Biomedical subjects

S Hirai

Publications and source records attributed to S Hirai.

At least 55 records · Page 3Linked to original sources

PubMed2000

Right frontal areas 6 and 8 are associated with simultanapraxia, a subset of motor impersistence.

The authors examined brain lesions that cause simultanapraxia, a subset of motor impersistence. Simultanapraxia was defined as the inability to perform two motor acts simultaneously: closing the eyes and protruding the tongue. Simultanapraxia was found in 9 (5.6%) of 160 hospitalized patients with cerebrovascular diseases. The lesions were located in areas 6 and 8 in the right middle cerebral artery territory. This site was spared in five patients who did not show simultanapraxia, even with a large infarction in the right middle cerebral artery area.

Apraxias↗

PubMed2000

Age-related amyloid beta protein accumulation induces cellular death and macrophage activation in transgenic mice.

In view of the importance of amyloid beta protein accumulation in Alzheimer's disease, this paper examines age-related amyloid beta protein (Abeta) deposition and accompanying cellular changes in a mouse model in vivo. Transgenic mice were studied which expressed a gene encoding 18 residues of signal peptide and 99 residues of the carboxyl-terminal fragment (CTF) of the Abeta precursor, under the control of the cytomegalovirus enhancer/chicken beta-actin promoter. In the pancreas, Abeta accumulated in an age-dependent manner. Abeta deposits appeared as early as 3 weeks of age and increased in size and number from 4 to 16 months of age. The largest Abeta deposits were observed in the transgenic pancreas at 16 and 20 months of age. Haematoxylin and eosin staining, macrophage immunostaining, and electron microscopy showed that the Abeta fibril deposits closely correlated with degeneration of pancreatic acinar cells and macrophage activation. Abeta1-42 and Abetap3E-42 were predominant components of Abeta deposits among amino- and carboxyl-terminal modified Abeta species. These findings suggest that overproduction of Abeta causes age-related accumulation of Abeta fibrils, with accompanying cellular degeneration and macrophage activation in vivo.

Aging↗

PubMed2000

Ataxin-3 is translocated into the nucleus for the formation of intranuclear inclusions in normal and Machado-Joseph disease brains.

Machado-Joseph disease (MJD)/spinocerebellar ataxia type 3 (SCA3) is one of the dominantly inherited cerebellar ataxias. The gene responsible for the disease, a novel gene of unknown function, encodes ataxin-3 containing a polyglutamine stretch. Although it has been known that ataxin-3 is incorporated into neuronal intranuclear inclusions (NIIs) in neurons of affected regions, the relationship between NII formation and neuronal degeneration still remains uncertain. In the present study we show two different conditions in which ataxin-3 is recruited into the nucleus and suggest a process to form nuclear inclusions. In normal brains, wild-type ataxin-3 localizes within the ubiquitin-positive nuclear inclusion, the Marinesco body, indicating that ataxin-3 is recruited into the nuclear inclusion even in the absence of pathologically expanded polyglutamine. In MJD/SCA3 brains, immunohistochemical analyses with anti-ataxin-3 antibody, anti-ubiquitin antibody, and monoclonal antibody 1C2 known to recognize expanded polyglutamine revealed differences in frequency and in diameter among NIIs recognized by each antibody. These results were confirmed in the same inclusions by double immunofluorescent staining, suggesting that expanded ataxin-3 forms a core, thereby recruiting wild-type ataxin-3 into the nucleus around the core portion, and then followed by activation of the ubiquitin/ATP-dependent pathway. Recruitment of ataxin-3 into the nucleus and formation of nuclear inclusion under two different conditions suggest that ataxin-3 may be translocated into the nucleus under certain conditions stressful on neuronal cells such as aging and polyglutamine neurotoxicity.

Ataxin-3↗

PubMed2000

Autonomic dysfunction in Machado-Joseph disease assessed by iodine123-labeled metaiodobenzylguanidine myocardial scintigraphy.

Iodine123-labeled metaiodobenzylguanidine, a radioiodinated analogue of norepinephrine, is a tracer for evaluating sympathetic function. We used iodine123-labeled metaiodobenzylguanidine myocardial scintigraphy and sympathetic skin response to study autonomic nervous functions in 19 patients with Machado-Joseph disease (MJD) and 20 control subjects. Planar imaging of all the participants was done to evaluate myocardial scintigraphy. The ratio of average counts in the heart to average counts in the mediastinum was calculated for both early and delayed images, the latter of which reflects the cardiac neural uptake of the tracer. Single photon emission computed tomography also was done on 12 patients with MJD to examine regional tracer uptake to the heart. The mean ratio of counts in the heart to counts in the mediastinum in the delayed images was lower for the patients with MJD than for the control subjects (p <0.01). Abnormal sympathetic skin response was present in 6 patients with MJD whose mean ratio of counts in the heart to counts in the mediastinum was lower than that of patients with MJD who had normal sympathetic skin response (p <0.01). A single photon emission computed tomography study showed significantly lower accumulation of the tracer in patients with MJD than in the control subjects in the anterior lateral sectors predominantly innervated by sympathetic nerves but not in the inferior septal sectors reported to be under main innervation by parasympathetic fibers. These results show that MJD is accompanied by cardiac sympathetic dysfunction, as detected by iodine123-labeled metaiodobenzylguanidine myocardial scintigraphy, which appears to be correlated with sudomotor sympathetic dysfunction.

3-Iodobenzylguanidine↗

PubMed2000

Alpha(v)beta3 expression on blood vessels and melanoma cells in primary lesions: differential association with tumor progression and clinical prognosis.

The alpha(v)beta3 integrin has emerged as a key mediator in angiogenesis. Its role in tumor-induced angiogenesis is supported by its up-regulation in vivo in the vasculature of a number of different types of carcinoma. The potential clinical significance of alpha(v)beta3 expression on blood vessels in carcinomas is suggested by its association with tumor progression. Currently no information is available about the clinical significance of alpha(v)beta3 expression on the vasculature of lesions of melanocytic origin. Since we have previously found that alpha(v)beta3 expression on melanoma cells in primary lesions is associated with a poor prognosis, in the present study we have compared alpha(v)beta3 expression on blood vessels and on cells of melanocytic origin in nevi and in malignant melanoma lesions. In addition we have examined the lesions for expression of the alpha(v) subunit to gain information on the regulation of alpha(v)beta3 expression on endothelial cells and on cells of the melanocyte lineage. alpha(v)beta3 expression on endothelial cells and on melanocytic cells was a relatively sensitive and specific marker for malignant lesions. However, alpha(v)beta3 expression on endothelial cells in primary melanoma lesions was not associated with the prognosis of the disease. The alpha(v) subunit and the alpha(v)beta3 complex were differentially expressed on endothelial cells and on melanocytic cells, implying that different regulatory pathways control their expression. This finding may account for the differential clinical significance of alpha(v)beta3 expression on tumor vasculature and on melanoma cells we observed in our patient cohort. Lastly, alpha(v)beta3 may be a useful target for immunotherapeutic approaches in melanoma because of its high expression on the vasculature of all metastatic lesions tested and its restricted distribution in normal tissues.

Blood Vessels↗

PubMed2000

NACP/alpha-synuclein and tau constitute two distinctive subsets of filaments in the same neuronal inclusions in brains from a family of parkinsonism and dementia with Lewy bodies: double-immunolabeling fluorescence and electron microscopic studies.

The co-localization of NACP/alpha-synuclein and tau epitopes was examined in the brain stem and hippocampal formation in two patients from a family of autosomal dominant parkinsonism and dementia with Lewy bodies (LBs) without two reported missense mutations in the NACP gene. Double-labeling immunofluorescence study revealed that some brain stem LBs, cortical LBs, pale bodies, Lewy-related neurites, and neurofibrillary tangles expressed both NACP epitopes and the PHF tau AT8 epitope. Double-immunolabeling electron microscopy demonstrated that the NACP antibody selectively labeled 9- to 13-nm-thick straight filaments (LB filaments), whereas AT8 recognized twisted tubules with 80-to 100-nm-interval constrictions in the same neuronal inclusions. We show that NACP and tau aggregate into different filamentous components even if both proteins are incorporated into the same inclusions.

Adult↗

PubMed2000

Simultaneous measurement of temperature and velocity maps by inversion recovery tagging method.

A new method, called the inversion recovery (IR) tagging method, for simultaneous measurement of temperature and velocity maps of flowing fluid has been developed. The present method employs a set of tagging pulses which acts as an inversion pulse of the conventional IR method, based on the temperature dependence of the spin-lattice relaxation of water proton in a fluid, and has the advantage of being able to compensate the reduction of the NMR signal intensity due to flow motion and to reduce the total time to measure these maps. First, the accuracy of the temperature measurement of stagnant doped water in a differentially heated cell using the conventional IR method, as the basic sequence of the IR tagging method, has been evaluated. The accuracy was within 10% of the temperature difference DeltaT = 17.2 degrees C and the measurable temperature resolution was within +/-0.5 degrees C. Then temperature and velocity maps of the flowing doped-water through a cooled pipe were measured simultaneously by the IR tagging method, and the accuracy of temperature measurement was evaluated. The accuracy obtained using the present method was within 15% of the temperature difference DeltaT = 15 degrees C.

Humans↗

PubMed2000

High-pressure magnetic resonance imaging up to 40 MPa.

A high-pressure vessel designed for use with commercial magnetic resonance imaging equipment at up to 40 MPa of pressure was used and tested. Special features of the vessel are the following: 1) 12.6 mm sample chamber i.d.; 2) only non-magnetic parts; 3) visible sample from the outside; 4) resistant to corrosive chemicals, and; 5) sample could be manually translated and rotated in situ. This apparatus was demonstrated through observation of CO(2) clathrate-hydrate growth in a water droplet injected into liquid CO(2) at 20 MPa.

Carbon Dioxide↗

PubMed2000

Occult vascular malformations of the spinal cord: report of four cases not detected by angiography.

Angiographically occult vascular malformations (AOVMs) are reported. Although cavernous malformations, the most common type among the spinal intramedullary AOVMs, have been well documented, the natural history and clinical features of non-cavernous type AOVMs of the spinal cord remain obscure. We have evaluated four cases of non-cavernous AOVMs in the past 9 years. Although the clinical features and magnetic-resonance imaging (MRI) of three cases were similar to those previously reported, the other one had unusual features of insidious onset with limb asymmetry. The natural history of intramedullary occult AVMs remains enigmatic. One speculation for the neurological deterioration is that it results from repeated hemorrhages around the vessels or from intralumenal thrombosis.

Adult↗

PubMed2000

Effects of anticonvulsants on local anaesthetic-induced neurotoxicity in rats.

The effects of various anticonvulsants on local anaesthetics procaine- and lidocaine-induced convulsions were investigated in rats. Pretreatment with diazepam (2.5-5 mg/kg, intraperitoneally) and clonazepam (5-10 mg/kg, intraperitoneally) completely protected the rats against both local anaesthetic-induced convulsions. Phenobarbital (12.5-50 mg/kg, subcutaneously) also significantly decreased the incidence of both convulsions and prolonged their latencies. Carbabazepine (10-40 mg/kg, intraperitoneally) did not completely repress both convulsions, but it prolonged their latencies. Phenytoin (5-20 mg/kg, intraperitoneally) and primidone (30-60 mg/kg, intraperitoneally) markedly enhanced both local anaesthetic-induced convulsions, as shown by shortening of latency and increase in mortality. Valproate (100-200 mg/kg, intraperitoneally) produced a protective effect against procaine-induced convulsions, while it strongly enhanced lidocaine-induced convulsions. These results suggest that the benzodiazepines are effective drugs to prevent neurotoxicity induced by local anaesthetics, while phenytoin and primidone potentiate them.

Anesthetics, Local↗

PubMed2000

Cure of Helicobacter pylori infection does not improve symptoms in non-ulcer dyspepsia patients-a double-blind placebo-controlled study.

BACKGROUND: It remains controversial whether the cure of H. pylori infection improves NUD symptoms. AIM: To conduct a double-blind placebo-controlled single centre study with concealed allocation to investigate this question. PATIENTS AND METHODS: Ninety NUD patients with H. pylori infection were randomly assigned to either the treatment group (50 patients) or placebo group (40 patients). The treatment group received omeprazole, amoxycillin, clarithromycin and the placebo group received omeprazole and placebos for 7 days. Symptoms were assessed every week for up to 12 weeks after completion of medication by a symptom questionnaire. Alteration of histological parameters for gastritis was also evaluated. RESULTS: The infection was cured in 41 out of 48 patients in the treatment group and none in the placebo group. There was no significant difference in the mean symptom scores at any assessment point up to 12 weeks between the treatment and placebo groups. Regarding histological parameters, activity and inflammation, not atrophy or intestinal metaplasia, were significantly improved in the treatment group. CONCLUSION: Although histological parameters were significantly improved in the treatment group, there was no significant improvement in symptoms of NUD in the treatment group compared to placebo.

Adult↗

PubMed2000

Clinical picture of intracranial non-traumatic dissecting aneurysm.

Non-traumatic intracranial arterial dissection has been accepted as a unique entity of 'cerebral infarction in otherwise healthy young adults', and is particularly prevalent in Western countries. A recent data collection and analysis have revealed additional clinical features. The nationwide study in Japan conducted in 1996 has provided new information on the natural history and current treatment of intracranial dissecting aneurysms in Japan. The incidence of symptomatic dissection was found to be much higher in the vertebrobasilar system than in the carotid system. The mean age of the patients was 51.3 years. Patients with carotid lesions were younger (mean 43.8 years). The male/female ratio was 2: 1. Fifty-eight percent of patients presented with subarachnoid hemorrhage. Recurrence was more frequent in patients with subarachnoid hemorrhage (14%) than in patients with no hemorrhage (4.2%). Common radiological findings were dilatation, 'pearl and string' sign and narrowing of the affected artery. Surgical treatment involved a variety of procedures including proximal occlusion, entrapment, wrapping and endovascular embolization. Patients with subarachnoid hemorrhage (61%) underwent surgical treatment more frequently than patients with no hemorrhage (17%). Good recovery was achieved in 64% of all patients. Outcome was better in patients with no subarachnoid hemorrhage compared with those with hemorrhage.

Aortic Dissection↗

PubMed2000

Idiopathic gastric perforation in neonates and abnormal distribution of intestinal pacemaker cells.

BACKGROUND/PURPOSE: The etiology of idiopathic gastric perforation (IGP) in neonates is unclear. Interstitial cells of Cajal (ICC) express tyrosine kinase receptor C-kit, and act as gastrointestinal pacemaker cells. Stem cell factor (SCF) is a C-kit ligand and plays an important role in immune system homeostasis in the gastrointestinal tract. The authors hypothesized that abnormal distribution of ICC or SCF in the gastric wall (ie, abnormal motility or impaired immunity) could predispose the stomach to IGP. METHODS: Stomachs obtained at postmortem from neonates who died of IGP (n = 7) and other causes (control group; n = 10) were used. Biopsy sections were taken at random from various sites in the stomach, including macroscopically intact areas, and labeled immunohistochemically using antibodies to C-kit(a marker for ICC) and SCF. RESULTS: In all control specimens, ICC were present between the muscle layers and around the myenteric plexuses of the stomach wall. In contrast, ICC were absent in all biopsy sections from 3 of the 7 IGP stomachs. In the remaining 4 IGP stomachs, there were fewer ICC in the muscle layers compared with controls, and ICC were absent around the myenteric plexuses. The distribution of SCF immunoreactivity in IGP and control specimens was similar. CONCLUSION: The findings suggest that a lack of ICC (ie, gastric hypomotility) may be implicated in the etiology of IGP in neonates.

Analysis of Variance↗

PubMed2000

Risk factors for poor outcome of untreated arteriovenous malformation.

This study was conducted to determine risk factors for poor outcome in the natural history of arteriovenous malformation (AVM). We statistically analysed the correlation between clinical or angiographical findings and clinical outcomes for 55 cases of untreated AVM. Subsequent haemorrhage from AVMs was the only significant risk factor for poor outcome (P< 0.0001). The odds ratio was 44.56 with a 95% confidence interval (CI) from 4.80 to 413.90. Risk factors for subsequent haemorrhage from AVMs were also determined. The size (P = 0.0483) and location (P = 0.0147) of an AVM were significant risk factors for subsequent haemorrhage. The odds ratios were 3.97 with a 95% CI from 1.18 to 13.33 and 3.89 with a 95% CI from 1.10 to 13.72, respectively. AVMs of more than 60 mm, and deep or infratentorial AVMs had more chance of subsequent haemorrhage, and hence of a poor outcome. We propose using an aggressive multidisciplinary approach to treating these AVMs.

Adolescent↗

PubMed2000

Alzheimer disease: current therapy and future therapeutic strategies.

Antidementia drugs can be defined as drugs that significantly improve the decreased cognitive functions and/or inhibit the progression of dementia, compared with placebo. The main target of antidementia drugs is Alzheimer disease (AD), and the advent of such drugs is ardently desired. Antidementia drugs that are currently in use or undergoing trial are briefly reviewed. To date, only a few acetylcholine esterase inhibitors have been licensed as antidementia drugs for AD, but more beneficial drugs are being actively sought by many different approaches. The development of additional drugs requires greater basic research on the pathogenesis of AD. Future therapeutic strategies for AD on the basis of recent findings concerning the pathogenesis of AD are also reviewed.

Alzheimer Disease↗

PubMed2000

Accumulation of NACP/alpha-synuclein in lewy body disease and multiple system atrophy.

OBJECTIVES: NACP/alpha-synuclein is an aetiological gene product in familial Parkinson's disease. To clarify the pathological role of NACP/alpha-synuclein in sporadic Parkinson's disease and other related disorders including diffuse Lewy body disease (DLBD) and multiple system atrophy (MSA), paraffin sections were examined immunocytochemically using anti-NACP/alpha-synuclein antibodies. METHODS: A total of 58 necropsied brains, from seven patients with Parkinson's disease, five with DLBD, six with MSA, 12 with Alzheimer's disease, one with Down's syndrome, one with amyotrophic lateral sclerosis (ALS), three with ALS and dementia, one with Huntington's disease, two with progressive supranuclear palsy (PSP), one with Pick's disease, one with myotonic dystrophy, and three with late cerebellar cortical atrophy (LCCA), and 15 elderly normal controls were examined. RESULTS: In addition to immunoreactive Lewy bodies, widespread accumulation of NACP/alpha-synuclein was found in neurons and astrocytes from the brainstem and basal ganglia to the cerebral cortices in Parkinson's disease/DLBD. NACP/alpha-synuclein accumulates in oligodendrocytes from the spinal cord, the brain stem to the cerebellar white matter, and inferior olivary neurons in MSA. These widespread accumulations were not seen in other types of dementia or spinocerebellar ataxia. CONCLUSION: Completely different types of NACP/alpha-synuclein accumulation in Parkinson's disease/DLBD and MSA suggest that accumulation is a major step in the pathological cascade of both diseases and provides novel strategies for the development of therapies.

Aged↗

PubMed2000

Preoperative assessment of trigeminal neuralgia and hemifacial spasm using constructive interference in steady state-three-dimensional Fourier transformation magnetic resonance imaging.

Results of microvascular decompression (MVD) for trigeminal neuralgia (TN) and hemifacial spasm (HFS) may be improved by accurate preoperative assessment of neurovascular relationships at the root entry/exit zone (REZ). Constructive interference in steady state (CISS)-three-dimensional Fourier transformation (3DFT) magnetic resonance (MR) imaging was evaluated for visualizing the neurovascular relationships at the REZ. Fourteen patients with TN and eight patients with HFS underwent MR imaging using CISS-3DFT and 3D fast inflow with steady-state precession (FISP) sequences. Axial images of the cerebellopontine angle (CPA) obtained by the two sequences were reviewed to assess the neurovascular relationships at the REZ of the trigeminal and facial nerves. Eleven patients subsequently underwent MVD. Preoperative MR imaging findings were related to surgical observations and results. CISS MR imaging provided excellent contrast between the cranial nerves, small vessels, and cerebrospinal fluid (CSF) in the CPA. CISS was significantly better than FISP for delineating anatomic detail in the CPA (trigeminal and facial nerves, petrosal vein) and abnormal neurovascular relationships responsible for TN and HFS (vascular contact and deformity at the REZ). Preoperative CISS MR imaging demonstrated precisely the neurovascular relationships at the REZ and identified the offending artery in all seven patients with TN undergoing MVD. CISS MR imaging has high resolution and excellent contrast between cranial nerves, small vessels, and CSF, so can precisely and accurately delineate normal and abnormal neurovascular relationships at the REZ in the CPA, and is a valuable preoperative examination for MVD.

Aged↗

PubMed2000

Long-term natural history of hemorrhagic moyamoya disease in 42 patients.

OBJECT: The purpose of this study was to delineate the long-term natural history of hemorrhagic moyamoya disease (MMD). METHODS: A retrospective review was conducted among 42 patients suffering from hemorrhagic MMD who had been treated conservatively without bypass surgery. The group included four patients who had undergone indirect bypass surgery after an episode of rebleeding. The follow-up period averaged 80.6 months. The clinical features of the first bleeding episode and repeated bleeding episodes were analyzed to determine the risk factors of rebleeding and poor outcome. Intraventricular hemorrhage with or without intracerebral hemorrhage was a dominant finding on computerized tomography scans during the first bleeding episode in 29 cases (69%). During the follow-up period, 14 patients experienced a second episode of bleeding, which occurred 10 years or longer after the original hemorrhage in five cases (35.7%). The annual rebleeding rate was 7.09%/person/year. The second bleeding episode was characterized by a change in which hemisphere bleeding occurred in three cases (21.4%) and by the type of bleeding in seven cases (50%). After rebleeding the rate of good recovery fell from 45.5% to 21.4% and the mortality rate rose from 6.8% to 28.6%. Rebleeding and patient age were statistically significant risk factors of poor outcome. All four patients in whom there was indirect revascularization after the second bleeding episode experienced a repeated bleeding episode within 8 years. CONCLUSIONS: The occurrence of rebleeding a long time after the first hemorrhagic episode was not uncommon. Furthermore, the change in which hemisphere and the type of bleeding that occurred after the first episode suggested the difficulty encountered in the prevention of repeated hemorrhage.

Adolescent↗