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Biomedical subjects

M Moriya

Publications and source records attributed to M Moriya.

At least 19 recordsLinked to original sources

Prominent expression of type 1 (gamma) protein kinase C in Purkinje cells located in the "central mass" of Reeler mutant mouse cerebellum as revealed by a computer image analysis technique.

In Reeler mutant mice, cerebellar Purkinje cells exhibit abnormal synaptogenesis. In this study, Purkinje cells in the "central mass" with abnormal afferent connections were compared with those located in their normal position in the cortex in terms of immunoreactivity for type 1 (gamma) protein kinase C. A "computer image analysis technique" was developed for the purpose of this quantitative study, and it revealed that the immunoreactivity in the central mass was significantly higher than that in the cortex. The results suggest that type 1 (gamma) protein kinase C may be related to the abnormal synaptic formation of the Purkinje cells.

Animals

Alpha 1-adrenoceptor blocking activities of bevantolol hydrochloride(NC-1400) and labetalol in rat isolated thoracic aorta--do they distinguish between subtypes?

1. alpha 1-adrenoceptor blocking activity of bevantolol(NC-1400) was tested in the rat thoracic aorta, comparing with that of labetalol. 2. In alpha 1-adrenoceptor blocking activity, bevantolol(NC-1400) was 1/20th as potent as labetalol. 3. The pA2 values of bevantolol(NC-1400) and labetalol estimated in the rat thoracic aorta were compared with those in the rabbit thoracic aorta, which were reported by Takayanagi et al. [Takayanagi I., Kizawa Y., Iwasaki S. and Nakagoshi A. (1987) Gen. Pharmac. 18, 87-89]. 4. The pA2 values of bevantolol(NC-1400) and labetalol were approximately 1 order of magnitude higher in rat aorta than in rabbit aorta, suggesting that both the drugs distinguish between subtypes of alpha 1-adrenoceptors.

Adrenergic beta-Antagonists

Effect of ageing on alpha 1A-adrenoceptor mechanisms in rabbit isolated bronchial preparations.

Effect of aging on alpha 1A-adrenoceptor mechanisms in rabbit bronchial preparations was studied. The potency (pD2 value) of norepinephrine increased with age from 5 to 13 weeks and thereafter did not alter with age from 13 to 180 weeks. The affinity of norepinephrine (pKA value) and of a selective alpha 1A-adrenoceptor blocker, 5-methylurapidil (pA2 value) did not alter with age. Efficacy of norepinephrine was proportional to receptor reserve (pD2-pKA). These results suggest that age-related changes in alpha 1A-adrenoceptor mechanisms are due to changes in receptor reserve or total concentration of receptors, but not to changes in affinity of drugs to alpha 1A-adrenoceptors and in contraction mechanisms.

Aging

Branches of the internal thoracic artery of rats supplying the heart, the sinus regions and the brachiocephalic veins.

Branches of the internal thoracic artery (ITA) of rats which supply the heart, the sinus regions (see Terminology 1) and the brachiocephalic veins, were macroscopically studied. Two major branches of the ITA, the pericardiacophrenic artery and the descending ramus of the bronchoesophageal artery, were found supplying branches to these central portions of the cardiovascular system (see Table 1). They constituted, together with the ordinal coronary arteries, a system of dual blood supply to the heart as reported by Grant & Regnier (1926), Halpern et al. (1953, 1954) and Hebel & Stromberg (1986). This finding also supports a proposal of Grant & Regnier (1926) that the rat ITA emits cardiac branches which should be classified on the vertebrate scale to the caudal or extracoronary artery. Branches of the ITA to the heart, the sinus regions and to the brachicephalic veins were found to be classified into 2 major groups depending on their choice of entrance--arterial portal and venous porta; the latter was further divided into 3 subgroups depending on their selection of the (lateral or pulmonary or esophageal) mesocardium for traveling to the venous porta (see Table 2).

Animals

A macroscopical study of the inferior phrenic artery of female rats, with reference to the embryological background of occurrence of the genital artery from this artery.

The principal aim of this study was to elucidate the general features of the inferior phrenic artery (IPA) of female rats which retain the original embryonic configuration of this artery. The artery of the right side was found to be detached from the renal artery, while that of the left side arose from the aorta. Between these fellow arteries, however, no essential morphological differences were discernible. At some point not far from their origin, they were found to break up into the ascending, suprarenal, suprareno genital and descending arteries. The ascending artery of the right side coursed along with the phrenic nerve, and vascularized a greatest portion of the total area of the partes sternalis et costalis of the diaphragm. Furthermore, the artery was found to be intimately associated with the inferior caval vein. Thus, it could be assumed that this artery of adult rats has been embryologically related to the musculus diaphragmaticus, transverse septum, ventral pleuroperitoneal fold, and the caval venous mesentery. The suprarenal artery took its course along the superior margin of this gland to reach the lateroinferior part of the pars costalis of the diaphragm. Its course and destination strongly indicates that in its development the suprarenal artery has been intimately related to the formation of the ventral pleuroperitoneal fold. The suprarenogenital artery was characterized as giving off a genital branch which entered first the diaphragmogenital ligament, and then took a descending course toward the ovary, in a quite similar manner of origin and course to those of the aberrant gonadal (testicular and gonadal) arteries observed in Japanese human adults (Shinohara et al., 1990; Hanie, to be published). The descending artery was observed to be closely associated with the major splanchnic nerve and the celiac ganglion. The variability of arteries of the IPA of female rats and also of humans, seems to reflect dramatic changes which have occurred in the early stages of development, and have influenced more or less the morphology of the uppermost abdominal anlages of the followings: transverse septum, musculus diaphragmaticus, dorsal and ventral pleuroperitoneal folds, suprarenal gland and celiac ganglion, urogenital organs, inferior caval vein in the caval venous mesentery. In conclusion, it could be said that the anatomy of female rats provide us valuable clues as to the essential configuration of the IPA of humans and the relationships of the IPA to structures which are thought to be directly involved in the development of this artery.

Adrenal Glands

Abnormalities of foliation and neuronal position in the cerebellum of NZB/BINJ mouse.

To analyze developmental abnormalities related to neural migration in the NZB/BINJ mouse, the pattern of cerebellar foliation and neural position were compared with that of a normal mouse (C57BL/6J). Three abnormalities of cerebellar foliation--(1) lobe isolated from other cerebellar lobes, (2) lobes imbalanced in relative amounts or ratio of granular cell layer and molecular layer, (3) lobes in which some Purkinje cells and the molecular layer was embedded in the granular cell layer--were observed in NZB/BINJ mice. These morphological abnormalities were not limited to a specific lobe. On the other hand, abnormalities of neural position were observed in both granule and Purkinje cells. The pattern of ectopically-situated granule cells, in general, could be divided into 3 types: (1) large cell clusters extending from granular cell layer to the pia mater or middle part of the molecular layer, (2) clusters of various sizes scattered within the white matter and (3) clusters formed by combination of granule cells extending from two opposed granular cell layers to the molecular layer. The pattern of ectopically-situated Purkinje cells could be divided into 4 types: (1) ectopia of a group of cells from one part of the Purkinje cell layer, (2) ectopia of a single Purkinje cell observed in the molecular layer, (3) single Purkinje cell scattered within the white matter accompanied by clusters of ectopic granule cells and (4) ectopic Purkinje cells embedded in the granular cell layer. The abnormalities in position of both granule cells and Purkinje cells was not limited to a particular cerebellar lobe.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Alpha 1A-adrenoceptors in rabbit bronchus.

In the presence of propranolol, bronchial preparations from rabbits were markedly contracted by norepinephrine and phenylephrine but only slightly by clonidine. The contractile responses to norepinephrine were inhibited by prazosin and by high concentrations of yohimbine. The concentration-response curve of norepinephrine was shifted in parallel by WB4101 and 5-methylurapidil but not by 60-min treatment with chloroethylclonidine. These results suggest strongly that norepinephrine-induced contraction of rabbit bronchus is mediated through alpha 1A-adrenoceptors. Furthermore, cyclooxygenase inhibitors did not influence the response to norepinephrine, so norepinephrine-induced contraction is considered not to be mediated through the release of prostaglandins.

Adrenergic alpha-Antagonists

Effects of ageing on nicotine-induced contraction and substance P-like materials release in guinea-pig bronchus.

1. Effects of ageing on nicotine-induced contraction and release of substance P-like materials in the bronchial preparations from guinea-pigs of different ages were studied. 2. The pD2 value (potency) of nicotine decreased with age from 10 to 100 weeks. The pD2 value of substance P did not change with age suggesting that substance P receptor mechanisms do not alter with age. 3. The amount of substance P-like materials released by nicotine (10(-4) M) decreased with age from 10 to 100 weeks, supporting our previous findings that nicotine contracts the guinea-pig bronchus through the release of substance P-like materials. 4. These results suggest that the age-related decrease in the pD2 value (potency) of nicotine is due to the reduction in the amount of substance P-like materials released by nicotine.

Aging

Effect of ageing on response to nicotine in rabbit bronchial preparation.

1. Effect of ageing on the response to nicotine was tested in the bronchial muscle preparations from 5, 13, 100 and 125 week-old rabbits. The pD2 value (potency) of nicotine significantly increased in the preparation from the 125 week-old rabbits. No age-related change was found in the pD2 value of carbamylcholine or pA2 value of atropine. 2. No age-related change in characteristics of nicotine receptors. Choline acetyltransferase activity, the amount of acetylcholine released by nicotine and acetylcholineesterase activity decreased in the preparations from the 125 week-old rabbits. 3. Decrease in the pD2 value of nicotine in the preparation from the older rabbit is due to a decline in choline acetyltransferase activity followed by a reduction in the acetylcholine released, and not to a change in characteristics of nicotine receptors. 4. These results also suggest that enzymes may be influenced more easily with age than drug receptors.

Acetylcholine

Site-specific mutagenesis using a gapped duplex vector: a study of translesion synthesis past 8-oxodeoxyguanosine in E. coli.

We have constructed a gapped plasmid vector in which a single defined lesion is introduced, site-specifically, within a single-strand region. Efficiency of translesional synthesis is determined by the number of colonies recovered following transformation of E. coli. The nucleotide sequence of progeny plasmids in the gapped region of the vector reflects incorporation of bases opposite and near the lesion. The analysis detects non-mutagenic as well as mutagenic events. This system was used to establish the mutagenic potential of 2'-deoxy-7,8-dihydro-8-oxoguanosine (8-oxodG), a lesion produced by the action of active oxygen species on DNA. The presence of 8-oxodG did not affect the number of transformants recovered. Most transformants (greater than 99%) contained G:C pairs at the site of the lesion; however, a limited number of targeted G----T transversions were observed in the presence and absence of SOS induction. Base substitutions neighboring the lesion, reported for an in vitro system, were not observed. We conclude that the 8-oxodG lesion in DNA is weakly mutagenic in E. coli.

8-Hydroxy-2'-Deoxyguanosine

Coding visual images of objects in the inferotemporal cortex of the macaque monkey.

1. The inferotemporal cortex (IT) has been thought to play an essential and specific role in visual object discrimination and recognition, because a lesion of IT in the monkey results in a specific deficit in learning tasks that require these visual functions. To understand the cellular basis of the object discrimination and recognition processes in IT, we determined the optimal stimulus of individual IT cells in anesthetized, immobilized monkeys. 2. In the posterior one-third or one-fourth of IT, most cells could be activated maximally by bars or disks just by adjusting the size, orientation, or color of the stimulus. 3. In the remaining anterior two-thirds or three-quarters of IT, most cells required more complex features for their maximal activation. 4. The critical feature for the activation of individual anterior IT cells varied from cell to cell: a complex shape in some cells and a combination of texture or color with contour-shape in other cells. 5. Cells that showed different types of complexity for the critical feature were intermingled throughout anterior IT, whereas cells recorded in single penetrations showed critical features that were related in some respects. 6. Generally speaking, the critical features of anterior IT cells were moderately complex and can be thought of as partial features common to images of several different natural objects. The selectivity to the optimal stimulus was rather sharp, although not absolute. We thus propose that, in anterior IT, images of objects are coded by combinations of active cells, each of which represents the presence of a particular partial feature in the image.

Animals

[Experimental study on the application of direct current to the intra-osseous implant].

The purpose of this study is to investigate the effect of the direct current electrical stimulation on surrounding tissue of the intra-osseous implant. The implant was composed of a peripheral hydroxyapatite layer and a central metal which was used as electrodes, and applied 10 microA constant direct current. They were implanted in femurs of four guinea pigs. These results were as follows: 1. When the bone marrow is stimulated electrically with 10 microA direct current for 28 days, large amount of bone formation around the implant was seen in wide area. 2. There was a different reaction surrounding tissue between cathode and anode. Around the cathode, bone formation on the surface of the implant was recognized remarkably. Around the anode, little amount of bone formation on the surface of the implant was recognized. 3. The electrical stimulation, with newly developed power unit and electrode, accelerated new bone formation.

Animals

Targeted mutations induced by a single acetylaminofluorene DNA adduct in mammalian cells and bacteria.

Mutagenic specificity of 2-acetylaminofluorene (AAF) has been established in mammalian cells and several strains of bacteria by using a shuttle plasmid vector containing a single N-(deoxyguanosin-8-yl)acetylaminofluorene (C8-dG-AAF) adduct. The nucleotide sequence of the gene conferring tetracycline resistance was modified by conservative codon replacement so as to accommodate the sequence d(CCTTCGCTAC) flanked by two restriction sites, Bsm I and Xho I. The corresponding synthetic oligodeoxynucleotide underwent reaction with 2-(N-acetoxy-N-acetylamino)-fluorene (AAAF), forming a single dG-AAF adduct. This modified oligodeoxynucleotide was hybridized to its complementary strand and ligated between the Bsm I and Xho I sites of the vector. Plasmids containing the C8-dG-AAF adduct were used to transfect simian virus 40-transformed simian kidney (COS-1) cells and to transform several AB strains of Escherichia coli. Colonies containing mutant plasmids were detected by hybridization to 32P-labeled oligodeoxynucleotides. Presence of the single DNA adduct increased the mutation frequency by 8-fold in both COS cells and E. coli. Over 80% of mutations detected in both systems were targeted and represented G.C----C.G or G.C----T.A transversions or single nucleotide deletions. We conclude that modification of a deoxyguanosine residue with AAF preferentially induces mutations targeted at this site when a plasmid containing a single C8-dG-AAF adduct is introduced into mammalian cells or bacteria.

2-Acetylaminofluorene

2,3,7,8-Tetrachlorodibenzo-p-dioxin reduces high-affinity binding of epidermal growth factor to cell surface receptors in C3H 10T1/2 cells.

The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on epidermal growth factor (EGF)-binding characteristics was studied in a cultured embryonic fibroblast cell line, C3H 10T1/2. At very low concentrations, TCDD was found to cause a persistent decline in EFG binding, the median effective concentration (EC-50) being 10(-12) M. This particular effect was most conspicuous when TCDD was added at the time of medium change with fresh Dulbecco's modified Eagle's medium. Cells at an early stage of confluency were more responsive to TCDD than those at a later stage. Although most reported TCDD-evoked biological changes are recognized to occur slowly during the course of a few days to weeks, the response of C3H 10T1/2 cells to TCDD was swift, showing a sign of decline of EGF binding as early as three hours after TCDD addition. C3H 10T1/2 cells appear to be an excellent in vitro model to study TCDD's biochemical action mechanisms.

Animals

Progression and reversibility of early light-induced alterations in rat retinal rods.

The temporal sequence of ultrastructural changes induced in the rat rod photoreceptor by 80 lux light-stress has been studied. The changes seen were compared with those produced by a much dimmer (3 lux) illumination. Some of the early signs of abnormality were (1) degradation of some disk membranes at the tips of outer segments, (2) disaggregation and detachment of ribosomes, (3) lighter matrices in swollen mitochondria, (4) disappearance of the Golgi apparatus, (5) proliferation of autophagic bodies in the inner segments, and (6) appearance of perimitochondrial membrane whorls in the synaptic terminals. No single change could be identified that would inexorably lead to cell death. The overall picture, however, suggested that an inability of the cell to maintain its anabolic balance is responsible for the pyknosis that occurs when the 80 lux exposure exceeds 12-15 h. All changes were reversible when exposure duration did not exceed 12 h, the normal length of the light cycle for these rats.

Animals

Alteration of disk-shedding patterns by light-onset of higher than normal intensity.

Rod outer segment (ROS) disk-shedding patterns were determined in the albino rat eye. All of the animals had the same, low-intensity-light histories, but on the day that shedding patterns were to be measured the rats were divided into three groups: one which did not have any lights turned on at 0700 hr ('contained dark' group); one which had normal, 3-lx light turned on ('colony' group); one which had a brighter-than-normal light turned on ('80-lx' group). The 'continued dark' group displayed a broad profile of shedding over time which persisted because phagosomes disappeared so slowly. The 'colony' group showed the same initial rate of phagosome production as did the 'continued dark' group but a much accelerated rate of phagosome disappearance. The '80-lx' group showed no rate of phagosome production; rather there was a simple, rapid exponential disappearance of those phagosomes which existed just prior to light onset. The kinetics of these phenomena are described in a model, rate constants for which were obtained from our data and simulated on an analog computer. The analysis of the three shedding patterns indicates the existence of an intensity-dependent disappearance rate and suggests an inhibition of shedding and/or phagocytosis by intensity greater than that of the usual environment.

Animals