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A Hirano

Publications and source records attributed to A Hirano.

At least 37 records · Page 2Linked to original sources

A single-channel method for evaluation of very magnitudes of Ca2+ ion fluxes through epsilon4/zeta1 N-methyl-D-aspartate receptor channels in bilayer lipid membranes.

A single-channel method for evaluating agonist selectivity in terms of the very number of Ca2+ ions passed through the epsilon4/zeta1 N-methyl-D-aspartate (NMDA) receptor ion channel in bilayer lipid membranes (BLMs) is described. The number of Ca2+ passed through the single-channel was obtained from single-channel recordings in a medium where the primary permeant ion is Ca2+. The recombinant epsilon4/zeta1 NMDA channel was partially purified from Chinese hamster ovary cells expressing the channel and incorporated in BLMs formed by the tip-dip method. It was found that the epsilon4/zeta1 channel in BLMs is permeable to Ca2+ and Na+, but the number of Ca2+ passed through the channel is much fewer than that of Na+. The integrated Ca2+ currents induced by three typical agonists NMDA, L-glutamate and L-CCG-IV were obtained at concentration of 50 microM, where the integrated currents for all the agonists reached their saturated values. The integrated Ca2+ currents obtained are (3.1+/-0.21) x 10(-13) C/s for NMDA, (4.6+/-0.31) x 10(-13) C/s for L-glutamate and (5.7+/-0.25) x 10(-13) C/s for L-CCG-IV, respectively, suggesting that the three kinds of agonists have different efficacies to induce permeation of Ca2+. The range of the agonist selectivity thus obtained is much narrower than that of binding affinities for the NMDA receptors from rat brain. The present method is able to detect Ca2+ permeation with a detection limit of approximately 10(5) Ca2+ ions/s.

Animals↗

Reduced immunogenicity of beta-lactoglobulin by conjugation with carboxymethyl dextran differing in molecular weight.

To reduce the immunogenicity of beta-lactoglobulin (beta-LG), two beta-LG-carboxymethyl dextran (CMD) conjugates (Conj. 40 and Conj. 162) were prepared by using water-soluble carbodiimide (EDC). The molar ratios of beta-LG to CMD in Conj. 40 and Conj. 162 were 8:1 and 7:1, respectively. Each conjugate maintained approximately 50% of the retinol binding activity of beta-LG. Structural analyses by intrinsic fluorescence, CD spectra, and ELISA with monoclonal antibodies indicated that the surface of beta-LG in each conjugate was covered by CMD without great disruption of native conformation. By conjugation with CMD, the antibody response to beta-LG was reduced in BALB/c, C3H/He, and C57BL/6 mice, which was eminent in Conj. 162. The results of B cell epitope scanning using overlapping synthesized peptides showed that the linear epitope profiles of the conjugates were similar to those of beta-LG, whereas the antibody response to each epitope was reduced, which was eminent in Conj. 162. It was concluded that conjugation with CMD of higher molecular weight is effective in reducing the immunogenicity of beta-LG and that masking of epitopes by CMD is responsible for the reduced immunogenicity.

Animals↗

Two novel single-nucleotide polymorphisms of the Caspase-9 (CASP9) gene in the Japanese population.

We identified two single-nucleotide polymorphisms (SNPs) in the human Caspase-9 (CASP9) gene (1p36.3), which encodes an apoptosis-related cysteine protease, by screening all exons and exon-intron boundaries. These SNPs were present in coding regions. One of coding SNPs reflected an amino-acid substitution; an A to G transition at codon 221 in exon 5 would encode arginine instead of glutamine. As the gene is implicated in apoptotic cascade, the polymorphic sites will serve as useful markers for genetic studying of disorders affecting immune response and cancer susceptibility in humans.

Caspase 9↗

Histological changes in the hypofunctional pituitary gland following conventional radiotherapy for adenoma.

AIMS: Although delayed hypopituitarism is a common complication of conventional radiotherapy of sellar tumours, histological changes that may account for it have been rarely reported. To elucidate the changes, hypofunctional pituitary glands following irradiation were studied. METHODS AND RESULTS: Two pituitary glands obtained at autopsy from patients who had been irradiated for adenoma and exhibited hypopituitarism were examined. In both cases diffuse fibrosis was observed in the adenohypophysis, whereas the neurohypophysis remained unchanged. Immunohistochemistry showed that stellate-shaped S100 protein-positive cells were increased in number and distributed among the endocrine cells. Some irradiated endocrine cells showed dense granular immunoreactivity for mitochondrial protein, cytochrome oxidase and manganese-superoxide dismutase. In addition to faint reactivity with anti-cytokeratin 8, 18 antibody, many cells were densely positive with anti-cytokeratin 1, 5, 10, 14 antibody. CONCLUSIONS: These results indicate that radiation- induced fibrosis is associated with an increased number of folliculo-stellate cells and the presence of metabolic dysfunctional mitochondria resembling mitochondria in oncocytes. Squamous metaplasia in the irradiated endocrine cells was also noted. Various intracellular changes may participate in delayed pituitary hypofunction following radiotherapy.

Adenoma↗

Embolization of the left portal vein to inferior vena cava shunts for chronic recurrent hepatic encephalopathy via the mesenteric vein.

Diagnostic imaging and embolization therapy for very rare intrahepatic portal-systemic shunts with liver cirrhosis are reported. An 82-year-old woman was admitted to the hospital (Yachiyo Hospital) because of hepatic encephalopathy. Computed tomography with contrast enhancement demonstrated anomalous vessels between the portal vein and the inferior vena cava. Those shunts were suspected as the cause of her encephalopathy with hyperammonemia. Portography through McBurney's laparotomy demonstrated two portal-caval shunts; one was from the bifurcation of the portal vein and the other was from the left portal vein. They seemed to originate from the vascular system of the caudate lobe, and were obstructed with stainless coils. The patient is well with a normal serum ammonia level 40 months following the intervention.

Aged↗

Formation of advanced glycation end-product-modified superoxide dismutase-1 (SOD1) is one of the mechanisms responsible for inclusions common to familial amyotrophic lateral sclerosis patients with SOD1 gene mutation, and transgenic mice expressing human SOD1 gene mutation.

Neuronal Lewy body-like hyaline inclusions (LBHI) and astrocytic hyaline inclusions (Ast-HI) are morphological hallmarks of certain familial amyotrophic lateral sclerosis (FALS) patients with superoxide dismutase-1 (SOD1) gene mutations, and transgenic mice expressing the human SOD1 gene mutation. The ultrastructure of inclusions in both diseases is identical: the essential common constituents are granule-coated fibrils approximately 15-25nm in diameter and granular materials. Detailed immunohistochemical analyses have shown that the essential common protein of the inclusions in both diseases is an SOD1 protein. This finding, together with the immunoelectron microscopy finding that the abnormal granule-coated fibrils comprising the inclusions are positive for SOD1, indicates that these granule-coated fibrils containing SOD1 are important evidence for mutant SOD1-linked disease in human and mouse. For immunoelectron microscopy, the granule-coated fibrils are modified by advanced glycation endproducts (AGE) such as N(epsilon)-carboxymethyl lysine, pyrraline and pentosidine (Maillard reaction). Based on the fact that AGE themselves are insoluble molecules with direct cytotoxic effects, the granule-coated fibrils and granular materials are not digested by the lysosomal and ubiquitin systems. The neurons and astrocytes of the normal individuals and non-transgenic mice show no significant immunoreactivity for AGE. Considered with the mutant-SOD1 aggregation toxicity, a portion of the SOD1 comprising both types of the inclusion is modified by the AGE, and the formation of the AGE-modified SOD1 (probably AGE-modified mutant SOD1) is one of the mechanisms responsible for the aggregation (i.e. granule-coated fibril formation).

Amyotrophic Lateral Sclerosis↗

Association of allelic losses at 3p25.1, 13q12, or 17p13.3 with poor prognosis in breast cancers with lymph node metastasis.

To identify specific allelic losses that might correlate with postoperative mortality of patients with node-positive breast carcinomas, we examined tumors from a cohort of 263 such patients, who were followed clinically for 5 years postoperatively, for allelic losses among 18 microsatellite markers. Patients whose tumors had lost an allele at 3p25.1, 13q12, or 17p13.3 had significantly higher risks of mortality than those whose tumors retained both alleles at those loci. At 3p25.1, the 5-year mortality rate was 33.8% among patients with losses vs. 16.8% with retention (P = 0.0154); at 13q12, 30.3% vs. 13.0% (P = 0.0241); and at 17p13.3, 30.4% vs. 16.2% (P = 0.0243). Combined losses at 3p25.1 and 17p13.3 increased the predicted postoperative mortality risk by a factor of 4.9 (5-year mortality rate of 38.2% vs. 8.0%, P = 0.0006), and combined losses at 3p25.1 and 13q12 raised the predicted postoperative mortality risks by a factor of 2.9 (34.7% vs. 12.7%, P = 0.0441). These data indicate that loss of heterozygosity (LOH) at any one or a pair of loci at 3p25.1, 13q12, or 17p13.3 is a significant predictor of postoperative mortality for breast-cancer patients.

Adult↗

Myopathic form of very-long chain acyl-coa dehydrogenase deficiency: evidence for temperature-sensitive mild mutations in both mutant alleles in a Japanese girl.

In a 14-year-old Japanese girl, manifested recurrent myalgia with elevated serum creatine kinase after moderate exercise became evident, and she was diagnosed as having a myopathic form of very-long chain acyl-CoA dehydrogenase deficiency. Her first clinical symptom of the disease was evident when she was 6 y of age. She had never had hypoglycemic attacks, and hepatomegaly and cardiomyopathy were absent. The diagnosis was suspected on the basis of the urinary organic acid profile after a 36-h fast, long-chain fatty acid-loading test, and the blood acylcarnitine profile. Acyl-CoA dehydrogenase activity with palmitoyl-CoA as a substrate was severely decreased in her fibroblasts, and the amount of very-long chain acyl-CoA dehydrogenase protein was reduced. She was a compound heterozygote of A416T from her father and R450H from her mother. Transient expression of mutant A416T cDNA retained a significant residual acyl-CoA dehydrogenase activity of 10% and 20% normal at 37 degrees C and 30 degrees C, respectively. Specific activity of A416T mutant protein was calculated to be one fifth that of control. In the case of R450H mutant expression, a low residual acyl-CoA dehydrogenase activity of 5% normal was detected at 30 degrees C although significant activity was absent at 37 degrees C. The R450H protein was not detected at 37 degrees C but was clearly detected at one fourth the normal amount at 30 degrees C. These results indicate that both mutations were temperature-sensitive mild mutations, the result being the mildest phenotype of very-long chain acyl-CoA dehydrogenase deficiency.

Acyl-CoA Dehydrogenase, Long-Chain↗

The immunohistochemical expression of stress-response protein (srp) 60 in human brain tumours: relationship of srp 60 to the other five srps, proliferating cell nuclear antigen and p53 protein.

This study analyzed the expression of stress-response (heat-shock) protein 60 (srp 60) in a series of 158 human brain tumours. Immunohistochemical procedures were employed; cells of the human cervical cancer line HeLa S3 exposed to hyperosmolar stress served as positive controls. Deposits of reaction products were found in the cytoplasm. Approximately half of the glioblastomas multiforme (17/31), breast carcinoma metastases (6/10), and lung carcinoma metastases (5/11) as well as about one-third of the astrocytomas (5/13) and meningiomas (8/23) had tumour cells that expressed srp 60. A positive reaction for srp 60 was also seen in some medulloblastomas (2/16), primitive neuroectodermal tumours (PNETs) (2/11), schwannomas (2/21), and pituitary adenomas (2/7), but no positive reactions were observed with oligodendrogliomas and ependymomas. Compared with srp 60-negative tumours, srp 60-positive tumours coexpressed one or more stress-related proteins, among which srp 90, srp 72, srp 27, alphaB-crystallin and ubiquitin occurred with higher frequencies; a high correlation between srp 60 and the other five srps (0.88 - 0.97, p<0.01, Pearson correlation coefficient) was observed in srp 60-positive tumours. In contrast, the correlation coefficient in srp 60-negative tumours was not significant (-0.26 - 0.71). There was a tendency for the proliferating cell nuclear antigen (PCNA)-labeling index to be higher in glioblastomas, astrocytomas, medulloblastomas, PNETs, and breast and lung carcinoma metastases that expressed srp 60 than in those that did not. No significant immunohistochemical reactions of srp 60, PCNA and p53 protein were seen with sections of normal brain tissues. We conclude that primary and metastatic tumours of the brain produce srp 60 and that srp 60 in certain brain tumour cells may coexpress the other five srps. In addition, srp 60 expression might depend, in part, on proliferating potential.

Adolescent↗

Factors related to relapse after Le Fort I maxillary advancement osteotomy in patients with cleft lip and palate.

OBJECTIVE: To identify factors associated with relapse after maxillary advancement in cleft lip and palate patient. SUBJECTS: Seventy-one cleft lip and palate patients underwent Le Fort I maxillary advancement osteotomy between 1988 and 1998, and 58 patients (42 unilateral cleft and 16 bilateral cleft) with complete data were investigated for relapse by clinical and cephalometric analysis. The clinical follow-up period ranged from 1.5 to 8.5 years (mean 2.5 years). RESULTS: Horizontal advancement averaged 6.9 mm. There was a significant correlation between surgical movement and postoperative relapse in both the horizontal and vertical planes. In vertical repositioning, 15 patients had maxillary intrusion and 31 had inferior repositioning. There was a significant difference between the intrusion group and the inferior repositioning group. There was a significant correlation between surgical and postoperative rotation regardless of the direction. Other factors were evaluated by the horizontal relapse rate. Type of cleft and the rate of relapse were statistically associated. A relapse was more likely to occur in patients with bilateral cleft. There were no significant associations with the rate of relapse in type of operations or previous alveolar bone grafting. There was no significant correlation between the rate of relapse and the number of missing anterior teeth, postoperative overbite and overjet, and age at operation. Four of 71 patients experienced major relapse, and 3 of them underwent jaw surgery again. CONCLUSIONS: Based on clinical and cephalometric analysis, two-jaw surgery should be performed in cases of severe maxillary hypoplasia, and overcorrection may be useful in inferior repositioning or surgical rotation. Special attention should be paid to the patient with bilateral cleft, multiple missing teeth, or shallow postoperative overbite.

Adolescent↗

A glass capillary ultramicroelectrode with an electrokinetic sampling ability.

A glass capillary ultramicroelectrode (tip diameter approximately 1.2 microm) having an electrokinetic sampling ability is described. It is composed of a pulled glass capillary filled with an inner solution and three internal electrodes (Pt working and counter electrodes and an Ag/AgCl reference electrode). The voltammetric response of the capillary electrode is based on electrokinetic transport of analyte ions from the sample solution into the inner solution across the conical tip. It was found that the electrophoretic migration of analytes at the conical tip is faster than electroosmotic flow, enabling electrokinetic transport of analyte ions into the inner solution of the electrode. By using [Fe(CN)6]4- and (ferrocenylmethyl)trimethylammonium (FcTMA+) ions as model analytes, differential pulse voltammetric responses of the capillary electrode were investigated in terms of tip diameter of the capillary, sampling voltage, sampling time, detection limit and selectivity. The magnitude of the response depends on the size and charge of analyte ions. With a capillary electrode having a approximately 1.2-microm tip diameter, which minimizes non-selective diffusional entry of analytes, the response after 1 h sampling at +1.7 V is linearly related to [Fe(CN)6]4- concentration in the range of 0.50-5.0 mM with the detection limit of 30 microM. Application of a potential of the same sign as that of the analyte ion forces the analyte to move out from the electrode to the solution, enabling reuse of the same capillary electrode. The charge-selective detection of analytes with the capillary electrode is demonstrated for [Fe(CN)6]4- in the presence of FcTMA+.

Algorithms↗

Potentiometric responses of polymeric liquid membranes based on hydrophobic chelating agents to metal ions.

The effect of hydrophobicity of acidic chelating agents as sensing materials on the potentiometric responses of polymeric liquid membranes was investigated. The chelating agents tested were 8-quinolinol (HOx), dithizone (HDz), 1-(2-pyridylazo)-2-naphthol (PAN) and their alkylated analogues, 5-octyloxymethyl-8-quinolinol (HO8Q), di(phexylphenyl)thiocarbazone (C6HDz), 7-pentadecyloxy-1-(2-pyridylazo)-2-naphthol (C15PAN) and a series of N-alkylcarbonyl-N-phenylhydroxylamines (CnPHA, n = 3, 6, 9, 12). The distribution coefficients between membrane solvent and water were determined to evaluate the hydrophobicity of the agents. The potential-pH profiles of the membranes containing hydrophobic chelating agents demonstrated the generation of potentiometric responses, while less hydrophobic agents gave no response. A possible model for the generation of membrane potential is proposed. The charge separation is attained by the permselective uptake of metal cations by the chelating agent anion at membrane/solution interface, where the high hydrophobicity of the agent enables the anionic or deprotonated form of the agents to remain at the membrane/solution interface.

Journal Article↗

[Successful treatment of an elderly patient with idiopathic thrombocytopenic purpura accompanied with chronic subdural hematoma, using a Chinese herbal medicine, EK-49, and ascorbic acid].

An 88 year-old woman was admitted complaining of headache. CT scan of the head revealed a right subdural hematoma. She had been followed by a local physician because of chronic thrombocytopenia. Her peripheral platelet count on admission was 0.5 x 10(4)/microliter, with a high serum level of PAIgG. Bone marrow examination revealed marked increase of megakaryocyte. Idiopathic thrombocytopenic purpura(ITP) accompanied with chronic subdural hematoma was diagnosed. Transient increase of platelet count and improvement of subdural hematoma was obtained by administration of prednisolone. However, platelet count decreased with tapering of prednisolone. Then combined administration of a Chinese herbal medicine, EK-49, and ascorbic acid was started. Platelet count gradually increased and no adverse effects were experienced. These results indicated that elderly patients with chronic subdural hematoma can be treated non-invasively, and that a combination of EK-49 and ascorbic acid may be effective in the treatment of refractory ITP.

Aged↗

[EEG findings in a case of acute necrotizing encephalopathy of childhood associated with influenza A virus infection].

We reported here a case of symptomatic partial epilepsy following acute necrotizing encephalopathy of childhood associated with influenza A virus infection. This 2-year-old boy underwent repeated EEG recordings, which at the acute stage was dominated by diffuse 1-2 Hz slow waves. The background activity was 5 Hz theta waves on the 49th day. Paroxysmal activities appeared after the 89th day of illness. On the 231st day, EEG showed spike-and-waves on the left and right frontal areas. Interestingly, paroxysmal activities preceded the onset of epileptic seizures by 7 months, and spike-and-waves by 2 months. After 10 months, he had generalized seizures with fever, and partial seizures on awakening without fever. Interictal EEG showed spike-and-waves on the bilateral frontal areas, and diffuse polyspikes and slow waves were occasionally seen. Though the background activity improved, his consciousness level did not recover probably because the thalamus, basal ganglia, brainstem were damaged more severely than the cerebral cortex.

Child, Preschool↗

Allelic losses of loci at 3p25.1, 8p22, 13q12, 17p13.3, and 22q13 correlate with postoperative recurrence in breast cancer.

We previously defined 18 chromosomal regions in which frequent allelic losses were observed in breast cancers (T. Sato et al., Cancer RES:, 50: 7184-7189, 1990; Y. Harada et al., Cancer (PHILA:), 74: 2281-2286, 1994; I. Ito et al., BR: J. Cancer, 71: 438-441, 1995; K. Tsukamoto et al., Cancer (PHILA:), 78: 1929-1934, 1996; S. Matsumoto et al., Genes Chromosomes Cancer, 20: 268-274, 1997; T. Yokota et al., JPN: J. Cancer RES:, 88: 959-964, 1997; K. Tsukamoto et al., Cancer (PHILA:), 82: 317-322, 1998; A. Iida et al., Genes Chromosomes Cancer, 21: 108-112, 1998; K. Fukino et al., Genes Chromosomes Cancer, 24: 345-350, 1999; T. Yokota et al., Cancer (PHILA:), 85: 447-452, 1999; Y. Utada et al., JPN: J. Cancer RES:, 91: 293-300, 2000). To identify specific allelic losses that might correlate with postoperative recurrence, we examined tumors from a cohort of 504 breast cancer patients, who were followed clinically for 5 years postoperatively, for allelic losses of 18 microsatellite markers. Patients whose tumors had lost an allele at 3p25.1, 8p22, 13q12, 17p13.3, or 22q13 had significantly higher risks of recurrence than those whose tumors retained both alleles at those loci; at 3p25.1, the 5-year recurrence rate was 27% among patients with losses versus 18% with retention (P = 0.0131); at 8p22, 27% versus 14% (P = 0.0129); at 13q12, 28% versus 15% (P = 0.0109); at 17p13.3, 27% versus 20% (P = 0.0482); and at 22q13, 29% versus 20% (P = 0.0477). These data indicate that loss of heterozygosity at any one of these five specific loci is a significant predictor of postoperative recurrence among patients who have undergone surgery for breast cancer. These allelic losses can serve as negative prognostic indicators to guide postoperative management of patients.

Adult↗

[A case of collecting duct carcinoma (Bellini duct carcinoma) producing carcinoembryonic antigen].

We report a case of collecting duct carcinoma (Bellini duct carcinoma) producing carcinoembryonic antigen (CEA). A 61-year-old man visited our hospital because of a left renal mass detected by ultrasonography in an other hospital. Computed tomography showed a low density tumor measuring about 3 cm in the left kidney. Angiography demonstrated a hypovascular tumor. The serum level of CEA was increased to 20 ng/ml. (normal < 7 ng/ml). Left radical nephrectomy was performed. Histological examination revealed collecting duct carcinoma with papillary growth (T1aN1M0). Cancer cells showed a positive immunohistochemical staining for CEA. Under a diagnosis of CEA-producing collecting duct carcinoma of the left kidney, the patient underwent systemic chemotherapy (M-VAC). The serum level of CEA decreased to the normal level after the nephrectomy, but six months postoperatively, metastatic bone tumor at the left pelvic bone was revealed on the plain film and at the same time, the CEA level was increased again.

Antineoplastic Combined Chemotherapy Protocols↗

[Effect of G-CSF (nartograstim) on neutropenia (leukopenia) induced by taxane in metastatic breast cancer--time-course changes in neutrophil and leukocyte counts].

Since 1997, we have used docetaxel and paclitaxel as the second-line and third-line chemotherapies against anthracycline-resistant metastatic breast cancer. However, these taxane compounds induced neutropenia and leukopenia, which may be reversed by G-CSF (Nartograstim). We thus examined the therapeutic efficacy of nartograstim for time-course changes in neutrophil and leukocyte counts in these patients. No difference was observed in neutrophil or leukocyte count whether the patient was treated with docetaxel or paclitaxel. Neutrophil and leukocyte counts reached a nadir on days 7 to 8 after administration. With a 5-6 day administration of nartograstim, neutrophil or leukocyte counts recovered by the second or third day after the nadir, indicating that the chemotherapy was given safely with nartograstim. In these same patients receiving a given treatment cycle, the number of days until reaching the nadir were almost identical for neutrophils and leukocytes; however, the duration of the nadir and the time to count recovery was significantly longer for neutrophils than for leukocytes. In the clinical setting, the parameter "leukocyte count" has been occasionally used for evaluation of the severity of myelosuppression, because the data is more readily available. However, at least during the nadir, the "neutrophil count" should be used as the parameter of choice.

Antineoplastic Agents↗