PubMed Health⌕ Search

Biomedical subjects

Y Hashizume

Publications and source records attributed to Y Hashizume.

At least 19 recordsLinked to original sources
PubMed1999

Age-related morphologic changes of the central canal of the human spinal cord.

To elucidate the role of the human central canal on the physiology and pathogenesis of acquired syringomyelia, we analyzed the age-related morphologic changes in the normal human central canal of the spinal cord. The subjects included 158 autopsy cases ranging in age from 1 week postnatally to 116 years of age. Each segment of the whole spinal cords was investigated from the C3 to S3 levels. The microscopic pictures of the central canal were classified as patent or occluded at each level for each age decade. The patency rate under 1 year of age was 100% in almost all the segments, which markedly decreased in the second decade, and the canals were occluded in all the segments with advancing age. According to the longitudinal pattern of the central canal occlusion, 19 of 20 cases where the canals were patent in all segment levels were less than 10 years of age. Cases in which the canals were occluded in all segment levels appeared in the second decade, and their number increased gradually with advancing age. The occlusion of the central canal started at the T6 and L5 to S2 levels. We suggest that the central canal does not function after infancy because of its occlusion, and that it is not involved in the development of syringomyelia in adult patients.

Adolescent↗
PubMed1999

Multiple system atrophy with remarkable frontal lobe atrophy.

The autopsy findings of a multiple system atrophy (MSA) patient with remarkable frontal lobe atrophy are described. The patient was a 65-year-old woman with a 13-year history of untreatable parkinsonism, dysautonomia and progressive motor aphasia. The brain weight was 810 g, and there was remarkable atrophy of the cerebrum predominantly in the frontal lobe, striatum, pons and cerebellum. Microscopic examination revealed a preserved cortical structure with laminar gliosis in the sixth layer of the precentral and superior frontal gyri of the frontal lobe, and postcentral gyrus and inferior parietal lobule of the parietal lobe. The second layer of the cortices of these regions were also revealed to be in a spongy state, and mild cell loss was seen in the fifth and six layers. The frontal lobe white matter showed a mild loss of myelinated fibers and axons, and mild gliosis. Glial cytoplasmic inclusions (GCIs) were abundantly observed in the deep layer of the cortex in the regions mentioned above, and were more abundant in the white matter of the frontal and parietal lobes, callosal body, and internal, external and extreme capsules. There was severe degeneration in the olivopontocerebellar and striatonigral systems, and GCIs in widespread regions of the brain. No Pick bodies, Lewy bodies, ballooned neurons, senile plaques, or significant amounts of neurofibrillary tangles were detected. There were no vascular changes. Thus, this was a verified MSA patient with progressive aphasia and remarkable frontal lobe atrophy. We indicate a possible involvement of the cerebral lobes in MSA.

Aged↗
PubMed1999

Pathological changes of the spinal cord in centenarians.

In order to study the changes that occur in the spinal cords of the aged, 19 centenarian spinal cords from two men and 17 women (age range, 100-116 years at death; mean, 103 years) were pathologically examined. Cross-sections at each segmental level of the 19 autopsied spinal cords were examined for histopathological changes. The cross-sectional area and flattening ratio at the level of the C7 segment were measured. The size of the cords had some negative correlation with age, but the individual variation was considerably large. Among the 19 centenarians, macroscopic anteroposterior flattening appeared in the lower cervical cords in six individuals. In these cases, various degrees of neuron loss were observed in the anterior horn. White matter degeneration appeared frequently, especially in the posterior column. In 12 cases, myelin loss in the fasciculus of Goll at the cervical level was observed. The degeneration of the fasciculus of Goll was considered to be upward wallerian degeneration secondary to posterior root damage at the lumbosacral level. These changes seemed to be produced by disorders in the spinal canal or surrounding tissue, such as cervical spondylosis, degeneration of the intervertebral disk and spinal canal stenosis. Argyrophilic structures such as neurofibrillary tangles and neuropil threads were observed in 16 cases; however, this incidence was less than in the brain. Medial thickening of the anterior spinal artery was found in four cords. Amyloidangiopathy was noted in only one cord. Necrosis and hemorrhage due to vascular disturbance were not found.

Aged↗
PubMed1999

Axonal and perikaryal involvement in chronic inflammatory demyelinating polyneuropathy.

OBJECTIVES: To assess the extent of loss of myelinated nerve fibres and spinal motor neuron loss in chronic inflammatory demyelinating polyneuropathy (CIDP), a clinicopathological study was conducted on biopsied sural nerves and necropsied spinal cords from patients with CIDP. METHODS: The myelinated fibre pathology of 71 biopsied sural nerves and motor neuron pathology of nine necropsied spinal cords at L4 levels in patients with CIDP were quantitatively and immunohistochemically assessed. RESULTS: Myelinated nerve fibre density was significantly diminished to 65.4% of the control values (p <0.0001), correlating inversely with the extent of segmental demyelination and remyelination (r = -0.43, p < 0.0005) and duration of illness (r = -0.31, p < 0.01). Numbers of large spinal motor neurons in CIDP were variably but significantly diminished (range from 46.0 to 97.6% of the age matched control value (p < 0.005)), and reactive astrogliosis was evident in the ventral horn in CIDP. The frequency of ventral horn neurons exhibiting central chromatolysis and the accumulation of phosphorylated high molecular weight neurofilament protein was significantly higher in CIDP than in controls (p<0.01 and p<0.05). CONCLUSIONS: The loss of nerve axons and spinal motor neurons is common in CIDP, and extensive in some cases. These neuronal and axonal losses may influence the functional prognosis in CIDP.

Adolescent↗
PubMed1998

Immunohistochemical detection of dityrosine in lipofuscin pigments in the aged human brain.

Lipofuscin is a yellowish brown fluorescent pigment which is sequestered within cytoplasmic granules during aging. To examine the contribution of protein oxidation to lipofuscin accumulation, we performed immunohistochemical detection of dityrosine, which is considered one of the specific markers for protein oxidation, in lipofuscin in the aged human brain using an antibody specific to dityrosine. By characterization using competitive enzyme-linked immunosorbent assay, the specificity of the antibody to dityrosine was confirmed. None of the other tyrosine-related compounds such as L-tyrosine, 3-nitrotyrosine, 3-chlorotyrosine, or 3,4-dihydroxyphenylalanine cross-reacted with the antibody. The anti-dityrosine antibody reacted with lipofuscin granules in the pyramidal neurons of the aged human brain. The results suggest that protein oxidation by free radicals and/or peroxidases may play an important role in lipofuscin accumulation.

Aged↗
PubMed1998

Elevated expression of PDI family proteins during differentiation of mouse F9 teratocarcinoma cells.

We investigated the expression of protein disulfide isomerase family proteins (PDI, ERp61, and ERp72) in mouse F9 teratocarcinoma cells during differentiation induced by treatment with retinoic acid and dibutyryl cAMP. Each member of this family was expressed at a constitutive level in undifferentiated F9 cells. During differentiation of F9 cells to parietal or visceral endodermal cells the protein level of all these enzymes increased, although the extent of this increase in both protein and mRNA levels varied among the enzymes. Certain proteins were found to be coimmunoprecipitated with PDI, ERp61, and ERp72 in the presence of a chemical crosslinker. Type IV collagen was significantly coprecipitated with PDI whereas laminin was equally coprecipitated with the three proteins. Furthermore, 210 kDa protein characteristically coprecipitated with ERp72. Thus, the induction of PDI family proteins during the differentiation of F9 cells and their association with different proteins may implicate specific functions of each member of this family despite the common redox activity capable of catalyzing the disulfide bond formation.

Animals↗
PubMed1998

Nuclear inclusions of the androgen receptor protein in spinal and bulbar muscular atrophy.

Spinal and bulbar muscular atrophy (SBMA) is an X-linked motor neuronopathy caused by the expansion of an unstable CAG repeat in the coding region of the androgen receptor (AR) gene. To study AR protein expression in normal and SBMA individuals, we used several antibodies that recognize AR protein, and analyzed neural and nonneural tissues by immunohistochemistry and western blotting. Both the normal and the mutant AR proteins were widely distributed, predominantly, but not exclusively, in the cytoplasm of neurons regardless of the pathological involvement, and predominantly in the nuclei of the nonneural tissues in both normal and SBMA individuals, with different expression levels of AR protein among different tissues. In the motor neurons of SBMA patients, there were AR-immunoreactive ubiquitinated nuclear inclusions that were detected by antibodies that recognize a small portion of the N terminus of the AR protein. Absence of other immunoreactive AR epitopes within the inclusion may be due to altered AR configuration, or masking of AR epitopes by other proteins, or proteolytic cleavage of the AR. Our data show that, in addition to the normal cellular distribution of the AR protein, mutant AR-bearing nuclear inclusions are present in SBMA.

Aged↗
PubMed1998

Loss of the dentate nucleus neurons is associated with torpedo formation: a morphometric study in progressive supranuclear palsy and dentatorubro-pallidoluysian atrophy.

Cerebellar torpedoes can be induced by direct damage to Purkinje cell axons. This raises the possibility that the loss of dentate nucleus neurons (DNNs) may also cause torpedo formation through synaptic detachment between DNNs and Purkinje cell axon terminals. To investigate this possibility, we conducted a morphometric study with an image analyzer in progressive supranuclear palsy (PSP) and dentatorubro-pallidoluysian atrophy (DRPLA). Using horizontal and sagittal sections of the cerebellar hemispheres containing the greatest proportion of the dentate nucleus, we determined the line densities of torpedoes, Purkinje cells, and DNNs. In PSP and DRPLA, the densities of DNNs were significantly lower, and the densities of torpedoes much greater than in controls, while those of Purkinje cells were normal in both diseases. In addition, the torpedo densities in PSP and DRPLA showed a strong negative correlation with the DNN densities. Thus, this study clearly demonstrated that torpedoes are formed in association with the loss of DNNs, suggesting that they may occur in consequence of synaptic disconnection of Purkinje cells from DNNs.

Adult↗
PubMed1998

Tissue distribution of pathological lesions and Hu antigen expression in paraneoplastic sensory neuronopathy.

We investigated the distribution of lesions and Hu antigen expression in two autopsied cases of anti-Hu antibody-positive paraneoplastic sensory neuronopathy (carcinomatous subacute sensory neuropathy). Pathological changes in both patients were limited to the primary sensory neurons, some of the sympathetic ganglia and hippocampal regions. The lesions showed a multifocal distribution that differed among the spinal segmental levels and in the individual dorsal root ganglia as well as in the nerve fascicles. Western blot analysis of the patients' serum revealed that Hu antigens were extensively and widely expressed throughout the central nervous system, sensory and sympathetic ganglia and cancer cells, but not in the non-neural visceral tissues. Reverse transcriptase-polymerase chain reaction also showed that the Hu D, Hu C, Hel-N1 and Hel-N2 mRNAs were extensively and widely expressed through the neural tissues and cancer cells, but not in the visceral tissues. Thus, the distribution of antigen expression was very different from that of the lesions. Taken together with the distribution of lesions and Hu antigen expression, it is suggested that factors other than anti-Hu antibodies are also involved in the pathogenesis of this neuronopathy.

Adenocarcinoma↗
PubMed1998

Upper motor neuron predominant degeneration with frontal and temporal lobe atrophy.

The autopsy findings of a 78-year-old man mimicking primary lateral sclerosis (PLS) are reported. He showed slowly progressive spasticity, pseudobulbar palsy and character change, and died 32 months after the onset of symptoms. Autopsy revealed severe atrophy of the frontal and temporal lobes, remarkable neuronal loss and gliosis in the precentral gyrus, left temporal lobe pole and amygdala, mild degeneration of the Ammon's horn, degeneration of the corticospinal tract, and very mild involvement of the lower motor neurons. The anterior horn cells only occasionally demonstrated Bunina body by cystatin-C staining, and skein-like inclusions by ubiquitin staining. This is a peculiar case with concomitant involvement in the motor cortex and temporal lobe in motor neuron disease predominantly affecting the upper motor neuron.

Aged↗
PubMed1998

Nonneural nuclear inclusions of androgen receptor protein in spinal and bulbar muscular atrophy.

Spinal and bulbar muscular atrophy is an X-linked motor neuronopathy caused by the expansion of an unstable CAG repeat in the coding region of the androgen receptor (AR) gene. Nuclear inclusions of the mutant AR protein have been shown to occur in the spinal motor neurons of spinal and bulbar muscular atrophy (Li M, Kobayashi Y, Merry D, Tanaka F, Doyu M, Hashizume Y, Fischbeck KH, Sobue G: Nuclear inclusions in spinal and bulbar muscular atrophy. Ann Neurol 1998 (in press)). In this study, we demonstrate the tissue-specific distribution, immunochemical features, and fine structure of nuclear inclusions of spinal and bulbar muscular atrophy. Nuclear inclusions were observed in affected spinal and brainstem motor neurons, but not in other, nonaffected neural tissues. Similar nuclear inclusions occurred in nonneural tissues including scrotal skin, dermis, kidney, heart, and testis, but not in the spleen, liver, and muscle. These inclusions had similar epitope features detectable by antibodies that recognize a small portion of the N-terminus of the AR protein only, and they were ubiquitinated. Electron microscopic immunohistochemistry showed dense aggregates of AR-positive granular material without limiting membrane, both in the neural and nonneural inclusions. These findings indicate that nuclear inclusions of AR protein are present in selected nonneural tissues as well as in neurons that degenerate in spinal and bulbar muscular atrophy, suggesting that a common mechanism underlies in the formation of neural and nonneural nuclear inclusions.

Aged↗
PubMed1998

Modulation of cAMP-mediated vasorelaxation by endothelial nitric oxide and basal cGMP in vascular smooth muscle.

Recent in vitro evidence shows a role of endothelial nitric oxide (NO) in the modulation of isoproterenol-induced vasorelaxation. To elucidate roles of endothelial cells and NO in cyclic adenosine monophosphate (cAMP)-mediated vasodilators we examined the effects of removal of endothelium and a NO synthase (NOS) inhibitor on relaxant responses in vitro of rat aortic strips to beta-adrenoceptor stimulants and colforsin dapropate, a water-soluble forskolin, and changes in cAMP and cyclic guanosine monophosphate (cGMP) contents. Relaxant responses of rat aorta to isoproterenol, denopamine, salbutamol, colforsin, and dibutyryl cAMP (dbcAMP) were blunted by removal of endothelial cells or treatment with NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). Relaxant response of endothelium-intact segments to isoproterenol was associated with increases in tissue cAMP and cGMP contents. Removal of endothelium or treatment with L-NAME markedly reduced basal cGMP and abolished the isoproterenol-induced increase in cGMP but not cAMP content. In endothelium-removed segments, pretreatment with sodium nitroprusside (SNP) restored the diminished relaxant response to isoproterenol and increased basal cGMP (from 0.08 +/- 0.01 to 0.16 +/- 0.02 pmol/mg protein), whereas it did not affect the isoproterenol-induced increase in cAMP. The diminished relaxant response of endothelium-removed segments to dbcAMP was not restored by SNP pretreatment. The results suggest that relaxant response of rat aorta to cAMP-mediated vasodilators is mediated, in part, by NO production in endothelium and subsequent increase in cGMP in vascular smooth-muscle cells.

Adrenergic beta-Agonists↗
PubMed1998

[The classification and mechanism of the hypnotics].

The various hypnotics are currently available. Today benzodiazepine (BZ) derivatives are most used, but non-benzodiazepines (non-BZ), are being used. BZs and non-BZs are classified four groups by means of pharmacokinetics, (1) ultra-rapidly elimination hypnotics, (2) rapidly elimination hypnotics, (3) relatively slow elimination hypnotics and (4) slow elimination hypnotics. BZs modulate gamma-aminobutyric acid (GABA)-ergic transmission, and specific receptors exist in the brain. GABA is the most abundant inhibitory neuro-transmitter in the central nervous system. BZs alter sleep by binding receptor-GABA receptor-chloride channel.

Animals↗
PubMed1998

[Patho-MR imaging study in the putaminal margin in multiple system atrophy].

The slit hyperintensity of the lateral margin of the putamen in T2 weighted MRI is a characteristic finding in those patients with multiple system atrophy (MSA) involving extrapyramidal system. In spite of some speculations such as demyelination, gliosis, iron deposition or increased extracellular fluid, the nature of the abnormal signal intensity has still been remained uncertain. In this paper, we report the coincidental findings of pathology and magnetic resonance imaging of the putaminal margin in a case of MSA. The patient was sixty three years old woman with nine years history of intreatable parkinsonism, mild ataxia and dysautonomia. At six months prior to her death, 0.5T MRI showed the pontocerebellar system atrophy, slit hyperintensity in the bilateral outer margin and left inner margin of the putamen in T2 weighted image as well as linear hypointensity in T1 weighted image. The neuropathological examinations showed severe degeneration in the olivopontocerebellar and striatonigral systems, and glial cytoplasmic inclusion in widespread regions in the brain. The putamen showed severe degeneration with rarefaction. The intertissue space was observed at the outer putaminal margin in both sides and inner margin in left side, which seemed to be caused by severe shrinkage and rarefaction of the putamen. Thus, slit hyperintensity in the putaminal margin in MSA was disclosed to represent widened intertissue space.

Female↗
PubMed1998

[An autopsied case of multiple system atrophy with remarkable cerebral atrophy].

In this paper, we report the pathological findings of a multiple system atrophy (MSA) patient with remarkable frontal lobe atrophy. The patient was a 65-year-old woman with a 13-year history of untreatable parkinsonism, dysautonomia and progressive motor aphasia. The cranial imaging study disclosed progressive atrophy of the frontal lobe, striatum and pontocerebellar system. She died of pneumonia. The brain weight was 810 g, and there was remarkable atrophy of the cerebrum predominantly in the frontal lobe, striatum, pons and cerebellum. The microscopic examination revealed a preserved cortical structure with laminar gliosis in the sixth layer of the precentral and superior frontal gyri of the frontal lobe, and postcentral gyrus and inferior parietal lobule of the parietal lobe. The cortices of these regions also revealed to be in a spongy state in the second layer, and mild cell loss was seen in the fifth and six layers. The frontal lobe white matter showed a slight pallor, a mild loss of myelinated fiber and axon, and mild gliosis. Glial cytoplasmic inclusions (GCIs) were abundantly observed in the deep layer of the cortex in the regions mentioned above, and were more abundant in the white matter of the frontal and parietal lobes, callosal body, and internal, external and extreme capsules. There were severe degenerations in the olivopontocerebellar and striatonigral systems, and GCIs in widespread regions of the brain. We could not detect any Pick bodies, Lewy bodies, ballooned neurons, senile plaques, or any significant amounts of neurofibrillary tangles. There were no vascular changes. Thus, this was a verified MSA patient with progressive aphasia and remarkable frontal lobe atrophy. We indicate a possible involvement of the cerebral lobes in MSA.

Aged↗