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Biomedical subjects

A Hirano

Publications and source records attributed to A Hirano.

At least 19 recordsLinked to original sources

Neurotrophic action of gliostatin on cortical neurons. Identity of gliostatin and platelet-derived endothelial cell growth factor.

Gliostatin is a polypeptide growth inhibitor of apparent M(r) = 100,000 with a homodimeric structure comprising two 50-kDa subunits, acting on astrocyte as well as astrocytoma cells (Asai, K., Hirano, T., Kaneko, S., Moriyama, A., Nakanishi, K., Isobe, I., Eksioglu, Y.Z., and Kato, T. (1992) J. Neurochem., 59, 307-317). The amino acid sequences of 13 tryptic peptides including the amino terminus were completely identical to those of platelet-derived endothelial cell growth factor (PD-ECGF) (Ishikawa, F., Miyazono, K., Hellman, U., Drexler, H., Wernstedt, C., Hagiwara, K., Usuki, K., Takaku, F., Risau, W., and Heldin, C.-H. (1989) Nature 338, 557-562). Gliostatin and PD-ECGF, purified from human placenta, shared growth inhibition on glial cells and growth promotion on endothelial cells, and exhibited similar values for half-maximal dose of glial growth inhibition (ID50 = 1.3 nM) and the half-maximal concentration of endothelial growth promotion (EC50 = 1.0 nM), suggesting that both factors evoke the biological actions through an identical receptor on each cell surface. We have further demonstrated evidence of a novel neurotrophic action of gliostatin/PD-ECGF toward embryonic rat cortical neurons in culture. The half-maximal concentration of gliostatin/PD-ECGF for neurotrophic action was 0.3 nM. All actions on glial, endothelial, and neuronal cells, were abolished by a monoclonal antibody against gliostatin. These data indicate that gliostatin/PD-ECGF may play important roles on development and regeneration of the central nervous system and may also involve the induction of angiogenesis for the formation of blood brain barrier.

Amino Acid Sequence

[Adverse reactions to low osmolar iodine contrast media (second report)].

From January to December 1990, we performed a prospective survey of adverse reactions to contrast media at two different institutes of Juntendo University. We collected a total of 4555 case sheets during the period. The radiological procedures we investigated were computed tomography, intravenous urography, arteriography, venography and myelography. Low osmolar iodine contrast medium was used almost exclusively (except for five cases). The overall incidence of adverse reactions was 7.0%, and there were no severe or fatal reactions. The incidence of adverse reactions was higher in females (8.5%) than in males (6.1%). The incidence of adverse reactions increased according to the dose of contrast medium, especially when more than 101 ml was injected. Intra-arterial injection caused adverse reactions most often, followed by regular intravenous injections, followed by bolus intravenous injections. Adverse reactions occurred most often during injection. The next occurred in 5 minutes after injection, and then, 5-10 minutes after the injection of contrast medium. The incidence of adverse reactions was higher in patients with a history of allergy or previous reactions. Allergic adverse reactions were observed at a higher frequency. Pretesting was performed in 56.7% of the cases.

Adolescent

The matrix proteins of neurovirulent subacute sclerosing panencephalitis virus and its acute measles virus progenitor are functionally different.

Persistence of measles virus in the brains of patients with subacute sclerosing panencephalitis (SSPE) is accompanied by changes in the viral matrix (M) protein. To understand the significance of these changes, cell culture and cell-free assays were developed to compare the functions of the M proteins of an SSPE virus Biken strain and its acute measles virus progenitor Nagahata strain. The Nagahata viral M protein is associated with the intracellular viral nucleocapsids and the plasma membrane, whereas the Biken viral M protein is localized mainly in the cytosol. The lack of M protein in the Biken viral nucleocapsids is due to a failure of the Biken M protein to bind to the viral nucleocapsids. The Biken M protein also fails to bind to the Nagahata viral nucleocapsids. Conversely, the Nagahata M protein can bind to the Biken viral nucleocapsids, although this association is not as stable at physiological salt concentration. These results offer concrete evidence that the M protein of an SSPE virus is functionally different from that of its progenitor acute measles virus.

Capsid

Expression and properties of the V protein in acute measles virus and subacute sclerosing panencephalitis virus strains.

Measles virus (MV) inserts one guanosine (G) residue at a specific site in a subpopulation of the mRNA transcribed from the phosphoprotein (P) gene to produce V mRNA. Using an antiserum against the unique carboxyl-terminal region of the predicted V protein, we found that a phosphorylated V protein was expressed in two acute MV strains (Edmonston and Nagahata) and three SSPE virus strains (Biken, Yamagata, and Niigata). The V protein of Biken strain SSPE virus was electrophoretically and antigenically indistinguishable from the V protein of Nagahata strain acute MV, the likely progenitor of the Biken strain. The V protein of these two viruses was not present in the intracellular viral nucleocapsids, but was found only in the cytosolic free protein pool. Pulse-chase experiments failed to show transport of the V protein to the plasma membrane. The V protein was also absent in the extracellular virions. The P protein synthesized from the cloned gene associated with the MV nucleocapsids in vitro, but the V protein had no affinity to the MV nucleocapsids. These results suggest that expression and properties of the V protein are conserved in chronic MV infection.

Animals

Calcineurin, a calcium/calmodulin-regulated protein phosphatase, in mammalian neuroendocrine cells and neoplasms.

Calcineurin is a calcium/calmodulin-regulated protein phosphatase. By using enzyme-immunoassay and immunocytochemistry with an affinity-purified specific antibody to this protein, we have found that calcineurin is expressed in the central and peripheral neuroendocrine cells, also termed amine precursor uptake and decarboxylation cells. In addition, calcineurin immunoreactivity was found in the central neuroendocrine neoplasms such as pineocytoma, olfactory neuroblastoma and paraganglioma. The present findings indicate that the activity of phosphatase regulated by calcium and calmodulin is involved in neuroendocrine functions, and that the enzyme can be useful for the identification and characterization of neuroendocrine cell tumors.

Animals

Calbindin-D28k in the basal ganglia of patients with parkinsonism.

An immunohistochemical study was carried out to investigate the topographic distribution of calbindin-D28k in the human basal ganglia and substantia nigra and its alterations in patients with idiopathic Parkinson's disease (PD), parkinsonism-dementia complex on Guam, progressive supranuclear palsy, and striatonigral degeneration. In normal control subjects, calbindin-D28k immunoreactivity was identified in the medium-sized neurons and neuropil of the matrix compartment of the striatum, the woolly fiber arrangements of the globus pallidus, and the fiber structures of the pars reticulata of the substantia nigra. Calbindin-D28k expression in the basal ganglia of patients with PD and parkinsonism-dementia on Guam was not different from that of control subjects, suggesting that the matrical output pathway is spared in these disorders. In contrast, its disruption is inferred from the observed disorganization of woolly fibers in the globus pallidus of patients with progressive supranuclear palsy and the reduced calbindin-D28k reactivity in the putaminal matrix and the pars reticulata of the substantia nigra of subjects with striatal degeneration. Thus, our results indicate that calbindin-D28k is a useful marker for the projection system from the matrix compartment and that its expression is modified in patients with progressive supranuclear palsy and striatal degeneration.

Aged

Ultrastructural and immunohistochemical studies on ballooned cortical neurons in Creutzfeldt-Jakob disease: expression of alpha B-crystallin, ubiquitin and stress-response protein 27.

This report concerns ultrastructural and immunohistochemical studies on ballooned neurons of ten patients with Creutzfeldt-Jakob disease (CJD). While abundant ballooned neurons and severe white matter degeneration was seen in six Japanese cases, only occasional ballooned neurons and no white matter degeneration was observed in four cases from the files of Montefiore Medical Center. Ultrastructurally, the ballooned neurons contained granule-coated fibrils of 25 to 40 nm in width and 10-nm neurofilaments. The immunohistochemical studies revealed that most ballooned neurons expressed alpha B-crystallin, with deposits of reaction products observed in the cytoplasm. A similar intracellular staining pattern was also seen with the antibody to phosphorylated neurofilament proteins (pNFP). Although the proportion of stained ballooned neurons was less, a positive reaction was also observed with antibodies against ubiquitin, stress-response protein 27 (srp 27) and synaptophysin, but not with an antibody to srp 72. Our findings suggest that expression of pNFP and synaptophysin by ballooned neurons may reflect axonal impairment and that the presence of alpha B-crystallin, srp 27 and ubiquitin may be related to the degenerative processes that neurons undergo in CJD.

Aged

Immunohistochemical studies on the new type of astrocytic inclusions identified in a patient with brain malformation.

Immunohistochemical studies were carried out on the new type of cerebral cortical astrocytic inclusions recently discovered in a 20-year-old patient with maldeveloped brain and micropolygyria. The inclusions appeared as eosinophilic structures (hematoxylin and eosin stain) and did not exhibit argyrophilia (modified Bielschowsky method). The inclusions were strongly stained by the antibody against S-100 protein (S 100) and to a lesser extent by the antibody to microtubule-associated protein 1B (MAP 1B). In contrast to Rosenthal fibers, the astrocytic inclusions did not react with antibodies to alpha B-crystallin, glial fibrillary acidic protein and ubiquitin. No positive reactions were obtained with antibodies against heat-shock protein 27 (HSP 27), HSP 72, actin, vimentin, desmin, cytokeratin, myelin basic protein, beta-tubulin, MAP 2, tau protein, paired helical filament, phosphorylated neurofilament protein (NFP), nonphosphorylated NFP, synaptophysin, cathepsin D, alpha 1-antichymotrypsin, alpha 1-antitrypsin and basic fibroblast growth factor. By immunoelectron microscopy, the products of the reaction with the anti-S 100 antibody appeared as heterogeneous granular deposits and with the antibody to MAP 1B they were randomly scattered throughout the astrocytic inclusions. Our results demonstrate that the immunohistochemical profile of the recently described inclusions differs from that of Rosenthal fibers. Whether the novel inclusions are involved in congenital astrocyte dysfunction and cerebral malformation remains to be established.

Adult

Stress-response (heat-shock) protein 72 expression in tumors of the central nervous system: an immunohistochemical investigation.

This report deals with the expression of stress-response (heat-shock) protein 72 (srp 72) in a series of 95 primary human brain tumors and 21 carcinoma metastases to the central nervous system (CNS). Immunohistochemical procedures were employed; cells of the human cervical cancer line HeLa S3 were used as positive controls. The protein was detected in 14/22 meningiomas and in 6/13 glioblastomas. Tumor cells expressing srp 72 were also found in 4/17 astrocytomas, 2/9 pituitary tumors, 2/14 primitive neuroectodermal tumors and 1/10 medulloblastomas. Whereas the majority (8/10) of the breast carcinoma metastases had tumor cells that expressed srp 72, only 2/11 lung tumor metastases were positively stained. These results document srp 72 expression by a variety of primary and metastatic tumors of the CNS.

Antibodies, Monoclonal

Increased iron content in the putamen of patients with striatonigral degeneration.

We measured the total content of iron, copper, zinc and manganese in the putamen of four patients with striatonigral degeneration (SND) and age- and gender-matched normal controls. The iron content in the SND patients was five times greater than in the controls. Electron microscopic histochemistry revealed the iron reaction products in the pigments showing a triphasic pattern of coarse, electron-dense globules, fine granular and fibrillary materials, and lamellated structures. These findings suggest that increased iron deposition may be related to pigment formation in the putamen of SND.

Aged

Ultrastructural identification of neurofibrillary tangles in the spinal cords in Guamanian amyotrophic lateral sclerosis and parkinsonism-dementia complex on Guam.

The immunohistochemical and ultrastructural characteristics of spinal cord neurofibrillary tangles (NFTs) were examined in Guamanian amyotrophic lateral sclerosis and in parkinisonism-dementia complex on Guam. The spinal cord NFTs reacted with antibodies to tau protein (tau-2), ubiquitin and paired helical filaments (PHFs). Ultrastructurally, the components of the NFTs were seen as randomly arranged fibrils which were often associated with osmiophilic granules; small bundle-like arrangements were also occasionally observed. Individual NFT fibrils appeared as straight fibrils with a diameter of approximately 15 nm and constricted fibrils with a periodicity of approximately 80 nm. Ultrastructural microscopic examination of specimens stained by the modified Bielschowsky method and with the antibodies revealed silver particles and the products of the tau, ubiquitin and PHF immunoreactions on the NFT fibrils. This is the first demonstration of the fine structure of the spinal cord NFTs.

Adult

Basophilic inclusions in sporadic juvenile amyotrophic lateral sclerosis: an immunocytochemical and ultrastructural study.

This report concerns immunocytochemical and ultrastructural studies on the basophilic inclusions in two cases of sporadic juvenile amyotrophic lateral sclerosis (ALS). The inclusion had a globular, irregular-shaped, or sometimes fragmented appearance. Ultra-structurally, the inclusions consisted mainly of thick filamentous structures associated with granules. Focal neurofilamentous accumulations were occasionally observed among the granulofilamentous structures. The basophilic inclusions occasionally showed granular reaction product deposits with an antibody to ubiquitin. The inclusions did not react with antibodies to phosphorylated neurofilament and to tau protein.

Adult

Complete correction of the tetralogy of Fallot in adults using separated extracorporeal circulation to block intrathoracic collateral circulation and improve perfusion of the renal vasculature.

During the last 10 years, complete correction of the tetralogy of Fallot (TOF) has been performed on 28 adult patients using the "separated extracorporeal circulation" (separated ECC) technique developed by us. In addition to the usual ascending aortic and dual right arterial cannulations for ECC, the separated ECC also involved femoral arterial cannulation and the insertion of a catheter with two balloons via the other femoral artery. Flow via the ascending aorta and femoral artery were maintained separately during ECC. The urine output during separated ECC was significantly better than that during ordinary ECC (P < 0.01) and the operative field for intracardiac correction was clearer as a result of blocking the collateral circulation. Thus we believe separated ECC to be a superior method for total correction of TOF in adults, which may enhance the operative outcome.

Adult

Anchorage densities associated with hemidesmosome-like structures in perivascular reactive astrocytes.

Electron microscopical examination of devastated and reticular gliosis-replaced areas of two human brains revealed novel anchorage densities (ADs) associated with hemidesmosome-like structures (HDLSs) in perivascular astrocytes; the densities, 200-300 nm away from the cell membrane overlying the basal lamina, ran parallel to the membrane. The subplasmalemmal ADs usually received fibrils from the main stream of the deeply located glial fibrils, and sent isolated 13- to 16-nm fibrils roughly perpendicularly to the unusually prominent and frequently continuous HDLSs on the inner leaflet of the cell membrane, undercoated by a thickened basal lamina. The variable profiles of the ADs indicated that they were cell membrane-connected sheets or meshes that were virtually completely composed of bundles of glial fibrils intercrossing at variable angles or running roughly parallel to one another. All these findings suggest that the ADs may provide a significant support to the cell membrane facing the perivascular space.

Adult

Results of adjuvant chemotherapy for invasive uroepithelial cancer.

Between June 1982 and July 1990, 55 patients (41 with bladder cancers and 14 with renal pelvic or ureteral cancers) who had undergone radical extirpative surgery and/or node dissection for pathological stage pT2-4 and/or nodal disease received adjuvant chemotherapy consisting of cisplatin alone or in combination with other agents. In all, 26 of the bladder-cancer patients also received preoperative chemotherapy consisting of arterial infusion of cisplatin, mitomycin C, and Adriamycin. Adjuvant chemotherapy was performed according to the following protocol. Between June 1982 and July 1987, 30-50 mg/m2 cisplatin either alone or in combination with Adriamycin and 5-fluorouracil (CAF) was given to 35 patients in an induction and maintenance setting for 1 year. After July 1987, short-course cisplatin (70 mg/m2) or cisplatin, etoposide, and Adriamycin combination chemotherapy (CVA) was given to 20 patients. Of the 55 patients, 38 are alive and show no evidence of disease, three are alive with disease, 13 have died of their disease, and 1 has died of an unrelated cause. The 5-year survival of all patients was 65.1%. The survival of the 20 patients who were treated after July 1987 was better than that of the 35 patients who were treated before June 1987. Local recurrence and/or distant dissemination occurred in 16 patients, 13 of whom died of cancer progression. Nausea and vomiting and anorexia occurred in most patients during the administration of cisplatin. Mild to moderate myelosuppression developed in patients who received CAF or CVA combination chemotherapy. Although adjuvant chemotherapy combined with radical surgery seemed to be effective in cases with a pathological stage of pT3a or less, more intensive pre- or postoperative chemotherapy is needed to improve the poor prognosis of patients with deeply invasive uroepithelial cancer.

Aged

Expression of stress-response (heat-shock) protein 27 in human brain tumors: an immunohistochemical study.

This report concerns the expression of the low molecular weight stress-response (heat-shock) protein 27 (srp 27) in a variety of human brain tumors. Immunohistochemical techniques were used; cells of the breast cancer line MCF7 served as positive controls. The reaction product was found exclusively in the cytoplasm. Srp 27 was detected in 5/5 breast tumor metastases to the brain and in 5/21 meningiomas. The protein was also detected in 5/11 glioblastomas and 2/5 pituitary adenomas. By comparison, positive staining was observed in only 1/15 astrocytomas and 1/7 medulloblastoma and no reaction was seen with the oligodendrogliomas, schwannomas and gangliogliomas tested. These observations demonstrate that srp 27 is expressed by certain primary intracranial tumors.

Adenoma

Morphological and functional study of free arterial grafts.

Morphological and functional changes of free arterial grafts in dogs were studied for 3 weeks after implantation and the changes were compared to those in implanted free vein grafts. In the arterial grafts, endothelial cells with abundant pinocytotic vesicles and some cytoplasmic folds were observed by transmission and scanning electron microscope and cell detachment was seen only at the site of anastomosis, while most cells were detached in the vein grafts. The site of mechanical damage in the arterial grafts was covered by regenerated endothelial cells which showed similar morphological findings to the normal arterial endothelial cells. In contrast, regenerated cells in the vein grafts started to cover the denuded area 7 days after the implantation and had completely covered it by 3 weeks. Prostacyclin was produced more abundantly in arterial grafts than in vein grafts at any phase after implantation. The level of prostacyclin production was between 30 and 40 pg/mg in any phase after implantation of free arterial grafts, while in vein grafts the level was 2.5 pg/mg at the day of implantation and increased to 13.6 pg/mg at 21 days. This study showed that the endothelial cells were well preserved and the level of prostacyclin production was high in the arterial grafts, and thus the grafts seemed to show potent anti-thrombogenicity after implantation. Although late changes in arterial and vein grafts were not investigated in this experimental protocol, these results may suggest that the arterial graft is superior to the vein graft even in the early period after its implantation as a free graft.

6-Ketoprostaglandin F1 alpha

Long-term follow-up results after reconstruction of the mitral valve by leaflet advancement.

In this study, we discuss the clinical results of mitral leaflet advancement performed on 29 patients over the past 10 years and attempt to determine the indication. Preoperative diagnosis of mitral valve lesion consisted of mitral regurgitation in 21 patients and mitral stenosis in 8 patients. Mitral valve repair was applied to the anterior mitral leaflet in 2, the posterior mitral leaflet in 25, and bilateral leaflets in 2 patients. Reoperation was performed on 13 patients, and 1 patient died of renal failure immediately after reoperation. No reoperation was needed for 96.6% of the patients at 1 year, 89.5% at 5 years, 75.0% at 8 years, 63.8% at 10 years, and 52.6% at 15 years postoperatively. At reoperation, the repaired mitral leaflet was found to be calcified in 3 patients more than 9 years after the initial operation. Of the 12 survivors without reoperation, mitral stenosis associated with regurgitation was obvious in 6 patients. Of the 21 patients with preoperative mitral regurgitation, 90.0% showed no deterioration at 5 years, 79.7% at 8 years, and 69.1% at 10 years. On the other hand, for the 8 patients with mitral stenosis, the rates were 87.5% at 1 year, 62.5% at 5 years, 50.0% at 8 years, and 25% at 10 years. Our results suggest that mitral leaflet advancement shows satisfactory results in patients with mitral regurgitation but is not successful for patients with mitral stenosis in the long term because the repaired valve tends to be stenotic in the late postoperative period.

Adolescent