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Biomedical subjects

Hitoshi Takahashi

Publications and source records attributed to Hitoshi Takahashi.

At least 145 records · Page 8Linked to original sources
PubMed2002

Spinal cord involvement of primary central nervous system lymphomas: histopathological examination of 14 autopsy cases.

The brain and spinal cord from 14 patients with primary central nervous system lymphomas (PCNSL) were systematically examined to determine the distribution and frequency of spinal cord lesions. Spinal cord involvement was observed in four cases (cases 1-4). In cases 1 and 2, tumor cells were spread widely in the brain and extended downward to C4 and Th8 in the spinal parenchyma and to C2 and Th2 in the subarachnoid space (SAS), respectively. In case 3, tumors were found in the cerebrum but not in the cerebellum or brainstem. In the spinal cord there was massive subarachnoid involvement from C2 to L4 and localized parenchymal invasion from Th8 to L4. In case 4, tumors were found in the parenchyma from brainstem to Th2 and in the SAS all around the cord. Diffuse subarachnoid proliferation with parenchymal invasion via the Virchow-Robin space was found in the spinal cord. The route of tumor spread in cases 1 and 2 was considered to be intra-parenchymal invasion from the medulla oblongata to the spinal cord because the cord lesions had continuity with the brain lesions. In contrast, the cord lesions in cases 3 and 4 were considered to be spread via the CSF because the lesions had no continuity with the brain lesions in case 3, and spinal SAS involvement was more extensive than the parenchymal lesions in both cases. These findings suggest that spinal cord involvement is not a rare event in PCNSL and that there are two routes of spread: direct invasion from the medulla oblongata and dissemination via the CSF.

Adult↗
PubMed2002

Genotype-phenotype correlation in CAG-repeat diseases.

The expansion of a CAG repeat is a common causative gene mutation in several hereditary neurodegenerative disorders, including dentatorubral-pallidoluysian atrophy (DRPLA). Although, in DRPLA, it is revealed that the variety of clinical manifestations is related to the variable expansion of the CAG repeat, there are still many problems in the correlation between the symptoms and neuropathologic findings. Recent immunohistochemical studies have revealed that diffuse intranuclear accumulation of mutant proteins with expanded polyglutamine stretches is a significant pathology in DRPLA, and involves a wide range of the CNS regions far beyond the lesion distribution previously established by neuronal loss. This novel pathology may become a clue for elucidating molecular mechanisms of neuronal dysfunction and establishing clinicopathological correlations in CAG-repeat diseases.

Animals↗
PubMed2002

Upregulation of alpha-synuclein by lipopolysaccharide and interleukin-1 in human macrophages.

Alpha-synuclein was originally identified as the presynaptic nerve terminal protein. Recently, we reported that alpha-synuclein is also expressed in cultured human astrocytes and that its levels are increased by stimulation with interleukin-1beta, suggesting that it may be involved in inflammatory processes. We therefore investigated the effect of inflammatory stimuli on alpha-synuclein expression in human macrophages. Alpha-synuclein mRNA and protein were detected in cultured human macrophages and levels of alpha-synuclein protein were increased by stimulation with lipopolysaccharide and interleukin-1beta in a time- and concentration-dependent manner. Immunofluorescent staining showed that alpha-synuclein protein was expressed within the cytoplasm and nucleus. Furthermore, alpha-synuclein immunoreactivity was present in alveolar macrophages from human lung tissues. These findings suggest that the function of alpha-synuclein is not exclusive to the nervous system and that alpha-synuclein may play a role in inflammatory processes and immune responses.

Blotting, Western↗
PubMed2002

Selective reduction of a PDZ protein, SAP-97, in the prefrontal cortex of patients with chronic schizophrenia.

Many postsynaptic density proteins carrying postsynaptic density-95/discs large/zone occludens-1 (PDZ) domain(s) interact with glutamate receptors to control receptor dynamics and synaptic plasticity. Here we examined the expression of PDZ proteins, synapse-associated protein (SAP) 97, postsynaptic density (PSD)-95, chapsyn-110, GRIP1 and SAP102, in post-mortem brains of schizophrenic patients and control subjects, and evaluated their contribution to schizophrenic pathology. Among these PDZ proteins, SAP97 exhibited the most marked change: SAP97 protein levels were decreased to less than half that of the control levels specifically in the prefrontal cortex of schizophrenic patients. In parallel, its binding partner, GluR1, similarly decreased in the same brain region. The correlation between SAP97 and GluR1 levels in control subjects was, however, altered in schizophrenic patients. SAP102 levels were also significantly reduced in the hippocampus of schizophrenic patients, but this reduction was correlated with sample storage time and post-mortem interval. There were no changes in the levels of the other PDZ proteins in any of the regions examined. In addition, neuroleptic treatment failed to mimic the SAP97 change. These findings suggest that a phenotypic loss of SAP97 is associated with the postsynaptic impairment in prefrontal excitatory circuits of schizophrenic patients.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Effect of a combination therapy between IL-12 and soluble IL-4 receptor (sIL-4R) on Candida albicans and herpes simplex virus type I infections in thermally injured mice.

The effectiveness of a combination using IL-12 and soluble IL-4 receptor (sIL-4R) to treat severe infections of herpes simplex virus type 1 (HSV-1) and Candida albicans in thermally injured mice was investigated. Although sIL-4R decreased burn-associated type 2 T-cell responses, the effect of sIL-4R was minimal on the morbidity and mortality of thermally injured mice exposed to 250 times LD50 of HSV-1 or 10 times LD50 of C. albicans. Compared with 100% mortality in control mice, mortality for HSV-1 and C. albicans was 40 and 20%, respectively, in thermally injured mice that received IL-12 and sIL-4R in combination. After stimulation with anti-CD3 monoclonal antibody, splenic T cells from thermally injured mice exposed to large amounts of HSV-1 or C. albicans did not produce gamma interferon (IFN-gamma) into their culture fluids. However, IFN-gamma was produced by splenic T cells from thermally injured and infected mice treated with IL-12 and sIL-4R in combination. These results suggest that therapeutic treatment with a combination of IL-12 and sIL-4R may be effective by inducing type 1 T-cell responses in thermally injured mice exposed to large amounts of HSV-1 or C. albicans.

Animals↗
PubMed2002

Association between -1438G/A promoter polymorphism in the 5-HT(2A) receptor gene and fluvoxamine response in Japanese patients with major depressive disorder.

Genetic polymorphism of the serotonin 5-HT(2A) receptor seems to be associated with therapeutic response to selective serotonin reuptake inhibitors (SSRIs). The present study investigated whether a novel -1438G/A polymorphism in the promoter region of the 5-HT(2A )receptor gene is associated with therapeutic response to fluvoxamine (an SSRI) in 66 Japanese patients with major depressive disorder. Fluvoxamine (50 to 200 mg) was administered twice daily for 6 weeks. Fifty-four patients completed this study. The genotype distribution and the allele frequencies showed no significant difference between responders and non-responders. The time-course of the Montgomery-Asberg Depression Rating Scale scores showed no significant difference among -1438G/G, -1438G/A, and -1438A/A genotype groups. The results demonstrated that the -1438G/A promoter polymorphism in the 5-HT(2A) receptor gene was unlikely to have a major role in therapeutic response to fluvoxamine in Japanese patients with major depressive disorder.

Adult↗
PubMed2002

Giant cell reparative granuloma of the temporal bone: neuroradiological and immunohistochemical findings.

A 38-year-old man presented with a giant cell reparative granuloma (GCRG) of the left temporal bone. Computed tomography showed a osteolytic middle cranial mass lesion. Magnetic resonance (MR) imaging showed the lesion as low intensity with heterogeneous enhancement by gadolinium on the T1-weighted images, and extremely low intensity on the T2-weighted images. Angiography showed the lesion as highly vascular and fed by branches of the left external carotid artery. After preoperative embolization, gross total removal of the tumor was performed. The postoperative course was uneventful and no evidence of recurrence has been found for more than 4 years. Histological examination revealed GCRG with multinucleated giant cells in the fibrous background, abundant collagen bundles, hemosiderin deposits, and trabeculae of reactive bone. Some of the mononuclear stromal cells and almost all of the giant cells were positive for CD68, suggesting histiocytic differentiation. These histological features reflect the marked decrease in signal intensity on T2-weighted MR images.

Adult↗
PubMed2002

Serial CT and MRI findings in a patient with isolated angiitis of the central nervous system associated with cerebral amyloid angiopathy.

We report serial CT and MRI findings in a biopsy-proven case of cerebral amyloid angiopathy (CAA) with isolated angiitis of the central nervous system (CNS). A 69-year-old man had developed dizziness, dementia, and generalized seizure during the preceding 4 years. An initial examination by brain CT and MRI showed bilateral symmetrical periventricular lesions closely resembling those of Binswanger's disease. Subsequently, the lesions expanded slowly, involving a large area of the right cerebral hemisphere with an obvious mass effect. Since a primary brain tumor was suspected, a brain biopsy was performed, and histopathological examination revealed amyloid beta protein CAA within the meningocortical vessels associated with perivascular monocytic cuffing, indicating the presence of isolated angiitis of the CNS. Multinucleated giant cells containing intracytoplasmic beta protein amyloid around a heavily amyloid-laden cortical vessel were also observed. This is the first case report to show sequential radiographical studies of the leukoencephalopathy associated with CAA and isolated angiitis of the CNS.

Aged↗
PubMed2002

Fusiform gyrus epilepsy: the use of ictal magnetoencephalography. Case report.

The authors report successful presurgical identification of an epileptic focus in the fusiform gyrus by using ictal magnetoencephalography (MEG), which was performed with the aid of an advanced whole-brain neuromagnetometer. A 22-year-old man had suffered from medically refractory complex partial seizures since he was 10 years of age. Seizure symptoms, magnetic resonance imaging, and ictal single-photon emission computerized tomography examinations indicated right temporal lobe epilepsy; however, ictal electroencephalography, including sphenoidal recordings, failed even to lateralize the seizure focus. The MEG studies revealed that equivalent current dipoles of interictal activities were scattered bilaterally around the medial temporal structures, but those of ictal onset and postictal activities formed a cluster in the left fusiform gyrus. After confirmation of each ictal and interictal MEG finding by using long-term electrocorticography recordings, focal cortical resection of the left inferior temporal and fusiform gyri was performed. The histopathological diagnosis was cortical dysplasia, and the patient has achieved a good seizure outcome, now 15 months after the operation. Ictal and also postictal MEG may be more specific than interictal MEG for identifying the ictal onset zone.

Adult↗
PubMed2002

Hemifacial spasm associated with an ependymal cyst in the cerebellopontine angle. Case report.

No previous case of hemifacial spasm associated with an ependymal cyst has been reported in the literature. In this article the authors report the first case in which hemifacial spasm accompanied an ipsilateral cerebellopontine angle ependymal cyst in a 27-year-old woman. Cyst fenestration and arterial decompression of the facial nerve at the root exit zone resulted in complete resolution of the patient's symptoms. A histopathological study including immunohistochemical methods identified an ependymal cyst.

Adult↗
PubMed2002

[A case suspected of acute gas poisoning by carbon monoxide (CO), presenting with progressive diffuse leukoencephalopathy associated with marked brain edema].

A 51-year-old man was found comatose in a decerebrate posture in a cottage. Brain MRI showed diffuse high-signal-intensity areas in the white matter on T 2-weighted and FLAIR images, and diffusion-weighted images showed marked diffuse high intensity areas in the white matter. Initially inflammatory demyelinating diseases were suspected and methylprednisolone pulse therapy was administered. However, no improvement was noted. On close inspection of the cottage, a gas generator was discovered in the poorly ventilated room. He was therefore suspected to have suffered from gas intoxication, including carbon monoxide (CO). Hyperbaric oxygen therapy was administered, but without any improvement. The diffuse white matter lesions and brain edema progressed with time and the patient died of cerebral herniation. Autopsy revealed no inflammatory processes. Most cases with CO intoxication show hyperintense lesions in the globus pallidus on both sides in T 2-weighted images, and some cases show lesions only in the white matter without any involvement of the globus pallidus. The progressive clinical course, diffuse leukoencephalopathy and brain edema may be due to apoptosis of oligodendrocytes. CO intoxication is thus important in the differential diagnosis of diffuse white matter lesions of the cerebrum.

Brain↗
PubMed2002

An essential role of macrophage inflammatory protein 1alpha/CCL3 on the expression of host's innate immunities against infectious complications.

Sepsis was induced by well-controlled cecal ligation and puncture (CLP) in macrophage inflammatory protein 1alpha (MIP-1alpha)/CCL3 knockout (CCL3(-/-)) and severe combined immunodeficiency (SCID) mice. CCL3(-/-) mice and their littermates (CCL3(+/+) mice) treated with anti-CCL3 monoclonal antibodies were susceptible (0-20% survival) to CLP-induced sepsis, and CCL3(-/-) mice supplemented with recombinant (r)CCL3 (250 ng/mouse) and CCL3(+/+) mice were resistant (70-80% survival). The resistance of SCID mice to CLP was markedly improved by the rCCL3 administration (88% survival), and SCID mice treated with saline were shown to be middling resistant to the same CLP (45% survival). However, the resistance of SCID-M mice (SCID mice depleted of the macrophage function) to CLP was not improved by the rCCL3 administration (11% survival), and 41% of SCID-M mice reconstituted with normal peritoneal macrophages and 79% of SCID-M mice inoculated with CCL3-treated peritoneal macrophages survived. In addition, the resistance of SCID-MN mice (SCID mice depleted of functional macrophages and neutrophils) to CLP was improved by the inoculation of CCL3-treated macrophages (78% survival), and all of SCID-MN mice inoculated with CCL3-treated neutrophils died. CCL3 is shown to be essential to the host resistance against bacterial sepsis. Macrophages but not neutrophils are highlighted as the major effector cells when protective innate immunities against sepsis are improved by CCL3.

Adoptive Transfer↗
PubMed2002

[Pathology of neurodegenerative diseases: with special reference to Parkinson's disease and amyotrophic lateral sclerosis].

The causes of Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS) are still unknown. Aging, environmental factors and genetic factors may be involved in the development of these illnesses, especially the sporadic phenotypes. The details of PD pathology have made remarkable advances in the last 5 years, after the discovery of mutation of the alpha-synuclein gene in families with PD: all of the Lewy bodies (Lewy filaments) in familial and sporadic PD contain the gene product alpha-synuclein. Further studies are necessary to elucidate the mechanisms underlying the development of PD, and to determine the therapeutic targets through which it may be possible to prevent the disease. With regard to the pathology of ALS, it is of great importance that in this disease, characteristic neuronal cytoplasmic inclusions (i.e., Bunina bodies and ubiquitinated inclusions) have been described in the lower motor neurons. At present, however, compared with the Lewy bodies in PD, much less is known about the profiles of the inclusions associated with ALS. Early identifications of the proteins that constitute these inclusions would be desirable if we are to elucidate the molecular pathology, and thus the mechanisms underlying ALS.

Amyotrophic Lateral Sclerosis↗
PubMed2002

[Neuropathological features in corticobasal degeneration and progressive supranuclear palsy].

Corticobasal degeneration (CBD) is a sporadic neurodegenerative disorder of late life with a range of clinical presentations such as progressive asymmetrical rigidity and apraxia, progressive aphasia or dementia. Focal cortical atrophy, ballooned neurons and degeneration of the substantia nigra and globus pallidus have been emphasized in previous descriptions. Recent immunohistochemical studies revealed that tau-positive neuronal and glial lesions in both gray and white matter, especially astrocytic plaques in the affected cerebral cortex, are the characteristic features in CBD. While cortical involvement is also recognized in progressive supranuclear palsy, ballooned neurons are sparse and limited to the paralimbic areas and tufted astrocytes are abundant in the precentral gyrus and striatum. From a neuropathological viewpoint, CBD is distinct from other sporadic tauopathies.

Dementia↗
PubMed2001

Alpha-synuclein immunoreactivity in normal and neoplastic Schwann cells.

Alpha-synuclein is known to play an important role in several neurodegenerative diseases. Moreover, it is expressed in central nervous system neuronal tumors, and another member of the synuclein family, gamma-synuclein, is overexpressed in breast and ovarian carcinomas. However, the expression of alpha-synuclein has not been reported hitherto in the peripheral nervous system (PNS). In the present study, we investigated normal PNS tissue and schwannomas in human postmortem and biopsy samples using both immunocytochemistry and immunoelectron microscopy with antibodies against alpha-, beta- and gamma-synuclein. In normal PNS tissue, Schwann cells, but not axons or myelin, were immunopositive for alpha-synuclein. In schwannomas, almost all of the tumor cells showed diffuse cytoplasmic staining for alpha-synuclein (30 cases). Ultrastructurally, alpha-synuclein immunoreactivity was found in the cytoplasm of normal and neoplastic Schwann cells, in association with the plasma membrane, ribosomes, rough endoplasmic reticulum, small vesicles, Golgi apparatus and the nuclear outer membrane. No beta- or gamma-synuclein immunoreactivity was found in those cells. These results indicate that in the PNS, alpha-synuclein is a useful marker of Schwann cells and that it is not involved in tumorigenesis.

Aged↗
PubMed2001

Immunocytochemical localization of synphilin-1, an alpha-synuclein-associated protein, in neurodegenerative disorders.

Alpha-synuclein is a major component of Lewy bodies (LB) in Parkinson's disease (PD) and dementia with LB (DLB), as well as of glial cytoplasmic inclusions (GCI) in multiple system atrophy (MSA). Recently, a novel protein called synphilin-1 has been identified that associates with alpha-synuclein, and it has been reported that co-transfection of both alpha-synuclein and synphilin-1 in mammalian cells yielded eosinophilic cytoplasmic inclusions resembling LB. Immunocytochemical and ultrastructural investigations have now been performed on the brain of patients with various neurodegenerative disorders using anti-synphilin-1 antibodies. These antibodies immunostained the neuropil in a punctate pattern throughout the brain of control subjects. In PD, most LB observed in the brain stem were positive for synphilin-1. These LB showed intense staining in their central cores, but their peripheral portions were only weakly stained or unstained. Pale bodies and Lewy neurites, which were positive for alpha-synuclein, were synphilin-1 negative. In DLB, a small fraction of cortical LB were immunolabeled by anti-synphilin-1. In MSA, numerous GCI were positive for synphilin-1. Immunoelectron microscopy revealed that the reaction product was localized within filamentous and circular structures in LB. Various neuronal and glial inclusions in neurodegenerative disorders other than LB disease and MSA were synphilin-1 negative. These findings suggest that abnormal accumulation of synphilin-1 is specific for brain lesions in which alpha-synuclein is a major component.

Brain↗
PubMed1998

Widespread neuronal degeneration in rats following oral administration of methylmercury during the postnatal developing phase: a model of fetal-type minamata disease.

The neurotoxicity of methylmercury (MeHg) treatment during the postnatal developing phase in rats was studied. Rats on postnatal day 1 were orally administered 5 mg/kg/day methylmercury chloride (MMC) for more than 30 consecutive days. Body weight loss began 26 days after MMC was administered, and severe paralysis of the hind-limbs and unsteadiness appeared subsequently. Histopathologically, the widespread neuronal degeneration was observed in the cerebral neocortex, neostriatum, red nucleus, brainstem, cerebellum and spinal dorsal root ganglia on day 32. The widespread distribution of the lesions was quite similar to that in fetal cases of MeHg intoxication in Minamata, Japan. These findings suggest that MMC treatment during the postnatal development phase in rats produce a good model of fetal-type Minamata disease.

Animals↗