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Biomedical subjects

J Naito

Publications and source records attributed to J Naito.

At least 109 records · Page 6Linked to original sources

Course of retinogeniculate projection fibers in the cat optic nerve.

The fiber courses of the cat optic nerve were studied by using wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP), which was iontophoretically applied to electrophysiologically defined positions in the lateral geniculate nucleus (LGN). Grossly, there were two distinct bends along the length of the optic nerve. The ventrally flexing anterior bend was located approximately 2 mm from the eyeball, while the dorsally flexing posterior bend was found at some 6 mm distant. The optic nerve fibers showed a tendency to scatter toward the chiasm. At the optic nerve head, the fibers from the different retinal areas maintained the retinal topography in a simplified form according to the trajectory of optic fibers surrounding the optic disc. Between the anterior and posterior bends, the fibers from the pericentral, middle-temporal, and most upper areas of the dorsal retina migrated ventrally and were arranged in the middle of the lateral, middle, and medial parts of the optic nerve, respectively, while fibers from the middle-temporal area of the ventral retina migrated dorsally and scattered into the lateral half. The fibers from the temporal and nasal horizontal meridian areas tended to hold their respective positions in the lateral and medial halves of the optic nerve. As a result, in this level they displayed a complex retinotopy in that the fibers from each part of the retina were mixed. Passing the posterior bend, as the optic nerve proceeded toward the chiasm, the characteristic pattern became less defined. Near the chiasm, the retinotopy became very scattered, showing a partial dorsoventral inversion of the retinal topography with substantial overlapping. It was noted from the present findings that the fibers from ventral retina scattered more quickly than the fibers from the dorsal retina, which tended to hold their grouping until the anterior bend, but the central or pericentral retinal fibers proceeded without significant scatter as far as the posterior bend. The analysis of labelled ganglion cells suggested that even if fibers that arise from one certain "mode" of ganglion cells are selected, it is unlikely that they maintain their initial fiber topography along the entire length of the optic nerve.

Animals↗

Anthranilic acid metabolism in the isolated perfused rat liver: detection and determination of anthranilic acid and its related substances using high-performance liquid chromatography with electrochemical detection.

In order to elucidate the anthranilic acid metabolism in animal tissue, the metabolism was studied in the isolated perfused liver of rats. A sensitive and rapid method was devised for determination of anthranilic acid and its related substances using high-performance liquid chromatography with electrochemical detection. 5-Hydroxyanthranilic acid and anthranilamide, which have not been detected in animal tissue, were found in the perfusate and in the bile secreted from the perfused liver, respectively. In addition, a non-enzymatic production of anthranilamide from anthraniloyl glucuronide in the presence of ammonium and bicarbonate ions was also observed. These present results suggest that, apart from undergoing glycine or glucuronide conjugation, anthranilic acid is metabolized to 5-hydroxyanthranilic acid and anthranilamide in the rat liver.

Animals↗

Commissural afferents to the cortex surrounding the posterior part of the superior temporal sulcus in the monkey.

Commissural afferents to the cortex surrounding the posterior part of the superior temporal sulcus were studied in Japanese monkeys by the horseradish peroxidase method. After injection of the enzyme, many callosal neurons were labeled contralaterally in the cortical area corresponding to the injection site (homotopical area) and in other regions (heterotopical area). Most of the callosal neurons were triangular in shape, occurring for the most part in layer III of both homotopical and heterotopical areas (about 75-90% of the total number of labeled cells). Mean diameters of the cell bodies were about 11-13 micron.

Animals↗

An HRP study of neural pathways to neocortical olfactory areas in monkeys.

Afferent fiber projections to the two orbitofrontal olfactory areas of monkeys were studied using the horseradish peroxidase (HRP) technique. After injections of HRP into the lateroposterior (LPOF) or centroposterior (CPOF) area of the orbitofrontal cortex, some differences were found in the distribution of labeled cells between the projections to the LPOF and CPOF. These results, along with those of previous electrophysiological investigations, suggest the following conclusions: (1) the extrathalamic olfactory pathway to the LPOF identified by Tanabe et al. has relay neurons primarily in the substantia innominata and the amygdala and, secondarily, in the prorhinal cortex and the hypothalamus; (2) direct fibers to the LPOF from the amygdala and the prorhinal cortex pass through the areas ventral to the thalamus; (3) the transthalamic olfactory pathway to the CPOF identified by Yarita et al. has relay neurons concentrated primarily in the magnocellular portion of the mediodorsal nucleus of the thalamus.

Animals↗

Corticocortical projections to the prefrontal cortex in the rhesus monkey investigated with horseradish peroxidase techniques.

The corticocortical afferents innervating the prefrontal cortex in the monkey were studied by means of the retrograde axonal transport of horseradish peroxidase. After injection of small amounts (0.3-0.5 microliter) of this enzyme into various parts of the prefrontal cortex, many labeled neurons (mostly pyramids of 15-25 microns in diameter) were found in various cortical regions of the ipsilateral hemisphere. A small part of the prefrontal cortex received fibers from other parts of the same cortex. For example, area 8 receives many fibers from both the rostral part of area 9 and a small area adjacent to the inferior branch of the arcuate sulcus. On the other hand, area 9 in the inferior prefrontal convexity receives fibers from localized parts of areas 8 and 9 in the dorsolateral convexity as well as from area 6. It is also apparent that association connections from the dorsolateral to the inferior convexity are stronger than those going in the opposite direction. The prefrontal afferents from other cortical regions include many fibers originating from the posterior association cortex as well as some fibers arising in the cingulate and orbital gyri. The prefrontal cortex does not receive direct corticocortical fibers from the motor and "primary" sensory cortices. There is a topographic pattern in the prefrontal projections from the cortical walls (STs area) surrounding the superior temporal sulcus. Thus, the caudal half of the STs area projects to area 8 and a small adjacent part of area 9. The dorsal wall of the rostral half of the STs area projects to areas 9-12, the fundus to the inferior convexity, and the ventral wall only to the caudal part of the convexity. Projections from the circumjacent association cortex of the STs area to the prefrontal cortex as well as to the STs area are likewise found to be topographically organized. This suggests that certain parts of the posterior association cortex projecting to particular areas of the prefrontal cortex, also send fibers to those parts of the STs area which project to the same prefrontal areas.

Animals↗

Role of cytosolic superoxide dismutase as a stimulator in anthranilamide hydroxylation by a microsomal monooxygenase system in rat liver.

We have isolated a protein factor from rat liver which stimulates anthranilamide hydroxylation by the microsomes in the presence of NADPH and oxygen and showed this factor to contain Cu and Zn and to have superoxide dismutase activity [Biochim. Biophys. Acta 365, 148-157 (1974)]. In the present study, this protein factor was confirmed to be a superoxide dismutase (SOD) by comparison of the recovery of SOD activity with that of anthranilamide hydroxylation-stimulating activity at each step of its purification, by inhibition of SOD activity with NaCN and hydrogen peroxide (H2O2), and by recovery of the SOD activity of the protein factor after reconstitution with Cu2+ and/or Zn2+. At a given SOD activity level, there was no difference among the rat liver SOD, Cu,Zn-SOD from bovine erythrocytes, and Mn-SOD from Serratia marcescens in their ability to stimulate anthranilamide hydroxylation not only by rat liver microsomes, but also by the reconstituted cytochrome P-450-containing monooxygenase system. Rat liver SOD stimulated anthranilamide hydroxylation by the reconstituted system in proportion to its amount below a protein concentration of 1 microgram/ml. In anthranilamide hydroxylation by the reconstituted system without SOD, only a slight hydroxylase activity was found at the initial stage of the reaction and a marked increase in the amounts of NADPH oxidized and H2O2 formed was observed after a lag time. In the presence of rat liver SOD, however, the hydroxylase activity was markedly and continuously increased almost proportionally to reaction time with a concomitant decrease in the amounts of NADPH oxidized and H2O2 formed. In addition, a trace of 3-OH anthranilamide, one of the products, not only stimulated NADPH-dependent H2O2 formation in the reconstituted system, but also inhibited the apparent reduction of cytochrome P-450 by NADPH in the reconstituted system. These effects of 3-OH anthranilamide were diminished by rat liver SOD. When a trace of 3-OH anthranilamide were added to a system composed of NADPH-cytochrome c (P-450) reductase and NADPH, H2O2 formation and NADPH oxidation were markedly stimulated. However, on addition of 3-OH anthranilamide to the system containing rat liver SOD, no stimulation on either H2O2 formation or NADPH oxidation was found.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Effect of N-5' on histamine release from rat peritoneal exudate cells induced by calcium ionophore and ATP.

We studied the effect of N-(3,4-dimethoxycinnamoyl)anthranilic acid (N-5'), an orally applicable anti-allergic drug, on the histamine release induced by calcium ionophores (A23187 and X537A) and ATP from rat peritoneal exudate cells (PEC). X537A (0.1-33.3 micrograms/ml) induced histamine release in a concentration-related manner, and 2.0 micrograms/ml of X537A induced release to the same extent as allergic histamine release. Histamine release induced by 2.0 micrograms/ml of X537A increased with longer incubation time, reaching a peak of about 100% at 120 min. N-5' had no effect on histamine release induced by X537A at the concentrations used (1-1000 microM), but DSCG exhibited significant inhibition at 1-100 microM. A23187 (0.05-0.5 microgram/ml) induced histamine release in a concentration-related manner, and it seemed that 0.033 microgram/ml of A23187 induces the same degree of histamine release as the allergic one. A23187 induced rapid histamine release which attained maximum 1 min after the addition. N-5' exhibited a significant concentration-dependent inhibitory effect on histamine release induced by A23187, and DSCG also exhibited significant inhibition (10 and 1000 microM). N-5' significantly inhibited histamine release induced by 100 microM ATP. These results indicate that N-5' and DSCG effect the histamine release induced by ionophore A23187 and X537A by different manners, and they suggest the possibility that N-5' inhibits some Ca++-dependent processes in histamine release, including the influx of Ca++ into cells, which is a trigger of the A23187 and ATP effects.

Adenosine Triphosphate↗

Effect of superoxide dismutase on hydroxylase activity and hydrogen peroxide formation in anthranilamide hydroxylation by a rat liver microsomal monooxygenase system.

Anthranilamide was slightly hydroxylated by a reconstituted rat liver microsomal monooxygenase system with NADPH, but a large amount of hydrogen peroxide was formed with a consumption of NADPH during the reaction. Superoxide dismutase stimulated the hydroxylation by depressing the hydrogen peroxide formation, in that there was a reverse correlation between the two effects due to the dismutase. In addition, a trace of 3-hydroxyanthranilamide, one of the products, not only stimulated NADPH-dependent hydrogen peroxide formation via NADPH-cytochrome c (P-450) reductase, but also inhibited the reduction of cytochrome P-450 by NADPH in the reconstituted system. These effects of 3-hydroxyanthranilamide were also diminished by superoxide dismutase.

Animals↗

Effects of thromboxane synthetase inhibitors on aggregation of rabbit platelets.

Thromboxane (TX) synthetase activity was selectively inhibited by (E)-3-[4-(1-imidazolylmethyl)phenyl]-2-propenoic acid hydrochloride monohydrate (OKY-046) and sodium (E)-3-[4-(3-pyridylmethyl)phenyl]-2-methyl-propenoate (OKY-1581) (OKYs). Their IC50 for the rabbit platelet enzyme were found to be 11nM and 3nM respectively. Arachidonic acid (AA) or collagen induced platelet aggregation, and generated TXA 2 and prostaglandins (PGs) in rabbit platelets. OKYs inhibited platelet aggregation and TXA2 generation without affecting PGs generation, while aspirin inhibited platelet aggregation, and TXA2 and PGs generation. There was a parallel relation between the degree of inhibition of platelet aggregation and TXA2 generation by OKYs, but the inhibitory effects of aspirin on platelet aggregation was related to that on both TXA2 and PGs generation. However, OKYs and aspirin did not inhibit ADP-induced platelet aggregation which did not involve the generation of TXA2 and PGs. These results suggested that TXA2 generation is related to platelet aggregation induced by AA or collagen, and that the inhibitory effect of OKYs on platelet aggregation is due to the inhibition of TX synthetase.

Animals↗

Retinotopic scatter of optic tract fibres in the cat.

The retinal fibers in the optic tract (OT) of the cat have a roughly retinotopic arrangement. The retinotopic scatter of OT fibres at the rostral pole of the superior colliculus (SC) and at the lateral margin of the lateral geniculate nucleus (LGN) was investigated using the retrograde transport of horseradish peroxidase. Small lesions and injections were made in the tract and from the distribution of labelled ganglion cells in the retina the retinotopic precision was measured. At an eccentricity of 30 degrees along the horizontal meridian the vertical scatter was 20-30 degrees. This is similar to the precision of the map in the SC. However a comparison with the retinotopic map of the LGN shows the precision there to be much better.

Animals↗

Studies on the mechanisms of the inhibitory effect of N-5' on histamine release from rat peritoneal exudate cells.

To investigate the mechanisms for the inhibition of IgE-mediated histamine release from rat peritoneal exudate cells (PEC) by N-5', we studied the relation between the inhibitory effect of N-5' on histamine release and the intracellular levels of adenine nucleotides such as ATP and cAMP. Evident histamine release was induced by the addition of specific antigen to rat PEC sensitized with IgE antiserum in vitro, and the release showed a maximum 30 sec after the antigen challenge. In the same time course as the histamine release, the intracellular levels of ATP and cAMP decreased. N-5' significantly inhibited the histamine release and a decrease in ATP level as a result of the antigen-antibody reaction. A decrease in cAMP level showed a tendency to be suppressed by N-5'. Antigen-induced 14CO2 production for 6-14C-glucose in the sensitized PEC was 3 times that seen in the case without antigen. N-5' dramatically suppressed the acceleration in the production of 14CO2. Differing from the action of papaverine, the inhibitory effect of N-5' on the IgE-mediated histamine release from rat PEC was identical both in the presence or in the absence of glucose. N-5' scarcely affected the ATP level in the non-sensitized PEC in the glucose-free medium. On the other hand, N-5' inhibited the activity of Na+, K+-ATPase, one of the ATP-consuming enzymes, in a dose-dependent fashion. From these results, it is presumed that the suppression of ATP-utilization through the inhibition of Na+, K+-ATPase activity is involved in the inhibition of histamine release by N-5'. The relation between the inhibitory effect of N-5' on histamine release and both nucleotides was also discussed.

Adenosine Triphosphate↗

[Effect of tranilast on the release of slow reacting substance of anaphylaxis (SRS-A) and contraction of the smooth muscle].

Slow reacting substance of anaphylaxis (SRS-A) and slow reacting substance (SRS) were released from actively sensitized guinea-pig lung with bovine serum albumin and from rat peritoneal exudate cells with ionophore A23187, respectively. FPL55712 markedly inhibited the contraction induced by SRS-A and SRS in guinea-pig ileum which was treated with atropine (10(-7) g/ml), mepyramine (10(-6) g/ml), and cyproheptadine (10(-7) g/ml). Tranilast and isoproterenol markedly suppressed the release of SRS-A in a dose-dependent manner; the concentrations of these drugs that gave 50% inhibition (IC50) were 1.1 X 10(-4)M and 8.3 X 10(-9)M, respectively. Although the inhibitory effect of tranilast (10(-3)M) was not affected in the presence of propranolol (3 X 10(-6)M), the inhibitory effect of isoproterenol was greatly diminished by propranolol. Also, tranilast markedly suppressed the release of SRS in a dose-dependent manner, its IC50 being 6.4 X 10(-5)M. However isoproterenol slightly inhibited the release of SRS. Disodium cromoglycate did not suppressed the release of SRS-A at all, and it suppressed SRS release a little. Tranilast inhibited the contraction induced by leukotriene C4 (0.5 ng/ml) and D4 (1 ng/ml) in guinea-pig trachea in a dose-dependent manner; the IC50 values were 2.2 X 10(-4)M and 2.0 X 10(-4)M, respectively, for these inhibitions. These results suggest that the inhibition of SRS-A release and SRS-A-induced contraction of smooth muscle by tranilast participates in the anti-asthmatic effect of tranilast, and its inhibitory mechanism is different from that of isoproterenol.

Animals↗