Search PubMed⌕ Search

Biomedical subjects

A Hirano

Publications and source records attributed to A Hirano.

At least 109 records · Page 6Linked to original sources

Presence of Cu/Zn superoxide dismutase (SOD) immunoreactivity in neuronal hyaline inclusions in spinal cords from mice carrying a transgene for Gly93Ala mutant human Cu/Zn SOD.

This investigation deals with the immunocytochemical localization of Cu/Zn superoxide dismutase (SOD) in the spinal cord neurons of transgenic mice that overexpress Gly93Ala mutant human Cu/Zn SOD and demonstrate clinicopathological features similar to human amyotrophic lateral sclerosis (ALS) with Cu/Zn SOD mutation. At low magnification of light microscopy, the gray and white matter of the spinal cord of Gly93Ala mice showed more intense Cu/Zn SOD immunoreactivity than that of control mice. At higher magnification, the cytoplasm of control mice neurons displayed a distinct staining for Cu/Zn SOD, whereas the surrounding neuropil was only weakly stained. In contrast, the intensity of Cu/Zn SOD immunoreactivity in the cytoplasm of the majority of Gly93Ala mice neurons was similar to that in the neuropil. Almost all neuronal hyaline inclusions (NHIs) of Gly93Ala mice were positively immunostained by antibodies to Cu/Zn SOD, ubiquitin and phosphorylated neurofilament protein (NFP), the intensities of which were much higher in the NHIs than in the surrounding cytoplasm. In control mice, significant Cu/Zn SOD precipitation was not observed to be limited to any particular region of the neuronal cytoplasm. Intracytoplasmic vacuoles in the neuronal soma and processes of Gly93Ala mice were not stained by any of these antibodies. These results indicate that Cu/Zn SOD colocalizes with ubiquitin and phosphorylated NFP in NHIs of mice expressing mutant Cu/Zn SOD; similar findings have been shown for Lewy body-like inclusions of familial ALS patients with Cu/Zn SOD mutation. Moreover, our results point to the possibility that Cu/Zn SOD mutation may have a role in the abnormal Cu/Zn SOD accumulation in the NHIs, in association with motor neuron degeneration.

Animals↗

Purkinje cells in olivopontocerebellar atrophy and granule cell-type cerebellar degeneration: an immunohistochemical study.

We carried out immunohistochemical studies on cerebellar Purkinje cells in sporadic olivopontocerebellar atrophy (OPCA) and in granule cell-type cerebellar degeneration (gc-CD). The cell bodies, axons and dendrites including spiny branchlets and dendritic spines of normal Purkinje cells were intensely stained by the antibody against P400 glycoprotein/inositol 1,4,5-trisphosphate receptor protein (P400/IP3R). The staining pattern of OPCA Purkinje cells was heterogeneous: some were negative, while others were stained with various intensities. Although a small number of P400/IP3R-positive Purkinje cells in OPCA were similar to the normal ones, the immunoreaction products in OPCA Purkinje cells disappeared from the dendritic spines and spiny branchlets toward the cell bodies. Some of OPCA Purkinje cells were stained by the antibodies to phosphorylated neurofilament proteins (pNFP), synaptophysin and alphaB-crystallin. Normal Purkinje cells did not express pNFP, synaptophysin or alphaB-crystallin. By contrast, the staining pattern of the Purkinje cells of gc-CD case was uniform: almost all the Purkinje cells expressed P400/IP3R in cell bodies, axons and dendrites, but not in the dendritic spines and spiny branchlets. Our data suggest that the function of OPCA Purkinje cells is impaired from the peripheral dendrites toward the cell bodies, and that the presence of aberrant phosphorylation of neurofilament proteins, synaptophysin and alphaB-crystallin may be related to the degeneration of Purkinje cells in OPCA. In the gc-CD, our results suggest that the lack of P400/IP3R immunoreactivity in dendritic spines and spiny branchlets of the Purkinje cells is related to the loss of inputs from the granule cells as well as the result of maldevelopment of the Purkinje cells.

Aged↗

Immunocytochemical demonstration of the expression and induction of manganese-superoxide dismutase in the adenohypophysis.

Immunocytochemistry for manganese-superoxide dismutase (Mn-SOD) was studied in 12 normal adenohypophyses and 38 various pituitary lesions. The proportions of cells with granular immunoreactivity for Mn-SOD in normal adenohypophysis ranged from 9.8% to 29.6% (mean +/- SD; 18.4+/-6.2%). Some positive cells tended to accumulate in clusters, distribution of which corresponded well with those immunopositive for mitochondrial protein and cytochrome oxidase. The number of Mn-SOD-positive cells increased in adjacent residual adenohypophysis in eight of nine recent infarcts, in two of five old infarcts, in all four cases of lymphocytic hypophysitis, in two of four abscess cases and in one of three metastatic tumour cases, whereas the immunoreactivities of mitochondrial protein- and cytochrome oxidase-positive cells either did not vary or decreased. The intensity of the histological inflammatory reactions showed a positive correlation with reactivity for Mn-SOD in these lesions. Of eight adenomas, the surrounding area of compressed adenohypophysis showed increased numbers of Mn-SOD- and mitochondrial protein-/cytochrome oxidase-positive cells in four and six cases respectively. It is suggested that positivity for Mn-SOD may be related to some functional activity of mitochondria. It is further suggested that adenohypophysial cells have a high potential to induce Mn-SOD by inflammatory and ischaemic stress and, in addition, by enhanced mitochondrial activity.

Adenoma↗

Comparative study of inferior alveolar disturbance restoration after sagittal split osteotomy by means of bicortical versus monocortical osteosynthesis.

The comparative study of neurosensory disturbance of the inferior alveolar nerve after bilateral sagittal split osteotomies was carried out. The 112 patients who underwent bilateral sagittal split osteotomies were divided into two groups: one group consisted of 62 patients (124 osteotomy sites) who received bicortical osteosynthesis using the lag screw principle (bicortical fixation group), and the other group consisted of 52 patients (104 osteotomy sites) who underwent monocortical osteosynthesis using miniplates (monocortical fixation group). The incidence of neurosensory disturbance of the inferior alveolar nerve as well as its recovery course was compared by patients' interview and Semmes-Weinstein pressure esthesiometer. Mean follow-up period was 12 months (minimum 3 months, maximum 36 months). The incidences of sensory disturbance of both groups were not significantly different at 2 weeks postoperatively. During the period 6 to 12 months postoperatively, the number of patients having light touch sensory disturbance was significantly less in the monocortical fixation group than in the bicortical fixation group. Moreover, the number of patients complaining of numbness during 6 to 18 months postoperatively was significantly less in the monocortical fixation group. These findings suggested that the monocortical osteosynthesis had less damage on the inferior alveolar nerve, leading to the better restoration of neurosensory disturbance in patients in whom the nerve damage was moderate.

Adolescent↗

Increased proliferative activity of osteoblasts in congenital hemifacial hypertrophy.

Congenital hemifacial hypertrophy is expressed in facial asymmetry resulting from unilateral overgrowth. We examined proliferative activity of primary cultured osteoblasts taken from the hemifacial hypertrophic side of an 18-year-old woman compared with the normal side. Both fetal calf serum and basic fibroblast growth factor stimulated osteoblast DNA synthesis, and cultured osteoblast proliferation was markedly increased in the hypertrophic side. Neutralizing antibody against basic fibroblast growth factor was effective to partially block fetal calf serum-induced DNA synthesis. These results suggest that fibroblast growth factor and its receptor signal transduction axis may be selectively involved in affected osteoblasts, leading to progression of congenital hemifacial hypertrophy.

Adolescent↗

[Improvement of MRA and 3D-CTA does away with the need for cerebral angiography in many cerebral aneurysm operations].

The purpose of this investigation was to study the indication of cerebral angiography in recent operations for cerebral aneurysms. Cerebral angiography has been used for diagnoses and operations for cerebral aneurysms, but, as the diagnostic procedures such as magnetic resonance angiography (MRA) and three dimensional computed tomographic angiography (3D-CTA) have made remarkable progress, cerebral angiography is not always an indispensable diagnostic tool for cerebral aneurysm operations. One hundred nineteen patients (including 40 patients with ruptured aneurysms) out of 165 patients (including 61 patients with ruptured aneurysms) were diagnosed and operated on following MRA and 3D-CTA. All of these cases of cerebral aneurysms were operated uneventfully without the need for cerebral angiography. We concluded that cerebral angiography is not needed for diagnoses and operations of small common cerebral aneurysms such as middle cerebral artery aneurysms, internal carotid artery-posterior communicating artery aneurysms and anterior communicating artery aneurysms. Cerebral angiography is necessary only in relatively large aneurysms to confirm the dynamic circulation of the cerebral blood flow before operation.

Adult↗

[Trial of new intraocular lens power calculation following phototherapeutic keratectomy].

We reviewed the SRK-II method and introduce a new equation to calculate the intraocular lens (IOL) power for eyes which underwent laser phototherapeutic keratectomy (PTK). The Gullstrand series was used to determine the power and the radius of curvature of planoconvex IOLs which alter the focal point from the cornea to reach the conjugate point on the retina. The radius of anterior corneal curvature (R), axial length (AXL), predicted postoperative anterior chamber depth (ACD), and lens thickness (LT) were employed in the following formula to calculate the IOL refractive power: K = R/7.7, DC = 337. 5/R, VC = 1,000/DC*1.336 where VC is the posterior vertex focal length. A1 = -(VC-ACD), B1 = AXL-0.5* K-ACD-0. 103 LT, S = 1/A1 + 1/B1; this determined the diopter (D) of IOL in liquid to be (D) = 1,000/(1/S)* 1.336. In eyes which underwent PTK, the keratometric value prior to cataract surgery was not applied. Instead, R' defined as R-dT, where R is the radius of corneal curvature prior to PTK and dT the amount of corneal tissue removed, was introduced. Further, the corneal thickness before cataract surgery (CT') was defined as CT-dT where CT is the corneal thickness prior to PTK. Although it is important to select a lens that has an acurate predicted anterior chamber depth, the new equation appears to be more useful than the SRK-II formula.

Cataract Extraction↗

[A case of diploic epidermoid invading intradurally, which was diagnosed by MR diffusion-weighted image].

A case of diploic epidermoid in the right parietal bone was presented. A 66-year-old male was admitted to our hospital because of aphasia. Plain skull radiogram showed an osteolytic lesion in the right parietal bone. Computed tomography revealed a mass with destruction of the parietal bone extending from an inner to an outer table. The mass was shown by MR imaging as hypointensity on the T1-weighted image and as hyperintensity on the T2-weighted image. The hyperintensity became more remarkable by using a diffusion technique. Based on these findings, a preoperative diagnosis of right parietal epidermoid was made. The mass was totally removed and diagnosed pathologically as epidermoid. It was concluded that diploic epidermoid invading intradurally could be differentiated from other osteolytic tumors by using MR diffusion-weighted image.

Aged↗

Antitumor effects of nonconjugated murine Lym-2 and human-mouse chimeric CLL-1 monoclonal antibodies against various human lymphoma cell lines in vitro and in vivo.

Lym-2 is a murine monoclonal antibody (MoAb) directed towards a human class II molecule variant reactive with both normal and neoplastic human B lymphocytes. Previous studies have shown that signals transmitted by class II molecules that stimulate normal lymphocytes can be inhibitory for B-cell lymphoma growth by signaling activation-induced cell death. Therefore, we sought to evaluate the effects of nonconjugated murine Lym-2 and a human-mouse chimeric Lym-2 (chCLL-1; with murine variable regions and human constant regions) MoAb on the growth of various human lymphomas by using both in vitro and in vivo assays. Cell lines derived from Burkitt's lymphomas, diffuse large cell B-cell lymphomas, anaplastic large-cell lymphomas, and Epstein-Barr virus-induced B-cell lymphomas were incubated with Lym-2 or chCLL-1 in vitro, and effects on proliferation were determined by [3H]-thymidine incorporation. The effects of Lym-2 in vitro were also compared with those of Lym-1, which is a similar MoAb that has been evaluated clinically. After immobilization, which enhances crosslinking of the MoAbs, both Lym-2 and chCLL-1 were capable of directly inhibiting the growth of various lymphoma lines in vitro. These human lymphomas were then transferred into mice with severe combined immunodeficiency to evaluate the efficacy of these MoAbs in vivo. Treatment with either murine Lym-2 or the chimeric chCLL-1 were significantly effective in improving the survival of tumor-bearing mice. These results indicate that stimulation by nonconjugated chCLL-1 may offer a biological approach to the treatment of various human lymphomas.

Animals↗

The CD46 transmembrane domain is required for efficient formation of measles-virus-mediated syncytium.

Two phosphatidylinositol (PI)-anchored versions of a measles virus (MV) receptor membrane cofactor protein (MCP; CD46) were generated by fusing the extracellular domain of MCP to the decay-accelerating factor (DAF; CD55) or its PI anchor. The PI-anchored forms of MCP expressed on Chinese hamster ovary cells, otherwise non-permissive to MV, conferred a smaller MV cytopathic effect than a wild-type MCP, a Ser/Thr-rich domain-deletion mutant and a cytoplasmic tail-deletion mutant of MCP. Therefore the differences in MV receptor properties between the two PI-anchored and three transmembrane forms were investigated. The PI-anchored forms were predominantly expressed on microvilli as in DAF, whereas the other transmembrane forms were found on intracellular membranes. The PI-anchored forms conferred high MV-binding capacity compared with the transmembrane versions. MV replication was, however, severely suppressed in cells expressing the PI-anchored forms, resulting in ineffective syncytium formation. In contrast, cell-to-cell fusion occurred efficiently after co-transfection of cDNA species encoding MV-H. MV-F and any version of MCP. Thus the PI-anchored forms, despite showing sufficient MV binding and cell-to-cell fusion competence together with MV-H and MV-F, mediate inefficient MV entry or replication, which causes severe suppression of the MV cytopathic effect. A biased receptor distribution on microvilli might participate in the selection of a low MV uptake pathway in the PI-anchored forms of MCP. Taken together, the transmembrane portion of MCP is a critical factor for effective virus-cell fusion and the subsequent MV replication.

Animals↗

The cytoplasmic domains of complement regulatory protein CD46 interact with multiple kinases in macrophages.

Membrane cofactor protein (CD46), which normally protects autologous cells from complement lysis, is the human cell receptor for measles virus (MV). Interaction between MV and CD46 on monocytes can lead to suppression of monocyte activation. We have investigated the interaction between the cytoplasmic sequences of CD46 and kinases in a mouse macrophage cell line. Glutathione-S-transferase (GST) fusion proteins bearing the Cyt1 or Cyt2 alternative cytoplasmic domain of CD46 associate with macrophage kinase activity, which phosphorylates multiple proteins co-purified with the GST fusion proteins. Association with the macrophage kinase activity correlates with tyrosine phosphorylation of the CD46 cytoplasmic domains. Removing the CD46 sequences or introducing a frame-shift mutation abrogates the association with macrophage kinase activity. Renaturation studies reveal multiple kinases with apparent molecular mass of 82, 79, 58, and 50/49 kDa, which associate specifically with both CD46 cytoplasmic domains. Alanine substitutions at a juxtamembrane Tyr-X-X-Leu motif in the Cyt1 domain completely abrogate the association with macrophage kinases and tyrosine phosphorylation of Cyt1; but similar substitutions in the Cyt2 domain only partially reduce the association with kinases and tyrosine phosphorylation of Cyt2. These results reveal a specific interaction between complement regulatory protein CD46 and macrophage kinases. These findings may provide an important clue for understanding immune modulation by MV.

Amino Acid Sequence↗

A histopathological study of craniopharyngioma with special reference to its stroma and surrounding tissue.

The numerous pathology reports on craniopharyngioma describe the classical features of squamous epithelium and keratin. Relatively little attention has been paid to its stroma and the surrounding tissue. We focused our observation on these two areas in a retrospective study of craniopharyngiomas in 36 operative cases and 5 autopsy cases. The tumor interdigitated with the brain and pituitary gland. At the interface, the brain was markedly gliotic with Rosenthal fibers simulating pilocytic astrocytoma. The tumor stroma had reactive changes and commonly showed cyst formation and calcification.

Adolescent↗

Epithelial differentiation in intraspinal meningiomas.

To investigate the epithelial features of intraspinal meningiomas, 25 intraspinal meningiomas and 25 intracranial meningiomas were examined for the presence of pseudopsammoma bodies with hematoxylin-eosin and periodic acid-Schiff staining. In addition, we investigated the expression of keratin and epithelial membrane antigen (EMA) by immunohistochemical methods. Pseudopsammoma bodies were found in 3 of 25 cases of intracranial meningiomas (12%), but no definitive pseudopsammoma bodies were observed the intraspinal meningiomas. Three cases (12%) of intraspinal meningiomas and 9 cases (36%) of intracranial meningiomas, including 3 cases with pseudopsammoma bodies, were immunoreactive for keratin. All 25 (100%) intracranial meningiomas and 20 of 25 (84%) intraspinal meningiomas were reactive for EMA. In the intraspinal meningiomas, 4 of 25 cases (16%) showed no reactivity for EMA. These findings suggest that the origin of certain cell components of meningiomas may be different according to the site of the tumor or that the nature of meningioma may be modified by the local environment.

Aged↗

Comparative study of ubiquitin immunoreactivity of hippocampal granular cells in amyotrophic lateral sclerosis with dementia, Guamanian amyotrophic lateral sclerosis and Guamanian parkinsonism-dementia complex.

This report concerns an investigation on ubiquitin immunoreactivity in the neuronal perikarya of hippocampal granular cells in Guamanian amyotrophic lateral sclerosis (G-ALS) and Guamanian parkinsonism-dementia complex (G-PDC). Specimens from two non-Guamanian cases of ALS with dementia (ALS-D) were included for comparison. Histologically normal hippocampi from five adults served as controls. Antibodies to ubiquitin and tau protein were used throughout. Most Guamanian patients examined had granular cells with perikaryal ubiquitin immunoreactivity in the dentate gyrus, but in comparison to ALS-D, the frequency of ubiquitin-positive neurons was significantly lower. Tau-positive granular cells were detected in most Guamanian patients, but not in ALS-D. There was a relationship between the numbers of ubiquitin-positive and tau-positive neurons in the dentate granular cell layer of G-ALS and G-PDC patients. This was verified on sections double immunostained for tau protein and ubiquitin. The present findings suggest that the ubiquitin-positive materials observed in the perikarya of the dentate granular cells of patients with G-ALS or with G-PDC seem to be Alzheimer's neurofibrillary tangles rather than the typical ubiquitin-positive intracytoplasmic neuronal inclusions, characteristics of ALS-D. Our data would indicate that different mechanisms are involved in the geneses of cortical neuronal degeneration and decline in cognitive function in ALS-D, G-ALS and G-PDC.

Adult↗