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T Kayahara

Publications and source records attributed to T Kayahara.

At least 19 recordsLinked to original sources

Efferent projections of infralimbic and prelimbic areas of the medial prefrontal cortex in the Japanese monkey, Macaca fuscata.

The infralimbic area (IL) and prelimbic area (PL) have been postulated as an autonomic motor region in the medial prefrontal cortex. The present study was conducted to reveal the projection sites of IL and PL of the monkey, Macaca fuscata, using biotinylated dextran amine as an anterograde tracer. IL and PL projected densely to the ventromedial caudate nucleus, the core and shell of the nucleus accumbens (Acb), parvicellular lateral basal and magnocellular accessory basal nuclei of the amygdala, lateral preoptic area, ventromedial hypothalamic nucleus, tubero-mammillary nucleus (TM), medial part of the magnocellular and dorsal part of the parvicellular (MDpc) dorsomedial thalamic nuclei, reunience and medial part of the medial pulvinar nucleus, and dorso-lateral part of the periaqueductal gray (PAGdl) in the mesencephalon. Moderately to weakly projected areas were the intermediate and lateral parts of the agranular insular cortex, orbital part of area 12, agranular and dysgranular part of the temporal pole cortex (TPa-g), auditory temporal cortex, lateral and medial (MS) septal nuclei, bed nucleus of the stria terminalis, diagonal band of Broca, substantia innominata, and medial preoptic area, dorsomedial, lateral, and posterior hypothalamic nuclei, magnocellular lateral basal and lateral amygdaloid nuclei, paratenial, paraventricular (PV), inter-antero-medial (IAM), reticular, central medial (CeM), parafascicular (PF) and limitans nuclei of the thalamus, lateral habenular nucleus, pedunculo-pontine nucleus, dorsal part of the lateral lemniscal nucleus, ventral tegmental area (VTA), dorsal raphe, superior central nucleus, medial and lateral parabrachial nuclei (PBl) and nucleus locus coeruleus (LC). A few scattered terminals were observed in the perifornical nucleus of the hypothalamus and substantia nigra pars compacta. PL and area 24 were characterized by projections to the entorhinal (Ent) and piriform (Pir) cortex as well as to the magnocellular part of the ventral anterior thalamic nucleus (VAmc). The morphology of the terminal arborization in each nuclei was different in appearance, perhaps reflecting the synaptic interaction between the nerve terminals and postsynaptic dendrites. PL projected uniquely to Ent, Pir and VAmc and IL projected uniquely to TPa-g, MS, IAM, CeM, MDpc, PF, PBl and LC. IL projected more strongly than PL to the shell of Acb, amygdaloid nuclei, PV, TM, VTA and PAGdl. The present results support the hypothesis that IL is a major cortical autonomic motor area and PL integrates limbic and autonomic inputs in the primate.

Animals↗

Discovery of a novel serine protease inhibitor utilizing a structure-based and experimental selection of fragments technique.

We report a set of strategies to develop novel ligands (Structure Based and Experimental Selection of Fragments: SbE-SF). First, a docking simulation utilizing DOCK3.5 is performed in order to screen the fragment database, which was generated with the in-house program FRAGMENT++ specifically for docking simulation purposes. Although the affinity of these small molecules (fragments) is expected to be low, the affinity of fragments selected by computation is assayed by experiment to determine which ones can be potent inhibitors. After determining such key fragments. additional fragments are attached to the key ones in order to increase the binding affinity,taking into account the binding modes predicted by computation. This method has been applied to a thrombin inhibitor study, resulting in the discovery of a novel inhibitor exhibiting pIC50 = 7.9.

Drug Design↗

Proline- and alanine-rich Ste20-related kinase associates with F-actin and translocates from the cytosol to cytoskeleton upon cellular stresses.

Proline- and alanine-rich Ste20-related kinase (PASK) is a Ste20-related protein kinase isolated from rat brain. Cell fractionation studies showed that PASK was present both in the cytosol and in Triton X-100-insoluble cytoskeletal fraction in rat tissues. In brain, PASK associated with protein complexes that contained actin and tubulin, confirming the association of PASK with the cytoskeleton in vivo. Glutathione S-transferase-PASK fusion protein cosedimented with F-actin, indicating that PASK binds to F-actin. In contrast to rat tissues, PASK was detected only in the Triton X-100-soluble cytosolic fraction in cultured PC12 and NIH 3T3 cells. Cytosolic PASK translocated to the cytoskeleton when these cells were stimulated with severe cellular stresses such as hypertonic sodium chloride, hydrogen peroxide, and heat shock at 45 degrees C. Our results suggest that PASK may be involved in the regulation of the cytoskeleton in response to cellular stresses such as hyperosmotic shock.

3T3 Cells↗

Neural circuits and functional organization of the striatum.

The basal ganglia and motor thalamic nuclei are functionally and anatomically divided into the sensorimotor, supplementary motor, premotor, associative and limbic territories. There exist both primary segregated basal ganglia-thalamocortical loops and convergence of functionally related information from different cortical areas onto these cortical basal ganglia-thalamocortical loops. The basal ganglia-thalamocortical loop arising from the sensorimotor area, supplementary motor area (SMA), premotor area and cingulate motor area provides distinct segregated subloops through the functionally distinct striatal, pallidal and thalamic regions with partial overlap. The subthalamic nucleus (STN) is also topographically organized. The ventrolateral part of the caudal 2/3 levels of the medial pallidal segment (GPi) projects to the primary motor area via the oral part of the ventral lateral thalamic nucleus (VLo) (Voa, Vop by Hassler's nomenclature). The thalamic relay nuclei of the GPi projection to SMA are identified in the transitional zone of the VApc (parvicellular part of the anterior ventral nucleus)-VLo and in the rostromedial part of the VLo. The thalamic nuclei relaying the cingulate subloop are not yet clearly defined. The supplementary motor subloop appears to be divided into the pre-SMA and SMA proper subloops. The premotor area is also divided into the dorsal premotor area subloop and the ventral premotor area subloop. It is suggested that the limbic loop consists of a number of subloops in the monkey as indicated by Haber et al. and in rats. We review here the microcircuitry of the striatum, as well as the convergence and integration between the functionally segregated loops. Finally, we discuss the functional implications of striatal connections.

Basal Ganglia↗

Afferent connections to the ventral striatum from the medial prefrontal cortex (area 25) and the thalamic nuclei in the macaque monkey.

The ventral striatal inputs in the macaque monkey were studied in relation to the connections from the orbitofrontal cortex, focusing on the infralimbic area (IL or area 25), thalamic nuclei and the vagal-solitary nuclear complex (NTS-X). The IL projects to more restricted parts of the ventral striatum (shell and core of nucleus accumbens, Acb; ventricular margin of caudate nucleus, CN), whereas the striatal projections of the prelimbic area (PL) are more extended than those of IL. The dorsal midline nuclei project densley to area 13, agranular insular cortex (Ia), and Acb. The nucleus ventralis anterior pars magnocellularis (VAmc) projects to the IL, perigenual area and to the region of CN between the limbic and association striatum with partial overlapping, and seems to play a role as an interface between the limbic and motor systems. The distribution pattern of retrogradely labeled neurons was similar in the midline-intralaminar thalamic nuclei following injections in the IL and ventral striatum.

Afferent Pathways↗

Projections of the vestibular nuclei to the thalamus in the rat: a Phaseolus vulgaris leucoagglutinin study.

Injections of the anterograde axonal tracer Phaseolus vulgaris leucoagglutinin were made into individual nuclei of the vestibular nuclear complex of the rat to identify specific projections to the thalamus. The results showed that the superior vestibular nucleus and the medial vestibular nucleus, especially its rostral-to-middle parts, project to the lateral part of the parafascicular thalamic nucleus (corresponding to the centromedian nucleus in primates), the transitional zone between the ventrolateral thalamic nucleus (VL) and the ventral posterolateral thalamic nucleus (VPL) (the region considered to be the nucleus ventralis intermedius of Vogt [Vogt C. 1909. La myeloarchitecture du thalamus du cercopitheque. J Psychol Neurol 12:285-324.]), the lateral part of the centrolateral thalamic nucleus and the dorsal part of the caudal VL; the spinal vestibular nucleus projects to the lateral part of the parafascicular thalamic nucleus, the transitional zone between the VL and the VPL, the caudal part of the ventrobasal complex, and the suprageniculate thalamic nucleus. These results suggest that vestibular information is transmitted not only to the cerebral cortex (mainly area 2V and area 3a) but also to the striatum. They also suggest that vestibular activity may affect gaze control by means of vestibulothalamocortical pathway in addition to vestibulo-ocular and vestibulopremotoneuronal routes.

Afferent Pathways↗

Long-term observation on the changes of somatotopy in the facial nucleus after nerve suture in the cat: morphological studies using retrograde labeling.

To examine the time course of plasticity of the cranial nucleus during axonal regeneration, we followed the topographical reorganization of the cat facial nucleus (FN) up to 24 months after facio-facial nerve suture using retrograde labeling methods. The trunk of the temporal-zygomatico-orbital and both superior and inferior buccolabial branches (defined as main branch) of the facial nerve was cut and sutured again under ketamine hydrochloride anesthesia. At 11-722 days after nerve suture, Fast Blue (FB) and 1,1'-dioctadecyl-3, 3, 3', 3'-tetramethylindocarbocyanine perchlorate (Dil) or horseradish peroxidase (HRP) were injected into the distal part of the sutured main branch and the unoperated posterior auricular branch, respectively. Until about 3 months after suture, the topographical pattern in FN was similar to that observed in normal cats. At about 4 months after suture, FB-labeled motoneurons were distributed not only in the lateral part (including intermediate, dorsal and ventrolateral divisions) but also in the medial subdivision of FN. After a survival period of 18-24 months, FB-labeled neurons were found all over the FN, and their number increased significantly. Interestingly, in the longer survival cases, we noticed that the Dil- or HRP-labeled posterior auricular branch motoneurons also showed a tendency to distribute outside the medial region. The present study showed that somatotopic disorganization starts at around 4 months after suture, which seems to be somewhat slower than that in rats, and continues until a much later postoperative period. Furthermore, we suggested a possibility that the regeneration of one branch may affect the somatotopy of the unoperated nerve branch. These phenomena may contribute to aberrant facial nerve functions such as abnormal associated movement and facial spasm observed after nerve injury.

Amidines↗

Molecular cloning and characterization of a novel Ste20-related protein kinase enriched in neurons and transporting epithelia.

A novel cDNA encoding a protein kinase (termed PASK) was isolated from rat brain. The PASK catalytic domain was most similar to Ste20-related protein kinases, showing 45.5 and 39.2% amino acid identity with human SOK1 and yeast Sps1, respectively. The amino-terminal noncatalytic domain of 71 amino acids was rich in alanine and proline and contained several proline-alanine repeats. PASK was widely expressed in rat tissues but negligible in liver and skeletal muscle. Immunohistochemical analysis revealed that PASK was localized to a distinct set of cells including neurons, adrenal glomerulosa cells, and transporting epithelia such as epithelial cells of brain choroid plexus, distal tubule and collecting duct of kidney, duct of salivary gland, and parietal cells of stomach. Subcellular fractionation showed that PASK was present in both the cytosol and the Triton X-100-insoluble cytoskeletal fraction in brain.

Alanine↗

The globus pallidus sends axons to the thalamic reticular nucleus neurons projecting to the centromedian nucleus of the thalamus: a light and electron microscope study in the cat.

We examined whether light and electron microscopically projection fibers from the globus pallidus (GP) of the cat might terminate on neurons of the thalamic reticular nucleus (RT) sending axons to the centromedian thalamic nucleus (CM). In the first group of experiments, wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) was injected into the GP, and anterogradely labeled preterminal and terminal-like elements were seen in the anterior part of RT. At the anterior pole of RT, these labeled elements were localized in its lateral portion. In the second group of experiments, the retrograde labeling method with WGA-HRP was combined with the degeneration method using kainic acid. In each cat, lesion was placed stereotaxically in the GP by kainic acid injection, and WGA-HRP was then injected into the CM ipsilateral to the kainic acid injection. In the rostral part of RT, a considerable number of degenerated axon terminals deriving from GP were seen to establish synaptic contact with dendritic and somatic profiles, which were retrogradely labeled by WGA-HRP injections in CM. The results indicate that GP innervates directly RT nucleus neurons projecting to CM.

Animals↗

[Cystic vein: as a perfusion vein of hepatic portion-angiographical study].

In order to determine the hepatic portions by cystic vein, we carried out abdominal angiography in 153 patients. The cystic vein was recognized in eleven patients, but only in nine cystic venous flow could be measured. In this group of patients, in which the cystic venous flow was detected, hepatic angiography was performed through the right hepatic artery (RHA) in six patients, the anterior branch of RHA in one patient, and the cystic artery in two patients. Simultaneously, angiographical CT was performed in five patients. As the results, it is presumed that the cystic venous flow perfused segment 4 portal branch (P4) + segment 5 (S5) in four patients, P4 in two patients, segment 6 portal branch (P6), S5 + right portal vein (RPV) + right hepatic vein (RHV), and S5 + RHV in one patient, respectively, and we concluded that in 70% of cases cystic venous flow perfused either P4 or S5.

Cysts↗

Long-term stress degenerates, but imipramine regenerates, noradrenergic axons in the rat cerebral cortex.

Exposed to a forced walking stress for 2 weeks, some rats became persistently inactive (depression-model rats), whereas others gradually recovered from exhaustion (spontaneous recovery rats). We also studied rats exposed to short-term stress, rats without stress, and the model rats treated with imipramine or saline. We examined the density of noradrenergic axons in the frontal cortex using retrograde labeling of the locus coeruleus with horseradish peroxidase injected into the cortex and immunohistochemical staining of cortical axons with dopamine beta-hydroxylase antiserum. The density was significantly lower in the depression-model rats, but tended to be higher in the recovery rats and short-term stressed rats. Chronic treatment with imipramine significantly increased the density in the model rats. There was also a correlation between the density of noradrenergic axons and the recovery rate of activity. Our results suggest that cortical noradrenergic degeneration is involved in the pathogenesis of depression.

Adrenergic Uptake Inhibitors↗

Anti-thrombotic effects and bleeding risk of AJvW-2, a monoclonal antibody against human von Willebrand factor.

1. A murine anti-human vWF monoclonal antibody, AJvW-2, was developed that inhibited the interaction between platelet glycoprotein Ib (GPIb) and von Willebrand factor (vWF) during the ristocetin- (IC50 = 0.7 +/- 0.1 microgram ml-1) and botrocetin- (IC50 = 1.8 +/- 0.3 microgram ml-1) induced aggregation of human platelets. 2. AJvW-2 inhibited the high shear stress (10.8 N m-2) induced aggregation of human platelets dose-dependently with an IC50 = 2.4 +/- 0.3 micrograms ml-1, but had no effect on low shear stress induced platelet aggregation (1.2 N m-2) up to 100 micrograms ml-1. 3. AJvW-2 also inhibited the high shear stress (5.0 N m-2) induced adhesion of human platelets to collagen I with the same efficacy (IC50 = 2.4 +/- 0.3 micrograms ml-1), but no effect at low shear conditions (1.5 N m-2). 4. AJvW-2 inhibited the botrocetin-induced aggregation of platelets from guinea-pig, rat, rabbit, dog and pig at the same concentration range as human platelets; it likewise also inhibited the high shear stress induced aggregation and adhesion to collagen I of guinea-pig platelets. 5. AJvW-2 prevented arterial thrombus formation in guinea-pigs at a dose of 100 micrograms kg-1 without prolonging the template bleeding time, whereas the GPIIb/IIIa antagonists lamifiban mediated inhibition of thrombosis at 1000 micrograms kg-1 was accompanied by a significant prolongation of the bleeding time. 6. These results suggest that AJvW-2 is a potent inhibitor of the GPIb-vWF interaction and a potential novel antithrombotic agent with lower bleeding risk than GPIIb/IIIa antagonists.

Animals↗

Isolation and characterization of an Escherichia coli mutant lacking the major serine transporter, and cloning of a serine transporter gene.

L-Serine as well as L-valine inhibits the growth of Escherichia coli cells, and L-isoleucine releases this growth inhibition. We isolated an E. coli mutant (designated as WAT9) that was able to grow on lactate (or glucose) as a carbon source even in the presence of L-serine, the parent not being able to. Cells of WAT9 were not able to grow on L-serine as a carbon source even if L-isoleucine was present in the culture medium, while the parental cells grew. This mutant was shown to lack the principal L-serine transporter in E. coli, the Na+/ serine symporter. This mutant is useful for analysis of the role(s) of the Na+/serine symporter in cell physiology and as a host for the cloning of L-serine transporter gene(s). In fact, we cloned a gene encoding a serine transporter from chromosomal DNA of E. coli using WAT9 as the host. The gene enabled the mutant cells to grow on L-serine. Transport activity for L-serine was restored in the mutant cells harboring a plasmid carrying the gene. We partially sequenced the gene and found that it was the tdcC gene. We showed that TdcC is an H+/serine symporter.

Amino Acid Transport Systems↗

Direct projections from the medial vestibular nucleus to the posterior hypothalamic area in the monkey (Macaca fuscata).

Direct projections from the medial vestibular nucleus to the posterior hypothalamic area was found in the macaque monkey by the anterograde and the retrograde tract-tracing methods. After injection of biotinylated dextran amine (BDA) into the ventrolateral part of the medial vestibular nucleus, anterogradely labeled axon terminals were seen bilaterally in the posterior hypothalamic area. After injection of wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) into the posterior hypothalamic area, retrogradely labeled neuronal cell bodies were observed bilaterally in the ventral part of the medial vestibular nucleus with a contralateral predominance.

Animals↗

Pallido-thalamo-motor cortical connections: an electron microscopic study in the macaque monkey.

We combined the retrograde transport of horseradish peroxidase conjugated to wheat germ agglutinin (WGA-HRP) technique and degenerating electron microscopic investigations to confirm the motor cortical area projection from the medial pallidal segment (GPm) via the thalamic nucleus ventralis lateralis pars oralis (VLo). We found first degenerated boutons arising from the GPm make synaptic contact with the somata and proximal dendrites of VLo neurons containing WGA-HRP reaction products transported retrogradely from motor area.

Animals↗

The vestibular nuclei of the rat project to the lateral part of the thalamic parafascicular nucleus (centromedian nucleus in primates).

To clarify the vestibular projections to the centromedian-parafascicular nuclear complex, the Phaseolus vulgaris leucoagglutinin (PHA-L) and horseradish peroxidase conjugated to wheat germ agglutinin (WGA-HRP), tracing studies have been done in rats. The data demonstrated that the lateral parafasicular nucleus received vestibular afferents mainly from the ventral part of medial vestibular nucleus, and the superior and inferior vestibular nuclei, with an ipsilateral predominance. These findings suggest the vestibular influence to the motor loop of the basal ganglia thalamocortical projections.

Afferent Pathways↗

[A case of atypical hemifacial spasm without involvement of orbicularis oculi muscles: possibility of functional topography in facial nerve].

We reported a case of atypical hemifacial spasm that did not involve orbicularis oculi muscles. A 60-year-old woman suffered from intermittent involuntary movement of the orbicularis oris and buccinator muscles. Operative findings revealed that the rostrodorsal portion of the facial nerve root was compressed by a loop of AICA. Transposing this AICA, it was found that it was compressing one portion on the rostrodorsal part of this nerve root. In most cases, facial spasm involves orbicularis oculi muscles and compression of the anatomically caudal portion of the facial nerve root. Differentiation of the compressed portions of the nerve, therefore, may indicate a functional topography of the facial nerve.

Facial Muscles↗