Pedicle injury). Surgical treatment was performed in 6 cases (9.3%). The major associated injuries were bone fracture in 33 cases (51.6%), lung injury in 20 cases (31.3%) and liver injury in 16 cases (25.0%). The literature is also reviewed briefly.

Accidents, Traffic↗

[A modified administrated schedule for combination therapy with irinotecan and cisplatin as a neoadjuvant chemotherapy in locally advanced cervical cancer--a report of 2 cases as a pilot study].

To shorten the treatment term of neoadjuvant chemotherapy (NAC) for locally advanced cervical cancer, a combination of irinotecan (CPT-11) and cisplatin was administered on a modified administrated schedule for 2 eligible patients as a pilot study. CPT-11 70 mg/m2 was administered (div) on days 1 and 8, followed by cisplatin 70 mg/m2 given (div) on day 1. Treatment was repeated every 3 weeks for a total of two cycles. Both patients showed a complete clinical response. No severer toxicities were observed than with the usual regimen, and both cases could undergo radical hysterectomy after NAC. The results suggest that this modified regimen of combination of CPT-11 and cisplatin can be effective as an NAC in cases of locally advanced cervical cancer, especially in terms of shortening treatment term. This regimen is worthy of further study.

Adult↗

[Evaluation of a combination chemotherapy with nedaplatin and 5-FU for oral cancers].

Nedaplatin (cis-diammine-glycolato platinum: CDGP) is a platinum compound with a molecular weight of 303.18 that was recently developed in Japan. There have been reports of the antineoplastic effects of Nedaplatin on cancers in the cranio-cervical region, lung, esophagus, urinary bladder, testis, ovary, and uterus. In this study, we performed combined therapy of CDGP and fluorouracil (5-FU) for 8 patients with oral cancers, and evaluated the results to elucidate the clinical effect and adverse side effects. The subjects were 8 patients with squamous cell carcinoma (5 males and 3 females aged 33-65 years). The primary carcinoma regions were the tongue in 5 patients, oral floor in 2 patients, and mandibular gingiva in 1 patient. The T-classification was T2 in 6 patients and T4 in 2 patients, and the clinical staging was Stage II in 5 patients, Stage III in 1 patient and Stage IV in 2 patients. We first administered 700 mg/m2 5-FU per day from day 1 to day 5 (total dose 3,500 mg/m2), then 90 mg/m2 CDGP on day 5. The clinical effect was evaluated as a partial response in all cases, showing a 100% success rate. The histopathological findings of resected tumors were evaluated by Ohboshi and Shimozato's classification. One patient was Grade IIA, 5 patients Grade IIB, and 2 patients Grade III. The adverse side effects were slight myelotoxicity, gagging, nausea, alopecia, and stomatitis less than Grade II. Although the oral cancers in this study were extroverted superficial ulcerative cancers, and the number of patients was low at 8, this combined therapy is considered useful and worth evaluating in further accumulated cases.

Adult↗

Emergency polytetrafluoroethylene-covered stent implantation to treat coronary ruptures.

BACKGROUND: Coronary perforation is a life-threatening complication of percutaneous interventions. In the past few years, the implantation of covered stents has emerged as a strategy for treatment when the traditional conservative approach (ie, prolonged balloon inflation and reversal of anticoagulation) fails. METHODS AND RESULTS: Since May 1997 (when polytetrafluoroethylene [PTFE]-covered stents were available at our institutions), 11 of the 12 consecutive patients who had coronary ruptures that were unsuccessfully sealed with prolonged balloon inflation and reversal of anticoagulation were treated with 12 PTFE-covered stents (PTFE group). The efficacy of the PTFE-covered stent was compared with that of noncovered stents, which were used to treat 17 perforations (non-PTFE group). One patient sustained a very distal perforation that was not suitable for covered stent sealing and underwent emergency surgery. All vessel ruptures treated with PTFE-covered stent implantation were successfully sealed. The time necessary to deploy the stent was 10+/-3 minutes (range, 4 to 15 minutes). All patients but one were discharged from the hospital and had an optimal early clinical outcome. One patient underwent emergency bypass surgery and died in the intensive care unit. The occurrence of cardiac tamponade and the necessity for emergency surgery was significantly lower in the PTFE group than in the non-PTFE group. At 14+/-4 months, the 10 discharged patients had not experienced any major adverse cardiac events. CONCLUSIONS: This preliminary study supports the utility of the PTFE-covered stent for the nonsurgical treatment of vessel ruptures.

Aged↗

Synergistic effect of TNF-alpha and IL-4 on the expression of thymus- and activation-regulated chemokine in human corneal fibroblasts.

Chemokine production by resident fibroblasts contributes to the recruitment of migratory leukocytes to sites of tissue injury. The effects of cytokines on the expression of thymus- and activation-regulated chemokine (TARC), a potent chemoattractant for Th2 cells, were examined in cultured human corneal fibroblasts. The culture supernatants of cells incubated for 24 h in the absence or presence of either TNF-alpha (10 ng/ml) or IL-4 (10 ng/ml) alone did not contain TARC detectable by ELISA. However, exposure of cells to both cytokines resulted in marked release of TARC into the culture medium in a time- and dose-dependent manner. Similarly, quantitative RT-PCR analysis revealed that the two cytokines induced a synergistic increase in the amount of TARC mRNA in the cultured fibroblasts. This synergistic effect of TNF-alpha and IL-4 on TARC production by fibroblasts may contribute to the Th2 cell infiltration and consequent tissue damage associated with allergic inflammation.

Base Sequence↗

Seasonal changes in the hypothalamo-pituitary-testes axis of the Japanese wood mouse (Apodemus speciosus).

Seasonal changes in the hypothalamo-pituitary-testes axis of the Japanese wood mice (Apodemus speciosus) were studied. The testes, epididymis, pituitary and hypothalamus were compared between mice in the breeding season (July) and non-breeding season (October) using morphological techniques, and the plasma testosterone level was evaluated by enzyme immunoassay. Significant differences in these tissues were observed between the breeding season and the non-breeding season. Specifically, differences in the non-breeding season included 1) a decline in testicular and epididymal weights, arrest of spermatogenesis and decrease of serum testosterone concentration; 2) a decrease in the number of luteinizing hormone (LH)-, follicle stimulating hormone (FSH)-, prolactin (PRL)-, and growth hormone (GH)-immunoreactive cells, and decrease in the size of FSH, PRL, and GH-immunoreactive cells; and 3) an increase in the size of gonadotropin-releasing hormone (GnRH)-immunoreactive neurons. Our findings indicate that the male adult Japanese wood mouse exhibits unique seasonal changes in the hypothalamo-pituitary-testes axis which are not found in laboratory mice.

Animals↗

Successful treatment of two patients with recurrent endometrial cancer by weekly paclitaxel.

OBJECTIVE: The aim of this study was to evaluate the toxicity and efficacy of weekly paclitaxel in patients with recurrent endometrial cancer. METHODS: Paclitaxel (70 mg/m(2) by 1-h infusion weekly) was administered to two patients with recurrent endometrial cancer of the lung. RESULTS: After 5 cycles, both patients with platinum-resistant disease achieved clinical partial responses confirmed by computed tomography (CT) scan. The serum CA125 levels of case 1 decreased to cut-off level. The response duration of both patients was 4 months. The toxicity was acceptable and probably less pronounced than that characterize of the standard tri-weekly schedules. CONCLUSION: Although conclusions regarding survival are premature, weekly paclitaxel might offer better quality of life during treatment.

Adenocarcinoma↗

Polytetrafluoroethylene-covered stent for the treatment of narrowings in aorticocoronary saphenous vein grafts.

We compared the outcome of patients with saphenous graft disease treated with polytetrafluoroethylene (PTFE)-covered stents or noncovered stents. Angiographic success was similar; non-Q-wave myocardial infarction was lower in the PTFE group (p = 0.06) and long-term major cardiac events and restenosis rate were similar in the 2 groups. Implantation of PTFE-covered stent in vein graft disease seems to reduce the occurrence of distal embolization.

Aged↗

Identity of urinary trypsin inhibitor-binding protein to link protein.

Urinary trypsin inhibitor (UTI), a Kunitz-type protease inhibitor, directly binds to some types of cells via cell-associated UTI-binding proteins (UTI-BPs). Here we report that the 40-kDa protein (UTI-BP(40)) was purified from the cultured human chondrosarcoma cell line HCS-2/8 by UTI affinity chromatography. Purified UTI-BP(40) was digested with trypsin, and the amino acid sequences of the peptide fragments were determined. The sequences of six tryptic fragments of UTI-BP(40) were identical to subsequences present in human link protein (LP). Authentic bovine LP and UTI-BP(40) displayed identical electrophoretic and chromatographic behavior. The UTI-binding properties of UTI-BP(40) and LP were indistinguishable. Direct binding and competition studies strongly demonstrated that the NH(2)-terminal fragment is the UTI-binding part of the LP molecule, that the COOH-terminal UTI fragment (HI-8) failed to bind the NH(2)-terminal subdomain of the LP molecule, and that LP and UTI-BP(40) exhibited significant hyaluronic acid binding. These results demonstrate that UTI-BP(40) is identical to LP and that the NH(2)-terminal domain of UTI is involved in the interaction with the NH(2)-terminal fragment of LP, which is bound to hyaluronic acid in the extracellular matrix.

Aggrecans↗

Edge restenosis after implantation of high activity (32)P radioactive beta-emitting stents.

BACKGROUND: A high restenosis rate has been reported at the edges ("edge restenosis") of (32)P radioactive stents with an initial activity level of 3 to 12 microCi. This edge effect might be due to balloon injury and to a low dose of radiation at the stent margins. The aim of this study was to evaluate whether the implantation of (32)P radioactive stents with a higher activity level (12 to 21 microCi) combined with a nonaggressive stent implantation strategy could solve the problem of edge restenosis. METHODS AND RESULTS: We compared the results of lesions treated with single radioactive BX stents with an activity of 12 to 21 microCi (group 2, n = 54 lesions) with the results of lesions treated by single radioactive BX stents with an initial activity level of 3 to 12 microCi (group 1, n = 42 lesions). There were no procedural events. At the 6-month follow-up, no myocardial infarctions, deaths, or stent thromboses had occurred. Intrastent binary restenosis was 0% in group 1 versus 4% in group 2 (n = 2, both at the ostium of the right coronary artery, P = NS). Intrastent neointimal hyperplasia was significantly lower in group 2 than in group 1. The intralesion (intrastent plus peri-stent) restenosis rate was 38% in group 1 versus 30% in group 2 (P = NS). Conclusions-Single (32)P radioactive stents with an initial activity level of 12 to 21 microCi reduced intrastent neointimal hyperplasia compared with stents of 3 to 12 microCi, but they did not solve the problem of edge restenosis, even if a nonaggressive stent implantation strategy was used.

Angioplasty, Balloon, Coronary↗

Modification of cullin-1 by ubiquitin-like protein Nedd8 enhances the activity of SCF(skp2) toward p27(kip1).

The periodic expression of cell cycle proteins is important for the regulation of cell cycle progression. The amount of CDK inhibitor, p27(kip1), one such protein, seems to be regulated by the ubiquitin-proteasome system. The ubiquitin ligase (E3) toward p27(kip1) is thought to be SCF(skp2). The activity of SCF(skp2) was increased by the addition of Roc1 protein to the complex. Furthermore, the ubiquitination of p27(kip1) seemed to be dependent on the phosphorylation of T187 of p27(kip1) because the mutant T187A was not ubiquitinated at all in an in vitro ubiquitination system. Cullin-1, a component of SCF, is modified by ubiquitin-like protein Nedd8. The modification site of cullin-1 was shown to be K696 because the K696R mutant was not modified. When the effect of the Nedd8 modification on the SCF(skp2) activity toward p27(kip1) was investigated, the activity was markedly decreased by using the Nedd8-unmodified mutant cullin-1 (K696R), indicating that the modification may play an important role on the SCF(skp2) activity toward p27(kip1).

Amino Acid Sequence↗

Effects of CTGF/Hcs24, a hypertrophic chondrocyte-specific gene product, on the proliferation and differentiation of osteoblastic cells in vitro.

Connective tissue growth factor/hypertrophic chondrocyte-specific gene product Hcs24 (CTGF/Hcs24) promotes the proliferation and differentiation of chondrocytes and endothelial cells which are involved in endochondral ossification (Shimo et al., 1998, J Biochem 124:130-140; Shimo et al., 1999, J Biochem 126:137-145; Nakanishi et al., 2000, Endocrinology 141:264-273). To further clarify the role of CTGF/Hcs24 in endochondral ossification, here we investigated the effects of CTGF/Hcs24 on the proliferation and differentiation of osteoblastic cell lines in vitro. A binding study using (125)I-labeled recombinant CTGF/Hcs24 (rCTGF/Hcs24) disclosed two classes of specific binding sites on a human osteosarcoma cell line, Saos-2. The apparent dissociation constant (Kd) value of each binding site was 17.2 and 391 nM, respectively. A cross-linking study revealed the formation of (125)I-rCTGF/Hcs24-receptor complex with an apparent molecular weight of 280 kDa. The intensity of (125)I-rCTGF/Hcs24-receptor complex decreased on the addition of increasing concentrations of unlabeled rCTGF/Hcs24, but not platelet-derived growth factor-BB homodimer or basic fibroblast growth factor. These findings suggest that osteoblastic cells have specific receptor molecules for CTGF/Hcs24. rCTGF/Hcs24 promoted the proliferation of Saos-2 cells and a mouse osteoblast cell line MC3T3-E1 in a dose- and time-dependent manner. rCTGF/Hcs24 also increased mRNA expression of type I collagen, alkaline phosphatase, osteopontin, and osteocalcin in both Saos-2 cells and MC3T3-E1 cells. Moreover, rCTGF/Hcs24 increased alkaline phosphatase activity in both cells. It also stimulated collagen synthesis in MC3T3-E1 cells. Furthermore, rCTGF/Hcs24 stimulated the matrix mineralization on MC3T3-E1 cells and its stimulatory effect was comparable to that of bone morphogenetic protein-2. These findings indicate that CTGF/Hcs24 is a novel, potent stimulator for the proliferation and differentiation of osteoblasts in addition to chondrocytes and endothelial cells. Because of these functions, we are re-defining CTGF/Hcs24 as a major factor to promote endochondral ossification to be called "ecogenin: endochondral ossification genetic factor."

3T3 Cells↗