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Biomedical subjects

T Nagahori

Publications and source records attributed to T Nagahori.

13 recordsLinked to original sources

Association of pontine small infarction (lacuna) with disturbance of postural stability.

Neuronal degeneration within the brainstem has been reported in patients with impaired postural stability. However, the functional significance of these abnormalities is unknown at present. In the present study, we evaluated the relationship between the presence of pontine lacunae and postural stability measured by stabilometry. A total of 209 consecutive patients without neurological signs were divided into three groups according to the territory of lacunae on magnetic resonance imaging: (1) non-lacunar group, (2) pontine lacunar group, and (3) non-pontine lacunar group. Stabilometry was performed and statokinesigram measures including each Romberg quotient were compared among the three groups. Using multivariate analysis, postural stability was found to be disturbed in the pontine lacunar group compared with the other groups. The data of stabilometry in this group were compatible with disturbance of the central controlling system for keeping postural stability. Pontine lacuna is associated with patients with postural instability. This result may be related to the deterioration of the central coordination system for posture and locomotion.

Adult↗

A profound hemispheric hypoperfusion with relatively small infarcts indicates a progressing stroke.

We determined clinical features of patients who had a profound hemispheric hypoperfusion with relatively small, acute cerebral infarcts. One hundred and thirty-five patients with acute cerebral infarction underwent both magnetic resonance imaging (MRI) and cerebral blood flow (CBF) measurement in the acute phase of stroke. Eleven (8.1%) had a profound hemispheric hypoperfusion with relatively small infarcts. In these patients, magnetic resonance angiography or conventional angiography was performed, demonstrating the internal carotid artery (ICA) stenosis or occlusion on the ipsilateral side of the infarcts. MRI and CBF measurement were repeated one month later. All of 11 patients suffered from a mild consciousness disturbance, and showed a progress of neurological symptoms during a few days, indicative of a progressing stroke. Five patients of 11 concomitantly had atherosclerotic lesions in the arteries distal to the circle of Willis. The remaining six patients had only the ICA lesions. The prognosis of the former was poor and the hemispheric hypoperfusion pattern did not improved. On the other hand, the prognosis of the latter was good and the hemispheric hypoperfusion was recovered soon. In conclusion, if the collateral flow through the circle of Willis could compensate the misery perfusion, the prognosis of low-flow infarctions with ipsilateral ICA lesions might be good.

Acute Disease↗

Interferon-gamma upregulates the c-Met/hepatocyte growth factor receptor expression in alveolar epithelial cells.

In the repair process after lung injury, the regeneration of alveolar epithelial cells plays an important role by covering the damaged alveolar wall and preventing the activated fibroblasts from invading the intra- alveolar spaces. Hepatocyte growth factor (HGF) is a potent mitogen for alveolar epithelial cells and has been reported to be capable of repressing the fibrosing process by connecting to the c-Met/HGF receptor on alveolar epithelial cells. However, it has been reported that the c-Met expression was downregulated in an acute phase of lung injury, which may limit the effect of HGF for therapeutic use. In the present study we observed that interferon (IFN)-gamma upregulates the c-Met messenger RNA (mRNA) and protein expression in A549 alveolar epithelial cells. We analyzed the mechanism of this upregulation and found that IFN-gamma enhances the transcription of the c-met proto-oncogene, and that it does not prolong the stability of the c-Met mRNA. HGF is known to act as a motogen as well as a mitogen for epithelial cells. We also found that the migratory activity of A549 cells induced by HGF is strongly enhanced by preincubation with IFN-gamma. Finally, we administered recombinant IFN-gamma to C57BL/6 mice and confirmed that this upregulation is also observed in vivo. These results suggest that the combination of HGF and IFN-gamma could be a new therapeutic approach for fibrosing pulmonary diseases.

Animals↗

Noninvasive system for evaluating the allergen-specific airway response in a murine model of asthma.

In the present report, we show that the enhanced pause (Penh), a novel indicator of airway responsiveness to bronchoconstrictors, can also be a good marker of airway response to an allergen challenge in a murine model of asthma. Male BALB/c mice were sensitized with ovalbumin (OVA) through a combination of intraperitoneal injection and aerosol inhalation. After this immunization, the OVA-specific IgE titer in serum increased to a significantly higher level than in a saline/PBS-treated control group. After the final OVA aerosol challenge, Penh was repeatedly measured in conscious, unrestrained mice, according to the time schedule. Penh increased gradually after the challenge and reached a maximal value at 24 hours that was significantly higher than the control value (p < 0.01). Histologic examination of the lung revealed airway inflammation with an invasion by eosinophils and lymphocytes from vessels into the peribronchial interstitium and the mucosal and submucosal areas of the bronchus. There was a strong correlation between the Penh value and eosinophil number in bronchoalveolar lavage fluid (r = 0.699, p < 0.0001). Moreover, Penh also correlated strongly with the intensity score of histologic findings. These results suggest that the bronchial response to a specific allergen could be followed in a particular individual through the noninvasive Penh method, and that Penh accurately reflects the intensity of eosinophilic bronchial inflammation. This system would be applicable to a noninvasive, chronological evaluation of various experimental interventions in a murine model of asthma.

Allergens↗

IL-15 promotes cytokine production of human T helper cells.

IL-15 is a newly identified cytokine that has T cell and B cell growth factor activity similar to that of IL-2. In this study, a novel biologic function of IL-15 to promote cytokine production by human Th cells has been elucidated. Dermatophagoides farinae 11 (a major allergen of house dust mite)-specific human T cell clones produced IL-5 in response to recombinant human IL-15 as well as to either anti-CD3 or IL-2 stimulation. IL-5 mRNA became detectable 3 h after IL-15 stimulation and reached a maximum at 9 h. Human IL-5 promoter/enhancer-luciferase gene construct transfected to T cell clones was clearly transcribed in response to IL-15, indicating that the approximately 500-bp human IL-5 promoter/enhancer segment 5' upstream of the coding region sufficiently responded to IL-15. IL-15-induced IL-5 synthesis was completely inhibited by the tyrosine kinase inhibitor, herbimycin A, suggesting the involvement of tyrosine kinases in the signal transduction leading to IL-5 synthesis as well as to proliferation of T cells induced by IL-15. Whereas IL-5 production by human peripheral T cells was abolished by the addition of anti-IL-2-neutralizing Abs into the culture, IL-15 restored the IL-5 synthesis despite effective IL-2 neutralization. IL-15 produced at the site of allergic inflammation may play a role in the recruitment and activation of eosinophils by inducing IL-5 (a Th2 cytokine) production by T cells.

Actins↗

Platelet-activating factor (PAF) and the development of chronic subdural haematoma.

Platelet activating factor (PAF) content and PAF-acetylhydrolase (PAFAH) activity were measured in the plasma and haematoma of 34 chronic subdural haematoma (CSH) patients. The plasma PAF level in patients with CSH was higher than that in healthy controls. Although there was no correlation between the plasma PAF levels and the interval between the onset of symptoms and the day of sampling, namely, the interval after bleeding, the haematoma PAF level gradually decreased according to the interval after the onset of symptoms. There was no difference between plasma PAFAH activity in patients with CSH and that in healthy controls, and haematoma enzyme activity gradually increased correlated with the interval between the onset of symptoms and surgery. In addition, the localization of PAF in haematoma capsules was histochemically determined. PAF was solely localized to the peri-sinusoidal vessels in the outer membrane of haematoma capsules. Based on these biochemical and histochemical studies, we speculated that PAF may play a role in the development of chronic subdural haematomas.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Ischemic brain damage induced by repeated brief occlusions of bilateral common carotid artery in rats.

Two temporary occlusions of the bilateral common carotid artery for 15 min with an interval of 15 min induced severe brain tissue damage in normotensive Wistar rats. Although no lesions were seen after a single 15-min occlusion, severe ischemic lesions were found in 68% (49/72) of the rats injected to two consecutive occlusions for 15 min with an interval of 15 min, and the incidence was significantly higher than that in the rats subjected to a single 30-min occlusion (32%, 6/19) or two 15-min occlusions with an interval of 30 min (11%, 1/9). The local cerebral blood flow (lCBF) in the caudoputamen, however, was decreased by only 40-60% of pre-occlusion level during occlusions. These results suggest that intermittent incomplete disruption of CBF with short intervals could be more hazardous than a continuous interruption of the same duration.

Animals↗

Analysis of plasma and hematoma lipids related to choline glycerophospholipid in patients with chronic subdural hematoma.

The levels of platelet-activating factor (PAF) and lipid metabolites related to choline glycerophospholipid were measured in the plasma and hematoma samples obtained from patients with chronic subdural hematoma. The ratio of lyso-choline glycerophospholipids (lysoPC) to choline glycerophospholipids (PC) in hematoma correlated with the interval between the onset of symptoms and surgery. PC and lysoPC fatty acyl moieties in plasma and hematoma were essentially similar. These results suggest that the lysoPC to PC ratio in hematoma can determine the age of the chronic subdural hematoma, and that the origin of hematoma may be circulating blood. The levels of PAF in the plasma of chronic subdural hematoma patients were significantly greater than in healthy volunteers. PAF may be involved in the enlargement of chronic subdural hematoma.

Aged↗

[Histological study of the outer membrane of chronic subdural hematoma: possible mechanism for expansion of hematoma cavity].

Relationship between the histological features of the outer membrane of chronic subdural hematoma and computed tomography (CT) findings, and the period from trauma to surgery were studied, and the mechanism of hematoma enlargement was discussed. This study included 43 patients aged 16 to 84 years. The outer membranes collected during operation were examined by hematoxylin and eosin staining and elasticavan Gieson staining. Histological features were classified into 4 types according to maturity and intensity of the inflammatory reaction and hemorrhage. Type I: Noninflammatory membrane. This type of membrane was observed in 3 cases. This membrane, containing immature fibroblasts and collagen fibers, was associated with very slight or sparse cell infiltration and neocapillaries. Type II: Inflammatory membrane. This type of membrane was observed in 21 patients. The type, consisting of one layer of immature connective tissue, was associated with marked cell infiltration and vascularization throughout the entire thickness. Type III: Hemorrhagic-inflammatory membrane. This type of membrane was observed in 14 patients. This type had a structure of 2 or 3 layers, and was associated with capillaries with a large lumen on the side of the dura mater and marked cell infiltration and many thin new vessels on the side of the hematoma cavity. Some patients showed a layer consisting of only collagen fibers and fibroblasts between two such layers. In addition, hemorrhage into the membrane was often observed. Type IV: Scar-inflammatory membrane. This type of membrane was observed in 4 patients. This type showed inflammatory cell infiltration, neovascularization and hemorrhage in the outer membrane of cicatricial tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Changes in the cerebral vascular bed in experimental hydrocephalus: an angio-architectural and histological study.

The angio-architectural and histological changes of small cerebral blood vessels in experimental hydrocephalus were studied to assess the changes of the vascular bed in the cerebral mantle. Change of the microvasculature assessed from microcorrosion casts by scanning electron microscopy (SEM) and the histological changes shown by light and electron microscopy were compared before and after shunting for hydrocephalus. The changes of the rCBF were also evaluated by the hydrogen clearance method. In hydrocephalus, a reduction in the number and caliber of the capillaries was noted in both the white and gray matter in the SEM study, but the capillaries were preserved and changes were mild and nonspecific in the electron microscopic examination. Shunting resulted in the reversal of all these changes to normal along with recovery of the rCBF, which had decreased in hydrocephalus. These observations suggest that changes of the vascular bed participate in the alteration of cerebral mantle width in the hydrocephalic process, and that the changes of the microvasculature result not only from damage to the capillaries themselves but also from changes of the perivascular structures.

Animals↗

Forebrain ischemia induced by temporary bilateral common carotid occlusion in normotensive rats.

Ischemic brain lesions were induced in adult Wistar and Fischer rats by temporary occlusion of the bilateral common carotid artery. The severity of ischemic lesions depended on the duration of carotid occlusion. While 2 h occlusion resulted in 15 deaths among 40 rats and the development of ischemic lesions in 16 of 25 asymptomatic survivors, none died after 0.5 h occlusion and yet 13 of 30 apparently asymptomatic rats had ischemic lesions when examined on day 7. Histological examination combined with immunohistochemistry of autologous albumin for assessing the integrity of the blood-brain barrier (BBB) revealed two distinct lesions: (1) ischemic neural damage with extensive tissue permeation of serum albumin, (2) death of individual neurons sparing other neural elements in the absence of the BBB breakdown. Ischemic neural damage with BBB breakdown was common in animals dying within 48 h after reflow. The lesions without BBB breakdown, on the other hand, were found solely in asymptomatic animals in which groups of severely degenerated neurons were preferentially located in the CA 1 region of the hippocampus, the caudoputamen and deeper layers of the neocortex. The sequential measurements of regional cerebral blood flow (rCBF) in the bilateral hippocampus by the hydrogen clearance method disclosed a steady decrease in rCBF after the occlusion, 51% of the pre-occlusion state at 10 min, 35% at 25 min and 32% at 40 min. The simplicity of procedure could make this model suitable for the study of the pathogenesis of ischemic neuronal damage in a critically low perfusion state.

Animals↗

Relation of supersensitivity to cerebral vasospasm induced by oxyhaemoglobin.

There have been reports that superior cervical ganglionectomy (SCG) is effective as a treatment for cerebral vasospasm following subarachnoid haemorrhage (SAH). On the other hand, denervation supersensitivity is supposed to play an important role in vasospasm. The two accounts contradict each other. To investigate this problem, various examinations were performed using the exposed basilar arteries of cats. We have accepted that oxyhaemoglobin (Oxy-Hb) is an important spasmogenic substance. Therefore, the change in vascular reactivity to Oxy-Hb was investigated after various kinds of denervations. It was confirmed that Oxy-Hb has no adrenergic receptor agonist properties because the Oxy-Hb inducing vasospasm was not suppressed by Prazosin or phenoxybenzamine. As a result of this, it is not likely that augmentation of Oxy-Hb inducing vasospasm is caused by deviation supersensitivity. Thus, the non-deviation supersensitivity became a topic of investigation. The basilar arteries were denervated by chemical treatment (reserpine, 6-hydroxydopamine) or bilateral SCG to examine the change in the reactivity to noradrenaline or Oxy-Hb. An increase in reactivity to noradrenaline was observed with the denervations. In contrast, no change in reactivity to Oxy-Hb was found. In conclusion, it was observed that deviation and non-deviation supersensitivity do not participate in vasospasm, in so far as vasospasm is caused by Oxy-Hb.

Animals↗