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Biomedical subjects

M Kusunoki

Publications and source records attributed to M Kusunoki.

At least 37 records · Page 2Linked to original sources
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↗
PubMed2000

Preventive efficacy of butyrate enemas and oral administration of Clostridium butyricum M588 in dextran sodium sulfate-induced colitis in rats.

Butyrate enemas have been reported to be effective in ulcerative colitis. However, long-term use is difficult because of the troublesome procedure and the unpleasant smell. We therefore investigated the effects of the oral administration of Clostridium butyricum M588 (CBM588), an enterobacterium producing butyrate, in dextran sodium sulfate (DSS)-induced colitis in rats. First, we confirmed the effects of pre-treatment with a butyrate enema on DSS colitis. We then studied the efficacy of oral administration of CBM588 which was started 1 week prior to the induction of DSS colitis. In the CBM588 group, the ulcer index and myeloperoxidase (MPO) activity in the distal colon were significantly lower than in the control group. Proliferating cell nuclear antigen (PCNA) immuno-positive cells were increased around the ulcer in the CBM588 group. In regard to the contents of the cecum and colon, the proportions of Lactobacillus and Eubacterium were increased in the cecum in the CBM588 group. Further, there were significant increases of n-butyrate, propionate, and acetate concentrations in the cecum in the CBM588 group. These results indicated that the oral administration of CBM588 alleviated DSS-induced colitis, and may be useful instead of butyrate enema.

Acetates↗
PubMed2000

The effectiveness of preoperative intraluminal brachytherapy in preventing wall penetration and nodal involvement of rectal carcinomas.

A retrospective review was conducted of 115 patients with middle or lower rectal carcinoma, without distant metastasis, who were consecutively treated with preoperative intraluminal brachytherapy and radical surgery (IBT group). Another 115 rectal carcinoma patients treated with surgery alone were reviewed as a control (NIBT group). We investigated whether conventional pathologic stagings were correlated with prognosis. All tumors were diagnosed by the TNM classification. According to the distribution of pathologic staging in the resected specimens, the prevalence of totally ablated tumors (stage T0) in the IBT group was significantly higher than that in the NIBT group, but there were no significant differences in the distribution of other T stages between the two groups. Good local control was achieved for the stage-T3 tumors in the IBT group, similarly to the T < or = 2 tumors in both groups. In the IBT group, the survival period of the patients with stage-T4 tumors even after radiotherapy was significantly shorter than that of those with T3 tumors (P = 0.042), while those with N < or = 2-stage tumors had significantly longer survival periods than those with N3-stage tumors (P = 0.047). These findings demonstrate the usefulness of analyzing clinicopathologic parameters to predict local control and the prolongation of survival. Determining these factors will also help to identify high-risk patients likely to require more effective adjuvant chemotherapy.

Adult↗
PubMed2000

Effect of the lipoprotein lipase activator NO-1886 on adriamycin-induced nephrotic syndrome in rats.

Hyperlipidemia associated with nephrotic syndrome may play a role in the deterioration of renal function. Tsutsumi et al have previously reported that the novel compound NO-1886 increases lipoprotein lipase (LPL) activity, resulting in a reduction of plasma triglycerides and an elevation of high-density lipoprotein (HDL) cholesterol in normal rats. The aim of this study was to ascertain whether NO-1886 suppresses the renal injury by treatment of the hyperlipidemia in an Adriamycin (Kyowa Hakko Kogyo, Tokyo, Japan) induced nephrosis rat model fed a high-protein diet that induced renal dysfunction and tubulointerstitial injury. Administration of Adriamycin caused hyperlipidemia, proteinuria, and edema with ascites in rats in 4 weeks. Furthermore, a combination of Adriamycin and a high-protein diet increased plasma creatinine and blood urea nitrogen (BUN) and decreased plasma albumin. Histologically, in Adriamycin-treated rats, marked interstitial cellular infiltration, tubular lumen dilation, and tubular cast formation in the kidney were observed. NO-1886 decreased plasma triglyceride and increased HDL cholesterol in Adriamycin-induced nephrotic rats. NO-1886 treatment reduced plasma creatinine and BUN levels and increased plasma albumin in Adriamycin-treated rats; it also ameliorated the ascites and proteinuria. Histologically, NO-1886-treated rats showed a quantitatively significant preservation of tubulointerstitial lesions. These data suggest that NO-1886 may have a protective effect against Adriamycin-induced nephrosis with tubulointerstitial nephritis in rats by a modification of the plasma lipid disorder.

Animals↗
PubMed2000

The lateral intraparietal area as a salience map: the representation of abrupt onset, stimulus motion, and task relevance.

Neurons in the lateral intraparietal area (LIP) of the monkey represent salient stimuli. They respond to recently flashed stimuli that enter their receptive fields by virtue of saccades better than they respond to stable, behaviorally irrelevant stimuli brought into their receptive fields by saccades. They respond transiently to abrupt motion onsets, but have no directional selectivity. They respond to stable stimuli that are the targets for saccadic eye movements, but far less before the same saccades without stimuli. LIP is important in the attentional mechanisms preceding the choice of saccade target rather than in the intention to generate the saccade itself.

Animals↗
PubMed2000

Crystallization and preliminary X-ray analysis of glucose dehydrogenase from Bacillus megaterium IWG3.

Glucose dehydrogenase from Bacillus megaterium IWG3 has been crystallized in the presence of NAD(+) using the hanging-drop vapour-diffusion method with PEG 2000 as the precipitant. Crystals belong to space group C2 and have unit-cell parameters a = 120.8 (1), b = 66.7 (1), c = 119.6 (1) A, beta = 93.25 (3) degrees with standard deviations in parentheses. Assumption of four subunits in the asymmetric unit gave the most probable Matthews coefficient V(M) of 2.1 A(3) Da(-1) (solvent content 41.7% by volume). X-ray diffraction data were collected to 1.7 A on a synchrotron-radiation source.

Bacillus megaterium↗