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Biomedical subjects

F Ikuta

Publications and source records attributed to F Ikuta.

At least 145 records · Page 8Linked to original sources

[An autopsy case of progressive supranuclear palsy showing "pure akinesia without rigidity and tremor and with no effect by L-dopa therapy (Imai)"].

Eleven cases of "pure akinesia without rigidity and tremor and with no effect by L-dopa therapy" were first reported by Imai in 1980. Three cases were added by Hayashi and Hayashi (1983). However there have been so far no autopsy cases, remaining the nosological position of this syndrome uncertain. The authors have had an opportunity of observing the third case in the report by Hayashi and Hayashi for 8 years and autopsy was done as well. Case report The patient was a female farmer. On account of postural-reflex troubles, the pulsion phenomenon and feet freezing, which had progressed since the age of 54, she easily tumbled over. Eight years after the beginning of those symptoms, vertical oculomotor palsy, pseudobulbar palsy and dementia were added; she was diagnosed as a progressive supranuclear palsy. Before this diagnosis, her illness was being regarded as "pure akinesia without rigidity and tremor and with no effect by L-dopa therapy". Neck dystonia was not observed even in the terminal stage. She died at the age of 65. The total clinical course was about 11 years. Pathological observation The brain weighed 1,170 g before fixation. Marked atrophy of the subthalamic nucleus, globus pallidus and pontine tegmentum was observed. The substantia nigra was shown to be severely depigmented. Microscopically, loss of neurons and gliosis were seen in the subthalamic nucleus, globus pallidus, substantia nigra, hypothalamus, superior colliculus, central grey matter, brain stem reticular formation, cerebellar dentate nucleus, etc. The characteristic finding was the appearance of neurofibrillary tangles in these regions.(ABSTRACT TRUNCATED AT 250 WORDS)

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The chronology of lesion repair in the developing rat brain: biological significance of the pre-existing extracellular space.

We observed the histological peculiarities of the repair process in a destructive lesion of the developing rat brain during neurogenesis. Degeneration was induced selectively in certain cells of the proliferating phase in the rat fetal neopallium on embryonic day 16 by transplacental administration of ethylnitrosourea. Successive elimination of necrotic cells and the restoration process were observed. The repair process was divided into the following steps: elimination of individually affected cells by phagocytes in the pre-existing extracellular space; successive restoration of the disintegrated area by cells which differentiated from remaining matrix cells. No reactive gliosis, fibrosis, abnormal vascularization or infiltration of granulocytes and lymphocytes was observed at any time. The thinned neopallium on postnatal day 21 revealed only a small number and abnormal distribution of the cortical neurons. It may be assumed that the fetal brain owes its unique repair features to the presence of a vast extracellular space under normal conditions. In this pre-existing extracellular space, every kind of cell seems to exist separately without the intracellular adhesions characteristic of the adult brain. When degeneration occurs in certain cells the phagocytes would be able to eliminate the degenerate cells completely in this space without having to break intercellular adhesions. As a result, after the completion of cell elimination, the injured brain is restored to its original state with no cell reaction, giving the appearance of a small brain with normal-looking histological architecture, save only for the sparseness of cells.

Animals↗

Distribution of serotonin-containing cell bodies in the brainstem of the human fetus determined with immunohistochemistry using antiserotonin serum.

The distribution of serotonin (5HT) neurons was investigated in the brainstem of 8 human fetuses ranging in age from 15 to 27 weeks of gestation. We conducted the peroxidase-antiperoxidase (PAP) immunohistochemical technique using antiserotonin serum to detect the cell bodies of 5HT-containing neurons. Positively stained 5HT neurons were clearly demonstrated in the brainstem of all fetuses examined. They varied in shape, showing round to oval cell bodies with unipolar, bipolar, or multipolar processes. A large number of 5HT neurons were located in the midline raphe nuclei. In addition, numerous 5HT neurons were observed widely in the other tegmental areas. The nuclei containing 5HT neurons were listed according to the terminology by Olszewski and Baxter for human brainstem, and an atlas was given. The distribution of 5HT neurons in the raphe nuclei of human fetuses was essentially similar to those of many mammals already reported. However, the lateral extension of 5HT neurons to the other tegmental areas beyond the midline raphe nuclei was much greater in human fetuses compared to other mammals.

Brain Stem↗

Virus-like particles in cultured C3H/St mouse cells treated with a carcinogenic polycyclic hydrocarbon.

Virus-like particles with cylindrical form were found in cultured alveolar macrophages and lung fibroblasts of C3H/St mice, after treating these cells with a carcinogenic polycyclic hydrocarbon, 1, 2, 5, 6,-Dibenzanthracene (DBA). Their morphology looked identical to those observed in vivo in the reactive cells which engulfed DBA crystals implanted into the brain and muscle of the same mouse strain. These particles were not found in either the untreated cells of C3 H/St mice or the treated cells of BALB/c mice. In the alveolar macrophages, these particles appeared first at 3 days after DBA treatment and reached the maximum number around the 30th day. They still kept their morphology in the degenerating cells which had lost the cytoplasmic organelles. These findings suggest the possibility that DBA induced the expression of the viral genome endogeneous to C3H/St cell.

Animals↗

[Topography of the catecholamine neurons in the brain stem of the human fetus: an immunohistochemical study using antibodies to tyrosine hydroxylase].

Immunohistochemistry using antibodies to tyrosine hydroxylase (TH), a rate-limiting enzyme which catalyzes the initial step in the catecholamine synthesizing pathway, has been widely accepted as one of the methods for identification of catecholamine neurons in the nervous system. In the present study, we performed immunohistochemical examination to elucidate the distribution of catecholamine neurons in brain stem of human fetuses. The brain stems were obtained from 8 human fetuses (CRL: 120-275 mm, GA: 15-27 wks) 1-3 h after death following therapeutic or spontaneous abortion. They were immediately fixed with 4% paraformaldehyde in 0.1 M phosphate buffer, pH 7.4, dehydrated with graded ethanol, and embedded in paraffin. Serial 6 microns sections were cut from 7 different levels of the brain stem of each fetus. These sections were stained by peroxidase-antiperoxidase (PAP) technique using TH antisera. The TH antisera used were raised in rabbits by injecting purified TH from bovine adrenal medulla. The preparation and the specificity of TH antisera were described in detail elsewhere (Nakashima et al, 1983). Catecholamine neurons were clearly demonstrated in the brain stem of all fetuses. They could be recognized as catecholamine cell groups in the same manner as is done in experimental mammals. Among these cell groups, the catecholamine neurons showed distinct cytological features in shape and size. The distribution of catecholamine positive neurons in the brain stem was almost the same in the 8 human fetuses, and an atlas was given with anatomical explanation under the terminology of Olszewski and Baxter (1982) for the human brain stem. In the mesencephalon, a large number of catecholamine neurons lay in the nucleus substantiae nigrae, pars compacta, the nucleus paranigralis, the middle of the ventral tegmentum and the tractus tegmentalis centralis, and fewer catecholamine neurons were scattered in the other tegmental area. In addition, a group of small catecholamine neurons was located in the griseum centrale mesencephali near the aqueduct. In the pons, catecholamine neurons occurred mainly in the nucleus locus coeruleus and the nucleus subcoeruleus. A band of TH-positive neurons extended from the nucleus locus coeruleus to the dorsolateral tegmentum, and further to the roof of the fourth ventricle. Occasional catecholamine neurons were present in the area medial to the upper portion of the nucleus locus coeruleus. More caudally, a small number of catecholamine neurons were scattered in the area medial to the nervus facialis and adjacent to the nucleus facialis and the nucleus olivaris superior.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic Fibers↗

Specialised contacts of endoneurial fibroblasts with macrophages in wallerian degeneration.

Wallerian degeneration was induced by crushing the mouse phrenic nerve at the neck. During a chronological study, a specialised cell contact was often observed between the activated endoneurial fibroblast and the macrophage at the period when the removal of myelin debris by macrophages was prominent in the endoneurium. The specialised contact was characterised by paired subplasmalemmal linear condensations with a relatively constant thickness and varied length. It was sometimes asymmetrical. In these specialised cell membrane areas the intercellular space was filled with fine granular material showing a midline denser stratum. Coated vesicles were occasionally found in association with the subplasmalemmal densities. The specialised contacts with these features are quite different from any type of previously described cell contact between fibroblasts but are morphologically identical to those reported between cells of the mononuclear phagocytotic system. The significance of specialised contacts between the fibroblasts and macrophages in Wallerian degeneration is discussed.

Animals↗

Ultrastructural alterations of perineurial cells in the early stage of Wallerian degeneration.

Ultrastructural changes of the perineurium in the distal segment of the mouse phrenic nerve after crush were studied at various intervals of up to 56 days. In the control, the perineurium of the phrenic nerves was composed of multilayered perineurial cells joined together by tight junctions forming concentric laminae surrounding the endoneurium which mainly contained myelinated fibers with a relatively small amount of unmyelinated fibers. In the experiment, perineurial cells showed prominent morphological changes from day 3 to day 6 with the presence of proteinaceous exudate between the cellular laminae of the perineurium. Some of the perineurial cells appeared hypertrophic and often showed mitotic figures. Newly formed gaps between the perineurial cells forming the same lamina as well as between those of adjacent laminae were frequently observed. Intracellular microcavities in the perineurial cells associated with increased pinocytotic vesicles were also observed. In addition, debris-free macrophages were occasionally seen in the perineurium. At this stage, axonal degeneration, myelin breakdown and interstitial proteinaceous exudate, which were already noticed on day 2, were evident in the endoneurium, demonstrating the early stage of Wallerian degeneration. From day 7 on, however, mitotic figures of perineurial cells were not encountered. Perineurial cells of inner laminae contained lipid droplets which increased in number with time. Our observations strongly suggest that perineurial cells play an important role in the early stage of Wallerian degeneration of the peripheral nerve.

Animals↗

Appearance and distribution of fetal brain macrophages in mice. Immunohistochemical study with a monoclonal antibody.

A study on the localization of fetal and neonatal brain macrophages of mice from embryonic day 10 (E10) to postnatal day 21 (P21) was carried out immunohistochemically using a monoclonal antibody against a macrophage differentiation antigen (Mac-1) and the labeled avidin-biotin technique. In the central nervous system, the macrophages recognized first were mainly located in the choroid plexuses of the fourth and lateral ventricles at E14. Their number increased at E17-P3 and gradually decreased thereafter. In the cerebral parenchyma, a few macrophages appeared at E14 in the matrix cell layer. They were also detected in the migrating zone at E15, E17 and in the cortical plate at E19. Mapping of positive cells at the stage of neuroblast formation (E15, E17, E19) disclosed the precise distribution of cerebral macrophages. The macrophages that appeared first in the choroid plexuses at E15 may be derived from the subarachnoid vessels, which extend into the stroma of the choroid plexuses when the matrix cell layer invaginates into the lateral ventricle to form the choroid plexuses. Almost all of the macrophages recognized in the cerebral parenchyma disappeared at P9 when the cytoarchitecture seemed to be completed. In the cerebellum, which develops later than the cerebrum, macrophages appeared after birth and were located mainly in the internal granular layer. The brain macrophages always appeared in the regions where cell proliferation and brain remodeling are most active at each stage. These findings suggest that fetal and neonatal brain macrophages may play an important role in scavenging degenerated cells and cell debris during histogenesis of the central nervous system.

Animals↗

Computed tomographic and histopathological studies of pontine glioma.

Correlative study of computed tomography (CT) and pathologic findings was performed in eight cases of pontine glioma. All patients except one had chemotherapy and radiotherapy, with no surgical intervention. On initial CT scans, all patients had hypodense lesions in part or the whole of the pons, and there was evidence of mass effect. Four of eight cases showed contrast enhancement. After chemotherapy and radiotherapy, swelling of the pons and the width of the hypodense areas decreased. The hypodense areas sometimes became isodense in correlation with clinical amelioration. After several months of remission in responding cases, ring-enhanced lesions reappeared at the primary site, together with recurrent neurological signs. Pathological study postmortem was focused on the histological counterparts of the CT findings of central and perifocal hypodense areas and contrast enhancement. In six of seven treated cases, the central hypodense area surrounded by ring enhancement was shown to be coagulation necrosis. Higher cellularity and hypervascularity with glomeruluslike structures of small vessels were generally observed in enhanced areas. The areas diffusely infiltrated by tumor cells, but not enhanced in CT scans, had few abnormal vessels. Tumor cells were seen not only in hypodense areas around the enhanced portion but also in areas far beyond the enhanced portion. Exophytic expansion of tumor was observed in two cases on postmortem examination. One of these was detected by CT scans before death.

Astrocytoma↗

Developmental microvascular architecture of the rat cerebellar cortex.

External and internal microvascular architectures of the developing rat cerebellar cortex, from embryonic day 18 to postnatal day 14 and in adults, were studied using a cerebrovascular casting method for scanning electron-microscopic observation. The external vascularization of the developing cerebellum showed the most significant alteration in vascular morphology at the stage of intensive proliferation of matrix cells in the external granular layer (EGL) from birth to postnatal day 4. It consisted of multiple luminal protrusion of the vessels, septum formation in the lumina, and small, ring-like anastomoses. Moreover, at the end of this stage, these structures of the vessels disappeared and the subarachnoid space was filled with newly-formed microvascular networks. Thereafter, architectural change of the developing pial vessels was mainly accomplished by elongation of each contorted vessel of the network. Concerning internal vascularization, a few vessels connected with the pial vessels were observed in the cerebellar plate forming a loose, simple network in the deeper neural parenchyma before the stage of foliation began. During the period of thickening of the EGL, however, there was no alteration in vascularity of the parenchyma other than the architectural changes proportionate to the newly-formed folia. It was during the synaptogenetic stage in the internal granular layer that the earliest intraneural vascular plexuses were formed. The vascular network in the molecular layer was formed after disappearance of the EGL. These findings suggest that vascular proliferation correlated with EGL-formation pertains to the pial vessels, and not the intraneural ones, which develop after neuronal cell migration in the developing cerebellum has taken place.

Animals↗

On the occurrence of the fenestrated vessels in Wallerian degeneration of the peripheral nerve.

Ultrastructural studies were made on the distal segments of the mouse phrenic nerve after crush injury. In the control, endoneurium contained only unfenestrated capillaries. In the experiment, from day 2 to day 6, endoneurial capillaries occasionally showed fenestrations with the attenuation of its cytoplasm. At this stage, axonal degeneration and myelin breakdown became evident showing early stage of Wallerian degeneration. In addition, detachment of the neighboring endothelial cells concomitant with the invasion of macrophage was also observed. These findings were previously unobserved changes of the endoneurial endothelium in Wallerian degeneration. The significance of the early occurrence of fenestrae was discussed briefly.

Animals↗

Catecholamine neurons with Alzheimer's neurofibrillary changes and alteration of tyrosine hydroxylase. Immunohistochemical investigation of tyrosine hydroxylase.

Immunohistochemistry with antisera against tyrosine hydroxylase was performed on neurons with Alzheimer's neurofibrillary changes in the substantia nigra and locus ceruleus. These specimens were obtained from brains with Alzheimer's disease, Pick's disease, progressive supranuclear palsy, Alzheimer's type parkinsonism, parkinsonism-dementia complex on Guam, and normal aging. Under these neurologic conditions the affected catecholamine neurons with Alzheimer's neurofibrillary changes were stained positively with antisera against tyrosine hydroxylase. The results suggested that in these neurons, Alzheimer's neurofibrillary changes seemed to develop independently before the reduction of tyrosine hydroxylase protein synthesis.

Adult↗

Immunohistochemical study on neuroglia identified by the monoclonal antibody against a macrophage differentiation antigen (Mac-1).

We have studied frozen sections of the developing and adult mouse central nervous system (CNS), with or without cold lesions, by immunohistochemical and histochemical methods. Using a monoclonal antibody against a macrophage differentiation antigen (Mac-1), we have shown that some neuroglia in the white matter of adult mice stained positively. In the developing CNS, with or without cold lesioning, Mac-1-positive glia were not detected. In the normal adult CNS, a small number of glia in the white matter stained faintly. After cold injury, the number of Mac-1-positive glia and their staining intensity increased for several months. Mac-1-positive glia were always negative for glial fibrillary acidic protein (GFA). Their morphology and distribution were similar to those of nucleoside diphosphatase-positive cells. Considering that the phagocytic activity of glia increases after injury to the CNS (Trachtenberg 1983) and that Mac-1 has been reported to be associated with the complement receptor (Beller et al. 1982), Mac-1-positive glia may play a role in phagocytosis in the damaged CNS.

Animals↗

Abnormalities in gangliosides and other lipids of monkey, rabbit and human brains with chronic organic mercury intoxication.

The distribution patterns of gangliosides and other major lipids in the monkey, rabbit and human brains with chronic organic mercury intoxication were examined. Various areas of the monkey brains were tested for alterations in the lipid composition in detail. Phosphatidylethanolamine and phosphatidylcholine slightly decreased, and sphingomyelin increased in all the areas tested of the intoxicated brains. The total ganglioside concentration was elevated in the frontal and basal ganglia gray matter tissues. In the percentage distribution of gangliosides, GD1b, GT1b and GQ1b (B pathway, [19, 20]) increased, while GM2, GM1 and GD1a (A pathway, [19, 20]) decreased. Similar ganglioside pattern changes were observed also in a human brain and in a rabbit brain with chronic organic mercury intoxication. The altered distribution patterns of gangliosides may be attributable to the proliferation of reactive astrocytes due to organic mercury.

Animals↗

Compositional changes in brain lipids, especially cerebroside and gangliosides, of rats treated with methylmercury chloride.

Rats were orally given 4 mg of methylmercury chloride per kg per day up to 14 days, and killed at 4-day or arbitrary intervals. Parietal gray matter and cerebellum were taken for lipid analyses. The ganglioside content increased during the early stage before the manifestation of clinical symptoms. After the onset of clinical signs, the total lipid concentration was elevated, and especially the levels of phosphatidylethanolamine and cerebroside were increased. The ganglioside distribution patterns were also altered in the late stage, showing decreased proportion of GD1a and increased percentages of GD1b and GQ1b.

Animals↗

Tyrosine hydroxylase protein in Lewy bodies of parkinsonian and senile brains.

Immunohistochemistry with the antisera against tyrosine hydroxylase (TH) was performed on the neurons with Lewy bodies (LBs) in the sections at the level of the basal ganglia, midbrain, pons, medulla oblongata and spinal cord. These were obtained from 3 autopsy cases with Parkinson's disease and 2 senile brains without parkinsonism. In catecholamine neurons, stained positively with the antisera to TH, specific immunoreactions were found in the LBs. These specific stainings were accentuated and/or restricted to the peripheral, less dense, zone of the LBs in the neurons of catecholaminergic regions. LBs in the neurons of the innominate substance, raphe nuclei of the brain stem and spinal cord did not stain positively with TH antisera. This suggests that the production of LBs is complicated, but that it is also closely correlated to the biochemical properties of each neuron in the various regions. In catecholamine neurons in which LBs frequently occurred, TH enzyme protein might play an important part in the productions of LBs.

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