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Biomedical subjects

M Kusunoki

Publications and source records attributed to M Kusunoki.

At least 73 records · Page 4Linked to original sources

The actions of a novel lipoprotein lipase activator, NO-1886, in hypertriglyceridemic fructose-fed rats.

High circulating fasting and prandial triglyceride levels are associated with both insulin resistance and the development of cardiovascular disease. The aim of this investigation was to study the effects of NO-1886, a novel lipoprotein lipase (LPL) activator, on triglyceride levels, fat oxidation, and glucose tolerance in fructose-fed rats, a hypertriglyceridemic model of insulin resistance. Adult male Wistar rats were fed for 4 weeks with a high-starch diet or a high-fructose diet without and with NO-1886 (50 mg x kg[-1] x d[-1] orally). Fructose feeding increased plasma triglyceride levels, an effect that was ameliorated by NO-1886 treatment (week 1/week 4: starch-fed, 2.4 +/- 0.1/2.8 +/- 0.2 mmol/L; fructose-fed, 3.6 +/- 0.5/5.5 +/- 0.5; fructose + NO-1886, 2.7 +/- 0.2/3.6 +/- 0.3). The mean 24-hour respiratory quotient (RQ) was significantly lower in the fructose + NO-1886 group compared with fructose-fed rats, indicating increased oxidation of fat. Fructose feeding elevated liver triglyceride levels by 74% (P < .01), an effect not altered by NO-1886. Red and white quadriceps hindlimb muscle triglyceride levels were not different between groups. Glucose tolerance (intravenous test in long-term cannulated rats) was mildly deteriorated and fasting insulin and glucose levels were elevated in fructose-fed rats, effects which were ameliorated by NO-1886. In conclusion, in the fructose-fed rat model of hypertriglyceridemia and insulin resistance, addition of a LPL activator reduced circulating triglyceride levels without causing increased muscle triglyceride accumulation or deterioration in glucose tolerance. LPL activators may prove to be a fruitful avenue to explore in the search for new therapeutic agents in the treatment of dyslipidemias and insulin resistance.

Animals↗

The effect of low intensity bicycle exercise on the insulin-induced glucose uptake in obese patients with type 2 diabetes.

OBJECTIVE: The present study was undertaken to reveal the effect of low intensity bicycle exercise on the insulin-induced glucose uptake in obese patients. SUBJECTS AND METHODS: Seven obese men with Type 2 diabetes (OBDM) and seven healthy young men (HY) participated in this study. The glucose infusion rate (GIR) was determined by glucose clamp procedure at an insulin infusion rate of 40 mU m-2 min-1 (plasma insulin concentrations: 700-800 pmol l-1). Confirming stabilized GIR, a 30-min bicycle exercise was performed during the glucose clamp which was continued for 120 min after exercise. RESULTS: Average GIR in OBDM for last 30 min prior to exercise were significantly lower than HY (28.3 +/- 1.7, 47.4 +/- 1.8 mumol kg-1 min-1 respectively, P < 0.05). GIR abruptly increased during exercise and gradually decreased after exercise to the nadir almost at the time from 30 to 60 min in recovery period in both groups. GIR in OBDM, however, gradually increased significantly over pre-exercise levels (P < 0.05), following exercise and reached the same levels compared to HY after 80 min of recovery period. CONCLUSION: These results indicated that in obese Type 2 diabetes, 30 min of low intensity bicycle exercise significantly enhances the lower level of insulin-induced glucose uptake shortly after exercise and might be useful for the treatment of post-prandial hyperglycemia.

Adult↗

Folding motifs induced and stabilized by distinct cystine frameworks.

Bioactive peptides of different sources and biological functionalities, like endothelins, sarafotoxins, bee and scorpion venom toxins, contain a consensus cystine framework, Cys-(X)1-Cys/Cys-(X)3-Cys, which has been found to induce and stabilize a homologous folding motif named the cystine-stabilized alpha-helix (CSH). This is composed of an alpha-helical segment spanning the Cys-(X)3-Cys sequence portion that is crosslinked by two disulfide bridges to the sequence portion Cys-(X)1-Cys, itself folded in an extended beta-strand type structure. Search for sequence homologies of peptides and proteins in the SWISS-PROT and PDB data banks provided additional multiple examples of this type of cystine framework in serine proteinase inhibitors, in insect and plant defense proteins, as well as in members of the growth factor family with the cystine-knot. A comparative analysis of the known 3D-structures of these peptides and proteins confirmed that the presence of this peculiar cystine framework leads in all cases to a high degree of local structural homology that consists of the CSH motif, except for the cystine-knot, of the superfamily of the growth factors. In this case the cyclic structure formed by the parallel cysteine connectivities of Cys-(X)1-Cys/Cys-(X)3-Cys framework is penetrated by a third disulfide bond with formation of a concatenated knot, and the two disulfide-bridged peptide chains Cys-(X)1-Cys and Cys-(X)3-Cys are located in beta-strands. Conversely, peptides and proteins containing Cys-(X)m-Cys/Cys-(X)n-Cys cystine frameworks that differ from m/n = 1/3 were found to fold only sporadically into local alpha-helical structures.

Amino Acid Sequence↗

Gastroesophageal reflux after distal gastrectomy: possible significance of the angle of His.

OBJECTIVE: We investigated whether the angle of His influences gastroesophageal reflux after distal gastrectomy. METHODS: Thirty-eight patients having distal gastrectomy and 10 controls underwent upper gastroesophageal fluoroscopy to measure the angle of His, and gastroesophageal reflux was assessed by scintigraphy. The association between scintigraphic reflux and the angle of His was then evaluated. RESULTS: In distal gastrectomy patients with and without reflux symptoms, the angle was 108.82 +/- 21.88 degrees and 96.07 +/- 13.25 degrees, respectively; it was 74.14 +/- 10.85 degrees in the controls. The angle was significantly larger in the patients than in the controls (p < 0.01). In addition, the angle in the symptomatic gastrectomy group tended to be larger than in the asymptomatic group. The angle was also significantly larger in patients with a scintigraphic reflux index > or =6% than in those with an index <6% (p < 0.05). CONCLUSIONS: These findings suggest that the angle of His plays a role in reflux after distal gastrectomy and that the severity of reflux may be estimated by measuring this angle.

Adult↗

Scintigraphic assessment of double tract reconstruction after total gastrectomy.

BACKGROUND/AIMS: This study was carried out to evaluate the clinical significance of double tract reconstruction after total gastrectomy. METHODS: 25 patients, 14 with jejunal pouch double tract reconstructions and 11 with rho-double tract reconstructions, were studied. Scintigraphy was used to evaluate duodenal and jejunal passage, and the jejunal/duodenal ratio was calculated. The patients were classified into 3 groups based on this ratio: group A (n = 14) ratio <1; group B (n = 6) ratio 1-2, and group C (n = 5) ratio >2. The reflux score, scintigraphic reflux index, emptying time of the jejunal pouch or rho-limb, and various nutritional parameters were compared between the 3 groups. RESULTS: The emptying time was shortest in group B, but there was no significant difference among the 3 groups in the Sigstad dumping scores. The reflux score, scintigraphic reflux index, and most nutritional parameters also showed no significant differences between the 3 groups. Leakage at the duodenojejunostomy did not occur in any patient. CONCLUSION: Our findings suggest that there was no preferential passage via the duodenum or jejunum after double tract reconstruction. This method is also useful for decompression of the duodenal stump and group B seemed to have the ideal reconstruction on the basis of emptying time.

Adult↗

A comparison of stapled and hand-sewn anastomoses in Crohn's disease.

Sixty-eight patients with Crohn's disease who underwent intestinal resection were randomly divided into 2 groups: the stapled group (32 patients, 40 anastomoses) with functional end-to-end anastomoses made with linear staplers and with circular stapling anastomoses, and the hand-sewn group (36 patients, 48 anastomoses), with anastomoses achieved by layer-to-layer suturing. There were no significant differences in operative indications, age, sex, blood loss, or length of hospital stay between the groups. The operation times for right hemicolectomy and total colectomy in the stapled group were significantly shorter than those in the hand-sewn group. There were no significant differences in anastomotic dehiscence or recurrence between the stapling and hand-sewn procedures. These results indicate that these stapling techniques, even though producing an everted anastomosis, are not an adverse procedure for Crohn's disease.

Adolescent↗

Effect of site directed mutagenesis in the CMGCC region of the alpha-subunit on immunoreactive human thyrotropin.

The cDNA of the common alpha-subunit of human glycoprotein hormone was mutated by site directed mutagenesis in the CMGCC region composed of cysteine-methionine-glycine-cysteine-cysteine (position 28-32). The cDNA of wild-type human thyrotropin (hTSH) beta-subunit and that of wild-type or mutant common alpha-subunits were co-transfected into COS-I cells. The concentration of hTSH determined by two immunoradiometric assay systems was detectable in culture media of COS-I cells transfected with wild-type (CMGCC) and a mutant (CRGCC) alpha-subunits but not four other mutants (YMGCC) (CMRCC) (CMACC) (CMDCC). The present data with the other studies on wild-type or mutant glycoprotein hormones support our hypothesis that an amino acid motif of "C-X-G-X-C" in the common alpha-(CMGCC in human) and beta-(CAGYC in human) subunits play an important role in biosynthesis of glycoprotein hormones in all species.

Amino Acid Substitution↗

Effects of pharmacokinetic modulating chemotherapy using oral UFT and continuous venous 5FU infusion on the prognosis of irradiated rectal carcinomas with p53 overexpression.

We previously found that patients with irradiated rectal carcinomas with p53 overexpression had poor prognoses after radical resection. In the present study, we attempted to improve the prognosis by the introduction of adjuvant chemotherapy. We administered pharmacokinetic modulating chemotherapy, based on the concept that the benefit of a continuous venous 5-fluorouracil (5FU) infusion can be potentiated by low-dose oral UFT, a combination of 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) and uracil at a molar ratio of 1:4. Forty-two of 107 patients examined between January 1992 and December 1997 with an irradiated rectal carcinoma (39%) showed positive immunohistochemical staining for p53. Among them, 14 patients received adjuvant chemotherapy (CT group). The percentage of highly malignant tumors in the CT group was higher than that in the no-chemotherapy (NCT) group (n=28). However, the rate of cumulative local recurrence in the CT group was 0%, while that in the NCT group was 28.6% (p=0.0392). The distant recurrence rate in the CT group was also significantly lower than that in the NCT group (7.1% vs. 42.9%, p=0.0376). The cumulative 3-year survival rate was 100% in the CT group and 64.3% in the NCT group (p=0.0245). These results suggested that the antitumor property of 5FU enhanced by pharmacokinetic modulation might have a lethal effect on rectal tumors with a loss of the p53-related apoptosis pathway. These preliminary findings are encouraging for the treatment of rectal cancers with possible poor prognosis.

Administration, Oral↗

Marginal adaptation of commercial compomers in dentin cavity.

The dentin cavity adaptation and setting characteristics of four commercial compomers were evaluated by measuring the wall-to-wall contraction gap width in the cylindrical dentin cavity and measuring the compressive strength for a maximum of 14 days after setting. The dentin cavity wall was pretreated by the dentin adhesives according to each manufacturer's instructions or the experimental contraction gap-free dentin bonding system. Complete marginal integrity was obtained in only one compomer and two resin composites which were combined with the experimental dentin bonding system. The compressive strength of two resin composites and two compomers ten minutes after setting was comparable to that after 14 days which indicated that the compomers exhibited setting characteristics as rapidly as the resin composite. It was concluded that a high efficacy dentin bonding system is required for commercial compomers to prevent gap formation during irradiation caused by the rapid setting shrinkage.

Analysis of Variance↗

Results of preoperative intraluminal brachytherapy combined with radical surgery for middle and lower rectal carcinomas.

BACKGROUND: Radiation therapy in the treatment of rectal carcinoma has received attention. We attempted to learn whether preoperative intraluminal brachytherapy (IBT) gives an advantage in local control and/or prolongation of survival. METHODS: One hundred and fifteen patients with middle and lower rectal carcinoma with penetration into or through the rectal wall were consecutively treated with preoperative IBT and radical operation. Patients were divided into the moderate-dose group (group A: 16-40 Gy; n = 96) and the high-dose group (group B: 40-80 Gy; n = 19). A control group of 115 rectal carcinoma patients who received no radiation prior to radical surgery was compared (group C). RESULTS: The rate of sphincter-saving resection was 72% in group A, 63% in group B, and 42% in group C (group A vs. group C; P < 0.0001). The local recurrence rate at 5 years was 11% in group A, 6% in group B, and 26% in group C (group A vs. group C; P = 0.005). The 5-year survival rate was similar among the three groups. CONCLUSIONS: These results suggested that IBT contributed to the improvement of local control but not survival after radical resection of rectal carcinomas. The application of IBT might be useful in preserving the intestinal continuity for rectal carcinomas.

Adult↗

Nitric oxide-related neural components in the rat small intestine after transplantation.

The changes in nitric oxide (NO)-related neural components in the transplanted small intestine are unknown. In this study, the NO neural component was examined using electrophysiological and NADPH-diaphorase histochemical techniques in a rat small bowel transplantation model. Syngeneic total small bowel transplantation was performed in 26 male Lewis rats using microsurgical techniques. The rats were divided into four groups: an untreated control group and animals at 1 (G1), 2 (G2), and 4 (G4) weeks after transplantation. Jejunal strips were mounted in a superfusion apparatus for examination. In the presence of atropine and guanethidine, the effect of the NO synthesis inhibitor L-NG-nitro-arginine (L-NNA, 100 microM) relaxation mediated by the nonadrenergic, noncholinergic (NANC) neural system was assessed following electrical stimulation at 2Hz. The inhibitory effect of L-NNA on relaxation was taken as an indicator of NO production. The percentage of inhibition in the control group, and in G1, G2, and G4 was 43.30% +/- 6.08% (mean +/- SE), 42.10% +/- 6.69%, 43.62 +/- 10.00%, and 52.46% +/- 6.00%, respectively. Inhibition in G4 was significantly higher than in the other groups (P < 0.01). The percentage of NADPH-diaphorase-positive fibers in the control group, G1, G2, and G4 was 25.06% +/- 4.70% (mean +/- SE), 26.27% +/- 2.17%, 24.73% +/- 2.87%, and 30.76% +/- 3.19%, respectively. Again, G4 showed a significantly higher level than the other groups (P < 0.01). We conclude that increased NO production may play a significant role in maintaining the intrinsic nervous system of the small intestine after transplantation.

Animals↗

Functional results after "high" coloanal anastomosis and "low" coloanal anastomosis with a colonic J-pouch for rectal carcinoma.

The aim of this study was to determine the postoperative function of neorectoanal components using two different types of very low coloanal reconstruction. The two groups of patients assessed were 22 who underwent abdominal rectal resection and stapled "high" coloanal anastomosis without a pouch, being the HCAA-P group; and 34 who underwent anoabdominal rectal resection and "low" coloanal anastomosis with a colonic J-pouch, being the LCAA + P group. Manometric examination was performed 1, 3, 6, and 12 months postoperatively, and the patients were also assessed by a questionnaire. The LCAA + P group had remarkably less daily stool frequency and urgency, but there were no significant differences in the other functional parameters. Maximum resting pressure (MRP) was significantly less, while threshold volume (TV) and maximum tolerable volume (MTV) were greater in the LCAA + P group than in the HCAA-P group. The colonic J-pouch compensated for decreased MRP. Thus, when HCAA-P is performed, 3.0 cm of residual rectum with internal anal sphincter may be required, and construction of the pelvic pouch is desirable in low coloanal anastomosis.

Adult↗

Stapled fistulectomy to treat enteroenteric fistulas in Crohn's disease.

We report herein our technique of performing stapled fistulectomy as minimum surgery for the resection of nine entero-enteric fistulas in six patients with Crohn's disease. The surgical outcome was successful in all patients. It would seem that fistulous sites without a severe affected lesion are a favorable indication for this procedure and we recommend this simplified fistulectomy for selected conditions in Crohn's disease.

Adult↗

The TINS Lecture. The parietal association cortex in depth perception and visual control of hand action.

Recent neurophysiological studies in alert monkeys have revealed that the parietal association cortex plays a crucial role in depth perception and visually guided hand movement. The following five classes of parietal neurons covering various aspects of these functions have been identified: (1) depth-selective visual-fixation (VF) neurons of the inferior parietal lobule (IPL), representing egocentric distance; (2) depth-movement sensitive (DMS) neurons of V5A and the ventral intraparietal (VIP) area representing direction of linear movement in 3-D space; (3) depth-rotation-sensitive (RS) neurons of V5A and the posterior parietal (PP) area representing direction of rotary movement in space; (4) visually responsive manipulation-related neurons (visual-dominant or visual-and-motor type) of the anterior intraparietal (AIP) area, representing 3-D shape or orientation (or both) of objects for manipulation; and (5) axis-orientation-selective (AOS) and surface-orientation-selective (SOS) neurons in the caudal intraparietal sulcus (cIPS) sensitive to binocular disparity and representing the 3-D orientation of the longitudinal axes and flat surfaces, respectively. Some AOS and SOS neurons are selective in both orientation and shape. Thus the dorsal visual pathway is divided into at least two subsystems, V5A, PP and VIP areas for motion vision and V6, LIP and cIPS areas for coding position and 3-D features. The cIPS sends the signals of 3-D features of objects to the AIP area, which is reciprocally connected to the ventral premotor (F5) area and plays an essential role in matching hand orientation and shaping with 3-D objects for manipulation.

Animals↗

Involvement of the nervous system in the control of glucose uptake in contracting hindlimb muscle in the rat.

To probe into the possibility of neural control of glucose uptake in contracting peripheral skeletal muscle, rats were divided into two groups: one group is the "normal" (N) group in which the nervous system is intact, and the other is the "denervation" (D) group in which all nerves innervating the hindlimb were cut. The immediate changes in blood glucose (BG) and plasma insulin (PI) levels were measured at the commencement and termination of hindlimb muscle contraction induced with electrical stimulation of the sciatic nerve (distal part in D group). BG in N group temporarily but significantly decreased (p < 0.01) immediately after starting the stimulation, while BG in D group remained unchanged. And the difference between the changes in BG observed in 2 groups was significant (p < 0.03). PI did not change in either group during the sample period. On the other hand, PI temporarily but significantly decreased (p < 0.03) immediately after terminating the stimulation in both groups. The results suggest that the nervous system has some role in controlling glucose uptake in contracting peripheral muscle, at least in the early stage of contraction, that some feedback loop, including the central nervous system, is considered essential for the control, and that some local mechanism promotes an increase in insulin binding to receptors on muscle cells immediately after terminating the contraction.

Animals↗

Effects of neuropeptides on smooth muscle contraction after small bowel transplantation.

We have previously shown that increased intestinal contraction after small bowel transplantation was associated with marked enhancement in the nonadrenergic, noncholinergic (NANC) intrinsic neural component. In the present study, we examined the effect of three NANC neurotransmitters (substance P, neurotensin, and cholecystokinin-octapeptide, CCK-OP) on jejunal longitudinal muscle strips after syngeneic total small bowel transplantation in rats. Fourteen rats were divided into a normal control group (n = 7) and a group tested 4 weeks after transplantation (n = 7). A superfusion system was used to evaluate the in vitro effects of the three neuropeptides in the presence of atropine and guanethidine. In the control group, maximum contractile response to substance P, neurotensin, and CCK-OP was 5.16 +/- 0.30, 1.46 +/- 0.15, and 1.13 +/- 0.17 mg tension/mg wet weight, respectively, while the values for the transplanted group were 5.71 +/- 0.29, 2.52 +/- 0.17, and 1.20 +/- 0.18 mg tension/mg wet weight. These results show that neurotensin-induced contraction increased significantly after transplantation, but substance P appeared to be the dominant NANC neurotransmitter in both normal and transplanted small bowel.

Animals↗

Reflux esophagitis after total gastrectomy with jejunal pouch reconstruction: comparison of long and short pouches.

OBJECTIVE: To evaluate the effect of the type of jejunal pouch (long or short) on reflux esophagitis after total gastrectomy. METHODS: Two groups of patients who underwent jejunal pouch reconstruction (long pouch, n = 9; short pouch, n = 9) after total gastrectomy were compared, and each was also compared with a group of healthy control subjects (n = 9). Reflux symptoms were assessed using a reflux score questionnaire derived from Moran's graded reflux questionnaire. Scintigraphy was performed to evaluate quantitatively intestinoesophageal reflux and pouch emptying time (t75%). RESULTS: Heartburn was more common in the long pouch group than in the short pouch group (56 vs 11%, p < 0.05), and the reflux score was significantly higher in the long pouch group (mean score 3.0 vs 1.0, p < 0.01). The scintigraphic reflux index in the long pouch group, short pouch group, and control group was 9.57 +/- 5.52, 7.05 +/- 3.35, and 1.55 +/- 0.70, respectively. The reflux index in the entire group of patients was significantly higher than that in the control group (p < 0.005). In addition, t75% was significantly longer in the long pouch group (46.0 +/- 16.2 min) than in the short pouch group (21.1 +/- 15.39 min). CONCLUSION: Our findings suggest that reconstruction with a short jejunal pouch is more effective than a long pouch in preventing reflux symptoms.

Aged↗