Biomedical subjects

A Hirano

Publications and source records attributed to A Hirano.

At least 91 records · Page 5Linked to original sources

PubMed1999

Increased expression of growth-associated protein 43 on the surface of the anterior horn cells in amyotrophic lateral sclerosis.

This study examined axonal terminal alterations in the anterior horn of amyotrophic lateral sclerosis (ALS) patients. An antibody against growth-associated protein 43 (GAP43), a phosphoprotein which is expressed in elongating terminals of neurites, was employed for immunohistochemical staining. Lumbar spinal cords taken at autopsy from five ALS patients and from six control adults were examined. In control patients, there were numerous GAP43-positive granules diffusely dispersed throughout the anterior horn neuropil, and individual large anterior horn cells (AHCs) showed numerous tiny immunoreactive granules and small dots on the surface. A small number of AHCs showed dense accumulation of GAP43 immunoreactivity on the surface of the cell body and proximal processes. In all ALS patients, similar accumulation of GAP43 immunoreactivity was seen on the surface of a large number of remaining AHCs. Statistical analysis revealed a significant increase in number of AHCs with such accumulation in ALS patients. These results suggest that during the ALS disease process there may be plastic alterations or a compensatory mechanism of the axonal terminals located on the surface of some AHCs for ongoing anterior horn presynaptic terminal degeneration.

Adult↗

PubMed1999

Immunohistochemical demonstration of oncocytes in nongonadotrophic pituitary adenomas.

An immunohistochemical study to demonstrate oncocytes in nongonadotrophic pituitary adenomas was performed. The adenomas were 10 prolactinomas, 2 ACTH-producing adenomas (ACTHomas), and 28 growth hormone-producing adenomas (GHomas); we also studied 5 pituitary oncocytomas. GHomas were divided into two groups: GHomas with (GHomas-1) and without (GHomas-2) fibrous bodies. A small number of solitary large cells showed intense cytoplasmic granular reactivity for mitochondrial protein and cytochrome oxidase, resembling oncocytes in oncocytomas. The proportions of the mitochondrial protein-positive cells ranged from zero to 2.1% (0. 3+/-0.4%). They were more frequent in GHomas, GHomas-1 in particular, than other types of adenomas (P<0.01), and were mostly negative in prolactinomas and ACTHomas. In multivariate analysis, the proportions showed positive correlation with age (P<0.01) and the Ki-67 (MIB-1) labeling index (P<0.01) and tended to increase in number with recurrence (P<0.05). In GHomas, these cells were more common in cases with low basal GH level (P<0.01) and large tumor volume (P<0.01). We consider that these cells represent oncocytes existing in varying numbers in adenomas. We suggest that oncocytic change in nongonadotrophic adenomas indicates poor differentiation and/or some aggressiveness, which lead to a decrease in the endocrine activity of the tumor.

Adenoma↗

PubMed1999

Percutaneous bowel drainage for jaundice due to afferent loop obstruction following pancreatoduodenectomy: report of a case.

A case of jaundice due to an obstruction of the afferent loop following a pancreatoduodenectomy is presented. The dilated loop of the jejunum was drained percutaneously with a 12-F gastrostomy tube. Localized peritonitis around the puncture site was managed conservatively and the obstructive jaundice improved. The treatment strategy for this type of jaundice is discussed.

Afferent Loop Syndrome↗

PubMed1999

A method for evaluating chemical selectivity of agonists for glutamate receptor channels incorporated in liposomes based on an agonist-induced ion flux measured by ion-selective electrodes.

A new method for evaluating chemical selectivity of agonists for the NMDA subtype of glutamate receptor (GluR) channels is described. The method is based on the magnitude of Ca2+ release from GluR-incorporated liposomes, which is measured by a Ca2+ ion-selective electrode with a thin-layer mode. The partially purified GluRs from rat whole brain were reconstituted into Ca2+-loaded liposomes. Small aliquots (each 50 microl) of the proteoliposomes, in the presence of an antagonist DNQX for blocking non-NMDA subtype, were subjected to potentiometric measurements of Ca2+ release under stimulation by three kinds of agonists, i.e. NMDA, L-glutamate and L-CCG-IV. The amount of the Ca2+ ion flux through the GluR channel induced by the agonists was found to increase in the order of NMDA < L-glutamate < L-CCG-IV, which was consistent with that of binding affinity of the agonists toward the NMDA subtype. However, the range of selectivity of the relevant agonists was much smaller compared with results based on binding affinities. The present method provides physiologically more relevant values for the agonist selectivity of GluRs as compared to that of the conventional binding assay in the sense that the selectivity is based on the very magnitude of Ca2+ flux through the NMDA receptor, i.e. the extent of signal transduction by a given agonist. The evaluation of agonist selectivity based on Na+ release was also investigated by using a Na+ ion-selective electrode, but agonist-induced Na+ release was not detected, because of low permeability of Na+ through the NMDA subtype.

Amino Acids, Dicarboxylic↗

PubMed1999

Human membrane cofactor protein (MCP, CD46): multiple isoforms and functions.

Human membrane cofactor protein (MCP, CD46) is a 45-70 kDa protein with genetic and tissue-specific heterogeneity, and is expressed on all nucleated cells. MCP consists from N-terminus of 4 short consensus repeats (SCRs), 1-3 serine/threonine-rich (ST) domains, a transmembrane domain (TM) and a cytoplasmic tail (CYT). More than 8 isoforms are generated secondary to alternative splicing due to combinations of various exons encoding the ST, TM and CYT domains. It serves as a cofactor of serine protease factor I for inactivation of complement C3b and C4b. Its primary role is to protect host cells from homologous complement attack by inactivating C3b/C4b deposited on the membrane. It also acts as receptors for measles virus (MV), some kinds of bacteria and for a putative ligand on oocytes. MV infection causes temporal host immune suppression, which may appear secondary to signaling events through MCP on macrophages and dendritic cells. These functional properties of human MCP may facilitate xenotransplantation and may be useful in the generation of animal models of measles by creating human MCP-expressing animals.

Amino Acid Sequence↗

PubMed1999

Immunoregulatory roles of interleukin-13 in cattle.

Interleukin-13 (IL-13) is produced predominantly by helper T lymphocytes of the Th2 phenotype and mediates its effects on several immune cells, including B lymphocytes and macrophages, stimulating their proliferation, differentiation, and effector functions. IL-13 activates human B cells but has no detectable activity on murine B lymphocytes, suggesting that the activity of IL-13 varies among species. Our studies show that IL-13 enhances proliferation and differentiation of bovine B cells and upregulates cell surface major histocompatibility complex (MHC) class II expression. We examined mRNA expression of the putative signaling component of the bovine IL-13Ralpha1 homolog in several peripheral blood populations. After stimulation with calcium ionophore and phorbol ester, IL-13Ralpha1 mRNA levels appeared to be downmodulated in T cells, upregulated in macrophages and B cells, and unchanged in neutrophils. Together, these studies begin to provide insight into the relative importance of IL-13 in immunoregulation in cattle.

Adjuvants, Immunologic↗

PubMed1999

Cloning of a cDNA encoding bovine interleukin-18 and analysis of IL-18 expression in macrophages and its IFN-gamma-inducing activity.

Interleukin-18 (IL-18) is a recently described cytokine that enhances interferon-gamma (IFN-gamma) production, either independently or synergistically with IL-12. These properties identify IL-18 as an immunoregulatory cytokine that may be pivotal in host defense against intracellular pathogens. We have isolated and sequenced a cDNA encoding bovine IL-18. The open reading frame (ORF) is 582 bp in length, encoding a predicted 192 amino acid (aa) precursor protein. Multiple sequence alignment demonstrated that bovine IL-18 has 65% and 78% identity with the predicted amino acid sequences of murine and human IL-18, respectively. IL-18 mRNA was constitutively present in bovine peripheral blood monocyte-derived macrophages (MDM), with no upregulation on stimulation with lipopolysaccharide (LPS). IL-18 transcripts were weakly detected in B lymphocytes but inducible in the B cell line BL-3. Human recombinant IL-18 (rHuIL-18) induced IFN-gamma production by PHA-stimulated peripheral blood mononuclear cells (PBMC), which was potentiated by rHuIL-12. Further, rHuIL-12 and rHuIL-18 enhanced proliferation of untreated PBMC. Antigen-specific T cell lines demonstrated IL-18-dependent enhancement of IFN-gamma production, indicating that bovine T cells are one of the leukocyte subsets that respond to IL-18. Analysis of IL-18 expression and its ability to induce IFN-gamma production by bovine lymphocytes are important considerations for understanding mechanisms of protective immunity and designing vaccines for intracellular pathogens.

Amino Acid Sequence↗

PubMed1999

Monoclonal antibody to human midkine reveals increased midkine expression in human brain tumors.

We produced a rat IgG2a monoclonal antibody against the carboxyl terminal region of human midkine (MK), a novel growth factor. This monoclonal antibody was used in immunohistochemical studies to compare the expression of MK, proliferating cell nuclear antigen (PCNA) and p53 protein in 133 primary brain tumors and 21 carcinoma metastases to the central nervous system. Approximately half of the glioblastomas multiforme (GBMs) (19/32), medulloblastomas (8/14), primitive neuroectodermal tumors (PNETs) (5/11), breast carcinoma metastases (Br-Mts) (6/10) and lung carcinoma metastases (L-Mts) (5/11) as well as some astrocytomas (2/14) had tumor cells that expressed MK; however, oligodendrogliomas, ependymomas, schwannomas, meningiomas, and pituitary adenomas did not express MK. The values of the PCNA-labeling index were statistically higher in GBMs, medulloblastomas, PNETs, Br-Mts, and L-Mts that expressed MK than in those that did not (Wilcoxon rank-sum test, p < 0.05). There was no correlation between MK and p53 protein in all tumor types. Normal and non-neoplastic brain tissues were negative for MK, PCNA, and p53 protein. We conclude that primary and metastatic tumors of the brain express MK and that the MK expression in brain tumors may depend, in part, on the proliferating potential.

Animals↗

PubMed1999

Inducible nitric oxide synthase immunoreactivity in the Alzheimer disease hippocampus: association with Hirano bodies, neurofibrillary tangles, and senile plaques.

Inducible nitric oxide synthase (iNOS) is involved in the generation of nitric oxide, a molecule with multiple biological activities. Although iNOS expression may be part of antimicrobial armamentarium, inappropriate expression of iNOS can potentially lead to damage to the host. In this report, we determined the expression of iNOS by immunocytochemistry in the hippocampus of the Alzheimer brains (AD) as well as in young and old normal brains. The results showed localization of iNOS immunoreactivity to Hirano bodies of the AD hippocampus. In addition, small granular iNOS immunoreactive profiles were detected associated with senile plaques and extracellular neurofibrillary tangles. In the hippocampus of control brains, morphologically similar profiles were immunoreactive for iNOS, but in far fewer numbers than in AD hippocampus. The results suggest that iNOS is expressed in a subset of pyramidal neurons in the AD hippocampus, and that iNOS may be involved in the pathogenesis of neuronal degeneration in AD.

Adult↗

PubMed1999

Human CD46 enhances nitric oxide production in mouse macrophages in response to measles virus infection in the presence of gamma interferon: dependence on the CD46 cytoplasmic domains.

CD46 is a transmembrane complement regulatory protein widely expressed on nucleated human cells. Laboratory-adapted strains of measles virus (MV) bind to the extracellular domains of CD46 to enter human cells. The cytoplasmic portion of CD46 consists of a common juxtamembrane region and different distal sequences called Cyt1 and Cyt2. The biological functions of these cytoplasmic sequences are unknown. In this study, we show that expression of human CD46 with the Cyt1 cytoplasmic domain in mouse macrophages enhances production of nitric oxide (NO) in response to MV infection in the presence of gamma interferon (IFN-gamma). Human CD46 does not increase the basal levels of NO production in mouse macrophages and does not augment NO production induced by double-stranded polyribonucleotides. Replacing the cytoplasmic domain of human CD46 with Cyt2 reduces MV and IFN-gamma-induced NO production in mouse macrophages. Deleting the entire cytoplasmic domains of human CD46 does not prevent MV infection but markedly attenuates NO production in response to MV and IFN-gamma. Mouse macrophages expressing a tailless human CD46 mutant are more susceptible to MV infection and produce 2 to 3 orders of magnitude more infectious virus than mouse macrophages expressing human CD46 with intact cytoplasmic domains. These results reveal a novel function of CD46 dependent on the cytoplasmic domains (especially Cyt1), which augments NO production in macrophages. These findings may have significant implications for roles of CD46 in innate immunity and MV pathogenesis.

Animals↗

PubMed1999

Recent advances in research on neuropathological aspects of familial amyotrophic lateral sclerosis with superoxide dismutase 1 gene mutations: neuronal Lewy body-like hyaline inclusions and astrocytic hyaline inclusions.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that primarily involves the motor neuron system. Of all patients with ALS, approximately 5%-10% of them are familial and most of the others are sporadic. Superoxide dismutase 1 (SOD1) gene mutations are shown to be associated with about 20% of familial ALS (FALS) patients. FALS is neuropathologically classified into two subtypes: classical FALS in which degeneration is restricted to only motor neurons and FALS which is characterized by the degeneration of the posterior column in addition to the lesion of the motor neuron system. The neuronal Lewy body-like hyaline inclusion (LBHI) is a characteristic neuropathological marker of mutant SOD1-linked FALS with posterior column involvement. Inclusions similar to the neuronal LBHIs have been discovered in astrocytes in certain patients with FALS exhibiting SOD1 gene mutations. The purpose of this review is to discuss the novel neuropathological significance of the astrocytic hyaline inclusions (Ast-HIs) and neuronal LBHIs in brain tissues from individuals with the posterior-column-involvement-type FALS with SOD1 gene mutations. In hematoxylin and eosin preparations, both Ast-HIs and neuronal LBHIs are eosinophilic inclusions and sometimes show eosinophilic cores with paler peripheral halos. Immunohistochemically, both inclusions are intensely positive for SOD1. At the ultrastructural level, both inclusions consist of approximately 15-25 nm-sized granule-coated fibrils and granular materials. Immunoelectron microscopically, these abnormal granule-coated fibrils and granular materials are positive for SOD1. Therefore, the FALS disease process originating from SOD1 gene mutations occurs in astrocytes as well as neurons and is involved in the formation of both inclusions.

Amyotrophic Lateral Sclerosis↗

PubMed1999

[Glioblastoma fed by meningeal branches of the external carotid artery: a case report].

A rare case of glioblastoma fed by meningeal branches of the external carotid artery was reported. A 63-year-old female was transferred to our hospital suffering from gait disturbance and dysarthria. CT and MRI revealed brain tumor and paratumoral hemorrhage with a large cyst that was heterogeneously enhanced and existed in the right fronto-temporal region. Right external carotid arteriography demonstrated the tumor stain markedly fed by the right middle meningeal artery and the accessory meningeal artery. Subtotal removal operation was carried out uneventfully using the right fronto-temporal craniotomy. The histological diagnosis was glioblastoma. After the operation the patient was in good condition, and was transferred to another hospital for the purpose of the synchronized chemoradiotherapy. It is well known that any glioma invades the meninges. However, we rarely encountered an intra-axial glioma fed by a meningeal blood supply. A meningeal-invaded glioma may make difficult its differentiation from meningioma. We concluded that there is necessity for close examination of the intra-axial brain tumors invaded and fed by meningeal blood supply.

Brain Neoplasms↗

PubMed1999

[Acute vincristine neurotoxicity in a non-Hodgkin's lymphoma patient with Charcot-Marie-Tooth disease].

A 44-year-old, previously healthy man with a diagnosis of non-Hodgkin's lymphoma (NHL, diffuse large B-cell type, stage IIA) was treated with combination chemotherapy including vincristine (VCR). After receiving a cumulative dose of VCR, he experienced rapid and marked weakening which progressed to quadriplegia and bulbar palsy. Prior to this therapy, the patient had no neurological problems, and his siblings were asymptomatic. Physical examination identified pes cavus (hollow foot), and electrodiagnostic studies showed markedly slower nerve conduction velocity of myelinated fibers, with abundant "onion bulb" formations. Chromosomal analysis detected 17p11.2-12 duplication, thus yielding a diagnosis of Charcot-Marie-Tooth (CMT) 1A. CMT disease is a familial neuromuscular disorder, and the incidence is approximately 1 in 2,500. We concluded that if CMT disease is diagnosed, vincristine should be avoided due to the potential severity of neurotoxicity to small doses.

Adult↗

PubMed1999

[Size and location of ruptured cerebral aneurysms diagnosed by three dimensional computed tomographic angiography].

The purpose of this study is to confirm the correct size and the location of ruptured cerebral aneurysms diagnosed and measured using three dimensional computed tomographic angiography. The size and the location were investigated in 136 ruptured cerebral aneurysms encountered in our hospital during 3 years and 10 months. As regards the location of 136 ruptured cerebral aneurysms, 40 were anterior communicating artery aneurysms, 35 were middle cerebral artery aneurysms, 33 were internal carotid artery aneurysms, 12 were distal anterior cerebral artery aneurysms and 16 were posterior circulatory aneurysms. Twenty-seven aneurysms (19.9%) were smaller than 3.0 mm, and 74 aneurysms (54.4%) were less than 5.0 mm in maximum diameter. The maximum diameter of aneurysms located on the anterior communicating artery was 4.8 mm. On the middle cerebral artery it was 6.7 mm, and on the internal carotid artery it was 7.4 mm. We concluded that the rate of small aneurysmal rupture was comparatively more frequent than is reported. The results led to the speculation that the aneurysmal rupture occurred more often in smaller size, and the rate of occurrence may be also related to the aneurysmal location.

Adult↗

PubMed1998

Expression of human complement regulatory protein CD46 restricts measles virus replication in mouse macrophages.

Measles virus (MV) can infect mouse macrophages to cause a prolonged non-cytopathic infection that produces low levels of infectious virus for days. We have generated RAW264.7 mouse macrophages expressing human CD46, a cell surface complement regulatory protein that serves as a receptor for laboratory-adapted strains of MV. Laboratory-adapted MV strains efficiently enter the CD46-positive mouse macrophages to cause a cytopathic infection with extensive multinucleated cells and pseudopodia-like extensions. However, MV infection of mouse macrophages through CD46 is self-limiting. Both viral protein synthesis and infectious virus production are abruptly terminated after the second day of infection. This novel virus-cell interaction is seen only in mouse macrophages but not in mouse or hamster fibroblasts expressing human CD46. The possible role of CD46 in macrophage antiviral response restricting MV replication is discussed.

Animals↗

PubMed1998

Effects of age and ethanol on dopamine and serotonin release in the rat nucleus accumbens.

Neural functions in the nucleus accumbens (ACC) play an important role in alcohol drinking behavior. In the present study, we observed the effects of age and ethanol (EtOH) on dopamine (DA) and serotonin (5-HT) release in the ACC of freely moving 4-, 10-, and 16-month-old rats using brain microdialysis techniques. After co-perfusion with 200 mM ethanol, ACC DA, and 5-HT release were decreased significantly in 16-month-old rats compared to those at 4 months old. ACC DA and 5-HT neurons of aged rats were less sensitive to ethanol. On the other hand, both basal extracellular DA and 5-HT release in the ACC were significantly higher in 16-month-old than in 4-month-old rats. Therefore, aging results in opposite changes in basal and alcohol-induced DA and 5-HT release in the ACC.

Aging↗

PubMed1998

CD40 ligand-dependent signaling of bovine B lymphocyte development and differentiation.

The role of IFN-gamma in B cell differentiation in cattle has not been completely elucidated. We have previously investigated the role of IFN- in the control of antibody production by bovine B cells using anti-bovine IgM antibody in the solid-phase as a source of costimulation. Using this mimic of a T1-2 antigen, we demonstrated that IFN-gamma can enhance the production of IgG2 but not IgG1 from sIgM+ cells. The positive effects of IFN-gamma were enhanced by co-addition to cultures of rboIL-2. Under these activation conditions, the frequency of cells expressing mRNA for the IgG2 heavy chain also increased at least two-fold. In these studies, we investigated the role of IFN-gamma in antibody expression under T-dependent (TD) activation conditions using mouse fibroblasts transfected with boCD40L as a surrogate T cell. Under TD conditions, IFN-gamma had less dramatic effects on the production of IgG2 with IgM predominating in the cultures. Interestingly, the production of IgA was modestly enhanced with little effect on the production of IgG1 above baseline levels obtained with medium alone. In comparison to results with T1-2 conditions of activation, IL-2 did not increase total amounts of antibody above two-fold. Our results suggest that TH1 cells in cattle may be limited in their ability to provide B cell help to levels obtainable in a TH2 cytokine microenvironment due to the effects of IFN-gamma on bovine B cells co-activated via CD40.

Animals↗

PubMed1998

Kinetics of expression and subset distribution of the TNF superfamily members CD40 ligand and Fas ligand on T lymphocytes in cattle.

CD40 and Fas are members of the tumor necrosis factor receptor (TNFR) superfamily. CD40 and Fas play key roles in T cell-B cell interactions. Cross linkage of these molecules induces cell activation and cell death, respectively. The interaction of CD40 with its ligand (CD40L), which is expressed on activated T cells, plays a pivotal role in the generation of the T-dependent (TD) immune response, and FasL-bearing T cells, which have been shown to be predominantly of either the TH0 or TH1 type, have the potential to induce the apoptotic death of Fas expressing B cells. We investigated bovine CD40L mRNA expression in established T cell clones by RT-PCR and Southern blotting. T cells analyzed included CD4+ TH0 and TH1 cell subpopulations, CD8+, and gamma/delta T cells stimulated with either specific antigen or Con A. All CD4+ clones but not all CD8+ or gamma/delta T cell receptor (TCR)-bearing clones expressed mRNA for CD40L. To determine the activation requirements for CD40L expression in cattle, we examined the kinetics and induction requirements for CD40L transcription in peripheral blood T cells using a phorbol ester and/or ionomycin, immobilized mouse anti-bovine CD3, or Con A. Our results demonstrate that CD40L mRNA appears relatively early after activation (1 h) and peaks at 2-4 h poststimulation. A rise in intracellular calcium concentration mediated by ionomycin treatment alone was sufficient to induce CD40L mRNA expression at relatively high levels. Ionomycin treatment in combination with other agonists (anti-CD3, PMA) did not enhance CD40L mRNA expression above levels obtained with ionomycin alone. The bovine Fas ligand gene was partially cloned and mRNA expression determined by RT-PCR in a panel of T cell clones. Our results demonstrate that TH0 and TH1 bovine T cell clones expressed Fas ligand transcripts although only one gamma/delta T cell clone did. This expression was upregulated within 3 h after mitogen stimulation and reduced by 24 h.

Animals↗