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M Kusunoki

Publications and source records attributed to M Kusunoki.

At least 19 recordsLinked to original sources
PubMed2001

From three-dimensional space vision to prehensile hand movements: the lateral intraparietal area links the area V3A and the anterior intraparietal area in macaques.

The posterior parietal cortex is included in the dorsal cortical visual pathway underlying the three-dimensional (3-D) visual recognition of space and objects. The neurons in the lateral intraparietal area (LIP) respond visually to the three-dimensional objects, whereas those in the anterior intraparietal area (AIP) respond to hand movements to grasp them. LIP receives visual inputs from V3A, whereas AIP projects to the premotor areas; however, it is not known whether the neurons in LIP project to AIP. We herein investigated the connectional substrates that underlie the transformation of three-dimensional vision to prehensile hand movements in the Japanese monkey (Macaca fuscata). After identifying the three-dimensional visually responsive region in the posterior part of LIP by the unit recordings, we injected a bidirectional tracer, wheat germ agglutinin conjugated to horseradish peroxidase, into one of the recording sites. We found that LIP receives neuronal projections from V3A and sends axons to AIP. To confirm our findings, we injected several orthograde tracers into V3A and retrograde tracers into AIP in the same hemispheres. We found that the V3A neurons projecting to LIP terminate in the vicinity of the LIP neurons projecting to AIP. The results suggest that the cortical connections of V3A-LIP-AIP in the lateral bank of the intraparietal sulcus play an important role in the visuomotor transformation for prehensile hand movements.

Animals↗
PubMed2001

Crystallization and preliminary X-ray studies of meso-2,3-butanediol dehydrogenase from Klebsiella pneumoniae IAM1063.

Meso-2,3-butanediol dehydrogenase (meso-BDH) has been crystallized and preliminary X-ray crystallographic characterization of meso-BDH crystals has been performed. Single crystals of meso-BDH were prepared in two forms by the hanging-drop vapour-diffusion method using polyethylene glycol as a precipitant. Form I crystals belong to space group C2, with unit-cell parameters a = 215.5, b = 79.4, c = 134.8 A, beta = 98.22 degrees, and form II crystals belong to space group P2(1), with unit-cell parameters a = 69.16, b = 109.78, c = 127.28 A, beta = 102.29 degrees. The crystals diffracted to 2.0 and 1.7 A resolutions, respectively, using synchrotron radiation.

Alcohol Oxidoreductases↗
PubMed2001

Dual antitumor effects of 5-fluorouracil on the cell cycle in colorectal carcinoma cells: a novel target mechanism concept for pharmacokinetic modulating chemotherapy.

5-Fluorouracil (5-FU) is one of the most widely used anticancer agents for advanced colorectal carcinoma, but its response rate is only 15%. The "pharmacokinetic modulating chemotherapy" (PMC) regimen that we have advocated has proved to be highly effective in treating colorectal carcinoma. PMC consists of a continuous i.v. infusion of 5-FU over 24 h for 1day a week at 600 mg/m2/day, and an oral dose of uracil-tegafur (UFT), a 5-FU derivative, at 400 mg/day for 5-7 days per week, repeated every week for more than 6 months. Assays of 5-FU in 23 patients receiving this treatment showed serum concentrations ranging from 88 to 1,323 ng/ml. We then analyzed the effects of clinically relevant concentrations of 5-FU found in colorectal cancer patients treated with the PMC regimen on the growth of three human colorectal adenocarcinoma cell lines, SW480 and COLO320DM (mutant p53) and HCT116 (wild-type p53). Exposure of these three cell lines to 5-FU resulted in growth inhibition in a dose-dependent manner. Exposure to 100 ng/ml of 5-FU in SW480 and COLO320DM caused G1 arrest after 24 h and G2 arrest after 72-144 h, and only a minority of the cell population showed apoptotic features, which indicated that most of the cells were killed through mitotic catastrophe, nonapoptotic cell death. On the contrary, exposure to 1000 ng/ml of 5-FU in SW480 and COLO320DM resulted in G1-S-phase arrest and the induction of apoptosis throughout the experimental period. Nuclear cyclin B1 expression was markedly induced with exposure to 100 ng/ml of 5-FU in SW480 and COLO320DM; and expression of 14-3-3sigma protein, a cell cycle inhibitor in the GG phase, was induced in SW480. ICT116 responded to lower concentrations of 5-FU more rapidly: G2 arrest was seen after 24-72 h of exposure to 10 ng/ml of 5-FU, and G,1rrest was seen after 12-24 h of exposure to 100 ng/ml. These results show that 5-FU acts via two different pathways, depending on dose: (a) G,1S-phase cell cycle arrest and apoptosis at 1,000 ng/ml in SW480 and COLO320DM, and 100 ng/ml in HCT116; and (b) G2-M-phase cell cycle arrest and mitotic catastrophe at 100 ng/ll in SW480 and COLO320DM, and 10 ng/ml in HCT116. These results suggest that the efficacy of our PMC regimen is based on targeting at least two different phases of the cell cycle. In our clinical trial, we showed efficacy independent of p53 status, ascertained by cell kinetic analysis in vitro, which may lead to a novel concept of schedule-oriented biochemical modulation of this drug.

Adenocarcinoma↗
PubMed2001

Structure of the electron transfer complex between ferredoxin and ferredoxin-NADP(+) reductase.

All oxygenic photosynthetically derived reducing equivalents are utilized by combinations of a single multifuctional electron carrier protein, ferredoxin (Fd), and several Fd-dependent oxidoreductases. We report the first crystal structure of the complex between maize leaf Fd and Fd-NADP(+) oxidoreductase (FNR). The redox centers in the complex--the 2Fe-2S cluster of Fd and flavin adenine dinucleotide (FAD) of FNR--are in close proximity; the shortest distance is 6.0 A. The intermolecular interactions in the complex are mainly electrostatic, occurring through salt bridges, and the interface near the prosthetic groups is hydrophobic. NMR experiments on the complex in solution confirmed the FNR recognition sites on Fd that are identified in the crystal structure. Interestingly, the structures of Fd and FNR in the complex and in the free state differ in several ways. For example, in the active site of FNR, Fd binding induces the formation of a new hydrogen bond between side chains of Glu 312 and Ser 96 of FNR. We propose that this type of molecular communication not only determines the optimal orientation of the two proteins for electron transfer, but also contributes to the modulation of the enzymatic properties of FNR.

Binding Sites↗
PubMed2001

Biological implications of circulating soluble intercellular adhesion molecule-1 in colorectal cancer patients.

BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1) is assumed to play a role in cell-cell and cell-extracellular matrix interactions. We evaluated the relationship between local expression of ICAM-1 and the circulating level of sICAM-1, and clarified its biological implications. METHODS: Serum concentrations of sICAM-1 in 94 colorectal cancer patients were determined. Tissue concentrations of sICAM-1 in the tumor, colorectal adenoma, and the normal mucosa were also determined. The expression of ICAM-1 in the tumor was evaluated immunohistochemically. RESULTS: The serum concentration of sICAM-1 in the patients was significantly higher than that in the controls, and the tumor size was the independent pathological factor that was associated with the serum ICAM-1 level. ICAM-1 immunoreactivity was seen intensively in the stromal cells in the tumor. The tissue concentration of sICAM-1 in the normal mucosa was significantly lower than that in the adenoma and the early carcinoma. The tissue concentration of sICAM-1 in the advanced carcinoma significantly decreased in association with the increase in tumor size. This fluctuation of ICAM-1 expression in the tumor was also associated with the metastatic potential even at an early stage of the disease. CONCLUSIONS: The tissue concentration of sICAM-1 increased during tumorigenesis and at an early stage of carcinoma, and decreased in association with progression of the disease. Serum sICAM-1 level reflected the fluctuation of ICAM-1 expression in the tumor. Evaluation of serum concentration of sICAM-1 may be associated with tumor load and can reflect disease progression in colorectal cancer patients.

Adenocarcinoma↗
PubMed2001

Serum concentration of hepatocyte growth factor predicts perioperative surgical stress in children.

OBJECTIVE: To find out whether preoperative serum concentrations of hepatocyte growth factor (HGF) can indicate the general condition of sick children and can predict their postoperative inflammatory response. DESIGN: Non-randomised study. SETTING: University hospital, Japan. SUBJECTS: 41 children who required operation and 41 healthy controls. INTERVENTIONS: Samples of peripheral venous blood were obtained during the operation. MAIN OUTCOME MEASURES: Circulating concentrations of HGF, interleukin-6 (IL-6), and C-reactive protein (CRP); neutrophil counts; and nutritional variables including serum cholinesterase, albumin, and body weight: ideal body weight ratio. RESULTS: The mean serum concentration of HGF in the patients was significantly higher than in the normal controls. Preoperative HGF was related to the preoperative nutritional state, the postoperative IL-6 response, and the development of infective complications. CONCLUSIONS: The serum HGF concentration may be a useful variable for evaluating general condition and predicting perioperative surgical stress in sick children.

Adolescent↗
PubMed2001

Crystal structure of meso-2,3-butanediol dehydrogenase in a complex with NAD+ and inhibitor mercaptoethanol at 1.7 A resolution for understanding of chiral substrate recognition mechanisms.

The crystal structure of a ternary complex of meso-2,3-butanediol dehydrogenase with NAD+ and a competitive inhibitor, mercaptoethanol, has been determined at 1.7 A resolution by means of molecular replacement and refined to a final R-factor of 0.194. The overall structure is similar to those of the other short chain dehydrogenase/reductase enzymes. The NAD+ binding site, and the positions of catalytic residues Ser139, Tyr152, and Lys156 are also conserved. The crystal structure revealed that mercaptoethanol bound specifically to meso-2,3-butanediol dehydrogenase. Two residues around the active site, Gln140 and Gly183, forming hydrogen bonds with the inhibitor, are important but not sufficient for distinguishing stereoisomerism of a chiral substrate.

Alcohol Oxidoreductases↗
PubMed2001

Crystal structure of glucose dehydrogenase from Bacillus megaterium IWG3 at 1.7 A resolution.

The crystal structure of glucose dehydrogenase (GlcDH) from Bacillus megaterium IWG3 has been determined to an R-factor of 17.9% at 1.7 A resolution. The enzyme consists of four identical subunits, which are similar to those of other short-chain reductases/dehydrogenases (SDRs) in their overall folding and subunit architecture, although cofactor binding sites and subunit interactions differ. Whereas a pair of basic residues is well conserved among NADP(+)-preferring SDRs, only Arg39 was found around the adenine ribose moiety of GlcDH. This suggests that one basic amino acid is enough to determine the coenzyme specificity. The four subunits are interrelated by three mutually perpendicular diad axes (P, Q, and R). While subunit interactions through the P-axis for GlcDH are not so different from those of the other SDRs, those through the Q-axis differ significantly. GlcDH was found to have weaker hydrophobic interactions in the Q-interface. Moreover, GlcDH lacks the salt bridge that stabilizes the subunit interaction in the Q-interface in the other SDRs. Hydrogen bonds between Q-axis related subunits are also less common than in the other SDRs. The GlcDH tetramer dissociates into inactive monomers at pH 9.0, which can be attributed mainly to the weakness of the Q-axis interface.

Amino Acid Sequence↗
PubMed2001

Mitotic checkpoint protein hsMAD2 as a marker predicting liver metastasis of human gastric cancers.

hsMAD2, the human homologue of mitotic arrest deficient 2 (MAD2), is a key component of the mitotic checkpoint system. Recently, mutations and decreased expression of mitotic checkpoint genes including hsMAD2 have been reported in cancer cell lines with defective mitotic checkpoint. However, the genetic alterations in the genomic hsMAD2 gene have not been determined in gastric cancers. Moreover, the biological implications of the overexpressed hsMAD2 in primary cancers are unknown. In this study, we analyzed 32 primary gastric cancers with polymerase chain reaction (PCR) amplification of all exons, including flanking intronic sequences, of the genomic hsMAD2 gene followed by direct DNA sequencing. We also measured the hsMAD2 protein levels in cancer and normal tissues by semi-quantitative immunoblotting. No mutations were found in the coding sequences, although three single nucleotide polymorphisms (SNPs) were identified in the noncoding sequences in 13 of 32 patients. These SNPs were not associated with either hsMAD2 expression or disease progression. The semi-quantitative western blot analysis showed hsMAD2 was significantly overexpressed in gastric cancer tissues compared with corresponding normal tissues (P < 0.001). The calculated ratio of the hsMAD2 protein in cancer tissue (C) to that in corresponding normal tissue (N) (C / N ratio) was significantly higher in patients with well differentiated adenocarcinoma (P = 0.0274) or with synchronous liver metastasis (P = 0.0025). A C / N ratio greater than 3 was observed more frequently in patients with synchronous liver metastasis. Therefore, C / N ratio > 3 may be clinically important as a predictive indicator for metachronous liver metastasis of gastric cancers.

Adenocarcinoma↗
PubMed2001

Exercise improved accumulation of visceral fat and simultaneously impaired endothelium-dependent relaxation in old rats.

Exercise decreases plasma total cholesterol and triglycerides, and simultaneously, increases high density lipoprotein (HDL) cholesterol. Furthermore, it has been reported that exercise improves insulin resistance. As a result, exercise is believed to aid in preventing atherosclerosis. However, we do not know whether exercise protects against the development of atherosclerosis in the elderly. The aim of this study was to ascertain whether exercise prevented atherosclerosis in aorta of old rats. Exercise for three months did not affect plasma lipid levels but decreased accumulation of visceral fat and body weight without the reduction of food intake in two year old rats. Exercise also decreased triglycerides in liver and gastrocnemius white muscle. Exercise resulted in an elevation of plasma lipid peroxide (LPO) levels without affecting superoxide dismutase (SOD). Exercise impaired the endothelium-dependent relaxation of the thoracic aorta caused by acetylcholine in old rats. In summary, the results of our study indicate that exercise induces the reduction of visceral fat, body weight and triglyceride contents in tissues in old rats. These results seems to show that exercise improves insulin resistance. However, exercise simultaneously may cause impaired endothelium-dependent relaxation by elevation of LPO in old rats.

Adipose Tissue↗
PubMed2001

[Long survival in a case of unresectable hepatic metastasis from rectal carcinoma treated with second-look hepatectomy plus pharmacokinetic modulating chemotherapy (PMC)].

A 67-year-old female with rectal cancer and multiple liver metastases underwent low anterior resection by total mesorectal excision (TME), cholecystectomy and hepatic arterial cannulation in June 1995. She was treated with hepatic arterial infusion chemotherapy (HAI) (5-FU 600 mg/m2/day x 2 days/w) and oral UFT (400 mg/body, 5 days/w) once a week for 6 months on an outpatient basis. As the metastatic foci of the liver significantly decreased (83.3%) and extrahepatic disease were not observed, partial resection of the liver (second-look hepatectomy) was performed in March 1996. She continued arterial infusion PMC and venous infusion PMC as an outpatient. During the follow-up period a lung metastasis appeared in November 1997. Her regimen was changed to modified PMC with MMC (mitomycin C) and CPT-11. She has been managed at our outpatient clinic while the lung metastasis remained but with no liver metastasis for 57 months after the first operation, until the present. Second-look hepatectomy and PMC with a two-way port system was a useful option for unresectable hepatic metastases from colorectal carcinoma.

Adenocarcinoma↗
PubMed2001

[Successful resection of multiple liver metastases from rectal cancer following initial treatment using hepatic arterial infusion chemotherapy and radiotherapy].

A 69-year-old-man was referred to our hospital because of rectal cancer with multiple liver metastases. He was initially treated by hepatic arterial chemotherapy using an infusion reservoir (HACR) and radiotherapy for the rectal cancer. An abdomino-perineal resection and extended left lobectomy of the liver were performed and resulted in a reduction in size of the liver tumor. He was diagnosed as having a recurrent liver metastasis (S7) at 3 months after the operation, and was retreated by HACR in the outpatient clinic. A partial hepatectomy was reperformed at 6 months after the operation. Adjuvant hepatic arterial infusion chemotherapy (HAIC) was performed on an outpatient basis and the patient is doing well without recurrence or relapse. Preoperative arterial chemotherapy for metastatic liver tumor may be of some benefit for certain patients with far advanced colorectal carcinoma.

Aged↗
PubMed2001

[Roles of posterior parietal cortex in stereopsis: characteristics of responses of axis-orientation-selective neurons in monkey caudal intraparietal area].

Patients with parietal lesions may fail to adjust the orientation of their hand to that of a target object, or may make errors in judging the orientation of a bar. This suggests that the parietal cortex has a function in the discrimination of the orientation of objects. In this study we investigated the responses of axis-orientation-selective neurons in caudal intraparietal (CIP) area to stereoscopic stimuli. Among the characteristics we investigated responses to the length and thickness of objects, sensitivity to binocular disparity, and position invariance in depth. Computer generated stereoscopic stimuli were presented to the monkey on a 70 inch screen. Most of the neurons responded better to long or narrow stimuli. All neurons which were orientation selective only in the frontal plane were not disparity sensitive. Most of the neurons which were orientation selective in the sagittal or horizontal plane were sensitive for binocular disparity. The majority of these neurons had wide receptive fields and their responses were position-invariant. These results suggest that the axis-orientation-selective neurons in CIP area encode the orientation of the longitudinal axis of objects in 3-dimensional space.

Animals↗
PubMed2000

Effects of Different Types of Disparity Cues on the Response of Axis-orientation Selective Cells in the Monkey Parietal Cortex.

Purpose: To specify the cues for the discrimination of orientation in depth in axis orientation selective (AOS) neurons.Method: We analyzed the responses of AOS neurons in the monkey caudal intraparietal sulcus (cIPS) region using binocular disparity stimuli generated by stereoscopic 3 D computer graphics.Result: Most AOS neurons (20/27) were sensitive to binocular disparity and showed tuning to the orientation of a slit in the sagittal plane with orientation disparity cues. For 12 neurons we also used an array of discs or dots instead of slits to eliminate orientation disparity. Half of the neurons (6/12) responded better to the slits than to the discs or dots, suggesting that they were sensitive to orientation disparity. Five neurons (5/12) responded equally well to the discs or dots suggesting that they were more sensitive to the gradient of horizontal disparity than to the orientation disparity.Conclusion: Both orientation disparity and disparity gradient were likely to be integrated in the cIPS area to represent axis orientation of an object in space.

Journal Article↗
PubMed2000

Results of pharmacokinetic modulating chemotherapy in combination with hepatic arterial 5-fluorouracil infusion and oral UFT after resection of hepatic colorectal metastases.

BACKGROUND: Pharmacokinetic modulating chemotherapy (PMC) is a new therapeutic concept in combination with continuous 5-fluorouracil (5-FU) infusion and UFT. UFT enhanced plasma 5-FU concentration and antitumor effects during 5-FU infusion. The authors report on their experiences with arterial 5-FU infusion and UFT after resection of hepatic colorectal secondaries. METHODS: Fifty-eight patients were divided into two groups after hepatectomy. Group A, 30 patients, underwent hepatic arterial infusion (HAI) via implantable port system with perfusion 5-FU for 2 consecutive days per week at 600 mg/m(2)/day, and oral administration of UFT at 400 mg/day for 5-7 days per week, repeated 10 times, and Group B, 28 patients, underwent oral administration of UFT at 400 mg/day for 6 months. All the patients were managed at the outpatient clinic at Hyogo College of Medicine, and recurrence, survival, and toxicity were documented. Plasma 5-FU concentrations during chemotherapy were detected using high performance liquid chromatography. RESULTS: Maximum plasma concentrations of 5-FU in Group A reached 144.0 ng/mL and in Group B 58.7 ng/mL. Cumulative 5-year survival rate after hepatectomy in Group A was 59% and in Group B was 27%. (P = 0.00001) HAI-PMC drastically decreased hepatic recurrence (median hepatic recurrence free times were 34.2 months in Group A vs. 18.4 months in Group B; P = 0.00002). Grade 3 toxicity in Group A was found in 3 patients CONCLUSIONS: Pharmacokinetic modulating chemotherapy was designed as a uracil-related biochemical modulation. HAI-PMC significantly decreased hepatic recurrence after curative resection. This new chemotherapy concept significantly improved prognosis in patients with hepatic colorectal metastases.

Administration, Oral↗
PubMed2000

The lipoprotein lipase activator, NO-1886, suppresses fat accumulation and insulin resistance in rats fed a high-fat diet.

AIMS/HYPOTHESIS: Fat balance is critical in the aetiology of obesity and related diseases. Lipoprotein lipase is of major importance in lipid metabolism. The aim of this study was to investigate the long-term effects of the lipoprotein lipase activator, NO-1886, on substrate utilisation, adiposity and insulin action in rats fed a high-fat diet. METHODS: Male, Sprague-Dawley rats were fed for 10 weeks on a chow diet or a high-fat diet with, or without, NO-1886 (50 mg x kg(-1) x day(-1)). Weight gain, fat accumulation and both hormone-sensitive and lipoprotein, lipase activities were measured. Insulin action was assessed by the euglycaemic hyperinsulinaemic clamp and metabolic rate/substrate utilisation by open-circuit respirometry. RESULTS: Compared with chow-fed controls, a high-fat diet increased weight gain, an effect lessened by NO-1886 [weight gain (g): chow, 37 +/- 3, high-fat, 222 +/- 9; high-fat + NO-1886, 109 +/- 6, all groups differed p < 0.001]. A similar pattern existed for fat accumulation [visceral fat (g): chow, 35.9 +/- 3.2; high-fat, 81.9 +/- 6.6; high-fat + NO-1886, 52.3 +/- 4.7, p < 0.01 high-fat vs the other groups]. A high-fat diet induced wholebody insulin resistance (clamp glucose infusion rate: 4.8 +/- 1.3 mg x kg(-1) x min(-1) vs 10.6 +/- 1.1 for the chow group, p < 0.01) with NO-1886 lessening this effect (8.3 +/- 0.5, p < 0.05 vs high-fat). The 24-h respiratory quotient was lower in the high-fat + NO-1886 group (0.825 +/- 0.010) compared with high-fat alone (0.849 +/- 0.004, p < 0.05). A high-fat diet increased lipoprotein and hormone-sensitive, lipase activities in epididymal fat, an effect not altered by NO-1886. In myocardium and skeletal muscle a high-fat diet lowered lipoprotein lipase activity, an effect lessened by NO-1886. CONCLUSION/INTERPRETATION: Lipoprotein lipase activators could have potential benefits for the treatment of obesity by increasing fat utilisation.

Adipose Tissue↗