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Biomedical subjects

A Hirano

Publications and source records attributed to A Hirano.

At least 73 records · Page 4Linked to original sources
PubMed2000

New consensus research on neuropathological aspects of familial amyotrophic lateral sclerosis with superoxide dismutase 1 (SOD1) gene mutations: inclusions containing SOD1 in neurons and astrocytes.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that primarily involves the motor neuron system. Approximately 5-10% of ALS is familial. Superoxide dismutase 1 (SOD1) gene mutations are shown to be associated with about 20% of familial ALS (FALS) patients. The neuronal Lewy-body-like hyaline inclusion (LBHI) and astrocytic hyaline inclusion (Ast-HI) are morphological hallmarks of certain SOD1-linked FALS patients with SOD1 gene mutant and transgenic mice expressing human SOD1 with G85R mutation. From the detailed immunohistochemical analyses, the essential common protein of both inclusions is SOD1. Ultrastructurally, both inclusions consist of granule-coated fibrils 15-25 nm in diameter. Based on the immuno-electron microscopical finding that these abnormal granule-coated fibrils are positive for SOD1, the formation (or aggregation) of the abnormal fibrils containing SOD1 would be essential evidence in diseases caused by various SOD1 mutations. The granule-coated fibrils are also modified by advanced glycation end products (AGEs). The AGEs themselves are insoluble molecules with direct toxic effects on cells. AGE formation of SOD1 composing the granule-coated fibrils (probable AGE-modified mutant SOD1) may amplify their aggregation and produce a more marked toxicity.

Amyotrophic Lateral Sclerosis↗
PubMed2000

Neuropathology of amyotrophic lateral sclerosis with extra-motor system degeneration: characteristics and differences in the molecular pathology between ALS with dementia and Guamanian ALS.

Amyotrophic lateral sclerosis (ALS) is classified into distinct subtypes mainly based on clinicopathological features, in addition to epidemiologic and genetic backgrounds. In addition to sporadic ALS with classical pathology, characteristics in the clinical features, in the histological findings and their topographical distribution, and in the molecular pathology, especially the intracytoplasmic neuronal inclusions, enable us to identify the following subtypes: ALS with dementia (ALS-D), ALS in the Western Pacific, ALS with multi-system degeneration, familial ALS, and superoxide dismutase 1-linked ALS. These subtypes not infrequently exhibit various types of extra-motor system degeneration, and even multi-system pathology. Some of the subtypes (for instance ALS-D or familial ALS) can be deduced, to a certain extent, from characteristic neuronal inclusions such as ALS-type ubiquitinated inclusions, Lewy body-like hyaline inclusions (LBHIs), or ubiquitinated intracytoplasmic neuronal inclusions as typically seen in the dentate fascia. The purpose of this article is to clarify the molecular pathogenesis of the cerebral cortex in ALS-D and Guamanian ALS and parkinsonism-dementia complex (PDC), in order to elucidate the relationship and distinction between these two subtypes. As indicated previously, investigations on ubiquitin-immunoreactivity in the hippocampus further support the view that the pathology of G-ALS/PDC may be that of a tau-related tangle disorder, whilst ALS-D has a feature of the motor neuron disease type-frontotemporal dementia.

Amyotrophic Lateral Sclerosis↗
PubMed2000

Leukemia inhibitory factor enhances bone formation in calvarial bone defect.

For bone defect reconstruction, locally administered cytokine plasmid was examined. Leukemia inhibitory factor (LIF) can bind to the osteoblast cell surface and induce bone formation both in vitro and in vivo. The authors investigated the local mouse LIF complementary deoxyribonucleic acid (cDNA) plasmid in the pcDNA 3 expression vector, which is promoted by cytomegalovirus and is stabilized by bovine growth hormone polyadenylation, with a gelatin sponge carrier. A total of 150 male Wistar rats were used. They were divided into three groups. Group 1 (N = 30) was treated with the gelatin carrier of the pcDNA 3 vector, group 2 (N = 90) was treated with three different doses of LIF cDNA (0.1, 1, and 10 micrograms) in the pcDNA 3-vector plasmid along with the gelatin carrier, and group 3 (N = 30) was treated with recombinant human bone morphogenetic protein -2. Ten animals in each group were euthanized at 1, 3, and 5 weeks postoperatively. Animals treated with LIF cDNA showed significantly enhanced bone mineral density (p < 0.05), as confirmed by dual-energy X-ray absorptiometry (DEXA), in 3 weeks compared with the control vehicle. By 3 weeks, the number of fibroblast-like cells and collagen fibers decreased, whereas the osteoblast-like cells increased inversely, as revealed during histological examination. LIF messenger ribonucleic acid demonstrated by in situ hybridization was observed most markedly in osteocytes of the LIF cDNA-treated group. Also, LIF peptide was detected in the same cell type by immunohistochemistry. Locally administered LIF cDNA plasmid in a gelatin carrier can increase bone density significantly, with subsequent bone formation, probably via osteocyte activation.

Analysis of Variance↗
PubMed2000

Human receptor for measles virus (CD46) enhances nitric oxide production and restricts virus replication in mouse macrophages by modulating production of alpha/beta interferon.

Complement regulatory protein CD46 is a human cell receptor for measles virus (MV). In this study, we investigated why mouse macrophages expressing human CD46 restricted MV replication and produced higher levels of nitric oxide (NO) in response to MV and gamma interferon (IFN-gamma). Treatment of MV-infected CD46-expressing mouse macrophages with antibodies against IFN-alpha/beta blocked NO production. Antibodies against IFN-alpha/beta also inhibited the augmenting effect of MV on IFN-gamma-induced NO production in CD46-expressing mouse macrophages. These antibodies did not affect NO production induced by IFN-gamma alone. These data suggest that MV enhances NO production in CD46-expressing mouse macrophages through action of IFN-alpha/beta. Mouse macrophages expressing a human CD46 mutant lacking the cytoplasmic domains were highly susceptible to MV. These cells produced much lower levels of NO and IFN-alpha/beta upon infection by MV, suggesting the CD46 cytoplasmic domains enhanced IFN-alpha/beta production. When mouse macrophages expressing tailless human CD46 were exposed to culture medium from MV-infected mouse macrophages expressing intact human CD46, viral protein synthesis and development of cytopathic effects were suppressed. Pretreating the added culture medium with antibodies against IFN-alpha/beta abrogated these antiviral effects. Taken together, these findings suggest that expression of human CD46 in mouse macrophages enhances production of IFN-alpha/beta in response to MV infection, and IFN-alpha/beta synergizes with IFN-gamma to enhance NO production and restrict viral protein synthesis and virus replication. This novel function of human CD46 in mouse macrophages requires the CD46 cytoplasmic domains.

Animals↗
PubMed2000

Comparative study of mandibular stability after sagittal split osteotomies: biocortical versus monocortical osteosynthesis.

OBJECTIVE: A comparative study of clinical mandibular stability following bilateral sagittal split osteotomies by means of monocortical versus bicortical osteosynthesis was undertaken. DESIGN: This retrospective study utilized cephalometric radiographs, which were taken at 1 week and 6 months postoperatively. SETTING: The research was carried out at the Department of Plastic and Reconstructive Surgery of the Nagasaki University School of Medicine. PATIENTS: A total of 32 patients who underwent only sagittal split osteotomies and mandibular set back in our unit was included in this study. Of these patients, 17 patients were osteosynthesized monocortically, and 15 patients were osteosynthesized bicortically. MAIN OUTCOME MEASURES: Four measurements--gonial angle (GA), mandibular plane (MP), SNB, and percentage of upper face to total face height (percent upper to total face)--were completed to evaluate postoperative mandibular movement. RESULT: Statistical analyses of cephalometric measurements (GA, MP, SNB, and percent upper face to total face height) showed that monocortical fixed mandibles were more changeable postoperatively on the GA and percent upper face to total face height, but MP and SNB showed no significant differences among the groups. CONCLUSION: These findings suggested that the postoperative excessive shear force stress, produced by the compressive action of the masseter muscle, transformed the mandibular shape as the distal segment rotated clockwise and proximal segment rotated counterclockwise. Consequently, the mandible was bent at the miniplate. It was concluded that bicortical osteosynthesis was more rigid against this shearing stress than monocortical osteosynthesis.

Adolescent↗
PubMed2000

[Intraocular lens calculation for cataract treated with photorefractive keratectomy using ray tracing method].

PURPOSE: Conventional methods (such as the SRK-II formula) do not accurately calculate the power of the intraocular lens (IOL) after refractive surgery. Therefore, we compared a new formula including a ray tracing method to the conventional method for foldable IOL lens implantation. METHOD: Foldable IOLs (MA 60 BM) were implanted in 26 patients (32 eyes) using the phakoemulsification technique. The power of the IOL was measured preoperatively using the SRK-II formula in all cases. From the results of postoperative refractive errors of these cases, the power of IOL calculated by the ray tracing method was compared to the SRK-II formula. Cataract patients first treated with photorefractive keratectomy (PRK) received IOL implants using our ray tracing method and their postoperative refraction was measured. RESULTS: The average postoperative refractive error was 1.32 D in SRK-II formula, 0.95 D in the ray tracing method with Ray 1 used and 0.89 D with Ray 2 used. Postoperative refraction of both eyes first treated with PRK was--1.00 D. CONCLUSION: The average postoperative refractive error was reduced in the ray tracing method using Olsen's predicted ACD (Ray 2) compared to SRK-II formula. This new tracing method appears to be useful for determination of IOL power and it may be applied for IOL calculation for cataract surgery after refractive surgery.

Cataract↗
PubMed2000

[Diffusion-weighted MRI in patients with occlusive cerebrovascular disease: the initial DWI findings within 6 hours after onset].

We performed this study to evaluate the accuracy of diffusion-weighted imaging (DWI) in detecting focal ischemia, and to predict the role of DWI in the management of patients with ischemia in the superacute phase. 99 patients with clinically diagnosed acute occlusive cerebrovascular disease were studied with DWI within 6 hours after onset of symptoms. In 88 of 99 patients, early ischemic lesions were identified on initial DWI as hyperintensity areas. The initial DWI findings were classified into 4 types according to the location and extent of the hyperintensity area. The patients with type 1 (no hyperintensity area) were clinically diagnosed as TIA or complete stroke within 2 hours after the onset. 28 patients out of the patients with type 2 (hyperintensity area in the perforator's territory) were diagnosed with lacunar infarction, and the remaining 13 patients were diagnosed as victims of stroke caused by main trunk occlusion. Except for 2 patients with TIA, the patients with type 3 (scattered hyperintensity areas in the cortex) had main trunk occlusion and showed a more extended ischemic area on SPECT than hyperintensity area on DWI. All the patients with type 4 (extended hyperintensity area) had main trunk occlusion and showed severe hypoperfusion in the affected area on SPECT, and the area of hypoperfusion was well matched with the hyperintensity area on DWI. Comparing DWI findings with rCBF on SPECT, a significant difference was noted in rCBF between hyperintensity and non-hyperintensity area. We considered that emergence of hyperintensity on DWI was related to both the time of duration and the degree of hypoperfusion, and the reduced perfusion area where DWI showed no hyperintensity was thought to be the "ischemic penumbra". Our study indicated DWI had high diagnostic accuracy in superacute occlusive cerebrovascular disease and could furnish useful information to reveal the pathologic condition. In addition, DWI is expected to be available for selection as a therapeutic strategy.

Acute Disease↗
PubMed2000

[Vertebral arterial dissection with subarachnoid hemorrhage after ischemic onset].

A case is reported of the vertebral arterial dissection presenting initially with cerebellar infarction, and which subsequently occurred with subarachnoid hemorrhage 14 days later. A 75-year old male was admitted because of vertigo and ataxia. MR T2-weighted imaging showed a hyperintensity areas on the left cerebellar hemisphere and MR angiography showed multiple stenotic lesions in the left vertebral artery. We diagnosed his illness as dissection of the left vertebral artery and antiplatelet therapy and the blood pressure control were carried out. Fourteen days after the onset, the patient complained of sudden onset of headache and subarachnoid hemorrhage was confirmed on CT scan. Proximal clip occlusion of the left vertebral artery and OA-PICA anastomosis was carried out immediately. The patient was discharged with slight truncal ataxia. We evaluated the features of this vertebral arterial dissection presenting with subarachnoid hemorrhage after ischemic stroke with reference to another reported cases.

Aged↗
PubMed1999

Maximum Density of Tumor Staining Obtained by Preoperative IV-DSA as a Prognostic Indicator for Node-Negative Breast Cancer.

BACKGROUND: We previously demonstrated that the density of tumor enhancement by intravenous digital subtraction angiography (IV-DSA) is correlated with the number of tumor microvessels and that the incidence of distant metastasis is highin patients with breast cancer who show a high maximum density of tumor enhancement (MAX) on IV-DSA. In the present study, we evaluated the prognostic value ofMAX for node-negative breast cancer patients. Patients and METHODS: A total of 128 node-negative breast cancer patients underwent preoperative IV-DSA, and the region of interest (ROI) was set in the areas enhanced by IV-DSA of the breast. MAX was calculated by the time-density curve. Patients were divided into two subgroups: those with MAX >/= 9 (n=35) and those with MAX < 9 (n=93). RESULTS: Patients with recurrence had a significantly higher MAX value than those without recurrence (11.8 +/- 3.8 vs 7.1 +/- 3.0, p<0.01). The disease-free survival rate was significantly worse in patients with higher MAX values than in those with lower MAX values (p <0.001). Multivariate analysis showed that MAX was the strongest predictor of disease-free survival (p =0.026). CONCLUSIONS: These results suggest that the maximum density obtained by IV-DSA is a strong, independent prognostic indicator for node-negative breast cancer patients.

Journal Article↗
PubMed1999

Inhibition of human breast carcinoma growth by a soluble recombinant human CD40 ligand.

CD40 is present on B cells, monocytes, dendritic cells, and endothelial cells, as well as a variety of neoplastic cell types, including carcinomas. CD40 stimulation by an antibody has previously been demonstrated to induce activation-induced cell death in aggressive histology human B-cell lymphoma cell lines. Therefore, we wanted to assess the effects of a recombinant soluble human CD40 ligand (srhCD40L) on human breast carcinoma cell lines. Human breast carcinoma cell lines were examined for CD40 expression by flow cytometry. CD40 expression could be detected on several human breast cancer cell lines and this could be augmented with interferon-gamma. The cell lines were then incubated with a srhCD40L to assess effects on in vitro growth. srhCD40L significantly inhibited the proliferation of the CD40(+) human breast cancer cell lines. This inhibition could also be augmented with interferon-gamma. Viability was also affected and this was shown to be due to increased apoptosis of the cell lines in response to the ligand. Treatment of tumor-bearing mice was then performed to assess the in vivo efficacy of the ligand. Treatment of tumor-bearing SCID mice with the ligand resulted in significant increases in survival. Thus, CD40 stimulation by its ligand directly inhibits human breast carcinoma cells in vitro and in vivo. These results suggest that srhCD40L may be of clinical use to inhibit human breast carcinoma growth.

Animals↗
PubMed1999

Cloning of cellulose synthase genes from Acetobacter xylinum JCM 7664: implication of a novel set of cellulose synthase genes.

Three sets of cellulose synthase genes were cloned from a cellulose-producing bacterium Acetobacter xylinum JCM 7664. One set of genes (bcsAI/bcsBI/bcsCI/bcsDI) were highly conserved with the well-established type I genes in other strains of A. xylinum, while the other two (bcsABII-A, bcsABII-B) were homologous to the known type II (acsAII). Unexpectedly, they were immediately followed by a gene cluster of bcsX/bcsY/bcsCII/ORF569, likely forming an operon. Western blotting demonstrated that the BcsY protein accumulated in cells. Since BcsY showed striking similarities to a number of membrane-bound transacylases, it was hypothesized that the type II cellulose synthase produces acylated cellulose, which might be anchored on the cytoplasmic membrane. An insertion sequence of IS1380-type was found just upstream of the one type II gene (bcsABII-B), suggestive of nonfunctioning.

Amino Acid Sequence↗
PubMed1999

Identification of a new glycosylphosphatidylinositol-anchored 42-kDa protein and its C-terminal peptides from bovine erythrocytes by gas chromatography-, time-of-flight-, and electrospray-ionization-mass spectrometry.

By treatment with phosphatidylinositol-specific phospholipase C (PIPLC), we obtained several candidates of glycosylphosphatidylinositol (GPI)-anchored proteins such as 55, 42, 40, and 30 kDa from bovine erythrocyte membrane, in addition to the well-known GPI-anchored protein acetylcholinesterase. In these proteins, the presence of myo-inositol was confirmed by gas chromatography (GC)-mass spectrometry. Among them, the 42-kDa protein was further analyzed by electrospray-ionization (ESI)-mass spectrometry (MS) after hydrolysis by lysyl endoprotease. By liquid chromatography (LC)-ESI-MS analysis, C-terminal peptides bearing the products of GPI (Ct. GPI-peptides) were effectively detected by combination with in-source collision and multifunctional scanning for the several characteristic fragment ions from the GPI-anchor structure. Existence of microheterogeneity was also observed in the Ct. GPI-peptides from the 42-kDa protein. This result was confirmed by analysis with time-of-flight (TOF)-MS. Furthermore, one of the Ct. GPI-peptides was analyzed in ESI-MS-MS mode. Characteristic fragment ions were effectively detected by collision-induced decay. By the result of MS-MS analysis, this GPI-anchor structure was revealed to contain additional N-acetyl hexosamine. By the above-mentioned method, the C-terminal GPI-anchor structure can be easily identified from the target protein even if its amino acid sequence data are not available.

Acetylcholinesterase↗
PubMed1999

A case of fibrous histiocytoma of the liver.

Malignant fibrous histiocytoma (MFH) is a rare disease. We describe a 68-year-old man admitted to the hospital because of malaise. On admission, hematologic and serum chemical examinations showed no abnormalities. A tumor measuring 6.0 x 6.0 x 5.5 cm was found in segment S6 of the right lobe of the liver. A computed tomographic scan of the abdomen revealed a mass surrounded by a capsule-like region with a nonuniform shadow at its margin. The mass contained a nonuniform low density area. A magnetic resonance imaging scan showed low intensity on T1-weighted images and high intensity on T2-weighted images. An angiogram of the abdomen revealed a tumor with a darkly stained margin during the venous phase. Partial resection of the liver, including S6 and part of S7, was performed. On histopathological examination, this case was characterized by a storiform pattern. The inside of the tumor showed a storiform-pleomorphic pattern with inflammatory cell infiltration and partial mucinous degeneration. On immunohistochemical studies, the tumor cells stained positively for CD6. The diagnosis was MFH.

Aged↗
PubMed1999

Immunocytochemical demonstration of oncocytes in normal adenohypophysis.

Immunocytochemical examination for mitochondrial protein and cytochrome oxidase was performed to demonstrate oncocytes in normal adenohypophysis obtained from 28 patients of various age. A small number of solitary large epithelial cells showed intense cytoplasmic granular immunoreactivities for mitochondrial protein and cytochrome oxidase. The proportions of the cells positive for the former and the latter ranged from 0% to 5.9% (mean+/-SD; 1.5+/-1.7%) and from 0% to 4.9% (1.4+/-1.6%), respectively. These cells were either absent or extremely rare in young patients (under 10 years) but tended to increase in number with age (P < 0.0001). On the other hand, the mirror section technique showed that most of these cells were negative for adenohypophysial hormones, but a few of them were faintly positive for: alpha-subunit (8.0%), beta-subunits of follicle-stimulating hormone (4.8%), luteinizing hormone (2.5%), thyroid-stimulating hormone (1.0%), and growth hormone (0.5%), and were negative for prolactin and adrenocorticotropic hormone. We considered that these cells represent oncocytes that exist in varying numbers in normal adenohypophysis. It was suggested that oncocytes in normal adenohypophysis share various common features with tumorous oncocytes of pituitary oncocytomas.

Adolescent↗
PubMed1999

Advanced glycation endproducts are deposited in neuronal hyaline inclusions: a study on familial amyotrophic lateral sclerosis with superoxide dismutase-1 mutation.

To determine the role of advanced glycation endproducts (AGE) in the pathogenesis of familial amyotrophic lateral sclerosis (ALS) with superoxide dismutase-1 (SOD1) mutation, we investigated the immunohistochemical localization of N(epsilon)-carboxymethyl-lysine (CML), one of the major AGE structures, in spinal cords from three familial ALS patients with a heterozygous Ala to Val substitution at codon 4 in the gene for SOD1. Neuronal hyaline inclusions (NHIs), the abnormal structures seen in some of the remaining lower motor neurons of familial ALS patients with SOD1 mutation, were intensely stained by a monoclonal antibody specific for CML in contrast to the only weakly stained cytoplasm. Immunoelectron microscopy depicted the CML determinants restricted to the granule-associated thick linear structures that mainly compose the NHIs. The NHIs were also recognized by antibodies to SOD1, phosphorylated neurofilament protein and ubiquitin. No focal collection of either CML or SOD1 was found in neurons of the control individuals. Our results indicate that CML is a component of the NHIs of familial ALS patients with SOD1 mutation, and suggest that the CML formation may be mediated by protein glycoxidation or lipid peroxidation in the presence of oxidative stress from mutant SOD1, in association with motor neuron degeneration.

Adult↗
PubMed1999

Astrocytic hyaline inclusions contain advanced glycation endproducts in familial amyotrophic lateral sclerosis with superoxide dismutase 1 gene mutation: immunohistochemical and immunoelectron microscopical analyses.

To clarify the neuropathological significance of the deposition of N(epsilon)-carboxymethyl lysine (CML), an advanced glycation endproduct, in astrocytic hyaline inclusions in familial amyotrophic lateral sclerosis (FALS), autopsy specimens from five members of two different families who had the superoxide dismutase 1 (SOD1) gene mutations were analysed. Immunohistochemically, most of the neuronal and astrocytic hyaline inclusions were intensely stained by the antibody against CML. The distributions and intensities of the immunoreactivities for CML and SOD1 were similar in the inclusions in both cell types. Immunoelectron microscopy showed that both inclusions consisted of CML-positive granule-coated fibrils and granular materials. No significant CML or SOD1 immunoreactivity was observed in the neurons and astrocytes of the normal control subjects. Our results suggest that astrocytic hyaline inclusions contain CML and SOD1 in FALS patients with SOD1 gene mutations, and that the formation of CML-modified protein (probably CML-modified SOD1) is related to the cell degeneration.

Adult↗