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R Ichikawa

Publications and source records attributed to R Ichikawa.

At least 19 recordsLinked to original sources

Preferential impairment of nitric oxide-mediated endothelium-dependent relaxation in human cervical arteries after irradiation.

BACKGROUND: Vascular abnormalities are a major cause of postoperative complications in irradiated tissues. Endothelial cell dysfunction characterized by diminished endothelium-dependent relaxation may be involved. We examined the endothelium-dependent relaxation and morphology of the endothelium in irradiated human cervical arteries. METHODS AND RESULTS: Irradiated arteries were taken from the neck region of patients who had radiation therapy. Arteries from patients who did not receive radiation therapy were used as controls. Endothelium-dependent relaxation to acetylcholine and A23187 was impaired in irradiated arteries. Norepinephrine-induced contraction and sodium nitroprusside-induced relaxation were unchanged. In control arteries, N(omega)-nitro-L-arginine and indomethacin each caused a partial inhibition of endothelium-dependent relaxation. In irradiated arteries, the impaired endothelium-dependent relaxation was unaffected by these agents, but it was abolished by high K(+). Acetylcholine produced similar degrees of hyperpolarization in control and irradiated arteries. Immunohistochemical examination for endothelial nitric oxide synthase indicated no expression in the endothelium of irradiated arteries. Electron scanning microscopy showed morphologically intact endothelial cells in irradiated arteries. CONCLUSIONS: In irradiated human cervical arteries, the nitric oxide- and prostacyclin-mediated endothelium-dependent relaxation, but not endothelium-derived hyperpolarizing factor-mediated relaxation, are specifically impaired, without significant morphological damage of the endothelium. The impaired nitric oxide-mediated relaxation was associated with a lack of endothelial nitric oxide synthase expression. Our results suggest the importance of impaired endothelial function in irradiated human blood vessels, which may partly explain the development of vascular stenosis and poor surgical wound healing in irradiated tissues.

Acetylcholine

Different expressions of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid and N-methyl-D-aspartate receptor subunit mRNAs between visceromotor and somatomotor neurons of the rat lumbosacral spinal cord.

The glutamatergic transmission system plays a key role in afferent and efferent pathways involved in micturition. By in situ hybridization combined with retrograde Fast Blue labeling, expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor (GluR-A to -D) and N-methyl-D-aspartate (NMDA) receptor (NR1 and NR2A-D) subunit mRNAs were examined in visceromotor and somatomotor neurons of the rat lumbosacral spinal cord. Parasympathetic preganglionic neurons (PGNs) in the intermediolateral nucleus highly expressed GluR-A and GluR-B subunit mRNAs, with very low levels for GluR-C and GluR-D subunits. As for the NMDA receptor, PGNs were associated with abundant signals for NR1 subunit mRNA, but without any NR2 subunit mRNAs. On the other hand, somatomotor neurons in the ventral horn (dorsolateral nucleus) express all four AMPA receptor subunit mRNAs, showing relatively abundant expressions of GluR-C and GluR-D subunit mRNA compared with PGNs. In addition to high levels of NR1 subunit mRNA, dorsolateral nucleus neurons moderately expressed NR2A and NR2B subunit mRNAs. These results suggest that molecular organization of both AMPA and NMDA receptor channels are distinct between PGNs and dorsolateral nucleus neurons. Considering that native NMDA receptors are heteromeric channels composed of NR1 and NR2 subunits, it seems likely that dorsolateral nucleus neurons, not PGNs, are provided with functional NMDA receptors, which could induce activity-dependent changes in synaptic transmission in the efferent pathway for the lower urinary tract.

Amidines

Early establishment of lesion-insensitive mature barrelettes corresponding to upper lip vibrissae in developing mice.

Vibrissae are tactile sense organs on the face of non-human mammals, and build up topographical representations in the brainstem trigeminal sensory nucleus called barrelettes. In the present study, we examined postnatal development of barrelettes corresponding to upper lip vibrissae by cytochrome oxidase (CO) histochemistry. At nuclear regions corresponding to upper lip vibrissae, a few segregated barrelettes first appeared at postnatal day 2 (P2), and segregation became clear for most upper lip barrelettes at P4. Compared with major barrelettes corresponding to mystacial vibrissae on the snout, the development of segregated pattern formation for upper lip barrelettes was retarded by 1-2 days. When vibrissa-related patterns were examined 5 days after infraorbital nerve transection, upper lip barrelettes became obscure in all mice lesioned at P1 and P2. Lesion-insensitive upper lip barrelettes first emerged in a few mice lesioned at P3 (33%), and the percentage attained 100% at P6. This temporal transition from lesion-sensitive to lesion-insensitive barrelettes was 3 days ahead of mystacial barrelettes. Therefore, upper lip barrelettes achieve rapid development within a narrow time frame during the first postnatal week. The early and rapid establishment of lesion-insensitive, mature barrelettes can be interpreted as suggesting the importance of oral sensory function in neonatal life.

Aging

Virus-associated haemophagocytic syndrome caused by rubella in an adult.

Haemophagocytic syndrome is a systemic clinicopathological entity characterized by systemic proliferation of benign haemophagocytic histiocytes, fever, cytopenia, abnormal liver function and, frequently, coagulopathy and hepatosplenomegaly. Its occurrence has been documented in association with viral, bacterial, fungal and parasitic infections, a wide spectrum of malignant neoplasms, autoimmune diseases and drugs. We report a case of rubella virus-associated haemophagocytic syndrome in a previously healthy 29-year-old woman. Blood tests showed cytopenia, especially severe thrombocytopenia, liver dysfunction, hyperferritinaemia and hypercytokinaemia. Bone marrow examination showed many mature histiocytes with active haemophagocytosis. A skin biopsy from the rash revealed perivascular lymphohistiocytic infiltrates with haemophagocytic histiocytes in the upper and mid-dermis. The patient was treated with antibiotics and immunoglobulin, and by supportive measures including platelet transfusion, and recovered completely.

Adult

[Morphometrical analysis of projection neurons in reeler mutant mice].

The projection neurons in the cerebral cortex are localized in the specific layers, and present the characteristic shape of cell bodies and dendritic arborization according to their properties. To examine what factors could cause the morphological characteristics of the reeler neurons, of which cortical layers are generally inverted, we morphometrically analyzed three types of projection neurons, callosal (CC-neurons), corticospinal (CS-neurons), and corticothalamic neurons (CT-neurons), by the retrograded labeling method. The results were as follows: 1) Although in the normal mice, the CC-neuron cell bodies in the layer 2 + 3 were significantly smaller than ones in the layer 5, the reeler CC-neurons were uniform regardless of their intracortical positions. 2) The cell bodies of the reeler CS-neurons were normal in size throughout the entire cortex. 3) The cell bodies of reeler CT-neurons were generally larger than normal ones, and they were larger in the location near the pia mater. 4) The apical dendrites of the normal CC-, CS- and CT-neurons were generally directed toward the layer 1 of neocortex, which is the plexiform zone (PZ) in the embryo stage, whereas those of the reeler CC- and CS-neurons were directed toward the upper-middle zone of neocortex, which is the interplexiform zone (IPZ) that corresponds with the normal PZ; however, those of the reeler CT-neurons were not oriented toward dominant direction. These results suggest that the sizes of CS-neurons vary depending upon the target of the projection, whereas CC- and CT-neurons are influenced by the volume of afferent inputs as well as the target of the projection. The afferent factors, especially thalamocortical fibers, may also influence the direction of the apical dendrites of CT-neurons.

Animals

Extra-junctional localization of glutamate transporter EAAT4 at excitatory Purkinje cell synapses.

We used silver-enhanced immunogold electron microscopy to reveal synaptic localization of the glutamate transporter EAAT4 in mouse cerebellar Purkinje cells (PCs). Gold-silver particles representing the EAAT4 were densely localized on extra-junctional membrane, but not on junctional membrane of PC spines in contact with parallel fiber or climbing fiber terminals. No particle accumulations were observed at inhibitory synapses formed on cell body and dendritic shafts of PCs. Therefore, the EAAT4 is selectively targeted to the extra-junctional site of excitatory PC synapses. The finding suggests that the EAAT4 transports glutamate or its related amino acids from outside the synaptic cleft, which would facilitate glutamate diffusion from the synaptic cleft to the extrasynaptic space and restrict glutamate spillover to adjacent synapses.

Amino Acid Transport System X-AG

Cerebellum of the adult reeler mutant mouse contains two Purkinje cell populations with respect to gene expression for the N-methyl-D-aspartate receptor channel.

Recent studies have identified five NMDA receptor subunits, which exhibit distinct cellular expressions in the normal rodent brain. The purpose of this investigation is to clarify the molecular-anatomical organization in the cerebellum of the reeler mutant mouse, in which various categories of the Purkinje cells are present as to the cell position and synaptic connectivity. In comparison with the distribution of the inositol 1,4,5-trisphosphate receptor mRNA, a molecular marker specific to the Purkinje cells, the epsilon 1 subunit mRNA of the NMDA receptor channel was found in the adjacent sections to be expressed in a subset of the Purkinje cells. In the rostrocaudal extent, the Purkinje cells expressing the epsilon 1 subunit mRNA were distributed preferentially in the rostral cerebellum, irrespective of the normal and heterotopic positions. In the mediolateral extent, they formed segregated cell clusters, interposed by epsilon 1 subunit mRNA-negative clusters. Hybridizing signals for the zeta 1 subunit mRNA were found in all the Purkinje cell population, whereas those for the epsilon 2, epsilon 3, and epsilon 4 subunit mRNAs were not detected in the cells. These findings suggest that the reeler cerebellum is topographically compartmentalized by two subpopulations of the Purkinje cells, one expressing the epsilon 1 and zeta 1 subunit mRNAs, and the other expressing the zeta 1 subunit mRNA alone.

Animals

Sex differences in the shapes of several parts of the young Japanese face.

For the purpose of studying the sex differences of the human face we collected five separate images, which consist of several parts of the face, from frontal view photographs of 48 male and 52 female college students. We traced outlines of their faces with simple lines (traced items), and made reproductions of the photographs of their eyes, mouth and nose by using a copying machine (reproduced items). The test subjects were 16 males and 8 females. They looked at parts of the face shown in each image, and categorized them individually by judging on their sex. Then, we calculated the percentages of correct judgments (percentage correct) for each image. By comparing the percentage correct between male and female we concluded that the sex of the subjects did not affect the results of their judgments. In the traced items the percentage correct for the face as a whole, which contained the outlines of the eyes, mouth, nose and the lower jaw, was 69%, but it decreased to 61% when the outline of the lower jaw was removed. Hence, the outline of the lower jaw apparently has a characteristic shape easily noticed by males. In the reproduced items the percentage correct was 65% for the eyes, 68% for the mouth and 58% for the nose. The mouth, therefore, has more distinguishing characteristics than the eyes or nose, especially with females. On the other hand, there is no correlation between the percentage correct for the eye, mouth and nose items. Hence, we concluded that the sexual specificity for the shape of the young Japanese face appears on their parts independently.

Adult

Distribution of guanine nucleotide-binding protein in the brain of the reeler mutant mouse.

The localization of a GTP-binding protein (G(o)) in the cerebellar and cerebral cortex and hippocampus of the normal and reeler mutant mouse was immunohistochemically examined using affinity-purified antibody raised against the alpha subunit of G(o). Although the general distribution pattern of G(o)-immunoreactive products in the brain of the normal mouse, i.e., abundant in the neuropil but absent from neuronal cell bodies, is also seen in the reeler brain, some differences are present, as described below. Strong G(o)-immunoreactive products are found in the molecular layer of the cerebellar cortex of the normal mouse. In the reeler cerebellum, in addition to the strong G(o)-immunoreactivity of the thin molecular layer, moderate G(o)-immunoreactivities are also found in the granular cell layer and the central cerebellar mass. G(o)-immunoreactive products are distributed throughout all layers of the cerebral cortex of the normal and reeler mouse. However, layer I of the normal cerebral cortex is more strongly stained with this antibody than the underlying layers, whereas the upper third of the reeler cerebral cortex is more strongly stained than the lower two-thirds. In the hippocampus of the normal mouse, G(o)-immunoreactive products are localized in the neuropil of the stratum oriens, stratum radiatum and stratum lacunosum-moleculare, but absent from the cell bodies of the pyramidal cells and their apical dendritic shafts. Such a distribution pattern of G(o)-immunoreactive products is also seen in the hippocampus of the reeler mouse, except that G(o)-immunonegative pyramidal cells split into 2 or 3 laminae.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Abnormal synaptic architecture in the cerebellar cortex of a new dystonic mutant mouse, Wriggle Mouse Sagami.

The 'Wriggle Mouse Sagami (WMS)' is a new neurological mutant with severe dystonic movements of the trunk and extremities whose pathological characters are transmitted by an autosomal recessive gene (wri). Manifestations first appear at 10 days to 2 weeks after birth and progress until 12 weeks of age. In spite of the severe dystonic movements, no marked abnormalities had been found in the cyto- or myeloarchitecture of the central nervous system or that of the peripheral nerves, except for the impaired development of the dendritic trees of the Purkinje cells. In this study we quantitatively demonstrated decreased synaptic connections of parallel fibers on the dendritic spines of the Purkinje cells as early as 2 weeks after birth. On the other hand, synaptic boutons on the dendritic shafts and somata of the Purkinje cells and synaptic bouton-like structures which contained synaptic vesicles but without synaptic membrane specialization, were significantly increased in the molecular layer at 9 weeks of age. Glutamic acid decarboxylase immunohistochemistry suggested that some of these increased synaptic boutons and other bouton-like structures may have originated in GABA interneurons, such as stellate cells, basket cells and Golgi cells, and in the cerebellar nuclei. Because of the severity of the manifestations, it appears that synaptic alteration in interneurons also occurs in the other parts of the CNS.

Animals

Developmental studies on the interparietal part of the human occipital squama.

The development of ossification centres in the membranous occipital squama is described, based on observations on human fetal skulls. The interparietal part develops basically from 3 pairs, 1 primary pair and 2 secondary pairs; an additional 4th pair is occasionally observed. The so-called separated interparietal bones (Inca bones) are formed by a failure of fusion between the primary and secondary centres, not between the supraoccipital and interparietal parts. The preinterparietal bones, which are developed from the additional 4th pair of interparietal ossification centres, are clearly differentiated from other anomalies in the lambda region by the shape of their territory and by their location. The issue still remains as to how to establish their identity in skulls from individuals of advanced age.

Adult

Dendritic arbolization of large pyramidal neurons in the motor cortex of normal and reeler mutant mouse.

Reeler, an autosomal recessive mutation in mice, is characterized by abnormal positioning of the neurons in the cerebral cortex. We performed a descriptive analysis on the arborization of dendritic processes of large pyramidal neurons in the motor cortex (hindlimb area) of normal and reeler mice, as seen in the Golgi preparations. In the normal mouse, somata of large pyramidal neurons were located in the layer V, and their apical dendrites ascend vertically to the pial surfaces. Their basal dendrites proceed horizontally or inferiorly. In the reeler mouse, typical large pyramidal neurons with a normal (upright) apical dendrite and a variety of atypical large pyramidal neurons with a disoriented apical dendrite were radially scattered within the motor cortex. Typical large pyramidal neurons occupied the lower half of the motor cortex, whereas atypical large pyramidal neurons were predominantly observed in the upper half of the motor cortex. Atypical large pyramidal neurons were further divided into inverted, tumbled, V-shaped, bipolar and superficial polymorphic cells, as previously reported (Terashima et al., J. Comp. Neurol. 218:314-326, 1983). Superficial polymorphic cells localized in the layer of polymorphic cells and the layer of the large pyramidal cells were characterized by the extremely poor dendritic arborizations and the smooth surface of the dendrites, which suggests development of dendrites of these neurons was deranged by the reeler genetic locus.

Animals

Immunoelectron microscopic study of a new D-amino acid oxidase-immunoreactive subcompartment in rat liver peroxisomes.

We report the presence of a new subcompartment in rat liver peroxisomal matrix in which only D-amino acid oxidase is localized and other matrix enzymes are absent. By electron microscopic observation, the rat liver peroxisome has generally been considered to consist of a single limiting membrane, an electron-dense crystalline core, and a homogeneous matrix. Immunohistochemical staining for D-amino acid oxidase by the protein A-gold technique revealed the presence of a small area in the matrix that was immunoreactive for the enzyme and was less electron-dense than the surrounding matrix. The localization of D-amino acid oxidase in this small area of the peroxisomal matrix was confirmed by immunoelectron microscopy on freeze-substituted tissues processed without chemical fixation. To analyze the characteristics of the electron-lucent area, immunoreactivity for various peroxisomal enzymes, including catalase, acyl-CoA oxidase, enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase bifunctional protein, 3-ketoacyl-CoA thiolase, L-alpha-hydroxy acid oxidase (isozyme B), and glycolate oxidase (isozyme A), was assayed. The electron-lucent area was negative for all of these. By double staining for D-amino acid oxidase and catalase, using colloidal gold particles of different sizes, these enzymes were shown to be located in separate areas in the matrix.

Animals

Immunoelectron microscopic evidence for organ differences in the composition of peroxisome-specific membrane polypeptides among three rat organs: liver, kidney, and small intestine.

We examined the distribution of peroxisome-specific membrane polypeptides (PMPs) among peroxisomes of the liver, renal cortex, and jejunal mucosa, using antibodies for 70 KD, 26 KD and 22 KD PMPs. Immunoblot analysis showed signals for 70 KD polypeptide in all three kinds of tissue, but for the other two only in the liver and renal cortex, with neither being detected in jejunal mucosa. The total amounts of PMPs increased in all three organs with DEHP (di-(2-ethylhexyl)phthalate) administration. By immunoelectron microscopic analysis using protein A-gold, the three PMPs were localized along the peroxisomal membrane. Quantitation of the gold particles associated with the peroxisomal membrane showed an increase in the density of 70 KD and 26 KD PMPs but a decrease in 22 KD PMP with the administration of DEHP. The presence of tissue-specific localizations of PMPs suggest the 70 KD PMP is a common constituent of peroxisomes of these three tissues, whereas 26 KD and 22 KD PMPs are absent in microperoxisomes of jejunal mucosal epithelium.

ATP-Binding Cassette Transporters

[Pterion and epipteric bones in Japanese adults and fetuses, with special reference to their formation and variations].

The formation and variations of the pterion and epipteric bones were examined in total of 614 Japanese skulls. The materials used consisted of 258 skulls of Japanese fetuses ranging from the fourth to the ninth month, 20 skulls of Japanese juveniles from the third month to 17 years of age, and 336 skulls of Japanese adults from 20 to 89 years of age. For the skulls examined the incidence of ossification in the fetal sphenoidal fontanelle was 3.6% on each side, whereas epipteric bones were observed in more than 10% of the juvenile and adult pteria. Great variation was seen in the form of the adult pterion. The most common form was a sphenoparietal contact in which the pteria were classified into usual (306 pteria), high (119), low (21), and narrow (32) types Another form of this type, a frontal process of the temporal bone without contact with frontal bone, was found in five pteria. The form of frontotemporal contact is classified into two types: One is with a frontal process of the temporal bone (17 pteria), and another is a K-shaped contact referred to as "stellate" (four). The two types were observable in adult skulls of all ages, although the fused pteria and fusing epipteric bones were most often seen in cases over 40 years of age. The results suggest that the pterion formation has two phases, the first occurring before the occlusion of sphenoidal fontanelle, and the second starting after 40 years of age.

Adolescent

Synthesis, from cellobiose, of a trisaccharide closely related to the GlcNAc----GlcA----GlcN segment of the antithrombin-binding sequence of heparin.

O-(2-Deoxy-2-sulfamido-6-O-sulfo-alpha-D-glucopyranosyl)-(1----4)- O-(beta-D- glucopyranosyluronic acid)-(1----4)-1,6-anhydro-2-deoxy-2-sulfamido-6-O-sulfo-beta-D-gl ucopyranose pentasodium salt (14) was synthesized as a heparin-related oligosaccharide. The glycosyl acceptor (derived from cellobiose) and a glycosyl donor, 6-O-acetyl-2-azido-3,4-di-O-benzyl-2-deoxy-alpha-D-glucopyranosyl bromide, were coupled in the presence of mercuric bromide and molecular sieves 4A to afford a 69% yield of fully protected trisaccharide, namely, O-(6-O-acetyl-2-azido-3,4-di-O-benzyl-2-deoxy-alpha-D-glucopyranosyl)-(1 ----4)- O-(methyl 2,3-di-O-benzyl-beta-D-glucopyranosyluronate)-(1----4)-3-O-acetyl- 1,6-anhydro-2 - azido-2-deoxy-beta-D-glucopyranose (10), which was converted into the partially sulfated trisaccharide 14. Compound 10 also underwent acetolysis to afford the glycosyl acetate, for further elongation of the glycosyl chain.

Antithrombin III