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Biomedical subjects

Y Hashizume

Publications and source records attributed to Y Hashizume.

At least 109 records · Page 6Linked to original sources

Adhesive substrates influence acid-productive activities of cultured rabbit osteoclasts: cultured osteoclasts with large vacuoles have enhanced acid-productive activities.

Since acid secretion of polarized osteoclasts on the bone surface has an important role in bone resorption, we examined the acid-productive activities of osteoclasts by measuring the pH of acidic organelles such as endosomes, lysosomes, and vacuoles in cultured rabbit osteoclasts with FITC-dextran as a fluorescent pH probe. The average pH value of acidic organelles of osteoclasts cultured on plain glass coverslips was 5.3 +/- 0.2. The pH of the acidic organelles correlated well with the size and amount of the vacuoles in the cells. Using this FITC-dextran method, we also examined the effects of adhesive substrates, such as type I collagen, vitronectin, and dentine, on the acid-productive activities of osteoclasts and found that the pH value of acidic organelles of osteoclasts cultured on dentine slices was significantly lower than that of osteoclasts cultured on plain glass coverslips. Likewise, in the case of the osteoclasts cultured on type I collagen- or vitronectin-coated glass coverslips, the pH values of acidic organelles were slightly lower and the proportion of osteoclasts having large vacuoles was increased compared with the cells cultured on the plain glass coverslips. These results indicate that osteoclasts containing large vacuoles have high acid-productive activities, and adhesive substrates such as type I collagen and vitronectin influence the formation of large vacuoles in cultured osteoclasts.

Acids↗

Clinical and neuropathological features of a neurodegenerative disorder in the central nervous system with progressive head drooping (Kubisagari).

The clinical and neuropathological features of a case of a neurodegenerative disorder with pronounced and progressive head drooping, in Japanese Kubisagari, are reported. This female patient died at the age of 72 years after an approximately 20-year history of peculiar posture with progressive head drooping (Kubisagari) and lordosis (bowed posture), parkinsonism, dysphonia and slight muscle wasting of the face, tongue, neck, and distal portions of the upper extremities. She did not display mental deterioration until the terminal stage of the illness. A simple macroscopic inspection formalin-fixed sections of the central nervous system (CNS) showed prominent atrophic frontal and temporal lobes, brownish discoloration of the putamen and an atrophic pyramidal tract. Light microscopy revealed severe neuron loss with fibrillary gliosis at both the above-mentioned lobes and the putamen. Both the facial and hypoglossal nuclei had almost disappeared. Motor neurons in the spinal cord were moderately to markedly decreased. Neither Bunina nor Lewy bodies, senile plaque, nor Pick's argyrophilic neuronal inclusions were observed, but very occasionally ubiquitin-positive neurons were found in the temporal cortex. In conclusion, the hitherto-unrecognized neuropathological findings in the CNS corresponding to progressive head drooping (Kubisagari) suggest that this is a neurodegenerative disorder of the CNS, possibly an atypical form of amyotrophic lateral sclerosis.

Aged↗

Elevated cerebrospinal fluid levels of manganese superoxide dismutase in bacterial meningitis.

We examined the mechanism of increase of manganese superoxide dismutase (Mn SOD) in the cerebrospinal fluid (CSF) in bacterial meningitis (BM). The elevated levels of Mn SOD in the CSF in BM, measured with an enzyme immunoassay method, were more prominent than those in aseptic meningitis (AM) and encephalitis (EN). In AM and EN Mn SOD levels well correlated with levels of neuron-specific enolase and S-100b protein, which are markers of damages to nervous tissues, but did not with any of them in BM. CSF concentrations of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 alpha (IL-1 alpha) were higher in BM than in AM and EN. From the serial measurements in BM, the peak values of these cytokines chronologically preceded or corresponded to those of Mn SOD. Immunohistochemically, a large number of the glial cells were stained for Mn SOD in the cerebral cortex from a patient with BM. By contrast, in the normal cerebral cortex, the glial cells were negative for Mn SOD staining. These results suggest that the marked increase of Mn SOD in the CSF in BM may be related to the increase of such cytokines as TNF-alpha and IL-1 alpha and that these cytokines may play a role in the induction of Mn SOD in nervous tissues.

Adolescent↗

Clinical, neurophysiologic, and neuropathological features of an infant with brain damage of total asphyxia type (Myers).

An infant who demonstrated clinical features compatible with total asphyxia is reported. Immediately after birth, the patient manifested severe hypotonia and total absence of cranial nerve functions. Magnetic resonance imaging revealed abnormal intensity of the thalamus and putamen, and atrophy of the brainstem. Late components of brainstem auditory evoked potential were absent, but electroencephalography was normal. Postmortem autopsy revealed destructive lesions of the brainstem tegmentum, thalamus, basal ganglia, and spinal cord, but preserved cerebral cortex; findings consistent with those of total asphyxia as reported by Myers, and attributable to prenatal insult.

Asphyxia Neonatorum↗

Spinal cord morphology and pathology in ossification of the posterior longitudinal ligament.

We analysed nine autopsy cases of ossification of the posterior longitudinal ligament (OPLL) to elucidate the relationship between morphology and pathology of the spinal cord. The cross-sectional shape of the spinal cord at the most severely affected segment was classified into two categories: boomerang (convex lateral surfaces and concave anterior surface) and triangular (angular lateral surfaces and flat anterior surface). In the cases with a boomerang shape, even when the compression was severe, major pathological changes were restricted to the grey matter and the white matter was relatively well preserved. No secondary descending degeneration of the lateral columns was seen, and ascending degeneration of the posterior column was restricted to the fasciculus cuneatus whose fibres were derived from the affected segments. In the cases with a triangular shape, pathological changes were more severe, both white matter and grey matter were involved, and only the anterior columns were free of pathological changes. There were severe pathological changes over more than one segment, and both descending degeneration of the lateral pyramidal tracts and ascending degeneration of the posterior column, including the fasciculus gracilis, were observed. The transverse area of the spinal cord was > 60% of normal in most of the cases with a boomerang shape, but it was reduced to < 60% of normal in more than one segment in the cases with a triangular shape. The compression ratio of the spinal cord (sagittal diameter/transverse diameter x 100%) was not related to pathological changes. In conclusion, a triangular-shaped spinal cord with transverse area of < 60% of normal in more than one segment appeared to be associated with severe and irreversible pathological changes in cases of OPLL.

Adult↗

Effects of acetazolamide on the sleep apnea syndrome and its therapeutic mechanism.

Twenty male patients with sleep apnea syndrome were treated with acetazolamide (AZM), a carbonic anhydrase inhibitor. In 14 of the patient a significant decrease was found in the number of apnea, apnea index and % apnea time (percentage of time spent with apnea to the total sleep time) with improvement in sleep structure, clinical symptoms, such as insomnia, daytime excessive sleepiness and snoring. A significant decrease was also observed in arterial blood pH and HCO-3 in the 14 improved patients. On the other hand, no improvement occurred in the parameters of sleep apnea and sleep with AZM in the remaining six patients. Moreover, metabolic acidosis and an improvement in arterial blood gases did not occur with AZM in the six patients.

Acetazolamide↗

[A 115-year-old woman: the oldest individual in Japan].

The purpose of this study was to assess the background to the longevity of a 115-year-old woman who was the oldest individual in Japan as of September, 1994. The secrets of her social and medical profile appeared to be hereditary factors, well-balanced meals, no smoking or drinking, sufficient sleep and adequate exercise. From the viewpoints of psychological aspects and comprehensive functional assessment of the elderly, she clearly has a tenacious personality. Furthermore, she has maintained independence in her activities of daily living, and did not suffer from senile dementia until 107 years of age. From the medical standpoint, she has suffered from transient hypertension, but her left ventricle function has remained within the normal echocardiography range and no greatly abnormal values have been observed in blood chemistry tests. She has suffered from pneumonia and urinary tract infection many times since the age of 109, and on these occasions she was promptly admitted to our hospital and received appropriate medical treatment. We consider that this also played an important role in her longevity.

Activities of Daily Living↗

[Neuroimaging and pathology of the spinal cord in compressive cervical myelopathy].

Magnetic resonance imaging (MRI) has enabled us to see the spinal intramedullary pathology as differences in signal intensity. Intramedullary high intensity lesions were observed on T2-weighted MRI in patients with cervical spondylotic myelopathy (20.0%) and ossification of the posterior longitudinal ligament (OPLL) of the cervical spine (25.7%). The frequency of this findings was proportional to the clinical severity of myelopathy and degree of spinal cord compression. The pathophysiological basis of such signal abnormality was presumed to vary from acute edema to chronic myelomalacia. The intramedullary lesion on MRI is considered to be the main site of lesion responsible for the neurological symptom because of a good correlation between the neurological level and high intensity level. We found from nine autopsy cases of OPLL that there are distinct differences in severity and extent of pathological changes between the spinal cord with a boomerang-shaped cross-section and that with a triangular-shaped cross-section. In the boomerang-shaped cases, major pathological changes were restricted to the gray matter and the white matter was relatively well preserved. Secondary wallerian degeneration was restricted to the fasciclus cuneatus the fibers of which were derived from the affected segments. In the cases of a triangular shape, pathological changes were more severe, both white and gray matter were involved. There were severe pathological changes over more than one segment, and both descending degeneration of the lateral pyramidal tracts and ascending degeneration of the posterior column, including the fasciclus gracilis, were observed. In conclusion, it is clinically very important to understand the pathological basis of the compressed spinal cord on neuroimages.

Cervical Vertebrae↗

[An autopsied case of dominantly affecting upper motor neuron with atrophy of the frontal and temporal lobes--with special reference to primary lateral sclerosis].

In this paper, the autopsy findings of a 78-year-old man mimicking primary lateral sclerosis (PLS) are reported. His clinical symptoms were slowly progressive spasticity, pseudobulbar palsy and character change. He died of sepsis 32 months after protracting the disease. The autopsy revealed severe atrophy of the frontal and temporal lobes. The histological findings were severe neuronal loss with gliosis in the precentral gyrus and left temporal lobe tip, loss of Betz cell, prominent demyelination throughout of the corticospinal tract, axonal swelling in the cerebral peduncule, severe degeneration of the amygdala, mild degeneration of the Ammon horn, normal substantia nigra, a few neuronal cells with central chromatolysis in the facial nerve nucleus and very mild neuronal cell loss in the spinal anterior horn. The anterior horn cell only occasionally demonstrated Bunina body by H & E and cystatin-C stainings, as well as, skein-like inclusion by ubiquitin staining. Thus, this is a case of uncommon amyotrophic lateral sclerosis (ALS) dominantly affecting the upper motor neuron including the motor cortex and temporal limbic system. In analysis of nine cases of putative primary lateral sclerosis in the literature, six cases showed loss of Betz cell in the precentral gyrus, and four cases very mild involvement of the lower motor neuron such as central chromatolysis and eosinophilic inclusion body. Degeneration of the limbic system was observed in two cases. We indicated a possible subgroup with concomitant involvement in the motor cortex and temporal lobe in motor neuron disease dominantly affecting the upper motor neuron.

Aged↗

[An autopsy case of gliomatosis cerebri with marked swelling of the spinal cord].

We report a 26-year-old male with diffuse infiltration of neoplastic glial cell to the bilateral hemisphere, basal ganglia, cerebellum, brain stem and markedly swollen spinal cord. Initial complaints were general malaise and disturbance of eye movements. The patient died after 30 months. The characteristics of this case included diffuse severe swelling of the brain stem and spinal cord (from the cervical to thoracic levels) shown on MRI without marked change of the hemispheres, cerebellum or basal ganglia. This is a rare case report of spinal swelling that was visually and radiologically apparent, although at present 11 cases of gliomatosis cerebri with histologically proven invasion to the spinal cord. From these facts, it is thought that this case is important from the aspect of the differential diagnosis of the spinal cord lesions.

Adult↗

[An autopsy case of intravascular malignant lymphomatosis with intracranial lymphomatous mass lesions].

A 50-year-old man was admitted to our hospital, because of weakness in his right leg. On admission, he had generalized hyperreflexia and positive Babinski signs bilaterally. After admission, weakness in his left leg and confusion developed. A cerebrospinal fluid examination revealed increases in cell counts and protein but was negative for malignant cells. Blood chemistry was normal except for elevated LDH. A bone marrow biopsy yielded lymphoma cells. Successive T2-weighted cranial MRI showed a progressively expanding high signal area in the right parieto-occipital lobe. His confusional state improved after chemotherapy; however, two months later another cranial CT showed multiple enhanced mass lesions. The patient died 20 months after the onset of illness. Postmortem examination revealed widespread intravascular aggregates of malignant lymphomatous cells in the cerebrum, lungs and kidney, as well as multiple infarcts without atherosclerosis in the cerebrum. These pathological findings are compatible with those of intravascular malignant lymphomatosis. In addition, extravascularly expanding tumor cells formed multiple nodular lesions in the cerebral hemisphere. An immunohistochemical study showed that the tumor cells were positive for B-cell marker L26. Intracranial lymphomatous mass lesion rarely occurs in cases of intravascular malignant lymphomatosis. In the present case, tumor cells were presumably restricted to intravascular spaces, occluded them and resulted in ischemic lesions in the cerebrum in the early phase, but they expanded extravascularly and developed mass lesions in the terminal stages. In conclusion, intravascular malignant lymphomatosis is considered to be phenotypes of malignant lymphoma. This is the first case of intravascular malignant lymphomatosis associated with intracranial lymphomatous mass lesions in Japan.

Brain↗

[Two siblings of familial amyotrophic lateral sclerosis with multisystemic degeneration characterized by mild involvement of the middle root zone of the posterior column, Clarke's nuclei and spinocerebellar tract].

The aim of this study is to clarify the clinicopathological characteristics of the multisystem degeneration seen in two male siblings with familial amyotrophic lateral sclerosis (FALS). A similar neurological disorder affected their elder sister and paternal uncle, but not their parents. The older brother (case 1) developed muscular weakness at 50 years of age and the younger brother (case 2), at 42 years of age. The duration of illness was 19 months in case 1 and 31 months in case 2. The clinical picture was the common (suspended) form in case 1 and the pseudopolyneuritic form in case 2. Pyramidal tract sign was obscure in both cases and cerebellar sign, sensory disturbance, sphincter disturbance and oculomotor palsy were not observed in either case. Neuropathological examination revealed similar findings in the two cases: 1) marked loss of lower motor neurons in the spinal anterior horn and motor nuclei of the lower brain stem in both cases, with neuronal loss of Onuf's nuclei in case 2; 2) very mild involvement in Clarke's nuclei, the dorsal and ventral spinocerebellar tracts and the middle root zone of the posterior column; 3) relatively well preserved Betz cells in the upper motor cortex with the appearance of a few macrophages, and mild changes in the pyramidal tract of the spinal cord; and 4) mild degenerative changes in the pallidoluysian system and the dentatorubral system. The most characteristic pathological findings common to both cases were the extremely mild involvement of the middle root zone of the posterior column, Clarke's nuclei and spinocerebellar tracts. The pattern of lower motor neuron system degeneration paralleled the development of clinical features. Genetic studies demonstrated no mutations in exons 1, 2 and 4 of Cu/Zn-binding superoxide dismutase gene. We emphasized the existence of mild involvement of middle root zone of posterior column, Clarke's nuclei and spinocerebellar tract in FALS with multisystemic degeneration.

Adult↗

Distribution of neuronal cytoplasmic inclusions in multiple system atrophy.

Neuronal cytoplasmic inclusions (NCIs) were demonstrated by means of silver staining (Gallyas staining) in the central nervous systems of 18 deceased patients with multiple system atrophy (MSA) - 6 with olivopontocerebellar atrophy (OPCA), 6 with striatonigral degeneration (SND) and 6 with Shy-Drager syndrome (SDS). We observed NCIs in the cerebral cortex, putamen, pons, medulla oblongata and spinal cord, and especially in the putamen and pons of all cases with MSA. No NCIs were observed in the cerebellum and midbrain. The findings were common to all 3 subtypes of MSA. NCIs were not present in patients with other neurodegenerative disorders and non-neurological disorders. Our findings indicate that NCIs represent a special neuronal alteration characteristic of MSA and support the theory that OPCA, SND and SDS represent manifestations of a single condition i.e. MSA.

Atrophy↗

[Pathology of intravascular malignant lymphomatosis].

On the basis of six necropsied cases of intravascular malignant lymphomatosis (IML), we elucidated its pathological characteristics. In the brain of IML, multiple softened areas of various size were observed, dominantly in the white matter of the cerebral hemisphere, which showed bilateral distribution with no relation to the supply area of the large vessels and intermingled fresh and old lesions. The spinal cord was one of the most often involved areas in IML, particularly at the lumbosacral segmental level. The origin of the tumor cells, based upon the findings that the tumor cell of all our cases were positive for SL-26, LN1, and LN2, were considered to be B-cell. We speculated that not only the circulatory failure due to the tumor cells which filled the vascular lumen, but also circulatory disturbances due to thrombosis, thickening of the intima and angiitis were significant findings for the necrosis in IML. IML is an important disease as the fourth type of central nervous system involvement due to malignant lymphoma, in addition to primary malignant lymphoma of the brain, meningeal lymphomatosis, compression of the spinal cord caused by extradural metastasis of lymphoma.

Aged↗

Morphometry of the normal cadaveric cervical spinal cord.

STUDY DESIGN: The authors measured the transverse area and diameters of the cadaveric cervical spinal without evidence of nervous system pathology and also investigated factors related to spinal cord size. OBJECTIVES: This study attempted to provide basic data that affords an accurate morphometric analysis of the human cervical spinal cord. SUMMARY OF BACKGROUND DATA: Several postmortem morphometric studies of the spinal cord have been performed, but the measurements are different among the reports, and no authorized standard has been established. METHODS: The authors measured the transverse area and diameters of the C7 segment in 152 cadaveric specimens and investigated the cord size in relation to age, body height, body weight, and brain weight. Of these, 14 cases were selected and their segments from C2 to T1 were measured. RESULTS: There was a considerable individual variation in spinal cord size. The transverse area of the C7 segment varied from 33.3 mm2 to 74.0 mm2 (mean 49.6 +/- 7.4 mm2). The cord size showed a strong correlation with brain weight, and to a lesser degree with age and body height. Although the size of the spinal cord varied from case to case, the relative ratio of the transverse area of each segment to that of the C3 segment was almost the same among the cases examined. CONCLUSIONS: This large variation in cord size should be taken under consideration in morphometric analyses of the spinal cord. When the pathologic cord conditions such as compression or atrophy exist, the normally expected transverse area of the affected segment in each individual is calculable from measurement of a given single normal segment.

Age Factors↗

Age-related changes of the myelinated fibers in the human corticospinal tract: a quantitative analysis.

A quantitative analysis was made of the myelinated fibers in the lateral corticospinal tract (LCST) at the levels of the 6th cervical, 7th thoracic and 4th lumbar spinal segments in 20 patients between 19 and 90 years old, and who died of non-neurological diseases. The diameter frequency histograms of myelinated fibers of LCST showed a bimodal pattern with a sharp peak of the small myelinated fibers and broad slope of the large myelinated fibers. The ratio of small fiber to large fiber densities was significantly higher in the 6th cervical (P < 0.05) and 4th lumbar segments (P < 0.01) than in the 7th thoracic segments. The density of small myelinated fibers was significantly lowered with advancing age (P < 0.05-0.001), while that of large myelinated fibers was not significantly decreased in the aged patients, although it showed a slight age-dependent declining tendency. Age-dependent decline of small fiber density was more prominent in the cervical and lumbar segments. Retraction of the axon-collaterals from large-diameter myelinated fibers, which are abundant in the cervical and lumbar segments, may contribute to the age-related diminution of the small myelinated fibers in the LCST.

Adult↗

An immunohistochemical study of the neuronal expression of manganese superoxide dismutase in sporadic amyotrophic lateral sclerosis.

Neuronal expression of manganese superoxide dismutase (MnSOD) in sporadic amyotrophic lateral sclerosis (sALS) was investigated by an immunohistochemical method. The brains and spinal cords from 11 patients with sALS and 20 normal controls (NCs) were used, and the following four nuclei (three motor nuclei and one autonomic nucleus) were examined: the oculomotor nucleus; the hypoglossal nucleus; the cervical motor nucleus; and Onuf's nucleus. Serial sections were stained by the Klüver-Barrera (KB) method and with human-MnSOD-specific antibodies. We counted the total number of neurons visible after KB staining and the total number of positive neurons after immunostaining. The average total number of neurons after KB staining was similar in sALS patients and NCs in both the oculomotor nucleus and Onuf's nucleus, but the number in the hypoglossal and cervical motor nuclei was significantly lower in sALS. The ratio of MnSOD-positive neurons to total neurons visible after KB staining, calculated as an index of the expression of MnSOD, was significantly higher in the oculomotor nucleus and Onuf's nucleus, and lower in the hypoglossal nucleus in sALS patients than in NCs. In the cervical motor nucleus, the ratio in sALS patients did not differ from that in NCs. These results suggest that production of toxic superoxide radicals might be increased in sALS, and that neurons that successfully induce the expression of sufficient MnSOD can survive the disease process, while those failing to activate adequate expression of the enzyme succumb to the toxic effects of the radicals and die.

Adult↗

Disease-specific patterns of neuronal loss in the spinal ventral horn in amyotrophic lateral sclerosis, multiple system atrophy and X-linked recessive bulbospinal neuronopathy, with special reference to the loss of small neurons in the intermediate zone.

The ventral horn cells of the fourth lumbar segment were morphometrically analysed in six cases of amyotrophic lateral sclerosis (ALS; there common forms and three pseudopolyneuritic forms), six of multiple system atrophy (MSA) with autonomic failure, four of X-linked recessive bulbospinal neuronopathy (X-BSNP), and seven age-matched autopsy cases of non-neurological disorders. In the common form of ALS, large and medium-sized neurons of the medial and lateral nuclei were markedly lost; small neurons in the intermediate zone were slightly diminished but fairly well preserved. In the pseudopolyneuritic form of ALS, marked loss was present in the large and medium-sized neurons, and in the small neurons located in the intermediate zone as well. In the MSA, in contrast to ALS, there was a marked reduction in small neurons in the intermediate zone, and large and medium-sized neurons of the medial and lateral nuclei tended to be preserved. In X-BSNP, large and medium-sized neurons were almost completely lost and small neurons were also markedly depopulated. These findings indicated that the pattern of neuron loss in the ventral horn is distinct among these diseases depending on size, location and function of the ventral horn cell population. These disease-specific patterns of neuron loss suggest a difference in the process of neuronal degeneration of ventral horn cells among the disease examined.

Adult↗