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Biomedical subjects

K Fujimoto

Publications and source records attributed to K Fujimoto.

At least 577 records · Page 32Linked to original sources

Facilitative effect of carbamazepine on previously induced hippocampal long-term potentiation.

The effects of carbamazepine (CBZ) on previously induced hippocampal long-term potentiation (LTP) were examined. Acute experiments were performed on 33 adult, male rabbits. Field potentials in the dentate gyrus were elicited by single shocks to the perforant path, and LTP was induced by tetanic stimulation to the pathway without induction of seizure discharge. At a CBZ serum level of about 5 micrograms/ml (value +/- SD = 5.40 +/- 1.28 micrograms/ml), the previously induced LTP in population spikes (PSs) and population excitatory postsynaptic potentials (EPSPs) was facilitated. At a CBZ serum level of about 15 micrograms/ml (value +/- SD = 14.28 +/- 1.29 micrograms/ml), the LTP in PS alone was decreased. The effects of carbamazepine on synaptic inhibition were examined by the paired-pulse test. The inhibition was enhanced with induction of LTP. After administration of CBZ, at a CBZ serum level of about 5 micrograms/ml the inhibition was further enhanced, while it was attenuated at a CBZ serum level of about 15 micrograms/ml. These results suggest that CBZ has a facilitative effect on previously induced LTP.

Animals↗

Increased expression of atrial myosin light chain 1 in the overloaded human left ventricle: possible expression of fetal type myocytes.

We examined the isoforms of myosin light chain 1 in the human left ventricles using pyrophosphate and sodium dodecyl sulfate polyacrylamide gel electrophoresis, peptide mapping, and immunoblotting with monoclonal antibodies against human atrial light chain 1. The relationship between hemodynamic parameters and light chain 1 isoform composition was compared among groups of patients with hypertrophic cardiomyopathy (n = 8), dilated cardiomyopathy (n = 9) and aortic stenosis (n = 5), and controls (n = 6). (1) The light chain 1, which differed from ventricular light chain 1 found in the normal adult ventricle, was highly expressed in the overload left ventricle, and was identical to atrial and fetal ventricular light chain 1 with respect to the physiochemical and immunological properties. (2) The expression of atrial/fetal light chain 1 was augmented in the subendocardial area in comparison with the mid- or subepicardial areas in the hypertrophied left ventricles. (3) The values (%) of the relative expression of atrial/fetal light chain 1 to total light chains 1 determined by densitometric analysis were significantly higher in patients with dilated cardiomyopathy (40.2 +/- 5.8) and those with aortic stenosis (43.1 +/- 6.2) than in the controls (16.9 +/- 2.5) (p less than 0.01), but there was no significant difference between the patients with hypertrophic cardiomyopathy (28.0 +/- 3.7) and the controls. (4) The values of the ratio significantly correlated with those of peak circumferential wall stress (r = 0.53, p less than 0.005). These results suggest that atrial/fetal light chain 1 is expressed in the left ventricles in response to the increased hemodynamic load.

Adult↗

Muscle spindles in the mylohyoid muscle of rats.

The mylohyoid muscle has several functions in relation to respiration, deglutition, and phonation, but these functions are not fully understood. The interaction of the mylohyoid nerve and muscle in 25 rats was studied by neurophysiologic and histologic methods. Stretching of the muscle elicited electrical responses from the branch of the mylohyoid nerve innervating the mylohyoid muscle, and stretch-sensitive receptors were demonstrated histologically in the mylohyoid muscle. This study indicates that the mylohyoid muscle plays an active role in functions such as swallowing, breathing, and phonation.

Animals↗

Establishment and characterization of monoclonal antibodies to carbohydrate antigens on peanut agglutinin receptor glycoprotein of gastric cancer KATO-III.

Eight mouse monoclonal antibodies, GOM-1, GOM-2, GOM-3, GOM-5, GOM-6, GOM-7, GOM-8 and GOM-9 were established that recognized carbohydrate antigens on the human gastric cancer cell line KATO-III. Their binding specificities were studied by enzyme-linked immunosorbent assay, cellular enzyme-linked immunosorbent assay, flow cytometry analysis and thin layer chromatography immunostaining. All these monoclonal antibodies bound to peanut agglutinin receptor glycoproteins and neutral glycolipids extracted from KATO-III cells, but they could be divided into three groups, namely GOM-1, -3, -9 group, GOM-5 and GOM-2, -6, -7, -8 group. GOM-3 specifically bound to the Le(a) structure, Gal beta 1-3 (Fuc alpha 1-4) GlcNAc beta 1-, and GOM-5 specifically bound to the Lec structure, Gal beta 1-3GlcNAc beta-. GOM-2 showed specific binding to KATO-III, but little or no binding to various other cell lines examined or to normal human leukocytic cells. It also did not bind to the synthetic glycoconjugates tested, carrying 10 different terminal sugar chains including T, Tn, Le(a), Lec and Le(x) structures. The binding specificity of GOM-2 was also different from those of the monoclonal antibodies anti-Le(x), anti-Leb and anti-Ley. These results suggest that GOM-2 recognizes a new carbohydrate antigen on KATO-III cells that is distinct from Le(a), Leb, Lec, Le(x), Ley, T and Tn structures.

Animals↗

Charting of daily weight pattern reinforces maintenance of weight reduction in moderately obese patients.

To maintain reduced body weight by behavioral therapy in moderately obese patients, body weight was measured four times daily and charted in a weekly graph. Seventy-two female patients with simple obesity were divided into two groups: 55 patients with appliance of charting of weight pattern (group-I), and 17 patients without the charting (group-II). The percentage of patients followed for 2 years was different between group-I (87%) and group-II (65%) during 2 years after completion of weight reduction therapy interviews (p less than 0.05). Forty-eight of group-I patients succeeded in decreasing their weight by 15.2 +/- 1.5 (mean +/- SEM) kg during the 6.5 +/- 0.8 months of the therapy interviews. They were followed up for 3.8 years with no rebound weight gain. Eleven patients in group-II also succeeded in decreasing their weight by 16.8 +/- 1.9 kg during 7.8 +/- 1.3 months but their body weight rebounded by 9.0 kg during the 2-year followup period. Twelve of 15 male patients with weight charting maintained reduced weight during 4.3 years. It was easier and more effective for obese patients to maintain weight graphs for the longer period than to record no weight graphs. Obese patients could themselves monitor irregular weight patterns produced by overeating and correct the irregularities in food intake and daily lifestyles. This seems to explain why the illustration of daily fluctuations of weight measurements was useful for long-term maintenance of weight reduction.

Adult↗

Increased apolipoprotein A-IV in rat mesenteric lymph after lipid meal acts as a physiological signal for satiation.

Chylomicron transport and apolipoprotein A-IV (apo A-IV) output in mesenteric lymph increases significantly after a lipid meal. Mesenteric lymph collected from lymph-fistula rats after lipid infusion exerted an anorectic effect on 24 h fasted rats after administration through chronically indwelling right atrial catheter. Lymph before lipid infusion and lymph collected from a rat fed lipid plus Pluronic L-81 (a potent inhibitor of chylomicron formation) had no anorectic effect. Chylomicron and apo A-IV-rich lymph lost its anorectic effect after specific immunoprecipitation of apo A-IV by a monospecific antibody. Intravenous infusion of the same amount of purified apo A-IV as in chylous lymph 6-8 h after a lipid meal suppressed food intake. This unique physiological function of apo A-IV is not shared by apolipoprotein A-I. It is proposed that apo A-IV is a circulating signal released in response to fat feeding and that it is likely to mediate the anorectic effect of a lipid meal.

Analysis of Variance↗

Advance shift of feeding circadian rhythm induced by obesity progression in Zucker rats.

To determine the relation between the circadian rhythm of ingestive behavior and the progression of obesity in Zucker rats, ingestion and ambulation were analyzed at four different developmental stages. The obese rats were disrupted gradually in nocturnal patterns of feeding, drinking, and ambulation with the progression of obesity, although the lean littermates maintained the patterns during whole test periods. Analysis of autocorrelogram revealed that circadian rhythms of those behaviors remained throughout the whole test periods. Least-squares spectrum ascertained the following. 1) The obese made advance shift of acrophases in feeding and drinking circadian cycles, but not in ambulation. 2) Amplitudes in those behavioral measures decreased with the progression of obesity. 3) Mesor in the obese feeding was not affected, although that in the lean feeding decreased. The findings indicate that disruption of the light-dark cycle in ingestion of the obese was not due to disappearance of circadian rhythm but to transformation by both decreased amplitude and advance shift of the circadian cycle.

Animals↗

Oxygen radical scavengers protect against eosinophil-induced injury in isolated perfused rat lungs.

The protective effect of oxygen radical scavengers on lung injury induced by activated eosinophils was examined in isolated perfused rat lungs. Eosinophils were obtained by bronchoalveolar lavage from rats infected with Toxocara canis and activated with phorbol myristate acetate (PMA). There were no changes in pulmonary vascular (RT) and airway (Raw) resistances and only minimal changes in vascular permeability assessed using the capillary filtration coefficient (Kf,c) in PMA control lungs and nonactivated eosinophil-treated lungs. In lungs receiving 3 x 10(6) PMA-activated eosinophils, there were significant increases from baseline of 7.3-fold in RT at 30 min, primarily due to the constriction of small arteries and veins; 3.6-fold in Kf,c at 90 and 130 min; and 2.5-fold in Raw. The lungs also became markedly edematous. Both superoxide dismutase and catalase pretreatment prevented the significant increase in Kf,c and lung wet-to-dry weight ratios and partially attenuated the increase in Raw, but did not significantly inhibit the increase in RT induced by activated eosinophils. Heat-inactivated catalase did not attenuate the eosinophil-induced increases in Kf,c, Raw, or RT. Thus, activated eosinophils acutely increased microvascular permeability primarily through production of oxygen free radicals. The free radical scavengers superoxide dismutase and catalase partially attenuated the bronchoconstriction but had no significant effect on the vasoconstriction induced by activated eosinophils.

Animals↗

Increased expression and regional differences of atrial myosin light chain 1 in human ventricles with old myocardial infarction. Analyses using two monoclonal antibodies.

BACKGROUND: This study was designed to examine the expression of atrial/fetal-type myosin light chain 1 (ALC1) in human ventricles with old myocardial infarction and in control hearts. METHODS AND RESULTS: The expression of immunoreactive (ir) ALC1 was examined in the subendocardial and subepicardial myocardium of the infarcted and the noninfarcted regions in the left ventricles with old myocardial infarction (n = 12) and of the control left ventricles (n = 8). For the analysis, we prepared two monoclonal antibodies, KA1 and KB1, that were specific for only ALC1 and for both ALC1 and ventricular myosin light chain 1 (VLC1), respectively. The ir-ALC1 expression ratio [ALC1/(ALC1 + VLC1), %] of the subendocardial myocardium, determined densitometrically by Western blotting with KB1, was significantly higher in the infarcted region (11.4 +/- 7.3%) than in the noninfarcted region (4.7 +/- 2.3%, p < 0.001) and the control ventricle (1.0 +/- 1.5%, p < 0.0001). In the infarcted region, the subendocardial myocardium contained a significantly greater percentage of ir-ALC1 than the subepicardial myocardium (5.8 +/- 6.7%, p < 0.005). The ir-ALC1 expression ratio had a significant negative correlation with the value of tissue protein concentration (milligrams protein per gram wet weight). The immunohistochemical study with KA1 revealed that the surviving myocytes included in the infarcted region, especially in the ventricular aneurysm, expressed ir-ALC1 strongly in comparison with those in the noninfarcted or the control ventricles. CONCLUSIONS: These results demonstrate increased expression of ALC1 and the regional differences in the failing left ventricles with old myocardial infarction. We conclude that the reexpression of ALC1 in infarcted ventricles occurs as one of the regional responses to increased load and may be a useful biochemical marker for the appearance of fetal-type myocytes.

Aged↗

Histamine and histidine decarboxylase are correlated with mucosal repair in rat small intestine after ischemia-reperfusion.

The aim of this experiment was to demonstrate whether histamine and histidine decarboxylase (HDC) contribute to mucosal repair in small intestine subjected to ischemia-reperfusion (I/R). The superior mesenteric artery was occluded for 15 min followed by reperfusion. In jejunal mucosa, histamine content and HDC activity increased after I/R. Histamine output in mesenteric lymph was also elevated after I/R. These increases in HDC activity, and mucosal and lymph histamine levels were suppressed by pretreatment of alpha-fluoromethylhistidine (alpha-FMH), a suicide inhibitor of HDC. alpha-FMH also attenuated the increase of ornithine decarboxylase (ODC) activity normally observed after I/R. Transport of dietary lipid into lymph markedly decreased at 24 h after I/R, yet it was restored to normal at 48 h after I/R. alpha-FMH inhibitor led to a sustained deficit in lipid transport at 48 h after I/R. This sustained functional impairment in alpha-FMH treated animals was associated with blunted responses of HDC activity and histamine content to I/R. Our results suggest that histamine and HDC contribute to the restoration in mucosal function observed at 48 h after I/R. This response may be related, at least in part, to stimulation of ODC activity by histamine.

Amine Oxidase (Copper-Containing)↗

Synthesis and antihypertensive activity of 3-acetoxy-2,3-dihydro-5-[2- (dimethylamino)ethyl]-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one (diltiazem) derivatives having substituents at the 8 position.

In order to improve the potency and duration of biological actions of diltiazem, a number of 1,5-benzothiazepine derivatives having the substituents at the 8 position were prepared and evaluated for their antihypertensive activity in spontaneously hypertensive rats. The introduction of methyl, ethyl, isopropyl, benzyl, methoxy, ethoxy, phenoxy, and methylthio groups increased the antihypertensive activity and prolonged duration of action, whereas cyclohexyl, cyclopentoxy, tolyloxy, p-methoxyphenoxy and phenylthio derivatives were less active than diltiazem. Among them, the 8-benzyl and phenoxy derivatives showed the most potent and long-lasting antihypertensive action.

Animals↗

Antitumor agents. I. DNA topoisomerase II inhibitory activity and the structural relationship of podophyllotoxin derivatives as antitumor agents.

Various podophyllotoxin derivatives from desoxypodophyllotoxin (DPT) were synthesized to examine the structural relationships between the biological significance (cytotoxic effect, effects on DNA topoisomerase II and tubulin polymerization) in vitro and antitumor activity in vivo (L 1210). An intact 6,7-methylenedioxy group of DPT is necessary to inhibit tubulin polymerization and topoisomerase II. 4'-Phenolic hydroxyl group of DPT is essential to inhibit DNA topoisomerase II and the inhibitory effect on DNA topoisomerase II contributes to a high cytotoxicity. The introduction of an aminoalkoxy group at 1-position of DPT enhances the inhibitory activity against DNA topoisomerase II and cytotoxic effect, causing the inhibitory activity against tubulin polymerization to disappear. The results of antitumor test in mice bearing L 1210 on podophyllotoxin derivatives suggest the following: 1) the strong cytotoxic effect itself is not a good indication of antitumor activity in vivo as long as it is associated with inhibition of tubulin polymerization. DNA topoisomerase II inhibitory effect contributes to an antitumor activity in vivo; 2) detailed measurements of cytotoxicity and inhibition on DNA topoisomerase II and tubulin polymerization in vitro are necessary to evaluate podophyllotoxin derivatives.

Animals↗

Incidentally identified multiple low-intensity areas on T2-weighted images by MR imaging.

Multiple small lesions of low intensity on T2-weighted images identified by MR imaging were observed in four patients. There were no definite associations between the patients' clinical symptoms and the lesions. MR imaging showed multiple, small areas with slightly high and/or low-intensities on T1-weighted images, and low intensities on T2-weighted images. IN two patients these low intensity areas were increased in size with field echo images. These MR studies indicate that multiple ruptures and/or hemorrhagic infarctions of microaneurysms may occur in the brain without any clinical manifestations.

Aged↗

Circadian rhythm of ornithine decarboxylase activity in small intestine of fasted rats.

The aim of this study was to determine whether the circadian changes in ornithine decarboxylase (ODC) activity of different segments of the small intestine were governed by factors other than food intake. First, the effects of fasting on mucosal ODC activity were examined. The results indicate that mucosal ODC activity in 24 hr and 48 hr fasted rats decreased significantly compared with ad libitum-fed rats. Second, the circadian rhythm of mucosal ODC activity was characterized by measuring mucosal ODC activity in fasted rats at four time points (09:00, 15:00, 21:00, and 03:00 hr; light period: 06:00-18:00 hr). The results from this study indicate that there is a detectable baseline ODC activity in different segments of fasting intestine. In duodenum, mucosal ODC activity was highest at 15:00 hr (light period), a time at which the rat was normally not eating. In jejunum and ileum, mucosal ODC activity increased between 21:00 and 03:00 hr (dark period). The observation that small intestine exhibits a distinct circadian rhythm of ODC activity in fasted rats suggests that not only food but also intrinsic factors can modulate physiologic oscillations in mucosal ODC activity.

Animals↗

[A pathological study of incidental carcinoma of the prostate. Pathological study of age-groups].

We reviewed 66 patients with stage A adenocarcinoma of the prostate who were treated at our 7 affiliated hospitals in Yokohama between 1984 and 1988. Of 1377 patients who underwent subcapsular prostatectomy (SCP) or transurethral resection of the prostate (TUR-P) for benign prostatic hyperplasia, 66 patients (4.8%) were diagnosed as an incidental carcinoma of the prostate. Of these patients, 36 and 30 were in stage A1 and A2, respectively. In the 66 patients, 59 (4.5%) were detected in 1315 TUR-P and 7 (11.3%) in 62 SCP. Elderly patients over 80 years of age had a higher risk of stage A2 disease. In histological grade, well, moderately and poorly differentiated adenocarcinoma were found in 48 patients (72.7%), 13 (19.7%) and 5 (7.6%), respectively. Among the patients with stage A prostate carcinoma the majority of the age-group less than 79 years old had well differentiated adenocarcinoma. In the age-group more than 80 years old, there were 6 (37.5%) moderately and 2 (12.5%) poorly differentiated tumors. In other words, the age-group more than 80 years old tended to have the moderately or poorly differentiated adenocarcinoma more frequently than those other decades. We expect an increase in the number of patients with stage A2 disease in the future with the expansion of the operative indication, especially in elderly patients.

Adenocarcinoma↗