Biomedical subjects

F Hazama

Publications and source records attributed to F Hazama.

At least 55 records · Page 3Linked to original sources

PubMed1994

Anticipation in hereditary dentatorubral-pallidoluysian atrophy.

Anticipation refers to the progressively earlier onset and increase in disease severity in successive generations. We studied four families with hereditary dentatorubral-pallidoluysian atrophy (DRPLA), a neurodegenerative disease, and anticipation was present in the mode of inheritance. In subsequent generations DRPLA shows an earlier onset and more severe as well as additional symptoms. Older onset patients suffer from cerebellar ataxia with or without dementia, whereas younger onset patients present as progressive myoclonus epilepsy syndrome, which consists of mental retardation, dementia, and cerebellar ataxia as well as epilepsy and myoclonus. Anticipation with paternal transmission was significantly greater than with maternal transmission.

Adult↗

PubMed1994

Increased basic fibroblast growth factor immunoreactivity in the brain of stroke-prone spontaneously hypertensive rats.

To obtain information about changes of basic fibroblast growth factor (bFGF) in the brain under a chronic hypertensive condition, we immunohistochemically studied the distribution and level of bFGF in the brain of stroke-prone spontaneously hypertensive rats (SHRSPs). The advanced cerebral lesions in SHRSPs demonstrated massive bleeding, cavity formation and diffuse degeneration of the white matter, whereas the early changes were petechiae, edema and massive glial accumulation around fibrin deposition containing necrotized microvessels. In the control normotensive rats, immunoreactivity for bFGF was demonstrated in nerve cells, especially in selective neuronal populations, ependymal cells and epithelial cells of the choroid plexus, while there was almost no reactivity in astrocytes. In SHRSPs, on the other hand, there was marked immunoreactivity in the densely accumulated reactive cells, particularly astrocytes, in and around cerebral cortical lesions. Slightly increased reaction for bFGF was found in the nerve cells around lesions. Astrocytes in the subcortical white matter on both ipsi- and contralateral sides of the cortical lesion also showed immunoreactivity for bFGF. The location of increased bFGF expression in SHRSPs corresponded very well with the site of extravasated plasma fluid demonstrated by anti-fibrinogen antibody. Electron microscopically, bFGF was shown in astrocytes along the rough endoplasmic reticulum, suggesting that the growth factor was produced in the cells and not taken up from the surroundings. These findings indicate the possibility that edema and the simultaneously generated free radicals or some extravasated plasma components express bFGF in astrocytes and probably in nerve cells, and that the thus expressed bFGF plays some role in the sequence of developmental events of hypertensive cerebral lesions.

Animals↗

PubMed1994

Increased expression of phosphotyrosine after axotomy in the dorsal motor nucleus of the vagus nerve and the hypoglossal nucleus.

To investigate the role of tyrosine kinase underlying glial cell proliferation after axotomy, the localization of phosphotyrosine was studied immunohistochemically in the dorsal motor nucleus of the vagus nerve and the hypoglossal nucleus after nerve transection in adult rats. An anti-phosphotyrosine antibody weakly stained the cytoplasm of the neurons and some glial cells on the control side of both nuclei, while preferentially staining the plasma membrane of perineuronal microglial cells and neurons weakly on the severed side 2 days after axotomy and intensely between 3 and 7 days. Some of the microglial cells reacted positively with both anti-bromodeoxyuridine and anti-phosphotyrosine antibodies, suggesting that tyrosine kinase is involved in microglial cell proliferation. Proliferation of numerous microglial cells was observed in the severed nuclei between 2 and 4 days after axotomy, while only a few were detected on days 5 and 7. These findings suggest that tyrosine kinase is involved in not only the proliferation of perineuronal microglial cells but also in some retrograde neuronal reactions such as differentiation and regeneration.

Animals↗

PubMed1994

Ischemia induces the expression of the platelet-derived growth factor-B chain in neurons and brain macrophages in vivo.

To elucidate the role of the platelet-derived growth factor (PDGF)-B chain in the brain, we examined its expression in rat brains with focal ischemia. Focal ischemia was induced by permanent tandem occlusion of the middle cerebral and common carotid arteries in spontaneously hypertensive rats (SHRs). Northern analysis demonstrated that ischemia transiently increased mRNA expression of the PDGF-B chain, but not the PDGF-A chain, in the injured neocortex. The larger transcript (3.5 kb) of the B chain gradually increased to threefold by 16 h, whereas the smaller transcript (2.6 kb) of the B chain markedly increased sixfold by 4 h. Immunohistochemistry revealed enhanced immunoreactivity in the neurons in the infarct and in the periinfarct area from 16 h to days 4-7, with a peak at 24 h. Furthermore, the brain macrophages that accumulated in the infarct showed intense immunostaining in their perinuclear region from days 2 to 14, with a peak at days 5-6. The present study demonstrates that ischemia induces the expression of the PDGF-B chain, first in neurons and later in brain macrophages, and suggests an important role of the PDGF-B chain in the healing process of the injured brain.

Animals↗

PubMed1993

Different stability of neurofilaments for trypsin treatment after axotomy in the dorsal motor nucleus of the vagal nerve and the hypoglossal nucleus.

In an attempt to obtain information about changes of neurofilaments in motor neurons after axotomy, we immuno-histochemically investigated the accumulated neurofilaments in the dorsal motor nucleus of the vagal nerve, which shows nerve cell loss and degenerative changes after axotomy, and in the hypoglossal nucleus, which shows regenerative changes. Affected neurons in the hypoglossal nucleus showed intensified immunoreactivities for neurofilament antibodies phosphorylated at the carboxy-terminal, and these reactions disappeared with trypsin treatment. Accumulated neurofilaments in the neuronal perikarya in the dorsal motor nucleus of the vagal nerve and axons in brain stem also showed intensified immunoreactivities for the same antibodies, and these reactions remained positive after trypsin treatment. Anti-ubiquitin antibody preferentially stained accumulated neurofilaments in the affected vagal neurons, while no reaction was found in the affected hypoglossal neurons. Phosphorylated neurofilaments in hypoglossal neurons are vulnerable to trypsin treatment probably because of the blocking of polymerization or the disassembly of neurofilaments due to amino-terminal phosphorylation. In vagal neurons, the deteriorated amino-terminal phosphorylation or hyperphosphorylation at the carboxy-terminal seems to cause the cross-linkage and polymerization of neurofilaments, and densely packed polymerized neurofilaments probably fail in axonal transport resulting in nerve cell degeneration and death in the dorsal motor nucleus.

Animals↗

PubMed1993

Pallidonigroluysian degeneration with iron deposition: a study of three autopsy cases.

In the basal ganglia of three autopsy cases of pallidonigroluysian degeneration, we found marked iron deposition, a finding which has not been mentioned previously in the literature. Besides severe astrogliosis and neuronal loss in the pallidum, Luysian body and nigra, granular deposits of brown pigments were found in the neuropil, microglias, oligodendrocytes and astrocytes in three such the nuclei and the striatum. These brown pigments proved histochemically to be iron. Our histochemical semiquantitative study showed a significantly stronger reaction for iron in the degenerated nuclei in these three cases than in control cases comprising non-degenerative and the other degenerative diseases. Quantitative study with inductively coupled emission spectrometry also demonstrated a markedly higher iron content in the globus pallidus and the striatum in comparison with the control cases. The possibility is discussed that iron deposition plays a role in generating the lesions of pallidonigroluysian degeneration.

Adult↗

PubMed1993

The possible role of lysosomal enzymes in the pathogenesis of hypertensive cerebral lesions in spontaneously hypertensive rats.

In an attempt to clarify the role of lysosomal enzymes in the developmental mechanisms of cerebral lesions under chronic hypertensive conditions, we biochemically investigated the activities of acid phosphatase (AcPase), N-acetyl beta-glucosaminidase (NAGase) and cathepsin B (CathB) in the cerebral cortex and subcortical white matter in stroke-prone spontaneously hypertensive rats (SHRSPs). We also investigated enzyme-histochemically the activities of AcPase and NAGase, and immunohistochemically the distribution of CathB. The activities of all enzymes tended to increase with advancing age. The enzyme activities in the aged SHRSPs were in general higher than those in normotensive rats, the differences being significant at 24 weeks of age. Histochemical investigation showed that SHRSPs had an increased number of cells with positive reaction to these enzymes in the edematous cortex with and without vascular changes, and degenerated subcortical white matter. These cells with positive reaction were made up of reactively increased astrocytes and microglia. Neurons in the edematous area also showed slightly intensified enzyme activities. The present studies suggest that chronic hypertension or chronic edema due to hypertension causes increased activities of lysosomal enzymes in the cerebral cortex and subcortical white matter and, thus, that activated lysosomal enzymes may take part in the developmental mechanisms of cystic formation as well as the diffuse degeneration of the white matter.

Acetylglucosaminidase↗

PubMed1993

Degenerative changes in the internal elastic lamina relating to the development of saccular cerebral aneurysms in rats.

In order to investigate the developmental mechanism of saccular cerebral aneurysms, changes in the internal elastic lamina at the junction of the anterior cerebral artery and the olfactory artery were electronmicroscopically studied in 6 control and 6 experimental rats undergoing ligation of the left carotid artery and branches of both renal arteries. In the control group, spontaneous destructive changes occurred on the luminal side of the internal elastic lamina and progressed from the luminal towards the abluminal side as the elastic lamina advanced to the apex. Close to the apex, these changes invaded and disrupted the whole elastic lamina. The elastic lamina was replaced by sparsely lined up lumps of elastic tissue in the walls of early aneurysmal alterations, and was atrophied and disappeared totally in the walls of aneurysmal alterations that had reached an advanced stage. These spontaneous changes were in agreement with reports in the literature and our own previous investigations. From the findings in the experimental rats it becomes likely that the aneurysmal changes in the elastic lamina are exaggerated forms of the normal catabolic metabolism. Therefore its synthesis on the abluminal side no longer balances with the catabolism on the luminal side. It is strongly suggested that aneurysmal alterations progress from the luminal towards the abluminal side of arterial walls and that the lytic process of elastase might play a role in the degenerative changes in aneurysmal development.

Animals↗

PubMed1993

Hypoxic effects on glutamate uptake in cultured glial cells.

Hypoxic effects on glutamate uptake and ATP content in glial cells were investigated by using cultured C6 glioma cells. Mild regressive changes were found depending on the duration of the hypoxic insult, but necrosis or detachment of the cells from the substratum was rarely observed. Glutamate uptake was relatively well preserved after a short hypoxic insult, while a marked decrease in glutamate uptake was observed after hypoxia of long duration. The uptake of sucrose was reduced in a similar pattern to glutamate uptake. Hypoxic insult resulted in a significant reduction of the ATP content in glial cells. Therefore, the decrease in glutamate uptake by glial cells under hypoxia is likely to be due to ATP dependency, and not to the failure of a specific glutamate uptake system, but the failure of a general uptake of the glial cells owing to the energy-dependent membrane dysfunction by ATP depletion. These findings suggest that there are phased changes of astrocytic functions in a hypoxic condition, a preservative phase in the initial stages and then a dysfunctional phase in the later stages of hypoxia.

Adenosine Triphosphate↗

PubMed1992

Alterations in cerebral vessels in experimental animals and their possible relationship to the development of aneurysms.

Aneurysmal changes were studied by light and electron microscopes in experimental monkeys to elucidate their pathogenesis. Early changes were found not at the medial defect but in one branch near the apex. Degeneration of the elastic lamina was always more than that of the media throughout the process of aneurysm formation. Endothelial injury was present even at the bifurcation without a bulge. The present study suggests that aneurysmal changes are initiated by degenerative changes in the endothelium, which are followed by alterations in the underlying elastic lamina and, in turn, in the medial layer.

Animals↗

PubMed1992

Effects of endothelial-cell-derived growth factors on cultured astrocytes.

To clarify the participation of endothelial-cell-derived growth factors (ECDGFs) in astrocytosis, the effects of endothelial-cell-conditioned medium (ECCM) derived either from normotensive rats or spontaneously hypertensive, stroke-prone rats (SHRSPs) on proliferation of C6 cells of an established rat glioma cell line were bioassayed. The ECCM from both strains stimulated proliferation of astrocytes, but the ECCM from SHRSPs showed a higher mitogenic activity for astrocytes than that from normotensive rats. Growth-promoting activity of the ECCM derived from SHRSPs showed an increase that was linear to the conditioning time. These results seem to indicate that endothelial cells produce and release factors that promote the growth of astrocytes. It seems also probable that chronic hypertension causes an increase in production and release of such ECDGFs that correlated with astrocytic proliferation.

Animals↗

PubMed1990

Hypoxia prevents seizures and neuronal damages of the hippocampus induced by kainic acid in rats.

The effects of hypoxia on the epileptic seizures and neuronal damages induced by kainic acid were studied in rats using hypoxic chamber equipment. Rats treated with kainic acid and placed in atmospheric pressure showed typical limbic seizures and regressive neuronal changes in CA3 and CA4 of the hippocampus, while those kept in a hypoxic chamber with 8.5% O2 and 91.5% N2 showed moderate hypoxia and a slight decline of mean arterial blood pressure. In these hypoxic rats, seizures were completely prevented and there was remarkably less regressive neuronal injury of the hippocampus. Thus hypoxia has a rather ameliorative effect on the occurrence of seizures and excitotoxic neuronal injuries induced by kainic acid. The contribution of oxygen radicals and endogenous adenosine to preventing excitotoxic neuronal damages by kainic acid was discussed.

Animals↗

PubMed1990

Increased 5'-nucleotidase activity induced by dibutyryl cyclic AMP treatment of cultured glial cells.

In an attempt to clarify the relationship between ecto-5'-nucleotidase (5'-N) activity and cell differentiation of glial cells, dibutyryl cyclic AMP (dBcAMP), which induces cell differentiation, was administrated to cultured rat glioma cells in logarithmic and confluent phases of cultivation. To evaluate the cellular differentiation, cell morphology and the number of glial fibrillary acidic protein (GFAP) positive cells were examined. Treatment with 1 mM dBcAMP decreased cell proliferation and induced cell differentiation in both the logarithmic and the confluent phases. The number of GFAP-positive cells increased with cellular aging and this tendency was enhanced by dBcAMP administration. Ecto-5'-N activity was higher in dBcAMP treated cells than in non-treated cells in both the logarithmic and the confluent phases. These findings suggest that ecto-5'-N activity of C6 glioma cells is increased by dBcAMP actions and is accompanied by cell differentiation.

5'-Nucleotidase↗

PubMed1990

5'-Nucleotidase activities in sera and liver tissues of viral hepatitis patients.

In order to disclose the mechanisms involving the elevation of serum 5'-nucleotidase (5'-N) activity in viral hepatitis patients, 5'-N activities in sera and liver tissues were examined in acute and chronic hepatitis patients and compared with normal controls. Serum 5'-N activities were 0.714 +/- 0.106 nanomoles adenosine/hour/mg protein in normal individuals, 1.162 +/- 0.479 in acute hepatitis patients, and 0.845 +/- 0.530 in chronic hepatitis patients. Tissue 5'-N activities were 298.8 +/- 86.7 in normal individuals, 598.1 +/- 198.3 in acute hepatitis patients, and 462.2 +/- 91.3 in chronic hepatitis patients. Serum 5'-N activity increased significantly in acute hepatitis patients, but not in chronic hepatitis patients. Tissue 5'-N activity increased in both acute and chronic hepatitis patients. The elevation of 5'-N activity in liver tissue was not an essential factor in the elevation of serum 5'-N levels. Other factors causing the release of 5'-N from liver tissue into the blood stream are thought to be more important. It is suggested that the shedding of plasma membrane with ecto 5'-N activity due to cell damage, or leakage of bile containing high 5'-N activity were causative factors.

5'-Nucleotidase↗

PubMed1990

Angiographic study of induced cerebral aneurysms in primates.

Five cynomolgus monkeys treated with unilateral carotid ligation, renal hypertension, and beta-aminopropionitrile feeding were studied repeatedly by cerebral angiography to clarify the growth process of saccular cerebral aneurysms. Repeated angiography demonstrated saccular cerebral aneurysms in three of five monkeys; two aneurysms were found 15 months and a third 12 months after the operation. At autopsy, one saccular aneurysm was found to be bilocular in shape, and the others were unilocular. Fusiform aneurysms were also observed in four monkeys. Microscopic studies revealed the walls of the saccular aneurysms were very thin and consisted of fibrous tissue. In one aneurysm, the aneurysmal sac was almost obstructed by a well-organized thrombus. No evidence of intramural hemorrhage was found in any of the saccular cerebral aneurysms. The conversion of early aneurysmal changes into saccular aneurysms was found to occur abruptly, and no consistent growth rate was noted. The multiloculation of saccular aneurysms was closely related to the size of an aneurysm. The present study indicates that a saccular cerebral aneurysm may grow abruptly from one of several different kinds of early aneurysmal changes.

Aminopropionitrile↗

PubMed1990

Elastic skeleton of intracranial cerebral aneurysms in rats.

In an attempt to clarify the developmental mechanism of cerebral aneurysms, we studied the elastic skeleton of experimentally induced cerebral aneurysms in rats under scanning electron microscopy after hot formic acid extraction followed by freeze-drying. We produced cerebral aneurysms in 19 rats by unilaterally ligating the common carotid artery, inducing renal hypertension, and feeding beta-aminopropionitrile fumarate. The first noted change was the loss of folds protruding from the internal elastic lamina. Morphologic changes of the internal elastic lamina, considered to be primarily responsible for aneurysmal formation, occurred after the loss or disintegration of the elastic skeleton of first the intima, then the media. In large aneurysms with thick domes, we found proliferation of elastic lamellae that may reduce the risk of rupture. It seems probable that the complex elastic skeleton of the arterial wall may account for the mechanical properties of the artery and that growth of an aneurysm occurs due to disintegration of the elastic skeleton and not simply to rupture of the internal elastic lamina. We believe that such changes in the elastic skeleton are a property of the functional state of the cells that produce elastin.

Animals↗

PubMed1990

Study of the elastic skeleton of intracranial arteries in animal and human vessels by scanning electron microscopy.

We studied the elastic skeleton of major cerebral arteries in rats, monkeys, and one human using scanning electron microscopy after hot formic acid extraction followed by freeze-drying. For comparison, we also examined the thoracic aorta and femoral artery of rats. The cerebral arteries of rats had one distinct internal elastic lamina connected to the thin adventitia with sponge-like medial elastic tissue. This internal elastic lamina had fenestrations, which we found to be less frequent in cerebral arteries than in extracranial arteries, and fold-like protrusions into the lumen. This finding has not been recognized before. Such protrusions were more prominent in cerebral arteries than in extracerebral arteries. At the apical intimal pad, the internal elastic lamina appeared to be continuous, making a honeycomb-like structure. The folds and fenestrations were numerous at the apex. There were no essential differences among species. Our study shows that the internal elastic lamina is not a simple sheet but part of the complicated architecture of the elastic tissue of the vessel wall. These differences in the elastic skeleton, including fenestrations and fold-like structures, in various sites of different arteries may explain the development of various localized vascular diseases.

Animals↗

PubMed1990

Histological and histometrical study of myocardial fibrosis in spontaneously hypertensive rats of the stroke-prone strain.

In order to obtain fundamental information about the developmental mechanisms of myocardial fibrosis in chronic hypertension, the hearts of male spontaneously hypertensive rats of the stroke-prone strain (SHRSP) and Wistar rats of the Kyoto strain (WKY) were histologically and histometrically examined. Fibrosis was a prominent histological feature of the hearts in SHRSP. In consisted of focal, interstitial, and perivascular fibrosis. For histometrical analysis the percentage areas of interstitial and perivascular fibrosis were calculated by using a color image processor. The percentage area of myocardial fibrosis increased with advancing age in both SHRSP and WKY. However, it was significantly higher in SHRSP than in WKY at 18 and 30 weeks of age. In SHRSP perivascular fibrosis of small arteries had already appeared at 8 weeks of age, while perivascular fibrosis of arterioles and interstitial fibrosis developed later. It is supposed that perivascular as well as interstitial fibrosis is induced by the exudation of some growth factors due to an increased vascular permeability. On the other hand, the focal fibrosis observed in old SHRSP is suspected to occur as a result of injury in myocardium due to stenosis or occlusion of vessels.

Animals↗