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Biomedical subjects

J Nakamura

Publications and source records attributed to J Nakamura.

At least 343 records · Page 19Linked to original sources

Abnormal excitability of hippocampal CA3 pyramidal neurons of spontaneously epileptic rats (SER), a double mutant.

The spontaneously epileptic rat (SER:zi/zi, tm/tm), a double mutant, shows both tonic convulsions and absence-like seizures characterized by low-voltage fast waves and by 5-7 Hz spike and wave-like complexes in the cerebral cortical and hippocampal EEG, respectively. Characteristics of hippocampal CA3 pyramidal neurons were examined to determine whether these neurons are abnormally excitable. When a single stimulus was given to the mossy fiber, there was repetitive firing and a depolarization shift in neurons of mature SER (over 12 weeks old), in which epileptic seizures had fully developed. However, in young SER (7-8 weeks old) and littermates (zi/zi, tm/+), which did not show any seizures, only a single spike was elicited with each single stimulation of the mossy fiber. Intracellular recording showed that the resting membrane potential was not significantly different among young and mature SER and littermates, but a long-lasting (100-200 ms) depolarizing shift accompanied by repetitive firing was observed following a single stimulation of the mossy fiber in half of the CA3 neurons of mature SER. Furthermore, the input impedance of the CA3 neurons in mature SER was lower than that in young SER and in littermates. These results indicate that SER hippocampal CA3 neurons become abnormally excitable in conjunction with the development of epileptic seizures.

Animals↗

Fluctuation of pancreatic peptide hormones in total-hepatectomy model in the rat.

A single-stage total-hepatectomy model in the rat is described. This model was successful in simulating the anhepatic phase for at least 4 h, with continuous intravenous glucose infusion. Advantages of the technique used for total hepatectomy in this study include ease of production, and resolution of problems encountered in previous models such as embolism and high postoperative mortality. This model was employed to observe fluctuation of pancreatic peptide hormones and glucose clearance during the anhepatic phase. Plasma insulin levels in portal blood did not vary for 120 min after removal of the liver. However, transient glucagon hypersecretion and depression in reactive secretion of somatostatin were observed during the anhepatic phase. These observations led to the following conclusions: (1) the liver seems to play an important role in regulating correlations between pancreatic peptide hormones by being part of a feedback system, and (2) hypersecretion of glucagon in the early anhepatic phase may be the initial signal for liver regeneration in the totally hepatectomized rat.

Animals↗

Changes in the incidence and duration of electroconvulsions after acute or subchronic treatment with methamphetamine in mice.

The effects of acute or subchronic treatment with methamphetamine on the incidence, intensity, and duration of electroconvulsion were investigated in mice. The convulsion was induced by electrical stimulation (100 Hz, 60 mA, 0.1-s duration) through electrodes located at each ear of mice, then analyzed by the vibration monitoring apparatus. Acute methamphetamine (3 mg/kg) reduced the incidence of the electroconvulsion in mice; however, the duration of each phase of the convulsion was prolonged by acute methamphetamine. Repeated administration of methamphetamine prolonged the duration of clonic phase of the convulsion and enhanced the acute methamphetamine-induced reduction in the incidence of electroconvulsion. These data indicate that the incidence of electroconvulsion is regulated by different mechanisms underlying the duration and intensity of the convulsion.

Animals↗

Effects of indeloxazine HCl on kindled amygdaloid seizures in rats: comparison with the effects of phenytoin, diazepam, ethanol, and imipramine.

The anticonvulsant effect of [(+/-)-2-[(inden-7-yloxy)methyl]morpholine (indeloxazine) HCl, a new cerebral activator, was investigated in rats against kindled seizures from the amygdala, an assumed model of secondarily generalized seizures in human. Indeloxazine (0.25-10 mg/kg, IP) dose-dependently depressed the kindled seizure and shortened the evoked amygdaloid afterdischarge. A high dose of indeloxazine (40 mg/kg, IP), however, induced generalized seizures. Comparison of the effects on the kindled seizures of indeloxazine to those of phenytoin, diazepam, ethanol, and imipramine revealed that the anticonvulsant actions of indeloxazine are similar to those of imipramine but not to those of phenytoin, ethanol, and diazepam. The results suggest that indeloxazine may exert its action through the monoaminergic system in the brain.

Animals↗

Bilateral anomalous insertion of flexor pollicis longus.

A case of bilateral insertion of flexor pollicis longus to the proximal as well as the distal phalanges is reported. Initially, this case was diagnosed as congenital absence of the flexor pollicis longus, but surgery revealed an intact tendon, with the abnormality only present in the site of insertion. A survey of the literature on congenital abnormalities of flexor pollicis longus failed to reveal any reports of similar abnormalities.

Congenital Abnormalities↗

Aromatase activity and the effect of estradiol and testosterone on DNA synthesis in endometrial carcinoma cell lines.

Human endometrial and breast carcinoma cell lines were examined for aromatase activity and the effects of sex steroids (estradiol and testosterone) on DNA synthesis. Aromatase activity was high (greater than 500 fmol/10(7) cells/24 h) in the cell lines MCF-7 and OMC-2, moderate (100-499 fmol/10(7) cells/24 h) in the cell lines HEC-59 and Ishikawa, and low (less than 100 fmol/10(7) cells/24 h) in the HHUA cell line. A substantial stimulation of DNA synthesis by estradiol (10(-9)M) was observed in cell lines HEC-59, OMC-2, and MCF-7, with an increase in [3H]thymidine uptake of over 250%. The Ishikawa cell line was stimulated moderately (115-249%). No estradiol-induced increase in DNA synthesis was observed in HHUA. Responsiveness of DNA synthesis to testosterone was observed in cell lines that showed the greatest response to estradiol, namely HEC-59, OMC-2, and MCF-7. Otherwise, estrogen-responsiveness did not always correlated with a significant aromatase activity. These data suggest that some but not all endometrial carcinomas may possess an aromatase-dependent growth stimulating system.

Aromatase↗

Aberrant alpha 1-->2fucosyltransferases found in human colorectal carcinoma involved in the accumulation of Leb and Y antigens in colorectal tumors.

Evidence indicates that the presence of aberrant alpha 1-->2fucosylation pathways is responsible for the accumulation of large quantities of Le(b) and Y antigens in human colorectal carcinoma. Significantly higher activities of alpha 1-->2 as well as alpha 1-->3 and alpha 1-->4fucosyltransferases were found in most of the tissues from carcinoma than in the adjacent normal tissues and in healthy subjects. alpha 1-->2Fucosyltransferases associated with the synthesis of Le(b) (Fuc alpha 1-->2Gal beta 1-->3[Fuc alpha 1-->4]GlcNAc beta) and Y (Fuc alpha 1-->2Gal beta 1-->4[Fuc alpha 1-->3]GlcNAc beta) structures from Le(a) (Gal beta 1-->3[Fuc alpha 1-->4]GlcNAc beta) and X (Gal beta 1-->4[Fuc alpha 1-->3]GlcNAc beta) ones, respectively, were demonstrated in colorectal carcinomas and in colorectal carcinoma cell lines (COLO201, LS174T and SW1116). The activation of alpha 1-->2fucosyltransferase with such new substrate specificities in colorectal carcinoma might result in the preferential synthesis of Le(b) and Y structures from Le(a) and X rather than from H type 1 and H type 2 structures.

Blood Group Antigens↗

Development and characterization of a novel anti-fucosylated antigen monoclonal antibody YB-2 and its usefulness in the immunohistochemical diagnosis of colorectal cancer.

A novel monoclonal antibody, YB-2 was obtained after immunization of mice with fucosylated antigens isolated from human saliva. The antibody was demonstrated to react with Y (Fuc alpha 1-->2Gal-beta 1-->4[Fuc alpha 1-->3]GlcNAc beta),Leb (Fuc alpha 1-->2Gal beta 1-->3[Fuc alpha 1-->4]GlcNAc beta) and H type 2 (Fuc alpha 1-->2Gal-beta 1-->4GlcNAc beta) antigens, but not with H type 1 (Fuc alpha 1-->2Gal beta 1-->3GlcNAc beta), Lea (Gal beta 1-->3[Fuc alpha 1-->4]GlcNAc beta), X (Gal beta 1-->4[Fuc alpha 1-->3]GlcNAc beta) or with non-fucosylated antigens. Inhibition assays of YB-2 antibody with such reactive antigens showed that YB-2 antibody preferentially reacted with Y antigen. Formalin-fixed and paraffin-embedded sections prepared from normal and malignant colorectal tissues were examined immunohistochemically with YB-2. The positive rates of staining with YB-2 antibody were 88.6% in malignant and 12.0% in normal tissues. The expression of fucosylated antigens detected by YB-2 antibody seemed to be correlated with survival among patients with primary colorectal cancer. Therefore, YB-2 antibody could be useful as an immunochemical tool for diagnosis and evaluation of the prognosis of colorectal cancer.

Antibodies, Monoclonal↗

A new aspect of tolbutamide metabolism in the rabbit: the role of 1-butyl-3-(p-formylphenyl)sulphonylurea.

We investigated the metabolism of tolbutamide by using synthetic 1-butyl-3-(p-formylphenyl)sulphonylurea (ATB), an intermediate in the metabolic pathway of tolbutamide. ATB (40 mg kg-1) administered intravenously to rabbits was oxidized to 1-butyl-3-(p-carboxyphenyl)sulphonylurea (CTB) and also reduced to 1-butyl-3-(p-hydroxymethylphenyl)sulphonylurea (HMTB). Therefore, it is likely that in the metabolism of tolbutamide, the oxidation of HMTB to ATB involved the reverse reaction, suggesting the reduction of ATB to HMTB. The oxidation of ATB to CTB was inhibited by disulfiram pretreatment. ATB was detected in the blood following intravenous administration of HMTB in rabbits pretreated with disulfiram. These results, confirm that ATB is an intermediate in the oxidative metabolism of tolbutamide in the rabbit.

Animals↗

[Study of bacterial flora in the stomach and the upper and lower respiratory tracts--the mechanism of lower respiratory tract infection].

To evaluate the mechanism of lower respiratory tract infection in the hospital, gastric juice, throat secretions, secretions in tracheal cannulae or tubes and aspirated sputum were cultured simultaneously in seven patients with tracheostomy and seven patients with tracheal intubation. Thirty-six strains of bacteria were isolated from gastric juice and only 22.2% of them were the same bacteria as those in the throat secretions. This suggested that there was little correlation between gastric and oropharyngeal flora. The bacteria isolated from throat secretions and aspirated sputum showed 38.5% coincidence in tracheostomized patients and 80% coincidence in intubated patients. In addition, the rate of agreement was 33.3% in tracheostomized patients and 88.9% in intubated patients between throat secretions and tracheal cannulae or tubes. These findings suggested that the correlation of bacterial flora between the upper and lower respiratory tracts was high in intubated patients and low in tracheostomized patients. Identical bacteria in the stomach and the upper and lower respiratory tracts (which may cause nosocomial infection) were isolated in only four of the 14 patients. It has been suggested that bacterial flora in the lower respiratory tract are transmitted from the stomach to the oropharynx and then cause lower respiratory tract infection in hospital. However, our study suggested that this was not a common pathogenic mechanism.

Aged↗

Acceleration of the N alpha-deprotection rate by the addition of m-cresol to diluted methanesulfonic acid and its application to the Z(OMe)-based solid-phase syntheses of human pancreastatin-29 and magainin 1.

In solid-phase peptide synthesis, the addition of m-cresol to diluted methanesulfonic acid (MSA) in dichloromethane accelerated the deprotection rate of the acid-labile alpha-amino protecting group, the p-methoxybenzyloxycarbonyl (Z(OMe)) group. Further, 0.1 M MSA, 20% m-cresol/CH2Cl2 was found to be a practically useful N alpha-deprotecting reagent system, since the deprotection of the Z(OMe) group occurred selectively within 30 min at room temperature, leaving intact the other side chain protecting groups, such as benzyloxycarbonyl, benzyl ester, S-p-methoxybenzyl and NG-mesitylene-2-sulfonyl groups. This reagent system was applied to the Z(OMe)-based solid phase syntheses of human pancreastatin-29 and magainin 1.

Amino Acid Sequence↗

Hormonal disregulation mechanism in the rat thyroid tumor induced by diniconazole.

To assess the toxicological significance of thyroidal tumor observed slightly in a long-term rat study with diniconazole, (E)-1-(2,4-dichlorophenyl)- 4,4-dimethyl-2-(1,2,4-triazol-1-yl)-1-penten-3-ol, a 3-month subacute feeding study was conducted in male Crj: CD (SD) rats by administering diniconazole in diet at concentrations of 0, 100, 1,000, or 2,000 ppm. Examinations mainly for thyroid functions were performed at Weeks 2, 4 and 13. Measurement of serum hormone levels revealed continuous decreases in serum thyroxine (T4) and free T4 levels at and above 1,000 ppm and increase in serum thyroid stimulating hormone (TSH) level at 2,000 ppm concurrently with liver weight and hepatic UDP-glucuronyltransferase (UDP-GT) increases at and above 1,000 ppm. No changes were observed in serum triiodothyronine (T3) and free T3 levels. Increase in thyroid uptake of 125I and organification of 125I in the thyroid at 2,000 ppm and thyroid follicular cell hyperplasia at and above 1,000 ppm were also observed. However, no compound-related changes were observed in autopsy and organ weight in the thyroid. Based on the above results, diniconazole induces increases in the hepatic UDP-GT activity and the thyroid hormone excretion from the liver. The increased excretion of thyroid hormones causes decrease in serum T4 and free T4 levels, triggering the feedback mechanism of the pituitary gland, promotion of TSH release from the pituitary gland and increase in serum TSH level. The increased serum TSH level probably leads to increased 125I uptake of thyroid and thyroid follicular cell hyperplasia. Thus, the thyroid tumorigenesis in rats treated with diniconazole is due to the secondary overstimulant effect on the thyroid by increased serum TSH level. The toxicological significance in humans is extremely low and it is unlikely that diniconazole would increase thyroid tumor in humans even if diniconazole were to alter normal thyroid hormone level in humans.

Animals↗

Long-term corneal endothelial changes after intraocular lens implantation. Anterior vs posterior chamber lenses.

The use of semiflexible anterior chamber intraocular lenses, widespread during the early 1980's, has been abandoned due to the many complications associated with their use. Patients who received these lenses currently represent the majority of patients with pseudophakic bullous keratopathy. We studied the morphologic characteristics of the corneal endothelium in 20 patients who had undergone extracapsular cataract extraction followed by anterior chamber or posterior chamber intraocular lens implantation. Specular microscopy and computer-assisted morphometry were performed preoperatively, 3 months postoperatively, and once a year thereafter. The follow-up period for each subject was 5 years or longer. The endothelial cell density of the central cornea in the anterior chamber lens group decreased from 304 to 196 (x 10 cells/mm2), and in the posterior chamber lens group decreased from 315 to 269 (x 10 cells/mm2). Four patients in the anterior chamber lens group developed pseudophakic bullous keratopathy 6 or 7 years after surgery. Severe endothelial cell loss and morphologic change were seen in patients who received anterior chamber lenses.

Aged↗

Stimulatory effects of islet amyloid polypeptide (amylin) on exocrine pancreas and gastrin release in conscious rats.

A rat islet amyloid polypeptide (amylin), 37-residue peptide amide was synthesized by the Fmoc-based solid phase method and the biological activity of synthetic rat amylin on exocrine pancreas was evaluated for the first time in conscious rat. Amylin (1, 10 nmol/kg/h) stimulated pancreatic exocrine secretion and plasma gastrin concentration. CR-1409, a CCK receptor antagonist, did not change amylin-stimulated pancreatic secretion. However, omeprazole (proton pump inhibitor) and atropine inhibited amylin-stimulated pancreatic secretion. This study suggests that amylin may play a role in biological action in the exocrine pancreas possibly mediated by gastric acid hypersecretion.

Amyloid↗