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Biomedical subjects

T Deguchi

Publications and source records attributed to T Deguchi.

At least 307 records · Page 17Linked to original sources

Entrainment of the circadian rhythms of blinded infant rats by nursing mothers.

New-born rats were optically enucleated on day 1 and the rhythms of pineal serotonin N-acetyltransferase activity and serum corticosterone levels were followed under various nursing schedules from 4 to 8 weeks of ages. When blinded pups born under DL (LD) cycle were reared by foster mothers under LD (DL) cycle, both of N-acetyltransferase and corticosterone rhythms were in phase with those of the pups born of and reared by their original mothers under LD (DL) cycle. The phases of the rhythms were regularly delayed at a similar rate in 4 groups as they grew, indicating that nursing mother rats can entrain the circadian rhythms of blinded pups. When intact and blinded pups were reared under LD cycle, the phases of N-acetyltransferase activity rhythm in both groups were identical at the first postnatal week, but the phase of the rhythm in blinded pups was gradually delayed after second week compared to intact pups. The observation indicates that the endogenous oscillation in blinded pups starts to free-run between 1 and 2 weeks after birth.

Aging↗

Regulation of choline acetyltransferase in primary cell cultures of spinal cord by neurotransmitter L-norepinephrine.

Neurotransmitter L-norepinephrine increased up to 8-fold the activity of choline acetyltransferase (CAT), the enzyme responsible for the synthesis of acetylcholine, in mouse spinal cord cells in culture grown for several days. The increase of CAT activity by L-norepinephrine was mediated by a beta-adrenergic receptor in the same manner as the response of intracellular cyclic AMP. Derivatives of cyclic AMP caused an increase of CAT activity to the level similar to that of L-norepinephrine. A cyclic AMP phosphodiesterase inhibitor, 3-isobutyl-1-methyl xanthine (IBMX), enhanced the elevation of CAT activity by L-norepinephrine. These results indicate that L-norepinephrine stimulated the synthesis of CAT molecules via the action of cyclic AMP. The pretreatment of cells with 5-fluoro-2'-deoxyuridine (FdU) markedly diminished the numbers of satellite cells and, in parallel, the responses of CAT activity to L-norepinephrine. The increase of cyclic AMP by L-norepinephrine was also reduced by pretreatment of the cells with FdU. In contrast, co-cultures of spinal cord with heart muscle markedly (30-fold) stimulated CAT activity both with and without pretreatment of FdU. The addition of L-norepinephrine and co-cultures with heart muscle showed an additive effect. These observations indicate that the stimulatory effect of L-norepinephrine on CAT activity is mostly, if not only, mediated via the interaction with satellite cells, and that the increase of CAT activity by L-norepinephrine is based on a mechanism different from that of co-cultures with heart muscle cells.

Animals↗

Studies on the phagocytic function of urinary leukocytes.

Urine specimens from patients with urinary tract infection (UTI) were examined to determine the rate of phagocytosis and viability of urinary leukocytes. The phagocytic function of urinary leukocytes was also studied in vitro. The mean rate of viable urinary leukocytes was 83 per cent and the phagocytic potency was confirmed by light and electron microscopic studies. In 99 per cent of 113 patients with UTI, urinary leukocytes were shown to have phagocytized bacteria. The rate of phagocytosis in chronic UTI was higher than that in acute UTI. Urinary osmotic pressure and the positive or negative of antibody coated bacteria were supposed to be factors influencing phagocytic potency of urinary leukocytes.

Antibody-Coated Bacteria Test, Urinary↗

Wide field fluorescein angiography by use of contact lens.

A system has been developed to obtain fluorescein angiographs with a field measuring to 90 degrees. This involves a contact lens and a new fundus camera with a basic field of 60 degrees. The contact lens, however, can be used with any fundus camera and will result in an increase in the area of the photographs of over 2X. There are numerous clinical applications for high resolution, high contrast, wide field fluorescein angiography.

Contact Lenses↗

Species heterogeneity of pineal hydroxyindole-O-methyltransferase.

Hydroxyindole-O-methyltransferase was purified from bovine and chicken pineal glands to apparent homogeneity and their properties were compared. The purified enzymes from both pineal glands differed in electrophoretic mobility and isoelectric point. Sodium dodecyl sulfate gel electrophoresis revealed that hydroxyindole-O-methyltransferase of both bovine and chicken pineals was a dimer consisting of a subunit of molecular weight 39,000. The two enzymes also differed in substrate specificity. Bovine hydroxyindole-O-methyltransferase showed a high specificity toward N-acetylserotonin, whereas chicken enzyme methylated N-acetylserotonin and, to some extent, serotonin and bufotenine. The methylation of the three substrates was probably catalyzed by the same enzyme of chicken pineal, because the ratio of substrate availability did not change throughout the purification steps. Using the purified enzymes, we prepared antibody to both bovine and chicken hydroxyindole-O-methyltransferase. The antibody to bovine enzyme cross-reacted with both avian and mammalian enzymes, whereas the antibody to chicken hydroxyindole-O-methyltransferase reacted with avian enzymes, but far less with mammalian enzymes, indicating an immunochemical difference between avian and mammalian hydroxyindole-O-methyltransferase. The results suggest that the properties of hydroxyindole-O-methyltransferase have changed during the evolutionary development of the pineal glands.

Acetylserotonin O-Methyltransferase↗

Effects of N-(4-methylbenzylthiocarbonyl)-L-phenylalanine (KF 1492), a new hypolipidemic drug, and clofibrate on lipids metabolism.

The effects of N-(4-methylbenzylthiocarbonyl)-L-phenylalanine (KF 1492) on the intestinal lipid absorption, the biliary lipid composition and alpha-glycerophosphate dehydrogenase (GPD) activity have been investigated in rats in comparison with clofibrate. KF 1492 did not have inhibitory activity on intestinal absorption of cholesterol and triglyceride. In the KF 1492-treated group (100 mg/kg, 8 d), an increase of bile flow (25.9%) per g liver was observed. The increase of excretion of bile acids (29.9%), phospholipids (45.2%) and cholesterol (33.4%) due to the increase of bile flow was clearly observed but no significant change in the concentration of each lipid was observed. In clofibrate-treated group, the concentration of bile acids and cholesterol in bile was decreased and output of biliary phospholipids was increased. Approximately 5 to 10 times increase of GPD activity was observed in mitochondrial fraction of the KF 1492- or clofibrate-treated rats (0.25% (w/w) in rat chow, 3 weeks). Thus, the increased degradation and excretion of cholesterol to bile may explain the hypocholesterolemic activity of KF 1492.

Animals↗

[An immunohistochemical study of prostate antigen using an enzyme-labeled antibody technique].

With an enzyme-labeled antibody technique, prostate antigen (PA) was studied immunohistochemically. PA was found to localize at epithelial cells and secretary materials in the lumen of prostatic tissue regardless of histological type. However, PA could not be detected in the interstitial area of the prostate. This technique may become useful for detection of local extension or distant metastasis of prostate cancer. An immunoelectronmicroscopical study of PA is now underway.

Adolescent↗

Cellular mechanism involved in the synthesis of cyclic GMP in nervous tissues.

Intracellular cyclic GMP content responds to the stimulation of muscarinic receptor in a variety of tissues. Several aspects of the cellular mechanism involved in the synthesis of cyclic GMP were investigated. 1. In cultured bovine chromaffin cells, acetylcholine as well as muscarine stimulated the 32Pi incorporation into phosphatidic acid, induced Ca2+ mobilization across the cells, and, in parallel, elevated intracellular cyclic GMP content. Phosphatidic acid added to culture medium also stimulated the efflux and influx of Ca2+ and the synthesis of cyclic GMP in bovine chromaffin cells and in neuroblastoma cells in the same fashion as acetylcholine. 2. We have succeeded in a purification of an endogenous activator for guanylate cyclase from rat brain and identified it as L-arginine. L-Arginine, but not D-arginine, activated soluble guanylate cyclase 10- to 20-fold at a low concentration (1-2 X 10(-5) M). The activation of the enzyme by L-arginine seemed to require Ca2+. Calcium accumulated in cells in response to muscarinic stimulation would activate guanylate cyclase in collaboration with L-arginine. 3. Using a specific monoclonal antibody, we demonstrated the cellular and subcellular localizations of guanylate cyclase in rat brain. An intense reaction was observed in the brain regions which were rich in muscarinic receptor. Electron microscopic examination revealed that guanylate cyclase was concentrated in the postsynaptic perikaryon and dendrites of some type of neurons indicating its involvement in neural transmission.

Acetylcholine↗

Effect of depolarizing agents on choline acetyltransferase and acetylcholinesterase activities in primary cell cultures of spinal cord.

In cultured neurons dissociated from the spinal cord of fetal mouse, high concentrations of KCl (47 mM) increased choline acetyltransferase (CAT) activity up to 5.5-fold but suppressed acetylcholinesterase (AChE) activity to less than half the level of control cells. Veratridine (3 microM) also increased CAT activity 1.6-fold and suppressed AChE activity to the same level as that induced by high KCl. The increase of CAT activity by the depolarizing agents was blocked by Ca2+ antagonists (verapamil and high Mg2+) and in a low Ca2+ medium, whereas the suppression of AChE activity by high KCl was restored by the same procedures. The synthesis of radiolabeled acetylcholine from [14C]choline was also enhanced 4-fold by incubating cells in high KCl medium. Although the uptake of L-[3H]leucine and [14C]choline into the cells was slightly enhanced by high KCl medium, neither the total amount of protein nor the incorporation of L-[3H]leucine into protein was increased by high KCl medium. These observations indicate that depolarization increased CAT activity in a specific manner, that the activities of CAT and AChE changed inversely under several conditions, and that the effect of depolarization presumably was mediated by the entry of Ca2+ into neuronal cells. The findings raise the possibility that trans-synaptic input could play a crucial role in the development of the activity of cholinergic neurons in spinal cord.

Acetylcholinesterase↗

[T-cell bearing IgG-Fc receptor in patients with bladder cancer].

The T-cell bearing Fc receptor (IgG-FcR+ T cell) has been considered as a suppressor or a part of the killer cell, as determined by its function. The population of IgG-FcR+ T cells was determined by Moretta 's method in patients with urinary bladder cancer, urological benign diseases and in normal subjects. The population of IgG-FcR+ T cells in the peripheral lymphocytes of 16 patients with urinary bladder cancer was 20.5 +/- 10.1%, that of 7 patients with urological benign diseases was 9.5 +/- 3.2%, and that of 8 normal subjects was 9.0 +/- 2.1. The population of IgG-FcR+ T cells in the peripheral lymphocytes patients with high stage bladder cancer was significantly higher than that of patients with low stage cancer. In low stage bladder cancer cases, the population of IgG-FcR+ T cells was decreased to the normal range at three weeks after removal of the tumor. But in high stage bladder cancer cases, it was not changed at 3 weeks.

Adult↗

[Safety evaluation of micronomicin IV. Acute toxicity in rats, rabbits and dogs after drip intravenous infusion].

Micronomicin (MCR) is a new aminoglycoside antibiotic produced by Micromonospora sagamiensis var. nonreducans which was isolated from soil collected at Sagamihara City by Nara et al. This antibiotic shows a close similarity to gentamicin C components in physical and chemical properties. The antibacterial activity of MCR is broad-spectrum and almost equal to that of gentamicin C complex. MCR exhibits particularly high activity against Pseudomonas, Proteus, Klebsiella pneumoniae, Serratia, etc, as well as against some Pseudomonas aeruginosa strains resistant to gentamicin C1a. Toxicological studies of MCR were carried out for safety evaluation as follows: Studies were carried out to assess acute toxicity, when administered in 1 hour by drip intravenous infusion to Wistar rats, Japanese White rabbits and Beagle dogs. The results of the studies are summarised as follows: There was no difference on acute toxicity between drip intravenous infusion (d.i.v.) and intramuscular injection (i.m.) in rats. However, acute toxicity of d.i.v. was less than that of bolus intravenous administration (i.v.) in rats. Acute toxicity of d.i.v. was stronger than that of i.m. in dogs when administered in rats. Acute toxicity varied with species, and it was ranked in rabbits not equal to dogs greater than rats. There was no difference on symptoms between d.i.v. and i.m.

Aminoglycosides↗

[Safety evaluation of micronomicin V. Subacute toxicity in rats after intravenous injection].

Micronomicin (MCR) is a new aminoglycoside antibiotic produced by Micromonospora sagamiensis var. nonreducans which was isolated from soil collected at Sagamihara City by Nara et al. This antibiotic shows a close similarity to gentamicin C components in physical and chemical properties. The antibacterial activity of MCR is broad-spectrum and almost equal to that of gentamicin C complex. MCR exhibits particularly high activity against Pseudomonas, Proteus, Klebsiella pneumoniae, Serratia, etc. as well as against some Pseudomonas aeruginosa strains resistant to gentamicin C1a. Toxicological studies of MCR in rats were carried out by intravenous injection for safety evaluation. Study on subacute toxicity: Wistar rats were injected intravenously with MCR at the dose levels of 4, 10, 25, 63 mg/kg and 100 mg/kg for 30 days. The results of the studies are as follows: In the subacute toxicity study, animals died at the dose level of 100 mg/kg (10 out of 30 animals). Main changes observed were renal disorders and ataxia which showed a close similarity to those seen in intramuscular toxicity studies in rats. The renal histological disorders occurred mainly at the dose levels of 25 mg/kg and over, but they were slight at the dose levels of 25 mg/kg. Ataxia was observed at the dose levels of 63 mg/kg and over, but its grade was slight at the dose level of 63 mg/kg. The maximum safety dose was equal to in the intramuscular subacute toxicity in rats, 10 mg/kg.

Aminoglycosides↗

[Safety evaluation of micronomicin VI. Subacute toxicity in rabbits after drip intravenous infusion].

Micronomicin (MCR) is a new aminoglycoside antibiotic produced by Micromonospora sagamiensis var. nonreducans which was isolated from soil collected at Sagamihara City by Nara et al. This antibiotic shows a close similarity to gentamicin C components in physical and chemical properties. The antibacterial activity of MCR is broad-spectrum and almost equal to that of gentamicin C complex. MCR exhibits particularly high activity against Pseudomonas, Proteus, Klebsiella pneumoniae, Serratia, etc. as well as against some Pseudomonas aeruginosa strains resistant to gentamicin C1a. Subacute toxicity studies of MCR in rabbits were carried out by drip intravenous infusion (d.i.v.) comparing with intramuscular injection (i.m.) for 30 days (doses; d.i.v. = 4, 25, 63 mg/kg, i.m. = 63 mg/kg). The results of the studies are as follows: Animals did not die at any dose. Renal disorders occurred mainly at the dose level of 63 mg/kg; they were almost similar to those observed when administered by i.m., and the grade of disorders in d.i.v. was the same as in i.m. The maximum safety dose was 4 mg/kg.

Aminoglycosides↗

[Safety evaluation of micronomicin VII. Fertility study by intravenous injection in rats].

Micronomicin (MCR) is a new aminoglycoside antibiotic produced by Micromonospora sagamiensis var. nonreducans which was isolated from soil collected at Sagamihara City by Nara et al. This antibiotic shows a close similarity to gentamicin C components in physical and chemical properties. The antibacterial activity of MCR is broad-spectrum and almost equal to that of gentamicin C complex. MCR exhibits particularly high activity against Pseudomonas, Proteus, Klebsiella pneumoniae, Serratia, etc. as well as against some Pseudomonas aeruginosa strains resistant to gentamicin C1a. Fertility studies of MCR in rats were carried out by intravenous injection for safety evaluation (Dose: 25, 50 mg/kg and 75 mg/kg). The results of studies are as follows. There was no adverse effect on fertility ability at any dose. Suppression of adult body weight gain was observed slightly at all dose level in male and at the dose level of 75 mg/kg in female.

Abnormalities, Drug-Induced↗

[Safety evaluation of micronomicin VIII. Teratogenicity studies in rabbits after intravenous injection].

Micronomicin (MCR) is a new aminoglycoside antibiotic produced by Micromonospora sagamiensis var. nonreducans which was isolated from soil collected at Sagamihara City by Nara et al. This antibiotic shows a close similarity to gentamicin C components in physical and chemical properties. The antibacterial activity of MCR is broad-spectrum and almost equal to that of gentamicin C complex. MCR exhibits particularly high activity against Pseudomonas, Proteus, Klebsiella pneumoniae, Serratia, etc. as well as against some Pseudomonas aeruginosa strains resistant to gentamicin C1a. Teratogenicity studies of MCR in rabbits were carried out by intravenous injection for safety evaluation (Dose; 25, 50 mg/kg and 70 mg/kg). The results of studies are as follows. Fetal malformation attributable to MCR was not observed at any dose. There was no adverse effect on new borns at any dose.

Abnormalities, Drug-Induced↗