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Biomedical subjects

Michiko Nakamura

Publications and source records attributed to Michiko Nakamura.

12 recordsLinked to original sources
PubMed2006

Abnormality of circadian rhythm accompanied by an increase in frontal cortex serotonin in animal model of autism.

Several clinical reports have indicated that autistic patients often show disturbance of the circadian rhythm, which may be related to dysfunction of the serotonergic system in the brain. Using rats exposed prenatally to valproic acid (VPA) as an animal model of autism, we examined locomotor activity and feeding under a reversed 12-h light/dark cycle, and found disturbance of the circadian rhythm characterized by frequent arousal during the light/sleep phase. In addition, measurement of brain serotonin (5-HT) level using in vivo microdialysis showed that the brain 5-HT level in VPA-exposed rats was significantly higher than that in control rats. These results suggest that a higher brain 5-HT level might be responsible for the irregular sleep/awake rhythm in autism.

Animals↗
PubMed2005

Genomewide high-density SNP linkage analysis of 236 Japanese families supports the existence of schizophrenia susceptibility loci on chromosomes 1p, 14q, and 20p.

The Japanese Schizophrenia Sib-Pair Linkage Group (JSSLG) is a multisite collaborative study group that was organized to create a national resource for affected sib pair (ASP) studies of schizophrenia in Japan. We used a high-density single-nucleotide-polymorphism (SNP) genotyping assay, the Illumina BeadArray linkage mapping panel (version 4) comprising 5,861 SNPs, to perform a genomewide linkage analysis of JSSLG samples comprising 236 Japanese families with 268 nonindependent ASPs with schizophrenia. All subjects were Japanese. Among these families, 122 families comprised the same subjects analyzed with short tandem repeat markers. All the probands and their siblings, with the exception of seven siblings with schizoaffective disorder, had schizophrenia. After excluding SNPs with high linkage disequilibrium, we found significant evidence of linkage of schizophrenia to chromosome 1p21.2-1p13.2 (LOD=3.39) and suggestive evidence of linkage to 14q11.2 (LOD=2.87), 14q11.2-q13.2 (LOD=2.33), and 20p12.1-p11.2 (LOD=2.33). Although linkage to these regions has received little attention, these regions are included in or partially overlap the 10 regions reported by Lewis et al. that passed the two aggregate criteria of a meta-analysis. Results of the present study--which, to our knowledge, is the first genomewide analysis of schizophrenia in ASPs of a single Asian ethnicity that is comparable to the analyses done of ASPs of European descent--indicate the existence of schizophrenia susceptibility loci that are common to different ethnic groups but that likely have different ethnicity-specific effects.

Chromosomes, Human, Pair 1↗
PubMed2005

Advanced renal pelvic carcinoma associated with dermatomyositis.

Dermatomyositis is an uncommon in flammatory myopathy with characteristic cutaneous manifestations which is frequently linked to several cancers. A 42-year-old man presented with left flank pain with typical symptoms of dermatomyositis. Computed tomography showed a solid mass in the pelvis of the left kidney and lymphadenopathy in the retroperitoneum. Since the general condition of the patient rapidly deteriorated because of marked muscle weakness of the respiratory muscles, the patient initially underwent medical treatment with prednisolone. After the improvement of respiratory function, the patient underwent radical nephroureterectomy and retroperitoneal lymphadenectomy. The pathological specimen showed moderately differentiated adenocarcinoma, stage pT3N2. After surgery, the patient showed a marked improvement of clinical symptoms related to dermatomyositis. Twenty-two months later, multiple organ metastases occurred and the patient died of cancer. We should point out the significance of surgical and medical treatment for these patients.

Adenocarcinoma↗
PubMed2005

[Conduct disorder--early detection and intervention].

Conduct disorder (CD) is a serious psychiatric disorder of children and adolescents. A common association is the presence of attention-deficit hyperactivity disorder. The present paper reviews empirical findings on CD. The correlative factors were analyzed according to their bio-psycho-social aspects. To be effective, early detection and intervention on CD must be multimodal. We should address treatments on multiple foci, and continue them over an extensive period of time.

Child↗
PubMed2004

MRI identification of dorsal hippocampus homologue in human brain.

We investigated hippocampal substructure in the rat, cat, dog, and human by means of magnetic resonance imaging to elucidate phylogenetic differences in longitudinal organization. Multidirectional high-resolution images obtained with a 3 T scanner revealed that the dorsal part of the hippocampus was well developed in the rat, cat, and dog brain, and was homologous to the hippocampal tail, a poorly-developed posterior part, in the human. We conclude that the dorsal hippocampus of laboratory animals corresponds to the hippocampal tail in the human brain, which is considered to be hypoplastic and of less importance clinically than more anterior regions. These data may help in understanding phylogenetic, and in correlating results from animal experiments with clinical findings on the functions and pathologies of the human hippocampus.

Animals↗
PubMed2004

Signaling complex formation of phospholipase Cbeta4 with metabotropic glutamate receptor type 1alpha and 1,4,5-trisphosphate receptor at the perisynapse and endoplasmic reticulum in the mouse brain.

Upon activation of cell surface receptors coupled to the Gq subclass of G proteins, phospholipase C (PLC) beta hydrolyses membrane phospholipid to yield a pair of second messengers, inositol 1,4,5-trisphosphate (IP3) and 1,2-diacylglycerol. PLCbeta4 has been characterized as the isoform enriched in cerebellar Purkinje cells (PCs) and the retina and involved in motor and visual functions. Here we examined cellular and subcellular distributions of PLCbeta4 in adult mouse brains. Immunohistochemistry showed that high levels of PLCbeta4 were detected in the somatodendritic domain of neuronal populations expressing the metabotropic glutamate receptor (mGluR) type 1alpha, including olfactory periglomerular cells, neurons in the bed nucleus anterior commissure, thalamus, substantia nigra, inferior olive, and unipolar brush cells and PCs in the cerebellum. Low to moderate levels were detected in many other mGluR1alpha-positive neurons and in a few mGluR1alpha-negative neurons. In PCs, immunogold electron microscopy localized PLCbeta4 to the perisynapse, at which mGluR1alpha is concentrated, and to the smooth endoplasmic reticulum in dendrites and spines, an intracellular Ca2+ store gated by IP3 receptors. In the cerebellum, immunoblot demonstrated its concentrated distribution in the post-synaptic density and microsomal fractions, where mGluR1alpha and type 1 IP3 receptor were also greatly enriched. Furthermore, PLCbeta4 formed coimmunoprecipitable complexes with mGluR1alpha, type 1 IP3 receptor and Homer 1. These results suggest that PLCbeta4 is preferentially localized in the perisynapse and smooth endoplasmic reticulum as a component of the physically linked phosphoinositide signaling complex. This close molecular relationship might provide PLCbeta4 with a high-fidelity effector function to mediate various neuronal responses under physiological and pathophysiological conditions.

Animals↗
PubMed2004

Morphological variations in brachial plexus of beagle dogs: evaluation of utility as sources of allogeneic nerve grafts.

Basic studies were carried out to apply frozen allogeneic nerve grafts in dogs after wide-ranging defects of the brachial plexus due to surgical resection of tumor. In this study, morphological variations in branching patterns of the brachial plexus were examined in ten beagle dogs, to evaluate whether the brachial plexus might represent a useful source of allogeneic nerve grafts. Spatial relationships between the axillary lymph node, which had the possibility of carcinomatous metastasis, and the musculocutaneous (MC) nerve, which was important for the function of the forelimbs, were also investigated. In all ten cases examined, the brachial plexus received ventral roots from the fifth cervical nerve to the first thoracic nerve. No significant variation in the branching pattern was found in any nerve except the phrenic, MC and dorsal thoracic nerves. Four communicating branches were observed and had some morphological variations which might be negligible for nerve grafting. Considering previous physiological and anatomical reports, the most important nerve to be reunited in graft operations for functional recovery is the radial nerve. The MC nerve and median or ulnar nerve should also be considered as possibilities for reuniting. Distances between the axillary lymph nodes and the MC nerve ranged from 11.2 mm to 21 mm (mean +/- SD: 16.1 +/- 2.3 mm). In conclusion, it was suggested that morphological variations in the brachial plexus were technically acceptable to apply allogeneic nerve grafts at least in beagle dogs.

Animals↗
PubMed2003

Possible roles of kainate receptors on GABAergic nerve terminals projecting to rat substantia nigra dopaminergic neurons.

GABAergic afferent inputs are thought to play an important role in the control of the firing pattern of substantia nigra pars compacta (SNc) dopaminergic neurons. We report here the actions of presynaptic kainite (KA) receptors in GABAergic transmission of rat SNc dopaminergic neurons. In mechanically dissociated rat SNc dopaminergic neurons attached with native presynaptic nerve terminals, GABAergic miniature inhibitory postsynaptic currents (mIPSCs) were recorded by use of conventional whole cell patch recording mode. In the voltage-clamp condition, KA (3 microM) significantly increased GABAergic mIPSC frequency without affecting the current amplitude. This facilitatory effect of KA was not affected in the presence of 20 microM GYKI52466, a selective AMPA receptor antagonist, but was completely inhibited in the presence of 20 microM CNQX, an AMPA/KA receptor antagonist. Presynaptic KA receptors on GABAergic terminals were mainly permeable to Na+ but impermeable to Ca2+ because KA-induced facilitation of mIPSC frequency was completely suppressed in either Na+-free or Ca2+-free external solutions, and in the presence of 200 microM Cd2+, a general voltage-dependent Ca2+ channel blocker. In the slice preparation, KA increased GABAergic spontaneous mIPSC frequency, but significantly suppressed evoked IPSC (eIPSC) amplitude. However, this inhibitory action on eIPSCs was reversed by 10 microM CGP55845, a selective GABAB receptor antagonist, implicating the possible involvement of GABAB autoreceptors in KA-induced modulation of GABAergic transmission. Thus presynaptic KA receptors on GABAergic nerve terminals synapsing onto SNc neurons may play functional roles contributing the fine control of neuronal excitability and firing pattern of SNc.

Action Potentials↗
PubMed2003

Mepanipyrim, a novel inhibitor of pharmacologically induced Golgi dispersion.

Mepanipyrim inhibited retrograde Golgi-to-ER trafficking induced by brefeldin A (BFA), nordihydroguaiaretic acid, clofibrate, and arachidonyltrifluoromethyl ketone in NRK and other types of cells, but did not inhibit anterograde trafficking of Golgi-resident proteins translocated to ER by BFA and newly synthesized VSV-G. However, mepanipyrim did not block the TGN38 dispersion induced by any of these compounds. Mepanipyrim acted on the Golgi, and swollen vesicular Golgi structures were formed and similar structures accumulated during rebuilding of the Golgi after BFA removal. These actions of mepanipyrim were readily reversed after its removal. Mepanipyrim did not stabilize microtubules, but prevented nocodazole-induced fragmentation and dispersion of the Golgi. These results suggest that the mepanipyrim-sensitive molecules participated in stabilizing the Golgi and its anchoring in the perinuclear region, and equally importantly, that the novel action of mepanipyrim may be used as a pharmacological tool for investigating membrane transport, Golgi membrane dynamics, and differentiation of the Golgi from TGN.

Animals↗
PubMed2003

[Ureteral and bladder metastases of renal cell carcinoma following synchronous renal cell carcinoma and bladder cancer; a case report].

A 73-year-old man presented with gross hematuria. Ultrasonography and computerized tomography showed small bladder tumors and a left renal mass protruding to renal pelvis. Transurethral resection of bladder tumor and ureteroscopic tumor biopsy were performed, and pathological examinations revealed transitional cell carcinoma in the bladder and renal cell carcinoma in the kidney. He underwent left radical nephrectomy. A 4-month postoperative cystoscopy revealed a solitaly non-papillary tumor in the bladder. Transurethral resection was performed and pathological diagnosis was metastasis from renal cell carcinoma. At that time, multiple metastases to ureteral stump and lung were found. He had undergone palliative treatment because of his poor general condition until he died 26 months postoperatively. Care should be taken for management of ureteral stump when diagnostic ureteroscopy was done for renal cell carcinoma invading the renal pelvis.

Aged↗
PubMed2002

Rapid tolerance to focal cerebral ischemia in rats is attenuated by adenosine A1 receptor antagonist.

Two types of ischemic tolerance in the brain, rapid and delayed, have been reported in terms of the interval between the conditioning and test insults. Although many reports showed that delayed-phase neuroprotection evoked by preconditioning is evident after 1 week or longer, there have been a few investigations about rapidly induced tolerance, and the reported neuroprotective effects become ambiguous 7 days after the insults. The authors examined whether this rapid ischemic tolerance exists after 7 days of reperfusion in a rat focal ischemic model, and investigated modulating effects of the adenosine A 1 receptor antagonist DPCPX (8-cyclopentyl-1,3-dipropylxanthine). Preconditioning with 30 minutes of middle cerebral artery occlusion reduced infarct volume 7 days after 180 minutes of subsequent focal ischemia given after 1-hour reperfusion. The rapid preconditioning also improved neurologic outcome. These beneficial effects were attenuated by pretreatment of 0.1 mg/kg DPCPX, which did not influence the infarct volume after conditioning (30 minutes) or test (180 minutes) ischemia when given alone. The results show that preconditioning with a brief focal ischemia induces rapid tolerance to a subsequent severe ischemic insult, the effect of which is still present after 7 days of reperfusion, and that the rapid ischemic tolerance is possibly mediated through an adenosine A 1 receptor-related mechanism.

Adaptation, Physiological↗