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Biomedical subjects

Y Kato

Publications and source records attributed to Y Kato.

At least 19 recordsLinked to original sources

Improved outcomes of renal transplantation from cardiac death donors: a 30-year single center experience.

Outcomes of renal transplantation from donation after cardiac death (DCD) donors over 30 years were analyzed. Between 1975 and 2004, 256 renal transplantations from DCD donors were performed. The recipients were divided into four groups according to a time period as follows: 1975-1979 (Group 1; n = 18), 1980-1989 (Group 2; n = 81), 1990-1999 (Group 3; n = 84) and 2000-2004 (Group 4; n = 73). Of the 256 transplanted kidneys from DCD donors, 38 (15%) functioned immediately after transplantation. The incidence of delayed graft function (DGF) was 72%. Warm ischemic time and total ischemic time were 7.4 +/- 9.4 min and 11.9 +/- 5.6 h, respectively. The overall graft survival rates at 1, 5 and 10 years were 80%, 72% and 53%, respectively. Graft survival rates in each group have continually improved over time (5-year graft survival; 23% vs. 64% vs. 74% vs. 91%, respectively). However, there was no significant difference in graft survival rates between the groups of patients who survived with a functioning graft for more than 1 year. A multivariate Cox regression analysis showed acute rejection and donor age to be independently associated with graft outcome. DCD donors are a valuable source of kidneys for transplantation with promising long-term outcomes.

Adult↗

Efficacy and safety of growth hormone (GH) in the treatment of adult Japanese patients with GH deficiency: a randomised, placebo-controlled study.

OBJECTIVE: The aim of this study was to assess the effect of growth hormone (GH) replacement therapy on lean body mass (LBM) and other variables including body fat mass, serum lipids and quality of life measures in GH-deficient Japanese adults. DESIGN: This was a multicentre, double-blind, placebo-controlled, parallel group study. Following initial screening, patients were randomly assigned to GH treatment (n=37) or placebo (n=36). GH treatment was started at an initial dose 0.003 mg/kg/day s.c. each day for the first 4 weeks after which the dose was increased to 0.006 mg/kg/day for 4 weeks and then to 0.012 mg/kg/day for the last 16 weeks (n=37). Body composition, serum lipids, serum IGF-I and IGFBP-3 levels were measured during the 24-week study. Short Form-36 and Quality of Life Assessment of GH Deficiency in Adults scores were also determined. RESULTS: LBM was significantly increased from baseline at 24 weeks in GH-treated patients, with a mean (+/-SD) increase of 4.7% (+/-5.3%) compared with an increase of 1.0% (+/-4.4%) in the placebo group (p<0.0001 versus baseline, p=0.0003 versus placebo). Percentage body fat decreased significantly from baseline in GH-treated patients (9.3%, p<0.0001), compared with a non-significant 0.2% increase in the placebo group (p<0.0004 for difference between treatment groups). In addition, significantly increased serum IGF-I and IGFBP-3 levels and improvements in the patients' serum lipid profiles were observed in patients who received GH therapy. Changes in quality of life measures did not differ between treatments, probably because of the small number of patients studied. GH therapy was well tolerated, with adverse events of any cause reported in 86.5% of the GH treatment group and 83.3% of the placebo group. CONCLUSION: GH treatment significantly improved body composition and serum lipid profiles in adult Japanese patients with GH deficiency compared with placebo and had no clinically relevant adverse effects.

Adult↗

PPARgamma insufficiency promotes follicular thyroid carcinogenesis via activation of the nuclear factor-kappaB signaling pathway.

The molecular genetic events underlying thyroid carcinogenesis are poorly understood. Mice harboring a knock-in dominantly negative mutant thyroid hormone receptor beta (TRbetaPV/PV mouse) spontaneously develop follicular thyroid carcinoma similar to human thyroid cancer. Using this mutant mouse, we tested the hypothesis that the peroxisome proliferator-activated receptor gamma (PPARgamma) could function as a tumor suppressor in thyroid cancer in vivo. Using the offspring from the cross of TRbetaPV/+ and PPARgamma+/- mice, we found that thyroid carcinogenesis progressed significantly faster in TRbetaPV/PV mice with PPARgamma insufficiency from increased cell proliferation and reduced apoptosis. Reduced PPARgamma protein abundance led to the activation of the nuclear factor-kappaB signaling pathway, resulting in the activation of cyclin D1 and repression of critical genes involved in apoptosis. Treatment of TRbetaPV/PV mice with a PPARgamma agonist, rosiglitazone, delayed the progression of thyroid carcinogenesis by decreasing cell proliferation and activation of apoptosis. These results suggest that PPARgamma is a critical modifier in thyroid carcinogenesis and could be tested as a therapeutic target in thyroid follicular carcinoma.

Animals↗

Gene expressions of canine angiopoietin-1 and -2 in normal tissues and spontaneous tumours.

The angiopoietin (Ang) family of proteins are central to the regulation of angiogenesis. The purposes of this study were to determine cDNA sequences of canine Ang-1 and Ang-2 and investigate their expressions in normal tissues and spontaneous tumours. The cDNA sequences of canine Ang-1 and Ang-2 were 1,494 and 1,488 bp, and the deduced amino acid sequences were 497 and 495 residues, respectively. The cDNA sequences of canine Ang-1 and Ang-2 showed high homology with those of the other mammalian species. Canine Ang-1 and Ang-2 mRNA were detectable in all 22 normal tissues and spontaneous tumours. Higher mRNA expression level of canine Ang-2 was demonstrated in mammary simple carcinomas, haemangiosarcoma and hepatocellular carcinoma in comparison with normal tissues.

Amino Acid Sequence↗

Clinical outcome of high segmental gastrectomy for early gastric cancer in the upper third of the stomach.

BACKGROUND: Reflux oesophagitis is commonly encountered in the surgical treatment of cancer of the upper third of the stomach. The aim of this study was to describe a novel surgical technique and evaluate the clinical outcome of high segmental gastrectomy for early-stage proximal gastric cancer. METHODS: Thirty consecutive patients with early gastric cancer located in the upper third of the stomach were included, of whom 12 underwent high segmental gastrectomy and 18 underwent proximal gastrectomy with jejunal interposition. The incidence of reflux oesophagitis and nutritional parameters were compared between the two groups at 1 year after operation. RESULTS: One patient had mild reflux symptoms and two had endoscopic evidence of oesophagitis 1 year after high segmental gastrectomy. Half of the patients who had proximal gastrectomy had reflux symptoms of varying severity and 14 had endoscopic evidence of oesophageal changes at 1 year after surgery. There were significant differences between groups in the incidence of reflux symptoms (P = 0.016) and endoscopically detected gastro-oesophagitis (P < 0.001). There were no adverse events in either group, and the survival rate after high segmental gastrectomy appeared favourable. CONCLUSION: Selected patients with early-stage proximal gastric cancer benefit from high segmental gastrectomy in terms of reduced reflex oesophagitis, without jeopardizing curability.

Aged↗

Transplantation of autologous rabbit BM-derived mesenchymal stromal cells embedded in hyaluronic acid gel sponge into osteochondral defects of the knee.

BACKGROUND: Mesenchymal stromal cells (MSC) have the potential to differentiate into distinct mesenchymal tissues including cartilage, suggesting that these cells are an attractive cell source for cartilage tissue engineering approaches. Various methods, such as using hyaluronan-based materials, have been employed to improve transplantation for repair. Our objective was to study the effects of autologous transplantation of rabbit MSC with hyaluronic acid gel sponges into full-thickness osteochondral defects of the knee. METHODS: Rabbit BM-derived MSC were cultured and expanded with fibroblast growth factor (FGF). Specimens were harvested at 4 and 12 weeks after implantation, examined histologically for morphologic features, and stained immunohistochemically for type II collagen and CD44. RESULTS: The regenerated area after autologous transplantation of hyaluronic acid gel sponge loaded with MSC into the osteochondral defect at 12 weeks after surgery showed well-repaired cartilage tissue, resembling the articular cartilage of the surrounding structure, of which the histologic score was significantly better than that of the untreated osteochondral defect. In the regenerated cartilage, type II collagen was found in the pericellular matrix of regenerative chondrocytes, while CD44 expression in the regenerative tissue could not be revealed. DISCUSSION: These data suggest that the autologous transplantation of MSC embedded in hyaluronan-based material may support chondrogenic differentiation and be useful for osteochondral defect repair.

Animals↗

Serological diversity demonstrable by a set of monoclonal antibodies to eight serotypes of the mutans streptococci.

A set of monoclonal antibodies were prepared by the conventional cell fusion of myeloma cells (SP2/0-Ag14) with spleen cells from BALB/c mice immunised with whole cells of a strain of mutans streptococci. Their specificities were examined against 35 reference strains of mutans streptococci, 34 reference strains of other oral streptococci and 8 reference strains of other microorganisms often inhabiting the oral cavity. Specificity was examined by enzyme immunoassay using whole cells. A total of 52 strains, consisting of 19 strains isolated in Japan, 19 strains isolated in Italy and 14 strains isolated in England, were characterised by conventional physiological and biochemical tests and then serotyped by the use of 8 monoclonal antibodies with different specificities. They were also confirmed by guanine-plus-cytosine contents of their nucleic acid and DNA-DNA hybridisation test. The results indicated that all monoclonal antibodies are useful for identification of 8 serotypes of the mutans streptococci responsible for dental caries. They also suggest the existence of more serological varieties among mutans species.

Antibodies, Bacterial↗

Weil's disease with elevated plasma D-dimer.

We report a case of Weil's disease manifesting elevation of plasma D-dimer in the acute phase. Later, in the convalescent phase after treatment, the plasma levels of D-dimer returned to normal. Plasma D-dimer can be used as a marker of fibrin formation and degradation. Based on our observations, we conjecture that fibrin formation and fibrinolysis may occur in the acute phase of Weil's disease.

Acute Disease↗

Frequent involvement of ras-signalling pathways in both polypoid-type and flat-type early-stage colorectal cancers.

The development of colorectal neoplasms proceeds mainly via the adenoma-carcinoma sequence. BRAF and RASSF1A are members of Ras-signaling pathways, but the roles of their aberrations in colorectal carcinogenesis remain unclear. The authors studied mutations of the BRAF and K-ras genes, RASSF1A promoter methylation, and p53 overexpression in 43 polypoid-type and 30 flat-type early-stage colorectal cancers. No tumor simultaneously showed any combination of K-ras mutations, BRAF mutations, and RASSF1A promoter methylation. Three of the 73 tumors (4.1%) had BRAF mutations. All BRAF mutation-positive tumors were flat-type cancers, not associated with coexisting adenoma or p53 overexpression. RASSF1A promoter methylation was detected in 12 out of 73 tumors (16.4%), and the proportion of positive cases was similar in polypoid-type and flat-type cancers. BRAF mutations, K-ras mutations, and RASSF1A promoter methylation independently participate in early-stage colorectal carcinogenesis. BRAF mutations are involved only in flat-type cancers, whereas RASSF1A promoter methylation is involved in both polypoid-type and flat-type cancers. Thus, BRAF mutations most likely participate in de novo colorectal carcinogenesis, K-ras mutations in the adenoma-carcinoma sequence of colorectal carcinogenesis, and RASSF1A promoter methylation in both cascades.

Adenocarcinoma↗

N-methyl-D-aspartate receptors play important roles in acquisition and expression of the eyeblink conditioned response in glutamate receptor subunit delta2 mutant mice.

Classical eyeblink conditioning has been known to depend critically on the cerebellum. Apparently consistent with this, glutamate receptor subunit delta2 null mutant mice, which have serious morphological and functional deficiencies in the cerebellar cortex, are severely impaired in delay paradigm. However, these mutant mice successfully learn in trace paradigm, even in '0-trace paradigm,' in which the unconditioned stimulus starts just after the conditioned stimulus terminates. Our previous studies revealed that the hippocampus and the muscarinic acetylcholine receptors play crucial roles in 0-trace paradigm in glutamate receptor subunit delta2 null mutant mice unlike in wild-type mice, suggesting a large contribution of the forebrain to 0-trace conditioning in this type of mutant mice. In the present study, we investigated the role of N-methyl-D-aspartate receptors in 0-trace eyeblink conditioning in glutamate receptor subunit delta2 null mutant mice. Mice were injected intraperitoneally with the noncompetitive N-methyl-d-aspartate receptor antagonist (+)MK-801 (0.1mg/kg) or saline, and conditioned with 350-ms tone conditioned stimulus followed by 100-ms periorbital shock unconditioned stimulus. Glutamate receptor subunit delta2 null mutant mice that received (+)MK-801 injection exhibited a severe impairment in acquisition of the conditioned response, compared with the saline-injected glutamate receptor subunit delta2 null mutant mice. In contrast, wild-type mice were not impaired in acquisition of 0-trace conditioned response by (+)MK-801 injection. After the injection solution was changed from (+)MK-801 to saline, glutamate receptor subunit delta2 null mutant mice showed a rapid and partial recovery of performance of the conditioned response. On the other hand, when the injection solution was changed from saline to (+)MK-801, glutamate receptor subunit delta2 null mutant mice showed a marked impairment in expression of the pre-acquired conditioned response, whereas impairment of the expression was small in wild-type mice. Injection of (+)MK-801 had no significant effects on spontaneous eyeblink frequency or startle eyeblink frequency to the tone conditioned stimulus in either glutamate receptor subunit delta2 null mutant mice or wild-type mice. These results suggest that N-methyl-D-aspartate receptors play critical roles both in acquisition and expression of the conditioned response in 0-trace eyeblink conditioning in glutamate receptor subunit delta2 null mutant mice.

Animals↗

Horizontal and vertical distribution of estrogenic activities in sediments and waters from Tokyo Bay, Japan.

Endocrine-disrupting chemicals with estrogenic activity (e.g., alkylphenols) have been detected in coastal Japan. We aimed to determine estrogenic activity in extracts of river water, seawater, sediments, and sediment cores from Tokyo Bay by in vitro gene expression assay. Fifty-one of 57 extracts had some estrogenic activity. E2 equivalents (ng E2 equivalents per gram dry weight or per liter above the limit of detection) in river water samples ranged from 0.70 to 4.01 ng/L; in seawater samples from 0.34 to 2.52 ng/L; and in surface sediments from 2.07 to 12.1 ng/g. The relationship between salinity and estrogenic activity in water samples suggested that fresh water is one source of environmental estrogens in Tokyo Bay. Fractionation of sediment extracts showed that the highest estrogenic activity was observed in the midpolar fraction. The observed activities were compared with activities mediated by known concentrations of nonylphenol, bisphenol-A, estrone, and 17beta-estradiol. In sediment collected near the sewage treatment plants, the estrogenic activity of the midpolar fraction could be explained about 34% by nonylphenol and estrone contained in this fraction. Core sediment measurements detected estrogenic activity from as far back as the 1960s. The regulations on the industrial wastewater in early 1970s would be one of the main reasons for the lower estrogenic activity in the upper section of the sediment core. The high estrogenic activities as measured in water and sediment samples from Tokyo might be restricted to certain coastal areas.

Biological Assay↗

Clinical value of multidetector row computed tomography in detecting lymph node metastasis of early gastric cancer.

AIMS: To evaluate the clinical value of multidetector row computed tomography (MDCT) as a pre-operative staging tool for lymph node metastasis in patients with early gastric cancer (EGC). METHODS: In 278 consecutive patients with EGC, lymph node metastasis was evaluated pre-operatively with MDCT at a slice thickness of 2.5mm (n=57), 5.0mm (n=188), or 7.5mm (n=33). RESULTS: Overall accuracy of nodal category from N0 to N3 was 86% for MDCT and 95% for operative assessment. Regarding accuracy in detecting at least one metastatic lymph node, area under curves (AUC) of receiver operating characteristics for 2.5, 5.0, and 7.5-mm slices and assessment during surgery were 0.87, 0.67 and 0.47, and 0.70, which were significantly different (P<0.0001). MDCT image with 2.5-mm could discriminate the presence of lymph node metastasis with diagnostic accuracy: sensitivity 80%; specificity 92%; positive predictive value (PPV) 50%; negative predictive value (NPV) 98%, whereas assessment during surgery was as follows: sensitivity 65%; specificity 98%; PPV 72%; and NPV 97%. CONCLUSIONS: These results suggest that pre-operative assessment with MDCT using thinner slices may detect at least one lymph node metastasis as accurately as assessment during surgery for patients with EGC.

Adenocarcinoma↗

Cyclosporine-sparing effect of basiliximab in renal transplant recipients with mycophenolate mofetil.

UNLABELLED: Basiliximab added to a maintenance regimen consisting of cyclosporine microemulsion and mycophenolate mofetil was studied for its effectiveness in allowing early steroid withdrawal in renal transplantation. Furthermore, the cyclosporine-sparing effects between groups with and without basiliximab induction therapy were compared. PATIENTS: Between September 2001 and June 2003, 90 patients underwent renal transplants with cyclosporine-based immunosuppression, namely, cyclosporine, mycophenolate mofetil, and methylprednisolone, (group 1; n = 25). During the latter half of the study basiliximab was administered during the induction phase (group 2; n = 65). In group 2, steroids were completely withdrawn on postoperative day 14 in 57 patients. RESULTS: The incidence of acute rejection was significantly higher among group 1 patients (P = .005). The incidence of steroid-resistant rejection in group 1 patients was significantly higher (P = .025). At each time point cyclosporine levels in group 1 patients were significantly higher (P < .01). The incidence of infection was comparable between the groups. Patient and graft survival rates in group 1 were 100% and 100%; in group 2, they were 99% and 99%, respectively. In group 2, steroids were discontinued in 57 patients with permanent withdrawal achieved in 32 patients (56%). CONCLUSION: The use of basiliximab, together with mycophenolate mofetil allowed for a significant reduction in the cyclosporine dose without increasing the risk of acute rejection. Although further follow-up is necessary to confirm the effect, this regimen may attenuate cyclosporine nephrotoxicity thereby affecting the long-term outcomes of renal transplantation.

Antibodies, Monoclonal↗

Genetic evidence of "American" and "European" type symbiotic algae of Paramecium bursaria Ehrenberg.

Paramecium bursaria is composed of a "host" ciliate and a "symbiont" green alga. Based upon physiology, DNA hybridization and virus infection, two types of symbionts, called "American" type and "European" type, have been reported to date. Here, we determined the 18S rDNA and internal transcribed spacer 2 (ITS2) regions for both "American" and "European" types. Sequence features clearly separated into two lineages; NC64A (USA), Syngen 2-3 (USA), Cs2 (Chinese), MRBG1 (Australian), and Japanese strains belong to the "American", whereas PB-SW1 (German) and CCAP 1660/11 (British) strains belong to the "European". In "American" 18S rDNA, three introns were inserted in the same positions as for previously described Japanese symbionts. In "European" 18S rDNA, a single intron occurred in a different position than in the "American". Between the types, sequence differences were seven or eight nucleotides (0.39 %) in the 18S rDNA exon, and more than 48 nucleotides (19.2 %) in ITS2 regions. We subsequently sequenced the host 18S rDNA. As a result, two groups: Cs2, MRBG1, and Japanese strains, and PB-SW1 and CCAP 1660/11 strains, were separated (with 23 substitutions and 4 insertions or deletions between the groups). The congruent separations between hosts and symbionts may imply that the type of symbiont depends on the host type.

Animals↗