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Biomedical subjects

H Tomimoto

Publications and source records attributed to H Tomimoto.

At least 73 records · Page 4Linked to original sources
PubMed1994

Distribution of nitric oxide synthase in the human cerebral blood vessels and brain tissues.

The distribution of nitric oxide synthase was investigated in human cerebral blood vessels and brain tissues. NADPH-diaphorase histochemistry, which is a marker for nitric oxide synthase in neurons and endothelial cells, revealed periadventitial nerve fibers in the arteries of the circle of Willis and their cortical branches, as well as the common carotid and subclavian arteries. The fibers were mostly nonvaricose in the periadventitial nerve trunk and were varicose within the adventitia. Patchy reaction products were distributed in the perinuclear region of each endothelial cell. Smooth muscle cells in the tunica media were weakly stained. Staining was particularly intense in regions with atherosclerotic changes, which consist of macrophage infiltration and proliferation of fibroblasts. In the neural parenchyma, two types of NADPH-diaphorase reactive neurons were differentiated. Type I neurons were intensely stained, medium-sized, and bipolar or multipolar. They were distributed in the cerebral cortex and white matter, mostly in the subcortical white matter. Type II neurons were lightly stained, small oval neurons with fine processes and were distributed in the cerebral cortex. Endothelial cells were intensely reactive for NADPH-diaphorase in the arteries, arterioles, and capillaries but weakly in veins. Immunohistochemistry for neural nitric oxide synthase labeled perivascular nerves in the larger arteries and those in the neural parenchyma. Both type I and type II neurons were labeled. Nitric oxide synthase in endothelial cells and the nerve encircling blood vessels further suggests a dual control of cerebral circulation by nitric oxide in human brain.

Aged↗
PubMed1994

Temporal profiles of accumulation of amyloid beta/A4 protein precursor in the gerbil after graded ischemic stress.

The neurons that accumulate beta/A4 amyloid protein precursor (APP) after transient cerebral ischemia were characterized by comparing their distribution with those destined to suffer delayed neuronal death or those with induction of 72-kDa heat-shock protein. With immunohistochemistry of APP in gerbil brains, no alterations were detected after ischemia for 2 min and subsequent reperfusion for up to 7 days, whereas after ischemia for 3 min and reperfusion for 48 h, a small number of neurons, intensely immunoreactive for APP, were found to be scattered in the CA1 subfield of the hippocampus and the layer V/VI of the frontoparietal cortex. After reperfusion for 24 h following ischemia for 5 or 15 min, a large number of densely stained neurons appeared in the subiculum, and CA3 subfield of the hippocampus, and layers III and V/VI of the frontoparietal cortex. The majority of these neurons did not undergo delayed neuronal death after reperfusion for 72 h and thereafter. APP and heat-shock protein were upregulated in the same regions, but mostly in distinct neurons. These results indicate that APP accumulates in the neurons marginating the regions destined to die, and the majority of these neurons seem to survive after ischemic insult.

Amyloid beta-Peptides↗
PubMed1994

[Changes in glial cells in Binswanger-type infarction].

Changes in glial cells were investigated immunohistochemically in the autopsy brains of patients with Binswanger-type infarction and the brains of rats with chronic cerebral hypoperfusion. Activated microglia, which are positive for MHC class II antigen, and GFAP immunoreactive astroglia were 3.1 times and 1.6 times, respectively, more numerous, in Binswanger-type infarction than in normal white matter. Chronic cerebral hypoperfusion after bilateral permanent occlusion of the carotid arteries elicited marked activation of microglia and an increase in astroglia in the medical corpus callosum after 1 day of occlusion, and these findings persisted up to 30 days after the occlusion. A decreased number of transferrin-immunoreactive oligodendroglia and rarefaction of the white matter were noted after 14 days of occlusion. These findings indicate that chronic mild ischemia may lead to rarefaction of the white matter, and that the activation of glial cells, which precedes rarefaction of the white matter, may be involved in the pathogenesis of Binswanger-type infarction.

Aged↗
PubMed1994

[Protective effect of nicardipine hydrochloride on the evolution of delayed neuronal death--an immunohistochemical study].

Alteration of evolution of delayed neuronal death in the gerbil after intraperitoneal injection of nicardipine was investigated by using immunohistochemistry for microtubule associated protein (MAP) which enables early detection of ischemic injuries. Male Mongolian gerbils were subjected to intraperitoneal injection of nicardipine at concentrations of 0.01-10 mg/kg and subsequent occlusion of bilateral carotid arteries for 5 min. Extent of the lesions estimated by immunohistochemistry for MAP was reduced at the dosages of 0.2 mg/kg nicardipine as compared with control, while lesser or larger amounts have failed to protect the brain tissue from ischemic insults. Furthermore, pre- and postoperative treatment of 0.2 mg/kg of nicardipine two times daily succeeded to partially attenuate the development of delayed neuronal death in gerbils which underwent ischemia for 5 min and subsequent reperfusion for 4 days. These results indicate that optimal concentration of nicardipine ameliorates delayed neuronal death, presumably because of the increase of cerebral blood flow and intervention of intracellular influx of calcium ions.

Animals↗
PubMed1993

Astroglial expression of ATL-derived factor, a human thioredoxin homologue, in the gerbil brain after transient global ischemia.

Distribution of adult T cell leukemia derived factor (ADF/TRX), a human thioredoxin homologue, was studied by immunohistochemistry in gerbil brain during reperfusion after transient cerebral ischemia. In control brains, immunoreactivity was observed widely in the central nervous system, including the ependyma, tanycytes, endothelial cells as well as subcommisural organs, and weakly in the neuronal cell bodies. During reperfusion, ADF/TRX was expressed in glial cells in the CA1 and dentate hilus of the hippocampus, and in a few cases in the lateral portion of the caudateputamen. ADF/TRX positive glias first appeared after reperfusion for 24 h, and the intensity of staining peaked at 72 h and diminished after 7 days of reperfusion. They were concentrated around microvessels and identified to be astroglia by double labeling immunohistochemistry with glial fibrillary acidic protein as marker. Immunoblotting analysis demonstrated an increase of ADF/TRX in the postischemic hippocampus. Astroglial expression of ADF/TRX in postischemic injuries suggests a role in neuroprotection by hydrogen peroxide reducing and protein-refolding activities or in modulation of local immune responses.

Animals↗
PubMed1993

Distribution of NADPH-diaphorase in the cerebral blood vessels of rats: a histochemical study.

NADPH-diaphorase (neuronal nitric oxide synthase) activity in the cerebral blood vessels was investigated by light and electron microscopic histochemistry to elucidate the sites of nitric oxide production. Networks of adventitial nerves containing NADPH-diaphorase were distributed in all parts of the circle of Willis. However, NADPH-diaphorase activity in adventitial nerves was much sparser in the region of the posterior cerebral artery, and absent in the pial arteries smaller than 100 microns in diameter. Endothelial cells were intensely stained in arteries and arterioles. These results support the hypothesis that vascular tone is regulated by nitric oxide, which is derived from endothelial cells and adventitial nerves.

Amino Acid Oxidoreductases↗
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

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

T-cell infiltration and expression of MHC class II antigen by macrophages and microglia in a heterogeneous group in leukoencephalopathy.

We report here on T-cell infiltration and diffuse expression of the major histocompatibility complex (MHC) class II antigen in a heterogeneous group of macrophages and microglia in leukoencephalopathy (LE). Microglia reacting positively for HLA-DR were five times more numerous in LE than those in non-LE cases and were distributed densely in the degenerated white matter but sparsely in the subcortical arcuate fibers. CD4- and CD8-positive lymphocytes were 9 and 15 times more plentiful, respectively, in LE cases; they aggregated in the expanded Virchow-Robin spaces and frequently infiltrated the neural parenchyma. An intimate association of T cells with macrophages, and the expression of leukocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1), accessory molecules in antigen presentation, were observed in each cell in the region of macrophage clusters. These results indicate that expression of MHC antigen is accompanied by cell adhesion molecules and by infiltration of T cells in a heterogeneous group in leukoencephalopathy and suggests their immunocompetence, although it may be secondary to destruction of myelin.

Aged↗
PubMed1992

Electron microscopic investigation of the cerebral cortex after cerebral ischemia and reperfusion in the gerbil.

Prompt dendritic damage has been observed in the hippocampus of the gerbil brain after transient cerebral ischemia. In the present study, we studied the frontoparietal cortex of the gerbil brain electron microscopically after brief bilateral carotid occlusion to assess the vulnerability of dendritic processes. After ischemia for 5 min, there was swelling of the periphery of dendrites accompanied by swelling of mitochondria, cytoplasmic vacuolation and disintegration of microtubules in layer I, which spread to layer III after ischemia for 20 min. After reperfusion for 3-24 h following ischemia for 20 min, swelling in the periphery of dendrites and of mitochondria inside receded but vacuole formation and disintegration of microtubules propagated proximally. In neuronal perikarya, polyribosomal disaggregation was observed after ischemia for 20 min and persisted thereafter, while fragmentation of rough endoplasmic reticulum (ER) and microvacuolation occurred after reperfusion for 3 h. Electron-dense clumping of neuronal perikarya was observed after reperfusion for 6 h particularly in layers III and Vb, which increased in number for up to 72 h. The observed progressive damage in dendrites may be common to neurons vulnerable to cerebral ischemia and may significantly contribute to development of delayed neuronal death.

Animals↗
PubMed1992

Regional accumulation of amyloid beta/A4 protein precursor in the gerbil brain following transient cerebral ischemia.

Alterations of beta/A4 amyloid protein precursor (APP) were investigated immunohistochemically in the gerbil brain after transient global ischemia and subsequent reperfusion. Marked accumulation of this protein peaking at 24 h occurred in the neurons of the CA3 and paramedian region of the hippocampus as well as layers III, V and VI of the cerebral cortex. On the contrary, the accumulation was not observed in the neurons of the CA1 region. These results indicate that distribution of APP is altered depending on tissue viabilities after cerebral ischemia.

Amyloid beta-Protein Precursor↗
PubMed1992

Immunoelectron microscopic study of tubulin and microtubule-associated proteins after transient cerebral ischemia in gerbils.

Differential vulnerability of microtubule components to cerebral ischemia has been reported previously. We investigated the disintegration of microtubules using immunoelectron microscopy for alpha-tubulin and microtubule-associated protein 1A and 2 (MAP1A and 2). Mongolian gerbils were subjected to bilateral carotid occlusion for 10 to 30 min and reperfusion for up to 72 h following ischemia for 10 min. After ischemia for 10 min, some dendrites in the stratum moleculare of the subiculum-CA1 region lost immunoreaction products for alpha-tubulin and MAPs. Loss of the reaction products spread to the medial CA1 region during progressive ischemia for 30 min. In some dendrites, electron-dense precipitates for MAPs were dispersed in the dendritic cytoplasm with little reaction product on microtubules and without alteration of the reaction for alpha-tubulin. After recirculation, loss of electron-dense precipitates for alpha-tubulin and MAPs, as well as disintegration of microtubules, propagated further to the medial CA1 region and to the proximal dendrites. The present study demonstrated prompt disintegration of microtubules with rapid disappearance of the reaction for MAPs which seemed to be caused by detachment of MAPs from the microtubule cores.

Animals↗
PubMed1989

[Xeroderma pigmentosum presenting clinical features of spinocerebellar degeneration].

A case of group D xeroderma pigmentosum is reported. This 26-year-old woman was normal delivery, and showed a normal psychomotor development. Her parents noted a patchy brownish pigmentation on her limbs, face and trunk soon after the birth. Gait disturbance appeared at 17 years old and progressed over 9 years. Neurological examination disclosed a severe loss of deep sensation, spastic weakness and mild cerebellar ataxia. Slight involvement of peripheral nerves was revealed by the elecrophysiological investigations. CT and MRI brain scans showed a cerebellar atrophy, however no atrophy was seen in the cerebrum. Adrenocortical hypo-function was noted by decreased 17 KS and 17 OHCS. Unscheduled DNA synthesis of the patient's skin fibroblast was 45% of normal controls, and the result was consistent with group D xeroderma pigmentosum. The neurological findings of this patient are well characterized by the degeneration of the posterior and lateral column of the spinal cord, cerebellum and peripheral nerves. We discussed symptomatological and etiological similarities of the present case to spinocerebellar degeneration. It may be necessary to consider the possibility of xeroderma pigmentosum in the differential diagnosis of spinocerebellar degeneration.

Adult↗
PubMed1988

[Report of a case of Kearns-Sayre syndrome associating with Isaacs-Mertens syndrome].

The patient is a woman who was born in 1936. Her father died of a valvular heart disease and her mother died of apoplexy. She was healthy until 1976 when she noticed stiffness of extremities and so she came to our hospital. At this time, her symptoms disappeared without any specific therapy. In 1979, she entered this hospital because of generalized edema. She was diagnosed as heart failure and treated effectively with frusemide. In 1982, stiffness and gait disturbance aggravated and entered the hospital. At this hospitalization, she was diagnosed as Kearns-Sayre syndrome. After the discharge, she was followed periodically. In May 1983, it was found that she could not abduct and spinate her thumbs. This abnormal hand posture was seen constantly thereafter although the severity of it varied. In April 1985, she was admitted to this hospital because of vomiting and the aggravation of the stiffness. EMG study disclosed spontaneous continuous motor unit discharges. F wave was exaggerated in both frequency and amplitude. The spontaneous activity of the thenar muscle was reduced by blocking the median nerve at the wrist. The patient was administered 250 mg of carbamazepine. Abnormalities of hand posture and EMG were markedly ameliorated by the regimen. We considered that the patient was a rare case of Kearns-Sayre syndrome which was complicated by a syndrome of continuous muscle fiber activity (Isaacs-Mertens syndrome). We speculated that disorders of energy metabolism of motor neurons and inter neurons in the spinal cord might causally relate to spontaneous neuronal discharges.(ABSTRACT TRUNCATED AT 250 WORDS)

Carbamazepine↗
PubMed1987

Descending projections of the basal forebrain in the rat demonstrated by the anterograde neural tracer Phaseolus vulgaris leucoagglutinin (PHA-L).

Descending pathways from the mediobasal forebrain were studied in the rat by injecting anterograde axonal tracer Phaseolus vulgaris leucoagglutinin into the substantia innominata and diagonal band of Broca. From both areas, positive fibers which varied in density were observed in the mediodorsal and ventral parts of the ventroposterior and ventromedial thalamic nuclei, the lateral habenula, the stria medullaris, the lateral hypothalamus and the ventral tegmental area. This descending complex appeared predominantly course through the medial forebrain bundle from which positive fibers ramified into the fasciculus thalamicus to distribute in the thalamic nuclei. A minor descending pathway through the stria medullaris was also noted which terminated in the lateral habenula and the mediodorsal thalamic nucleus. An obvious difference in terminal distribution in the medial habenula, mediodorsal thalamic nucleus and pons could be observed following substantia innominata or diagonal band injection.

Animals↗
PubMed1987

Transplantation of cultured human spinal cord cells into the rat motor cortex: use of Phaseolus vulgaris leucoagglutinin as a cell marker.

Successful transplantations have been made of cultured explants of human fetal spinal cord into surgically created cavities in the motor cortical area of non-immunosuppressed young adult rats. The cultured cells were marked by brief incubation with Phaseolus vulgaris leucoagglutinin (PHA) just prior to transplantation. Following sacrifice of the rats 1.5 months later, PHA immunohistochemistry clearly outlined the demarcation zone of the explants. The transplanted neurons possessed long, somewhat tortuous fibers with occasional varicosities, as well as some thick processes. These findings extend our previous studies in which it was shown that cultured human fetal adrenal medulla and sympathetic ganglia cells could be successfully transplanted to non-immunosuppressed rat brain. They also suggest that PHA may be a valuable marker for transplanted cells at least for 1.5 months post-transplantation.

Culture Techniques↗