Search PubMed⌕ Search

Biomedical subjects

T Yanagihara

Publications and source records attributed to T Yanagihara.

At least 181 records · Page 10Linked to original sources
PubMed1995

[Molecular pathology of Charcot-Marie-Tooth disease type 1A: abnormal expression of PMP-22].

In the majority of Charcot-Marie-Tooth disease type 1A (CMT1A) patients, the peripheral myelin protein 22 (PMP-22) gene maps within 1.5 megabase duplication on chromosome 17p11.2-12. The PMP-22 gene dosage is believed to be a major determining factor in the molecular pathology of CMT1A. Median nerve conduction velocities were below 35 m/sec in 17 CMT1A patients examined. Northern blot analysis showed that the mean relative ratio of PMP-22 mRNA levels in biopsied nerves of 5 patients with CMT1A is significantly higher than that in disease controls. Immunohistochemical analysis demonstrated that Schwann cell cytoplasm including onion bulbs as well as the myelin sheath was positive for PMP-22 in some patients with CMT1A, while PMP-22 was expressed only on compact portion of the myelin sheath in non-CMT1A patients and normal subjects. A minority of CMT1A are known to carry dominant and recessive point mutations in PMP-22. Some patients with Dejerine-Sottas syndrome (DSS) also have dominant and recessive point mutations in PMP-22. Instead of being two completely distinct disease entities, DSS and CMT1A form a spectrum of inherited PMP-22 related neuropathies, including hereditary neuropathy with liability to pressure palsies which carries a deletion of the PMP-22 gene.

Animals↗
PubMed1994

Involvement of the central nervous system in myotonic dystrophy.

To investigate the etiological factors responsible for intellectual impairment and mood changes in patients with myotonic dystrophy (DM), we evaluated 14 patients with DM by means of neuropsychological evaluation and magnetic resonance images (MRI). There were significant differences between patients and controls in regard to the Barthel index, Zung's depression scale, attention, verbal fluency and digit span. All patients had ventricular enlargement and white matter abnormalities on MRI. However, the severity was variable and there was no difference in neuropsychological testing between patients with mild ventricular dilatation and those with severe dilatation. On the other hand, significant differences were present between patients with mild white matter lesions and those with severe white matter abnormalities in regard to verbal fluency and attention. Neuropathologic examination of an autopsied brain showed an increase in the interfascicular space of the white matter which produced pallor on myelin staining. The present findings suggested that the white matter abnormalities were the cause of cognitive impairment among patients with DM.

Activities of Daily Living↗
PubMed1994

Cloning and expression of myelin-associated oligodendrocytic basic protein. A novel basic protein constituting the central nervous system myelin.

We have screened genes predominantly expressed in the rat spinal cord, and we report here cloning of the most abundant unknown gene. It is a novel member of the central nervous system (CNS) myelin-constituting proteins, myelin-associated oligodendrocytic basic protein (MOBP). MOBP is abundantly expressed specifically in oligodendrocytes at the mRNA level only next to myelin basic protein (MBP) and proteolipid protein. Two isoforms have been confirmed. One of them has proline-rich tandem repeats and has 84% homology with human counterpart in terms of predicted amino acid sequences. The cDNA-derived primary structure predicts a small, soluble, basic protein. The immunoelectron microscopy has shown that MOBP is expressed throughout compact myelin. All these characteristics are similar to MBP. One definite difference between MBP and MOBP is that MOBP is expressed exclusively in the CNS myelin. These findings suggest that MOBP shares some important functions with MBP in the CNS myelin such as myelin compaction.

Amino Acid Sequence↗
PubMed1994

Elevated expression of messenger RNA for peripheral myelin protein 22 in biopsied peripheral nerves of patients with Charcot-Marie-Tooth disease type 1A.

The human peripheral myelin protein 22 (PMP-22) gene has been mapped to chromosome 17p11.2 in the duplicated region associated with Charcot-Marie-Tooth disease type 1A. Southern blot analysis using PMP-22 as a probe indicated that the PMP-22 gene was duplicated in 5 patients from unrelated Japanese families with Charcot-Marie-Tooth disease type 1. In order to investigate whether or not an extra copy of PMP-22 has an effect on its gene expression, we analyzed relative expression of messenger RNA for PMP-22 and protein 0 (P0) against beta-actin by Northern blotting in biopsied nerves of the patients with type 1A disease, and compared the results with those of patients having other demyelinating neuropathies and the autopsied nerves of patients without neuropathies. The relative expression of PMP-22 messenger RNA in 5 patients with Charcot-Marie-Tooth disease type 1A was significantly higher than that in 5 patients with other demyelinating neuropathies (p < 0.05). There was no statistically significant difference in P0 expression between them. This study provided direct evidence for elevated expression of PMP-22 in peripheral nerves of patients with Charcot-Marie-Tooth disease type 1A as the result of a gene dosage effect. However, the relation between elevated expression of PMP-22 and the mechanism causing demyelination remains undetermined.

Adult↗
PubMed1994

Fluoride distribution in dentine and cementum in human permanent teeth with vital and non-vital pulps.

Twenty-two selected permanent teeth [11 with vital pulps and 11 with non-vital (necrotic) pulps] were obtained from patients aged from 20 to 73 yr in Nagoya, Japan. Fluoride (F) profiles in tooth samples were examined by using an abrasive micro-sampling technique. F levels in the pulpal dentine were significantly higher in vital than non-vital teeth for each age group, although there were observed increases of F with age. In the cementum the F levels were strongly related to age and there were few differences in profiles and levels of F between vital and non-vital teeth. It was concluded that vital pulp is an important factor for the pulpal dentine to absorb fluoride.

Adult↗
PubMed1994

Golgi electron microscopic study of the cerebral cortex after transient cerebral ischemia and reperfusion in the gerbil.

Fine structures of defined neurons and their dendritic processes were studied in the cerebral cortex of gerbil brains by using Golgi electron microscopy during progressive cerebral ischemia for 10 and 20 min and after reperfusion for up to 72 h following transient ischemia for 20 min. The periphery of ascending dendrites of the vulnerable neurons in layers III and Vb became distended immediately after ischemia with swollen mitochondria and disintegrated microtubules, but the proximal portion of the same dendrites remained unchanged. After reperfusion for 6 h, distension of the dendroplasm of the impregnated dendrites in layer I receded, but the proximal portion of the same dendrites showed indentation caused by swollen astrocytic processes and derangement of microtubules inside. Polyribosomes in most neuronal perikarya were disaggregated, but severe neuronal damage was rarely found among those neuronal cell bodies impregnated by the Golgi method. Recovery with reaggregation of polyribosomes and realignment of microtubules was more clearly observed after reperfusion for 24 h and thereafter in impregnated neurons. These results indicated that impregnation during progressive ischemia occurred in many neurons with progressive structural damage but that impregnation during reperfusion occurred in a limited number of neurons with limited damage, allowing us to observe the recovery process, and that neuronal derangement in the dendrosomatic direction initially occurred both in the irreversibly damaged neurons and in the reversibly damaged ones. It is possible that disintegration of microtubules and the resulting disruption of dendritic transport may contribute to subsequent development of delayed neuronal death, if the recovery process does not take place promptly. Golgi electron microscopy is useful for ultrastructural investigation of defined neurons and their dendrites together and may be applicable for investigation of selected neuropathologic conditions.

Animals↗
PubMed1994

Multifocal eosinophilic granuloma presenting as progressive brainstem and cerebellar dysfunction.

A 55 year old woman with multifocal eosinophilic granuloma (MEG) is described. She developed facial numbness and twitching followed by slowly progressive cerebellar symptoms. Two years later polyuria and polydipsia were noted. A CT of the brain showed multifocal enhancing lesions, and MRI showed areas of hyperintensity on T2 weighted studies in the cerebellar peduncles, pons, and midbrain. Radiographs of the skull, pelvis, and long bones were normal, but a 99mTc diphosphonate bone scan and MRI showed bone lesions compatible with granuloma. The diagnosis of MEG was made by bone biopsy. This is believed to be the first case of MEG with such unusual clinical profiles and radiographical findings. Skeletal surveys are indicated for patients with unexplained focal or multifocal inflammatory changes in the cerebellum.

Biopsy↗
PubMed1994

Incidence of cluster headaches: a population-based study in Olmsted County, Minnesota.

The epidemiology of cluster headache is virtually unknown. Using the unique resources of the Rochester Epidemiology Project for population-based studies, we identified 26 Olmsted County, Minnesota, residents who fulfilled the International Headache Society criteria for newly diagnosed cluster headache between 1979 and 1981. As part of a large study of migraine and cluster headache, we screened more than 6,400 patient records from several diagnostic rubrics to obtain this cohort, accomplished case ascertainment exclusively through medical record review, and assigned diagnoses by the consensus of two neurologists. The age-adjusted incidence was 15.6 per 100,000 person-years (p-y) (95% CI, 8.9 to 22.3) for males and 4.0 per 100,000 p-y for females (95% CI, 0.4 to 7.6). The overall age- and sex-adjusted incidence was 9.8 per 100,000 p-y (95% CI, 6.0 to 13.6) or approximately 1/25 that of migraine. The peak incidence was among men aged 40 to 49 years and women 60 to 69 years. There was a higher than expected prevalence of history of smoking among males with cluster headaches (p < 0.05), supporting the possibility that smoking predisposes to the development of cluster headaches in men.

Adolescent↗
PubMed1993

Molecular cloning of a novel putative G protein-coupled receptor (GPCR21) which is expressed predominantly in mouse central nervous system.

A novel cDNA clone encoding a putative G protein-coupled receptor (named GPCR21) was isolated from a mouse brain cDNA library along with its homologue, GPCR01 (the mouse counterpart of previously reported rat receptor R334 [(1991) FEBS Lett. 292, 243-248]) by the polymerase chain reaction using degenerate oligonucleotide primers. Northern blotting and reverse transcription-polymerase chain reaction analyses showed predominant expression of these two receptors in the central nervous system. In situ hybridization analysis revealed their prominent expression in the limbic system and further demonstrated the differential distribution of their mRNAs in mouse brain. Although the ligands for these receptors are yet to be identified, the significant sequence homology between these receptors suggests that they constitute a new receptor subfamily and they possibly represent different receptor subtypes for an unknown neurotransmitter.

Amino Acid Sequence↗
PubMed1993

Internucleosomal DNA cleavage involved in ischemia-induced neuronal death.

Pyramidal neurons of the hippocampal CA1 are known to be particularly vulnerable to transient ischemia resulting in "delayed neuronal death". Recent studies using aurintricarboxylic acid suggested that ischemia- or excitotoxin-induced neuronal death should share intracellular mechanisms in common with apoptosis. It is, however, unclear about involvement of endonucleases. Here using a transient (5 min) forebrain ischemia model in gerbils, we found that internucleosomal DNA fragmentation developed between 48 and 54 hr recirculations, accompanied with simultaneous or slightly preceding destruction of microtubule-associated protein 2. These results suggest that endonucleases, maybe activated by elevated intracellular Ca2+, play an important role in delayed neuronal death as well as in apoptosis.

Animals↗
PubMed1993

Expression of the D3 dopamine receptor gene and a novel variant transcript generated by alternative splicing in human peripheral blood lymphocytes.

The sequential reverse transcription and polymerase chain reaction amplified the mRNA coding for the D3 dopamine receptor (D3R) in human peripheral blood lymphocytes. Pharmacological analysis confirmed the binding of the D3R specific ligand to the lymphocytes. In addition, there was a novel shorter variant transcript of the D3R gene generated by alternative splicing in lymphocytes and brain. This variant, termed D3(TM4-del), has a 143 bp deletion and encodes a 138 amino acid protein containing the first three transmembrane domains of the native D3R.

Adult↗
PubMed1993

Identity of the dorsal hippocampal region most vulnerable to cerebral ischemia.

Our previous investigations demonstrated that neurons in the area between the subiculum and the medial CA1 region and another area between the lateral CA1 and the CA3 region of the hippocampus are very vulnerable to cerebral ischemia in gerbils, where irreversible damages have been observed occur as early as 4-5 min after unilateral or bilateral common carotid artery occlusion. The present study was aimed to characterize these areas anatomically by using the immunohistochemical and zinc histochemical as well as Golgi silver impregnation methods. Our results indicated that these two areas which are topographically apart on the coronal section actually had a common origin in the rostral part of the hippocampus and that they were separated by insertion of the Ca1 neurons between them in the more caudal part of the hippocampus. The distribution pattern of mossy fibers indicated that these areas belonged to the CA2 region. The double immunohistochemical and zinc histochemical procedure confirmed that these areas developed ischemic lesions promptly even without reperfusion but that the CA1 region did not develop similar lesions until after reperfusion for 12-24 h if the ischemic period was brief. While the reason for the observed susceptibility of the CA2 region is not certain at the present time, it is important to distinguish the ischemic lesions in the CA2 region from those in the CA1 and CA3 regions.

Animals↗
PubMed1993

Immunoelectron microscopic investigation of creatine kinase BB-isoenzyme after cerebral ischemia in gerbils.

Alteration of creatine kinase BB-isoenzyme (CK-BB) was investigated in the vulnerable CA1 region of the hippocampus of ischemic and postischemic gerbil brains using immunoelectron microscopy. CK-BB existed in the neuronal perikarya, dendrites and axons as well as in astroglias in the normal gerbil brain. Immunocytochemical reaction products were associated with microtubules and polyribosomes. Propagation of ischemic and postischemic damage with disintegration of microtubules was observed in the dendro-somatic direction in neurons, which progressed in parallel with dispersion and loss of the immunocytochemical reaction for CK-BB in the dendroplasm. After reperfusion for longer than 24 h, CK-BB was also observed in the extracellular space. The present result supported the notion that loss of the immunohistochemical reaction for CK-BB which has been observed by light microscopy after cerebral ischemia, was at least partly due to dispersion of this enzyme caused by disintegration of microtubules and extracellular leakage of this enzyme, although other processes, including degradation of CK-BB per se, were also possible. The loss of CK-BB from the neuronal structure may delay the recovery from ischemic damage and may eventually lead to neuronal death.

Animals↗
PubMed1993

Nephrosialidosis: ultrastructural and lectin histochemical study.

The neuropathological findings in a Japanese male with nephrosialidosis are reported. Clinically, coarse face, psychomotor retardation, macular cherry-red spot and proteinuria were noted at 1 year and 7 months. He was diagnosed to have nephrosialidosis on the basis of a deficiency of alpha-neuraminidase activity in both lymphocytes and cultured skin fibroblasts, and of severe glomerular and tubular involvement on renal biopsy. He died of multiple organ failure at 8 years and 6 months. There were numerous vacuoles and storage materials in visceral organs, particularly in the glomerular and tubular epithelial cells of the kidney and Kupffer cells as well as hepatocytes in the liver. Neuropathological examination revealed severe neuronal storage in the selected part of the central nervous system: lower motor neurons of the brain stem and spinal anterior horn cells, as well as neurons in the basal nucleus of Meynert. In the peripheral nervous system, sympathetic ganglia were severely affected. There was little or no neuronal storage in the basal ganglia, cerebral cortex or cerebellum, and demyelination was not found. Electron microscopic examination showed fine wavy multilamellar structures in the spinal anterior horn cells or Zebra body-like structures in the neurons of the Meynert's basal nucleus. Lectin histochemistry was positive for wheat germ agglutinin, Ricinus communis agglutinin-1 and peanut agglutinin within distended neurons. We conclude that the neuropathological feature in nephrosialidosis is not specific except for the selectiveness of the anatomical sites of involvement. It shares some aspects found in other types of sialidosis or galactosialidosis.

Brain↗
PubMed1993

Paraneoplastic cerebellar degeneration with a circulating antibody against neurons and non-neuronal cells.

We describe a woman with paraneoplastic cerebellar degeneration associated with para-ovarian adenocarcinoma, who had a circulating antibody with a corresponding antigen not only in cerebellar Purkinje cells but also in neurons located in the molecular layer of the human and rat cerebellum. The antigen was also present in neurons in the cerebral cortex, brain stem, anterior horn cells, dorsal root ganglia, intestinal autonomic neurons, retinal ganglion cells, Schwann cells of the peripheral nerve and epithelial cells of the renal glomerulus in rats. Immunoelectron microscopy revealed immunoprecipitates in the smooth and rough endoplasmic reticulum and polyribosomes in human and rat cerebellar Purkinje cells and other neuronal cell bodies as well as Schwann cells of the peripheral nerve. Even though patients with this disorder manifest primarily with cerebellar and some extracerebellar signs, the antigen also exists in many neurons other than cerebellar Purkinje cells and even in non-neuronal cells. The clinicopathologic significance of the observed immunologic reaction in diverse neurons remains to be determined.

Adenocarcinoma↗
PubMed1993

Fluoride uptake in human dentine from glass-ionomer cement in vivo.

The purpose was to examine F uptake and distribution in dentine from a F-containing glass-ionomer cement in vivo. Nine volunteers were selected from dental students who were scheduled for extraction of their third molars. Two cavities were prepared on the same occlusal surface of the third molars for each subject; one was restored with glass-ionomer cement (Virtabond), the other with zinc phosphate cement as a control. After 3 months the teeth were extracted. F profiles in the dentine from the cavity floor to the pulpal surface were determined in tissue immediately adjacent to the restorations. An abrasive micro-sampling technique was used. The F concentration of the dentine was highest immediately beneath glass-ionomer cement filling, decreasing towards the pulpal surface. Overall F concentrations were greater in the dentine beneath the glass-ionomer cement than in that beneath the zinc phosphate cement. It was concluded that the glass-ionomer cement markedly enhanced fluoride uptake by underlying dentine in vivo.

Adult↗
PubMed1993

Mercury and selenium contents in amyotrophic lateral sclerosis in Hokkaido, the northernmost island of Japan.

We evaluated the pathogenicity of mercury (Hg) and selenium (Se) which are supposed to be one of the risk factors in the development of amyotrophic lateral sclerosis (ALS). Hg and Se contents were measured in plasma, blood cells, scalp hair samples of 21 sporadic ALS patients and 36 controls, who included 19 patients with other neurological diseases, in Hokkaido, the northernmost island of Japan. Hg and Se levels in plasma and blood cells of ALS patients were significantly lower in advanced staged ALS patients than controls. Low Hg and Se contents in ALS, being correlated with their disabilities and nutritional conditions, would rather reflect the disease contracted states than the pathogenic roles in ALS.

Adult↗