Biomedical subjects

K Kato

Publications and source records attributed to K Kato.

At least 19 recordsLinked to original sources

PubMed2007

Sequence determination and functional analysis of the Akabane virus (family Bunyaviridae) L RNA segment.

Akabane virus (AKAV) causes epizootic congenital deformities in cattle, sheep, and goats. Due to the lack of a complete genome sequence, the molecular biological properties of this virus are not known. We have cloned and sequenced the functional large (L) RNA segment of AKAV, and shown that it has polymerase activity using a minireplicon system with RNA polymerase I. The complete L RNA segment is 6868 nucleotides long and encodes an L protein of 2251 amino acids, which functions as an RNA-dependent RNA polymerase. A minireplicon reporter plasmid was constructed by flanking either the firefly luciferase or the green fluorescent protein gene in the antisense orientation with the 5'- and 3'-terminal noncoding regions of the small RNA segment. HmLu-1 cells were transfected with the reporter plasmid, and the L protein and nucleoprotein (N protein) expression plasmids. The reporter activity was upregulated in a dose-dependent manner with increasing concentration of either the L or N protein expression plasmid. Furthermore, the reporter activity could be downregulated by the AKAV NSs protein as well as by other orthobunyaviruses. These results show that the AKAV minireplicon system is a powerful tool for studying transcription and for rescuing infectious viruses from cloned cDNAs.

Animals↗

PubMed2007

Pharmacokinetic study of darbepoetin alfa: absorption, distribution, and excretion after a single intravenous and subcutaneous administration to rats.

KRN321 is a hyperglycosylated analogue of recombinant human erythropoietin (rHuEPO, epoetin alfa), and its absorption, distribution, and excretion have been studied after a single intravenous and subcutaneous administration of 125I-KRN321 at a dose of 0.5 microg kg-1 to male rats. The half-lives of immunoreactive radioactivity in the terminal phase after intravenous and subcutaneous administration were 14.05 and 14.36 h, respectively, and the bioavailability rate after subcutaneous administration was 47%. The total radioactivity in tissues was lower than that in the serum in all tissues excluding the thyroid gland and skin at the injection site (subcutaneous administration). The maximum concentrations were observed in the bone marrow or skin at the injection site followed by the thyroid gland, kidneys, adrenal glands, spleen, lungs, stomach and bladder. The radioactivity found in trichloroacetic acid-precipitated fractions suggested that a high-molecular weight compound, unchanged or mixed with endogenous protein, distributed to the tissues after administration. The whole-body autoradiographic findings in both groups were in agreement with the tissue distribution mentioned above. The blood cell uptake of KRN321 was low for both groups. The excretion ratios of radioactivity into urine and faeces up to 168 h were 71.4 and 14.1% after the intravenous administration and 74.9 and 12.0% after the subcutaneous administration. There was no difference in the excretion profile of radioactivity between the two groups.

Absorption↗

PubMed2006

Omission of lymphadenectomy is possible for low-risk corpus cancer.

AIM: The objective of this study is to ascertain whether omission of lymphadenectomy is possible when endometrial cancer is considered low-risk based on intraoperative pathologic indicators. PATIENT AND METHODS: A total of 128 patients were deemed to be low-risk based on intraoperative evaluation, including frozen-section determination of grade and myometrial invasion. We divided these 128 patients into 2 groups, the total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH-BSO) with lymphadenectomy (LA group, n=68) and the TAH-BSO without lymphadenectomy (non-LA group, n=60) group. The only adjuvant treatment used was chemotherapy, and the decision to use chemotherapy was based on stage, grade, or lymphovascular space involvement. A retrospective review of the medical records was performed, and disease-free survival (DFS), overall survival (OS), operative time, estimated blood loss during operation, percentage of transfusion requirement, incidence of post-operative leg lymphedema and post-operative deep vein thrombosis were evaluated. RESULTS: The 5-year DFS and OS rates were 95.6% and 98.5% in the LA group, and 98.3% and 98.3% in the non-LA group, respectively, and were not significantly different. In the LA group, pelvic lymph node metastasis was observed in only 1 case. In the LA group, blood loss during operation, percentage of transfusion requirement and the incidence of post-operative leg lymphedema were significantly higher than those in the non-LA group. CONCLUSION: Lymphadenectomy did not provide a significant survival advantage in the patients with low-risk corpus cancer. Additionally, some peri- and post-operative morbidities and complications were increased by the addition of lymphadenectomy. The present findings suggest that lymphadenectomy should be limited for low-risk corpus cancer.

Adult↗

PubMed2006

Gamma-glutamyl compounds and their enzymatic production using bacterial gamma-glutamyltranspeptidase.

Some amino acids and peptides, which have low solubility in water, become much more soluble following gamma-glutamylation. Compounds become more stable in the blood stream with gamma-glutamylation. Several gamma-glutamyl compounds are known to have favorable physiological effects on mammals. Gamma-glutamylation can improve taste and can stabilize glutamine in aqueous solution. Because of such favorable features, gamma-glutamyl compounds are very attractive. However, only a small number of gamma-glutamyl amino acids have been studied although many other gamma-glutamyl compounds may have characteristics that will benefit humans. This is mainly because gamma-glutamyl compounds have not been readily available. An efficient and simple method of producing various gamma-glutamyl compounds, especially gamma-glutamyl amino acids, using bacterial gamma-glutamyltranspeptidase has been developed. With this method, modifications of reactive groups of the substrate and energy source such as ATP are not required, and a wide-range of gamma-glutamyl compounds can be synthesized. Moreover, bacterial gamma-glutamyltranspeptidase, a catalyst for this method, is readily available from the strain over-producing this enzyme. The superiority of producing gamma-glutamyl compounds with bacterial gamma-glutamyltranspeptidase over other methods of production is discussed.

Animals↗

PubMed2006

Photon emissions from rice cells elicited by N-acetylchitooligosaccharide are generated through phospholipid signaling in close association with the production of reactive oxygen species.

Biophotons are ultraweak light emissions from biochemical reactions in a living body. They increase in suspension-cultured rice (Oryza sativa L.) cells when elicited by N-acetylchitooligosaccharide. Biochemical analyses were undertaken to investigate the relationship between disease response and biophotons in order to clarify the emission mechanism of biophotons caused by this elicitor. Photon emissions induced by N-acetylchitohexaose were suppressed when cells were pretreated with the reactive oxygen species (ROS)-generating inhibitors: pyrocatechol-3,5-disulfonic acid disodium salt (Tiron); diphenylene iodonium (DPI); and salicylhydroxamic acid (SHAM). Conversely, exogenously applied ROS (superoxide and hydrogen peroxide) were able to induce photon emissions. The effects of protein phosphorylation (K-252a) and the Ca(2+) signaling inhibitors, ethylene glycol-bis(beta-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA) and LaCl(3), caused photon emissions to decrease. It is clear that photon emissions from rice cells elicited by N-acetylchitohexaose are closely associated with the ROS-generating system, and are regulated by Ca(2+) signaling and protein phosphorylation. Exogenously applied phosphatidic acid (PA), the second messenger in the signal transduction of disease response, raised photon emissions in rice cells. Comparisons of photon emissions from PA and N-acetylchitohexaose regarding time courses, spectral compositions, and the inhibition ratios of several inhibitors, as well as a loss- and gain-of-function assay using the protein synthesis inhibitor cycloheximide (CHX) and PA, showed the possibility that photon emissions from rice cells elicited by N-acetylchitooligosaccharide were generated through PA, an intermediate of phospholipid signaling.

Oligosaccharides↗

PubMed2006

A phase II study of single-agent gefitinib as first-line therapy in patients with stage IV non-small-cell lung cancer.

The aim of this study was to evaluate the efficacy and tolerability of gefitinib ('IRESSA') in Japanese patients with previously untreated stage IV non-small-cell lung cancer (NSCLC). This was a multi-institutional phase II study. Thirty-four patients with previously untreated stage IV NSCLC were enrolled between May 2003 and September 2004. Gefitinib was administered orally 250 mg once a day and was continued until there was either disease progression or severe toxicity. Objective tumour response rate was 26.5% (95% confidence interval, 11.7-41.3%). Adverse events were generally mild (National Cancer Institute-Common Toxicity Criteria grade 1 or 2) and consisted mainly of skin rash, fatigue and liver dysfunction. No pulmonary toxicity was observed. The global health status revealed that there was no change in quality of life during the study. This study found that single-agent gefitinib is active and well tolerated in chemo-naive Japanese patients with advanced NSCLC.

Adult↗

PubMed2006

Transcriptional targeting of adenovirus vectors with the squamous cell carcinoma-specific antigen-2 promoter for selective apoptosis induction in lung cancer.

Squamous cell carcinoma antigens SCCA1 and SCCA2 are highly homologous serine proteinase inhibitors which have been widely utilized as serological markers for squamous cell cancers, but it has recently been demonstrated that only SCCA2 is truly specific for certain forms of lung cancer. Using a construct containing the 5'-flanking region of the SCCA2 gene between -460 and +0 bp and the luciferase reporter gene, SCCA2 promoter activity was detected in SCCA2-producing SCC cell lines (LK-2, LC-1), but not in SCCA2-nonproducing lung adenocarcinoma cell lines (A549, ABC-1, and RERF-LC-MS) or normal cells (WI-38, SAEC, and NHEK-Adult). Infection with a recombinant adenovirus vector, Ad-SCCA2-DsRed, resulted in cell-specific expression of the SCCA2 promoter-driven DsRed marker gene only in LK-2 and LC-1 cells. The same strategy was used for SCCA2-driven expression of a proapoptotic gene, (KLAKLAK)2, which can cause mitochondrial disruption by triggering mitochondrial permeabilization and swelling, resulting in the release of cytochrome c and induction of apoptosis. Infection with Ad-SCCA2-KLAKLAK2 specifically reduced the growth of the two human lung SCC cell lines compared to the SCCA2 nonproducing cell lines both in vitro and in vivo, suggesting that the SCCA2 promoter had a tumor-specific effect. These results suggest that transduction of SCCA2 promoter-controlled suicide genes by adenoviral vectors can confer transcriptionally targeted cytotoxicity in SCCA2-producing lung SCC cells, and represents a novel strategy for gene transfer specifically targeted to SCC in the lung.

Adenoviridae↗

PubMed2006

Association of soluble CD40 ligand with carotid atherosclerosis in Japanese type 1 diabetic patients.

AIMS/HYPOTHESIS: It has recently been shown that the soluble form of CD40 ligand (sCD40L) interacts with CD40 on vascular cells, leading to a variety of proinflammatory responses, and that serum sCD40L levels can be a predictive marker of cardiovascular events. The aim of this study was to estimate sCD40L levels in type 1 diabetic patients to examine a possible association with carotid atherosclerosis. SUBJECTS AND METHODS: Human sCD40L levels in serum and intima-media thickness (IMT) of carotid artery were examined in 80 Japanese type 1 diabetic patients (27 men and 53 women, age 22.8+/-3.4 years (mean+/-SD), duration of diabetes 13.2+/-6.1 years) and 20 healthy age-matched non-diabetic individuals. RESULTS: Serum sCD40L levels were significantly (p=0.0185) higher in subjects with type 1 diabetes (2.10+/-1.33 ng/ml) compared with non-diabetic subjects (1.35+/-0.88 ng/ml). The greatest IMT (Max-IMT) and averaged IMT (Mean-IMT) were also significantly greater in patients with type 1 diabetes than in control subjects (0.73+/-0.14 vs 0.64+/-0.07 mm, p=0.0041, 0.63+/-0.09 vs 0.57+/-0.06 mm, p=0.0066, respectively). Levels of sCD40L were statistically significantly associated with Max-IMT (r=0.383, p<0.001) and Mean-IMT (r=0.275, p=0.0058). Furthermore, stepwise multivariate regression analyses demonstrated that sCD40L is a determinant of both Max- and Mean-IMT, independently of conventional risk factors. CONCLUSIONS/INTERPRETATION: It is suggested that increased levels of serum sCD40L are associated with accelerated atherosclerotic change observed in young patients with type 1 diabetes.

Adult↗

PubMed2006

Phase II study of combination therapy with S-1 and irinotecan in patients with advanced colorectal cancer.

BACKGROUND: A combination of irinotecan with continuous intravenous infusions of 5-fluorouracil (5-FU) and leucovorin (LV) is often used to treat advanced colorectal cancer. However, recent concerns about safety and convenience have prompted the development of new oral fluoropyrimidine derivatives and improved regimens. This phase II study evaluated the efficacy and safety of the oral fluoropyrimidine S-1 plus irinotecan in patients with previously untreated advanced or recurrent colorectal cancer. PATIENTS AND METHODS: Forty eligible patients with histologically confirmed colorectal adenocarcinoma received this treatment. S-1 was administered orally on days 1 to 14 of a 21-day cycle. Patients were assigned on the basis of body surface area (BSA) to receive one of the following oral doses twice daily: 40 mg (BSA < 1.25 m(2)), 50 mg (BSA > or = 1.25 to < 1.50 m(2)), or 60 mg (BSA > or = 1.50 m(2)). Irinotecan (150 mg/m(2)) was administered by intravenous infusion on day 1. RESULTS: A total of 327 courses of treatment were administered to 40 patients. Five patients had complete responses, and 20 had partial responses. The overall response rate was 62.5% (95% confidential interval, 47.5%-77.5%). Median progression-free survival was 8.0 months (95% confidential interval, 5.2-11.4 months). The rates of grade 3 or 4 toxicity were as follows: neutropenia, 15%; anemia, 7.5%; anorexia, 12.5%; and diarrhea, 7.5%. CONCLUSIONS: Combined treatment with S-1 and irinotecan is an effective, well tolerated, and convenient regimen in patients with advanced colorectal cancer. Our findings suggest that combined treatment with S-1 and irinotecan is a promising regimen, offering benefits in terms of safety and survival as compared with conventional regimens in patients with advanced colorectal cancer.

Adenocarcinoma↗

PubMed2006

Genetic analysis of calicivirus genomes detected in intestinal contents of piglets in Japan.

Enteric caliciviruses, noroviruses, and sapoviruses are emerging pathogens responsible for diarrhea or gastroenteritis in their respective hosts. In this study, swine enteric caliciviruses were detected in ten samples of intestinal contents from 24 piglets in Japan by reverse transcription-polymerase chain reaction using a broadly reactive primer pair (P290/289) that targeted the highly conserved RNA polymerase regions of the enteric caliciviruses. From the positive samples, the entire viral genome of strain K7/JP and 3'-end parts of the genomes of strains K5/JP and K10/JP were cloned and sequenced. K7/JP had an RNA genome of 7144 bases, excluding its 3' poly (A) tail. The K7/JP genome possessed two open reading frames and characteristics common to sapoviruses. In phylogenetic analysis using amino acid sequences of VP1, K5/JP was demonstrated to be close to the noroviruses previously detected in pigs, and K7/JP and K10/JP were considered to be classified as a new genogroup of sapoviruses.

Animals↗

PubMed2006

Spontaneous formation of vanadium "molecules" in a geometrically frustrated crystal: AlV2O4.

We investigated the charge-ordered (CO) state in spinel AlV2O4 by electron diffraction, synchrotron x-ray diffraction, and magnetic measurements. It was found that the CO structure appearing below 700 K is characterized by the formation of V clusters (heptamers), each of which is consisting of 7 vanadium atoms and is in a spin-singlet state as a total. Theoretical consideration indicates that this unique molecularlike V heptamer is stabilized by a strong bonding of vanadium t(2g) orbitals.

Journal Article↗

PubMed2006

Balloon occlusion test of the internal carotid artery: correlation with stump pressure and 99mTc-HMPAO SPECT.

PURPOSE: To evaluate the correlation of stump pressure during balloon occlusion test and relative cerebral blood flow (relative CBF) as measured by 99mTc-hexamethylpropyleneamine oxime (99mTc-HMPAO) single-photon emission computed tomography (SPECT) after test occlusion. MATERIAL AND METHODS: Balloon occlusion test of the internal carotid artery (ICA) was performed in 25 patients. The count ratio of occluded hemisphere to non-occluded hemisphere was calculated on 99mTc-HMPAO SPECT. The ratio of mean stump pressure to mean arterial pressure during carotid occlusion during the balloon occlusion test was compared with the count ratio of 99mTc-HMPAO SPECT. RESULTS: Two patients failed to tolerate even brief carotid occlusion. The other 23 patients showed no ischemic deficit during occlusion of the ICA. In 13 of these 23 patients, the ratios of mean stump pressure to mean arterial pressure were more than 50%, and the count ratios on SPECT were more than 85%. In 10 of 23 patients, the ratios of mean stump pressure to mean arterial pressure were less than 50%, and the count ratios on SPECT were variable. CONCLUSION: Maintenance of a mean stump pressure of 50% or more of the mean systemic pressure during test occlusion indicates adequate cerebral blood flow during carotid occlusion.

Adult↗

PubMed2006

Chemical removal and recovery of phosphorus from excess sludge in a sewage treatment plant.

We describe a process for the recovery of phosphorus from excess sludge in a sewage treatment plant that currently uses polyaluminium chloride for chemical phosphorus removal. Instead, we employed alkaline dissolution of excess sludge with calcium phosphate precipitation to recover phosphorus from sewage. The recovery ratio for phosphorus from sewage using the phosphorus recovery system is approximately 50%. In addition, the amount of excess sludge in the phosphorus recovery system is approximately half that of conventional chemical phosphorus removal. Alkaline dissolution of excess sludge resulted in dissolution of aluminium into the supernatant. Furthermore, since dissolved aluminium can be reused as a coagulant, the phosphorus recovery system could be used to economize coagulant consumption. Operation and maintenance costs of the phosphorus recovery system are 25.9 U.S. cents per 1 m3 of sewage compared to 32.0 U.S. cents per 1 m3 of sewage for conventional chemical phosphorus removal, representing a decrease of 20% in the operation and maintenance costs.

Aluminum Chloride↗

PubMed2006

Effect of multimer size and a natural dimorphism on the binding of convulxin to platelet glycoprotein (GP)VI.

BACKGROUND: Convulxin (CVX), a C-type lectin from the venom of Crotalus durissus terrificus, is a potent activator of human platelets, binding predominantly to glycoprotein (GP)VI. Native CVX is an octamer composed of four alphabeta-heterodimers [(alphabeta)(4)]. Two different native sequences have been reported, one bearing lysine (K), the other glutamic acid (E), at beta chain residue 89, but the physiological relevance of this difference is unknown. OBJECTIVE: We used the Drosophila S2 system to express recombinant CVX (rCVX) heterodimers (alphabeta) and site-directed mutagenesis to evaluate the influence of multimer size and the substitution betaK89E on CVX function. METHODS: By flow cytometry, native CVX and both recombinant forms bind to human platelets in whole blood. By surface plasmon resonance (BIAcore, Piscataway, NJ, USA), the calculated equilibrium dissociation constants (K(D)) were: rCVX alphabeta89K, 11.3 x 10(-8) m; rCVX alphabeta89E, 9 x 10(-8) m; and native CVX, 2.8 x 10(-8) m. RESULTS: Thus, the affinities of the two rCVX forms for human, recombinant GPVI are essentially the same, but the relative affinity of native CVX is about 3-fold higher. The minimum concentration of native CVX that induces maximal human platelet aggregation (70 pm) is roughly 400-fold lower than that of either rCVX (29 nm). CONCLUSIONS: These results are consistent with the hypothesis that the ability of the native CVX octamer to cluster mobile GPVI molecules within the platelet membrane may be the single most important factor that contributes to the efficiency with which CVX is able to induce platelet activation.

Animals↗

PubMed2006

Dentin resorption and cementum-like tissue formation by bone morphogenetic protein application.

BACKGROUND AND OBJECTIVE: Recent studies have shown that bone morphogenetic protein-2 (BMP-2) stimulates mineralization and osteoclast differentiation. Osteoclastic resorption by BMP-2 application may play an important role in the regulation of new cementum-like tissue formation on the dentin surfaces. Therefore, this study aimed to examine the effect of BMP-2 application on dentin resorption and cementum-like tissue formation at the dentin surfaces. MATERIAL AND METHODS: Seventy-two flat dentin blocks were prepared from rat roots and treated with 24% EDTA. Each block was assigned to group 0, group 100, or group 400, and immersed correspondingly in 0, 100, or 400 microg/ml BMP-2. The dentin blocks were then implanted into palatal connective tissue of rats, and specimens were prepared 2, 4 and 8 wk after surgery for histologic and histomorphometric analyses. RESULTS: BMP-2 caused a dose-dependent increase in dentin resorption by osteoclastic cells. New cementum-like tissue was randomly formed on parts of the nonresorbed and resorbed dentin surfaces in groups 100 and 400. Dentin resorption in groups 100 and 400 was significantly greater than group 0 (p < 0.01). However, at 8 wk, new cementum-like tissue formed in 41.8% of group 100, as compared with 16.2% of group 400 (p < 0.05). CONCLUSION: Dentin resorption was stimulated by a high dose of BMP-2, and cementum-like tissue was induced by a low dose of BMP-2, effectively suggesting that BMP-2 application, at an appropriate dose, to a dentin surface may enhance periodontal regeneration.

Animals↗

PubMed2006

Parry-Romberg syndrome with a clinically silent white matter lesion.

We performed a detailed neuroimaging study in a patient with Parry-Romberg syndrome. Proton MR spectroscopy demonstrated normal spectral patterns, though conventional MR imaging revealed high-intensity areas in the entire white matter in the left hemisphere. Single-photon emission tomography showed increased perfusion in the cortex of the affected hemisphere. Pyramidal tracts and optic radiations were preserved on diffusion tensor tractography. We will correlate these neuroimaging findings with normal psychomotor development in our patient.

Brain Diseases↗

PubMed2006

[Acute type A aortic dissection with partial disruption of the right coronary ostium; report of a case].

A 64-year-old man with a history of hypertension was admitted to another hospital, presenting with sudden chest pain. Although his symptoms resolved after admission, chest computed tomography (CT) revealed acute type A aortic dissection, and he was referred to our hospital for surgery. On arrival, his hemodynamic status was stable. Electrogram showed no ST-T change, and transthoracic echocardiography demonstrated pericardial effusion, mild aortic regurgitation and good left ventricular wall motion. We immediately decided on an emergency operation. Commencing a median sternotomy, the pericardial cavity was found to be filled with old blood. Standard cardiopulmonary bypass was instituted with right atrial drainage and right femoral arterial return, and with right upper pulmonary venous venting. When antegrade cold blood cardioplegia was selectively administered, we noticed the partial disruption of the upper aspect of the right coronary ostium. The right coronary sinus was resected in a scallop shape. Partial aortic root remodeling using a trimmed tube graft and coronary artery bypass grafting to the right coronary artery with saphenous vein were performed under deep hypothermic circulatory arrest. Weaning from cardiopulmonary bypass was not difficult. The postoperative course was uneventful.

Aortic Dissection↗

PubMed2005

Differential glycosylation of polyclonal IgG, IgG-Fc and IgG-Fab isolated from the sera of patients with ANCA-associated systemic vasculitis.

Post-translational modifications (PTMs) of proteins produced in vivo may be tissue, developmentally and/or disease specific. PTMs impact on the stability and function of proteins and offer a challenge to the commercial production of protein biotherapeutics. We have previously reported a marked deficit in galactosylation of oligosaccharides released from polyclonal IgG isolated from sera of patients with the anti-neutrophil cytoplasmic antibodies (ANCA) associated vasculitides; Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA). Whilst normal polyclonal IgG molecules are glycosylated within the IgG-Fc region, approximately 20% of molecules also bear oligosaccharides attached to the variable regions of the light or heavy chain IgG-Fab. It is of interest, therefore to compare profiles of oligosaccharides released from the IgG-Fc and IgG-Fab of normal IgG with that isolated from the sera of patients with WG or MPA. This study shows that whilst the oligosaccharides released from ANCA IgG-Fc are hypogalactosylated those released from IgG-Fab are galactosylated and sialylated. These results show that hypogalactosylation of IgG-Fc is not due to a defect in the glycosylation or processing machinery. It rather suggests a subtle change in IgG-Fc conformation that influences the addition of galactose. Remarkably, this influence is exerted on all plasma cells. Interestingly, a licensed monoclonal antibody therapeutic, produced in Sp2/0 cells, is also shown to be hypogalactosylated in its IgG-Fc but fully galactosylated in its IgG-Fab.

Antibodies, Antineutrophil Cytoplasmic↗