Search PubMed⌕ Search

Biomedical subjects

S Hirai

Publications and source records attributed to S Hirai.

At least 109 records · Page 6Linked to original sources
PubMed1998

Immunoelectron-microscopic demonstration of NACP/alpha-synuclein-epitopes on the filamentous component of Lewy bodies in Parkinson's disease and in dementia with Lewy bodies.

We examined brains from Parkinson's disease and from dementia with Lewy bodies (LBs) by using antibodies to NACP/alpha-synuclein. Immunohistochemically, all of the antibodies against the amino-terminal region, NAC domain, and carboxyl-terminal region of NACP labeled not only LBs, pale bodies (PBs), and dystrophic neurites, but also fine thread-like structures in the neuronal perikarya (perikaryal threads) in the hypothalamus and brainstem nuclei. On electron microscopy, immunoreactive products were found to label the 9 to 12 nm-thick filamentous component (LB-filaments) of LBs, PBs, and perikaryal threads. The NACP-immunoreactive perikaryal threads, consisting of small bundles of LB-filaments and randomly oriented LB-filaments, presumably represent an initial stage of LB- or PB-formation. The present study indicates that the entire molecule of NACP is involved in the neuronal filament-aggregating processes of LB disorders.

Brain↗
PubMed1998

An atypical PKC directly associates and colocalizes at the epithelial tight junction with ASIP, a mammalian homologue of Caenorhabditis elegans polarity protein PAR-3.

Cell polarity is fundamental to differentiation and function of most cells. Studies in mammalian epithelial cells have revealed that the establishment and maintenance of cell polarity depends upon cell adhesion, signaling networks, the cytoskeleton, and protein transport. Atypical protein kinase C (PKC) isotypes PKCzeta and PKClambda have been implicated in signaling through lipid metabolites including phosphatidylinositol 3-phosphates, but their physiological role remains elusive. In the present study we report the identification of a protein, ASIP (atypical PKC isotype-specific interacting protein), that binds to aPKCs, and show that it colocalizes with PKClambda to the cell junctional complex in cultured epithelial MDCKII cells and rat intestinal epithelia. In addition, immunoelectron microscopy revealed that ASIP localizes to tight junctions in intestinal epithelial cells. Furthermore, ASIP shows significant sequence similarity to Caenorhabditis elegans PAR-3. PAR-3 protein is localized to the anterior periphery of the one-cell embryo, and is required for the establishment of cell polarity in early embryos. ASIP and PAR-3 share three PDZ domains, and can both bind to aPKCs. Taken together, our results suggest a role for a protein complex containing ASIP and aPKC in the establishment and/or maintenance of epithelial cell polarity. The evolutionary conservation of the protein complex and its asymmetric distribution in polarized cells from worm embryo to mammalian-differentiated cells may mean that the complex functions generally in the organization of cellular asymmetry.

3T3 Cells↗
PubMed1998

Combination assay of CSF tau, A beta 1-40 and A beta 1-42(43) as a biochemical marker of Alzheimer's disease.

Cerebrospinal fluid samples from a total of 157 subjects consisting of 55 patients with sporadic Alzheimer's disease (AD), 34 normal controls, 23 patients with non-AD dementia, and 45 with other neurological diseases were examined by ELISA of tau, A beta 1-40, and A beta 1-42(43). The AD group had a significantly higher level of tau than the normal control group (P < 0.001), and the diagnostic sensitivity was 31% and specificity was 94%. CSF A beta 1-40 levels did not show any significant differences. Although the level of A beta 1-42(43) was decreased significantly in the AD group compared to the control group (P < 0.005), the overlap of A beta 1-42(43) levels among all groups meant that none of the AD samples exceeded the cut-off value, the mean 2SD of normal control subjects. Reduction of A beta 1-42(43) levels in AD resulted in a significant increase in the ratio of A beta 1-40 to A beta 1-42(43) (A beta ratio) as an improved marker. The diagnostic sensitivity and specificity of A beta ratio were 51% and 82% respectively. The three indexes, using the tau level and A beta ratio (tau or A beta ratio, deviation score and tau x A beta ratio), showed better sensitivity (58%, 67%, 69%) and specificity (82%, 86%, 88%) than previously reported methods. Combination assay for CSF tau, A beta 1-40 and A beta 1-42(43) in CSF is a biological marker of AD and may be useful to biochemically monitor subjects under treatment.

Adult↗
PubMed1998

Activated microglia cause iron-dependent lipid peroxidation in the presence of ferritin.

Ferritin contains most of the iron found in the brain, and the release of iron from ferritin has an essential role in iron-dependent lipid peroxidation. We examined the effect of cultured microglia on the ferritin-dependent lipid peroxidation of phospholipid liposomes monitored by the formation of thiobarbituric acid-reactive substances. Microglia stimulated by phorbol myristate acetate caused lipid peroxidation in the presence of ferritin. This lipid peroxidation was mediated by superoxide produced by the microglia and iron released from the ferritin. Lipid peroxidation induced by activated microglia may be partly responsible for the oxidative damage that is thought to occur in Parkinson's disease and other neurodegenerative disorders.

Animals↗
PubMed1998

Antioxidant properties of nicergoline; inhibition of brain auto-oxidation and superoxide production of neutrophils in rats.

Oxidative stress has been suggested to adversely influence cerebrovascular disorders and some neurodegenerative disorders. We examined whether nicergoline, an agent widely used for treating cerebrovascular disorders and senile mental impairment, possesses antioxidant activities and some beneficial effect on neutrophils generating free radicals. Although nicergoline did not scavenge superoxide produced from a superoxide-generating system, it significantly inhibited superoxide secretion from stimulated neutrophils. Auto-oxidation of brain homogenate of rats, monitored by formation of thiobarbituric acid-reactive substances, was suppressed by nicergoline in a dose-dependent manner. The oxidation of the homogenate was accelerated by activated neutrophils and was significantly suppressed by nicergoline. These observations suggest that nicergoine is an antioxidant that inhibits not only lipid peroxidation but also free radical generation from neutrophils. These properties of nicergoline should be beneficial in some pathological conditions including cerebrovascular and neurodegenerative disorders in which oxidative stress may have a pathoetiological role.

Animals↗
PubMed1998

Differential activation of two JNK activators, MKK7 and SEK1, by MKN28-derived nonreceptor serine/threonine kinase/mixed lineage kinase 2.

MKN28-derived nonreceptor type of serine/threonine kinase/mixed lineage kinase 2 (MST/MLK2) directly phosphorylates and activates SEK1/MKK4/JNKK1/SKK1 in vitro, thereby acting as a mitogen-activated protein (MAP) kinase kinase kinase in the JNK/SAPK pathway (Hirai, S. -i., Katoh, M., Terada, M., Kyriakis, J. M., Zon, L. I., Rana, A., Avruch, J., and Ohno, S. (1997) J. Biol. Chem. 272, 15167-15173). The in vitro reconstitution system for the kinase cascade allowed us now to identify JNK/SAPK activators involved in the MST/MLK2-dependent activation of JNK/SAPK in vivo. We show that at least two distinct MST/MLK2-dependent JNK/SAPK activators are present in the fractionated COS-1 cell lysate, and that they appear to be SEK1/MKK4/JNKK1/SKK1 and MKK7/JNKK2/SKK4 by Western blot analysis. Notably, a majority of the MST/MLK2-dependent JNK/SAPK-activating activity is found in MKK7-containing fractions, whereas the MEKK1-dependent activity is comparably distributed in SEK1- and MKK7-containing fractions. Moreover, MST/MLK2 activates recombinant MKK7 more effectively than recombinant SEK1, whereas MEKK1 activates both to a similar extent. In addition, the deletion analysis on MST/MLK2 showed that the kinase domain is responsible for the determination of substrate specificity. These results provide a molecular aspect to the differential regulation of the two JNK activators by a variety of cellular stimuli.

Animals↗
PubMed1998

Longitudinal study of cerebrospinal fluid levels of tau, A beta1-40, and A beta1-42(43) in Alzheimer's disease: a study in Japan.

To clarify the alterations of tau, amyloid beta protein (A beta) 1-40 and A beta1-42(43) in the cerebrospinal fluid (CSF) that accompany normal aging and the progression of Alzheimer's disease (AD), CSF samples of 93 AD patients, 32 longitudinal subjects among these 93 AD patients, 33 patients with non-AD dementia, 56 with other neurological diseases, and 54 normal control subjects from three independent institutes were analyzed by sensitive enzyme-linked immunosorbent assays. Although the tau levels increased with aging, a significant elevation of tau and a correlation between the tau levels and the clinical progression were observed in the AD patients. A significant decrease of the A beta1-42(43) levels and a significant increase of the ratio of A beta1-40 to A beta1-42(43) were observed in the AD patients. The longitudinal AD study showed continuous low A beta1-42(43) levels and an increase of the ratio of A beta1-40 to A beta1-42(43) before the onset of AD. These findings suggest that CSF tau may increase with the clinical progression of dementia and that the alteration of the CSF level of A beta1-42(43) and the ratio of A beta1-40 to A beta1-42(43) may start at early stages in AD. The assays of CSF tau, A beta1-40, and A beta1-42(43) provided efficient diagnostic sensitivity (71%) and specificity (83%) by using the production of tau levels and the ratio of A beta1-40 to A beta1-42(43), and an improvement in sensitivity (to 91%) was obtained in the longitudinal evaluation.

Aged↗
PubMed1998

Cerebral hypoperfusion and hypometabolism with altered striatal signal intensity in chorea-acanthocytosis: a combined PET and MRI study.

We studied cerebral perfusion and oxygen metabolism in three patients with chorea-acanthocytosis using positron-emission tomography and oxygen-15 labeled O2 and CO2. High-field magnetic resonance imaging also was performed. Regional cerebral blood flow (rCBF) and oxygen metabolism (rCMRO2) were significantly reduced in the caudate and putamen when compared with seven control subjects. Mild but significant reductions of rCBF (lower than the normal control values -2 SD) were found in the bilateral frontal, left temporal and parietal, and bilateral thalamic areas; rCMRO2 was reduced in the bilateral frontal and left temporal areas. Magnetic resonance imaging showed increased signal intensity accompanied by scattered bright spots in the caudate head and putamen on T2-weighted images; decreased signal intensity was shown at these sites on T1-weighted images. These findings were not observed in 10 neurologically normal volunteers and are rare in the common hyperkinetic form of Huntington's disease. Reduced cerebral perfusion and oxygen metabolism seem to be related to the intellectual and personality changes that occur in chorea-acanthocytosis. Combined positron-emission tomography and magnetic resonance imaging studies may improve diagnostic accuracy in patients with chorea-acanthocytosis and related disorders.

Acanthocytes↗
PubMed1998

Combined coronary artery bypass, mitral valve plasty, and abdominal aneurysmectomy in an 80-year-old patient: report of a case.

An 80-year-old man suffering from angina on exertion due to stenosis of the left main coronary artery, heart failure due to mitral valve regurgitation, and an abdominal aortic aneurysm (AAA) was successfully operated on with simultaneous surgical procedures. A coronary cineangiography revealed 90% stenosis of the left main coronary artery in segment 5, and 99% and 90% stenosis in segments 2 and 4AV, respectively, of the right coronary artery. Left ventriculography and aortography showed moderate mitral valve regurgitation and the presence of a fusiform-shaped AAA with a maximum diameter of 6 cm. It was thought that insertion of an intraaortic balloon pump (IABP) would prove difficult due to AAA; therefore, simultaneous surgery combining triple coronary artery bypass grafting (CABG), mitral valve plasty, and prosthetic replacement of the AAA was undertaken. The patient's postoperative course was uneventful, and subsequent angiography showed good patency of all coronary bypass grafts and the abdominal prosthesis, along with the disappearance of mitral regurgitation. This patient's clinical course suggests that an extended surgical procedure is effective for the treatment of complicated cardiovascular disease, even in very elderly patients.

Aged↗
PubMed1998

Clinical significance of reduced cerebral metabolism in multiple sclerosis: a combined PET and MRI study.

Magnetic resonance imaging (MRI) in patients with multiple sclerosis (MS) has provided major insights into the disease's natural history, and many studies have focussed on possible correlations between MRI findings and the clinical manifestations of MS. In contrast, there are few reports on possible relationships between functional imaging data and cognitive function. The present study assessed the relationship between clinical presentation and combined anatomical and functional imaging data in MS. Twenty patients with definite MS underwent MRI and positron emission tomography (PET) to evaluate cerebral blood flow (rCBF) and oxygen metabolism (rCMRO2). The relationships between these neuroimaging findings and clinical data, including the Expanded Disability Status Scale (EDSS), Mini-mental status scale, Hasegawa Dementia Scale and relapse time, were evaluated with Spearman's rank correlation coefficients. A general reduction in rCBF and rCMRO2 in the gray and white matter were found in the MS patients. EDSS was correlated with the number and size of the lesions on MRI and was negatively correlated with rCMRO2. A correlation between the decrease in rCMRO2 and the level of cognitive impairment was also found. The severity of cerebral hypometabolism was also related to the number of relapses. Morphological and functional findings obtained by MRI and PET are closely related to the clinical status in MS. Our results suggest that measurement of cerebral metabolism in MS has the potential to be an objective marker for monitoring disease activity and to provide prognostic information.

Adult↗
PubMed1998

[Left atrial isolation for chronic atrial fibrillation associated with aortic arch dissection and aortic valve disease in a 70-year-old man].

A 70-year-old male with aortic regurgitation, chronic atrial fibrillation (Af) and chronic aortic dissection of the aortic arch was treated simultaneously. We found a limited dissection in front of aortic arch during operation. We performed total arch replacement using a branched prosthesis and aortic valve replacement in addition to a modified left atrial isolation for chronic Af under the aid of extracorporeal circulation, and selective cerebral perfusion. Left atrial isolation is a simpler procedure than maze procedure and left side maze procedure for eliminating Af. This simple procedure makes possible a simultaneous extended operation for complicated aortic and cardiac disease even in an elderly patient.

Aged↗
PubMed1998

Decrease of protein kinase C in the spinal motor neurons of amyotrophic lateral sclerosis.

The expression of protein kinase C (PKC), a calcium- and phospholipid-dependent signaling molecule, was studied immunohistochemically in the spinal motor neurons of cases of sporadic amyotrophic lateral sclerosis (SALS). In the normal spinal cord, intense PKC immunoreactivity was found in subsets of large motor neurons. PKC immunoreactivity was markedly decreased in the spinal motor neurons of SALS. The result suggests that down-regulation of PKC is associated with the degeneration of spinal motor neurons in SALS.

Amyotrophic Lateral Sclerosis↗
PubMed1998

Immunohistochemical and ultrastructural characterization of ubiquitinated eosinophilic fibrillary neuronal inclusions in sporadic amyotrophic lateral sclerosis.

We found eosinophilic fibrillary neuronal inclusions (EFNI) that were argyrophilic and immunoreactive for anti-ubiquitin in the cerebral cortex of a patient with sporadic amyotrophic lateral sclerosis (ALS) and mild personality changes. Both hematoxylin and eosin and Bodian's preparations revealed the EFNI to be rod-, flame-shaped, or spherical structures existing within the swollen neuronal perinuclear region in the third, fifth, and sixth layers of the fronto-parieto-temporal cortices including the primary motor cortex. On electron microscopy, filamentous profiles aggregated and formed a single bundle or globule in the neuronal perikaryon without any limiting membrane. Most EFNI had a characteristic multiple layer arrangement. The inner core consisted of randomly oriented granule-free tubules with a fuzzy outer contour, measuring 15-20 nm in diameter. The surrounding layer was made up of granule-associated filaments, electrondense free granules, and small vesicular profiles. Large autolysosome-like membrane-bound vesicular profiles were found scattered at the periphery. Neurofilaments were usually mingled with in the surrounding cytoplasm. Many EFNI were also found in dendrites, but only a few in axons. Both granule-free tubules and granule-associated filaments expressed ubiquitin protein epitopes. Aberrant phosphorylation of neurofilament protein and induction of alphaB-crystallin were shown to exist in EFNI-bearing swollen neurons. Despite having a variety of histological appearances, our observations revealed that EFNI all have common immunocytochemical and ultrastructural characteristics, and thus we assume that EFNI represent a series of cytological alterations in the motor and extra-motor cortices of ALS patients.

Amyotrophic Lateral Sclerosis↗
PubMed1998

Expression of phosphotyrosine and SNAP-25 immunoreactivity in grumose (foamy) spheroid bodies suggests axonal regeneration.

To investigate the origin of grumose (foamy) spheroid bodies (GFSB), the expression of two proteins associated with axonal regeneration, i.e., phosphotyrosine and 25-kDa synaptosomal-associated protein (SNAP-25), was immunohistochemically assessed in GFSB in the substantia nigra pars reticulate (SNPR) of progressive supranuclear palsy (PSP). Phosphotyrosine immunoreactive (-IR) and SNAP-25-IR were found in many GFSB. Both were expressed intensely on eosinophilic debris and grumose aggregates in GFSB. Our result suggests that GFSB are structures associated with aberrant sprouting of axons in the degenerated SNPR from other regions such as the globus pallidus to the SNPR, and that the aberrant sprouting may be associated with cell signaling involving tyrosine kinase systems.

Aged↗
PubMed1998

NACP/alpha-synuclein immunoreactivity in fibrillary components of neuronal and oligodendroglial cytoplasmic inclusions in the pontine nuclei in multiple system atrophy.

We examined neuronal cytoplasmic inclusions (NCIs) and oligodendrocytic glial cytoplasmic inclusions (GCIs) in the pontine nuclei in multiple system atrophy (MSA) using antibodies against the non-amyloid beta component of Alzheimer's disease amyloid precursor protein (NACP/alpha-synuclein). Our immunohistochemical study revealed that anti-NACP antibodies labeled both NCIs and GCIs. Immunoelectron microscopy showed that positive reaction products were localized on the 15- to 30-nm-thick filamentous components of NCIs and GCIs. The present study demonstrates that NACP is associated with cytoplasmic inclusions of MSA, and suggests a role of NACP in abnormal filament aggregation in neuronal degeneration.

Adult↗
PubMed1998

Clinical course of atopic dermatitis in Japanese patients.

We conducted a questionnaire study of 117 patients, who had first consulted the Department of Dermatology Kumamoto University Hospital 20 or 30 years ago, regarding the clinical course of atopic dermatitis (AD). Forty-one patients responded to the questionnaire. Seventeen patients (41.4%) had recovered and 24 patients (58.6%) still had AD. The AD had resolved in 12 of 13 (92.2%) with mild disease severity, four of 18 (22.2%) with moderate severity and one of ten (10%) with severe disease. The outcome was significantly better in the mild group than in the moderate or severe group (chi2=15.5, P=0.0008/chi2=14.8, P=0.00012, respectively). The resolution of the disease was not correlated with the sex of patient, age at onset, period of disease or family history.

Adolescent↗
PubMed1998

An aortic balloon catheter incorporating a conduit for percutaneous cardiopulmonary support.

Circulatory support using both intraaortic balloon pumping (IABP) and percutaneous cardiopulmonary support (PCPS) can improve general hemodynamics; however, sometimes brain damage occurs caused by hypoperfusion. Such cerebral hypoperfusion is likely to be caused by PCPS when applying the conventional femoral cannulation. We have developed a new IABP catheter which incorporates a conduit for PCPS with an outlet at the catheter tip, the goal of which is the improvement of cerebral perfusion. The hemodynamic characteristics of this new IABP catheter were compared with those of the conventional combination of IABP and PCPS. Studies were performed by mock test using a pulsatile artificial heart. A polyvinyl chloride tube acted as the aorta with 2 branches at the proximal and distal portions representing the upper and lower portions of the body. The IABP balloon was positioned between the 2 branches, and changes in flow at the 2 branches were examined at varying PCPS flow rates. Flow in the proximal branch using the new device was greater than it was using the conventional PCPS device. We conclude that cerebral perfusion could be improved with the use of this new special IABP catheter.

Angioplasty, Balloon, Coronary↗