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Biomedical subjects

Y Ariyoshi

Publications and source records attributed to Y Ariyoshi.

At least 199 records · Page 11Linked to original sources

Immunoassay of three enolase isozymes in human serum and in blood cells.

Sandwich enzyme immunoassay procedures for measurement of three human enolase isozymes (alpha alpha, alpha gamma and gamma gamma forms) were developed by use of purified antibodies specific to the alpha or the gamma subunit of enolase. The assay systems consisted of polystyrene balls with immobilized antibody F(ab')2 fragments and antibody Fab' fragments labeled with beta-D-galactosidase from E. coli. The measurable range was from 3 pg to 10 ng of each enolase isozyme per assay tube, and the levels of the three enolases in human sera and isolated blood cells were determined. Serum samples from healthy adults contained about 60, 8, and 2 ng/ml of alpha alpha, alpha gamma, and gamma gamma enolases, respectively. Red blood cells and platelets had about 4, 1, and 0.1 ng/10(6) cells of alpha alpha, alpha gamma, and gamma gamma enolases, respectively. Lymphocytes (mononuclear cells) contained larger amounts of all three enolases (alpha alpha, 370 ng/10(6) cells; alpha gamma, 30 ng/10(6) cells; gamma gamma, 2.7 ng/10(6) cells). The levels of three enolase isozymes in sera of patients with small-cell cancer of the lung were also determined.

Blood Platelets↗

Production and characterization of a monoclonal antibody to human nervous system-specific gamma gamma enolase.

A mouse hybrid cell line producing an antibody to human nervous system-specific gamma gamma enolase has been isolated by fusions between gamma gamma-immunized mouse spleen cells and mouse myeloma cells (P3-NS-1/1-Ag4-1), followed by a screening procedure with an enzyme immunoassay. This particular cell line (E1-G3) has secreted the antibody bearing gamma 2a/kappa immunoglobulin chains. Specificity of the E1-G3 antibody was tested by immunoprecipitation of enolase activities with anti-mouse IgG, and by use of enzyme immunoassay systems for enolase isozymes which consisted of polyclonal rabbit antibodies. The E1-G3 antibody was found to be specific for the gamma subunit of enolase, showing reactivities with human gamma gamma and alpha gamma enolases, and also with rat gamma gamma enolase. However, the monoclonal antibody did not cross-react with the alpha or beta subunit of human enolase.

Animals↗

Secretory component and IgA in endometrial adenocarcinomas. An immunohistochemical study.

The localization of secretory component (SC) and IgA was immunohistochemically studied in 6 normal endometrium and 55 endometrial adenocarcinomas including 34 well, 11 moderately and 10 poorly differentiated ones. In normal endometrium, SC localization was found in the cytoplasm of epithelial cells and luminal contents of the gland. IgA showed similar localization of SC. Secretory phase endometrium contained proportionally larger numbers of positive cells for SC and IgA than proliferative phase endometrium. SC localization was found in all cases of well and moderately differentiated carcinomas, while it was found only in 4 cases out of 10 poorly differentiated carcinomas. IgA localization was similar to that of SC and this condition was thought to reveal the binding of IgA to SC existing in the tumor cells. The present immunohistochemical study revealed that the staining intensity of SC well correlated with the histological grade of differentiation of the tumors.

Adenocarcinoma↗

Evaluation of serum neuron-specific enolase as a tumor marker for carcinoma of the lung.

Serum neuron-specific enolase (NSE) was measured in 80 normal subjects, 20 patients with small cell carcinoma of the lung (SCCL) and 54 patients with non-small cell carcinoma (non-SCCL). The mean value in the control group was 2.1 +/- 0.4 ng/ml (range, from 1.3 to 3.0 ng/ml). Serum levels exceeding 7.5 ng/ml were tentatively defined as positive. Thirteen of 20 patients (65%) with SCCL had positive serum NSE levels, whereas 6 of 54 patients (11%) with non-SCCL had positive levels. Positive NSE in sera of patients was observed only in patients with advanced clinical stage of SCCL or non-SCCL. No correlation between serum NSE levels and metastatic sites could be found. The serum NSE levels in subtypes of SCCL were positive in 9 of 10 patients with oat cell carcinoma and 4 of 10 patients with intermediate cell carcinoma. Histological types of all positive cases with non-SCCL included large cell carcinoma. Serum NSE levels changed in parallel with the clinical course during the treatments. The data suggested that serum NSE may be a useful marker for monitoring the clinical course of lung carcinoma, especially of SCCL. Furthermore, the detection of NSE in non-SCCL is of interest in relation to the histogenesis of lung carcinomas which exhibit the properties of neuroendocrine tumors.

Adenocarcinoma↗

[Neuron-specific enolase as a new tumor marker].

Enolase is a glycolytic enzyme widely distributed in each mammalian tissue and consists of three distinct subunits alpha, beta, and gamma. In the brain enolase exhibits three dimetric isozymic forms: alpha alpha, alpha gamma and gamma gamma. The gamma protein subunit has recently been found to be identical with the nervous system-specific and species-nonspecific protein, 14-3-2; therefore, alpha gamma and gamma gamma types of enolase were characterized as neuron-specific enolase (NSE). NSE has been also detected in the pituitary gland, thyroid gland, adrenal medulla and pancreas, all of which contain neuroendocrine cells. Recently NSE was observed by immunostaining or radioimmunoassay in neuroendocrine tumor such as glucagonomas, insulinomas, gut carcinoids, medullary thyroid carcinomas or neuroblastomas. Furthermore, small cell carcinoma of the lung which has been known to frequently exhibit neuroendocrine properties was found to produce NSE. In this paper NSE as a tumor marker in various cancers was evaluated by immunostaining or enzyme immunoassay which was developed by a co-worker Kato. The data revealed that serum NSE was clinically useful as a tumor marker, especially a monitoring marker of disease extent. NSE productions were also observed in adenocarcinoma of the colon or the lung and large cell carcinoma of the lung as well as small cell carcinoma of the lung and the esophagus, all of which were considered to share the biochemical features of neuroendocrine tumor. The evidence challenges a speculation that small cell carcinoma of the lung has an origin separated from the other histological types of lung carcinoma. In this meaning NSE is an important tumor marker for both clinical medicine and basic research.

Animals↗

[Serum cortisol fractions in breast cancer].

Serum cortisol fractions were determined by isocolloidosmolar equilibrium dialysis in 93 women with breast cancer and 29 normal women. In breast cancer patients, the percentage of protein-unbound cortisol was increased at any concentration of total serum cortisol; this was accompanied by a relative decrease in the percentage of transcortin-bound cortisol. A significant increase in the unbound fraction is indicative of accelerated physiological activity of cortisol in breast cancer patients. In the breast cancer cases, there was a high incidence of obesity (61%) and impaired glucose tolerance (85%). In obese and/or diabetic patients, more remarkable increases of unbound cortisol were observed. We suggest that obesity and impaired glucose tolerance may increase the risk for breast cancer, and that the characteristic increase in the unbound cortisol fraction in women with breast cancer may reflect such risk factors.

Adult↗

[Chemotherapy for metastatic lung cancer].

The effects of chemotherapy for lung metastasis in 284 cancer patients using various anti-tumor drugs, including classic ones and modern active agents for the past 18 years, were presented. Lung metastasis for lung cancer was excluded. The response was achieved in cervical carcinoma of the uterus (17/62, 27%), endometrial carcinoma of the uterus (1/7, 14%), colorectal cancer (6/39, 15%), breast cancer (5/28, 18%) and stomach cancer (4/28, 14%). A high response was achieved in myosarcoma (5/12, 42%), testicular cancer (5/11, 45%) and also in ovarian cancer (3/10, 30%). Though there were few cases, a high response was achieved in malignant melanoma (2/3), choriocarcinoma (2/4) and esophageal cancer (1/3). In total patients the response rate was 20%. In these cases a complete response was achieved in 4 cervical cancers; one testicular cancer, ovarian cancer, esophageal cancer and renal cancer, respectively. However, the effect was temporary and no longterm survivor was observed except for one case of renal cancer treated continuously with interferon (3 X 10(6) units daily) and showing complete remission after 7 months of therapy. The effect of chemotherapy for lung metastasis was compared between nodular metastasis (NM) and lymphagiosis carcinomatosa (LC). In cervical carcinoma of the uterus, the response rate in NM (39%) was higher than in LC (11%). However, no difference was observed in breast cancer (NM 15%, LC 13%) nor in stomach cancer (NM 13%, LC 18%).

Antineoplastic Agents↗

The response to endocrine therapy in patients with advanced breast cancer in Great Britain and Japan.

A prospective study has been carried out to compare the response rates to endocrine therapy of Japanese and British women with breast cancer. Premenopausal women were treated by ovarian ablation, patients who were up to five years postmenopausal were prescribed androgen therapy and patients who were more than five years postmenopausal were treated with oestrogens. No differences in response rate, response time or survival could be detected in the three categories of patients. Significantly more Japanese patients presented with pulmonary metastases in the pre- and postmenopausal groups. In postmenopausal Japanese patients treated with oestrogens, those with pulmonary metastases survived significantly longer.

Adult↗

Effects of N-beta-phenylpropionyl-L-tyrosine and its derivatives on the excitability of an identifiable giant neuron of Achatina fulica férussac.

1. Previously the authors demonstrated the inhibitory effects of the two aromatic amino acid derivatives, N-beta-phenylpropionyl-L-Tyr (critical concentration (c.c.), 3 x 10(-7) - 10(-6) M) and N-beta-phenylpropionyl-L-Trp (c.c., 10(-6) M) on the excitability of an identifiable giant neuron, TAN (tonically autoactive neuron), of Achatina fulica Férussac. The effects of the derivatives of the two inhibitory compounds on the same neuron are examined in the present study. 2. N-beta-Cyclohexylpropionyl-L-Tyr (c.c., 3 x 10(-8) - 10(-7) M) and N-beta-cyclohexylpropionyl-L-Trp (c.c., 10(-6) M) had marked inhibitory effects, whereas N-beta-p-methyl-phenylpropionyl-L-Tyr had none. 3. N-gamma-Phenylbutyroyl-L-Tyr and N-phenylacetyl-L-Tyr, in which the chain length of the phenyl group is different, had no effect. 4. N-beta-Phenylpropionyl-N-methyl-L-Tyr, in which the imino group of the peptide bond is methylated, had no effect. 5. N-beta-Phenylpropionyl-L-Tyr (c.c., 3 x 10(-7) - 10(-6) M) and N-beta-phenylpropionyl-L-Tyr methylester (c.c. 1-3 x 10(-6) M) had marked inhibitory effects, suggesting that their carbonyl group acts as a proton acceptor. 6. N-beta-Phenylpropionyl-L-p-hydroxyphenylglycine, in which the chain length of the hydrogen binding group is shorter, had no effect. 7. N-beta-Phenylpropionyl-L-3,4-dihydroxy-Phe (c.c., 3 x 10(-6) M), N-beta-phenylpropionyl-L-3-nitro-Tyr (c.c., 3 x 10(-5) M) and N-beta-phenylpropionyl-L-p-amino-Phe (c.c., 3 x 10(-5) - 10(-4) M) had inhibitory effects, weaker than that of N-beta-phenylpropionyl-L-Tyr. N-beta-Phenylpropionyl-L-p-chloro-Phe and N-beta-phenylpropionyl-L-p-nitro-Phe showed the same effect only at high concentrations.

Animals↗

Structure-activity relationships of N-beta-phenylpropionyl-L-tyrosine and its derivatives on the inhibition of an identifiable giant neurone of an African giant snail (Achatina fulica Férussac).

1 Inhibitory effects of N-beta-phenylpropionyl-L-tyrosine, N-beta-phenylpropionyl-L-tryptophan and their derivatives on an identifiable giant neurone, TAN (tonically autoactive neurone) of an African giant snail (Achatina fulica Férussac) were examined in an attempt to elucidate which structural features are necessary to produce the effect. 2 Of the compounds examined, N-beta-cyclohexylpropionyl-L-tyrosine showed the strongest effect. Its critical concentration (c.c.) was 3 X 10(-8)-10(-7)M, about ten times lower than that of N-beta-phenylpropionyl-L-tyrosine (c.c., 3 X 10(-7)-10(-6)M). N-beta-cyclohexylpropionyl-L-tryptophan (c.c., 10(-6)M) had an effect almost similar to that of N-beta-phenylpropionyl-L-tryptophan (c.c., 10(-6)M). 3 N-beta-Phenylpropionyl-N-methyl-L-tyrosine had no effect at a high concentration. 4 Effects of N-beta-phenylpropionyl-L-tyrosine amide (c.c., 3 X 10(-7)-10(-6)M) and N-beta-phenylpropionyl-L-tryptophan amide (c.c., 10(-6)M) were very similar to those of N-beta-phenylpropionyl-L-tyrosine and N-beta-phenylpropionyl-L-tryptophan respectively. 5 N-beta-Phenylpropionyl-p-amino-L-phenylalanine (c.c., 3 X 10(-5)-10(-4)M) and N-beta-phenylpropionyl-p-chloro-L-phenylalanine (c.c., 10(-4)M) had only a weak effect. 6 It is proposed that the structural features producing the effect are as follows: the active compound has a phenyl or a cyclohexyl group (hydrophobic binding group), after a suitable distance a peptide bond (proton donor and proton acceptor), adjacently a carbonyl group (proton acceptor), and a phenolic hydroxyl or an indolyl imino group (proton donor) in the molecule.

Animals↗

The serum concentrations of unbound, transcortin bound and albumin bound cortisol in patients with dysproteinemia.

Three cortisol fractions, protein-unbound (U-F), transcortin-bound (Tr-F) and albumin-bound cortisol (Al-F) were measured in patients with dysproteinemia by a newly devised isocolloidosmolar equilibrium dialysis method. Total cortisol (Total-F) concentrations in patients with liver cirrhosis (LC), anorexia nervosa (AN) and cachexia due to cancer (CA) were higher than in normal subjects, and those in patients with nephrotic syndrome (NS) and multiple myeloma (MM) remained within the normal range. In all groups of patients, the U-F concentration, which is believed to be the sole active fraction of cortisol, showed significantly higher values than in the normal subjects. We, therefore attempted to find which of the two binding proteins contributes to the elevated U-F concentrations. Concentrations of each cortisol fraction are greatly changed by alterations in the Total-F concentration. We therefore compared the Tr-F against Total-F and Al-F, and U-F against Total-E of patients with those of normal subjects. It was found that decreased transcortin-binding and not albumin-binding in the patients with cirrhosis, nephrotic syndrome and myeloma contributed to an increase in the U-F concentration. Although decreased binding of albumin due to hypoalbuminemia was found in LC, NS, MM, CA and AN, it had relatively little effect on cortisol distribution in the serum.

Anorexia Nervosa↗

[Optimal administration schedules of antineoplastic antibiotics based on their pharmacokinetics, with special reference to bleomycins and anthracyclines].

Optimal dose schedule of administration of antitumor antibiotics-bleomycin, adriamycin and aclacinomycin A-was reviewed from a point of view of pharmacokinetics. In case of bleomycin, according to its fast disappearance from blood, fast and significant excretion into urine, cell-cycle-dependent antitumor action, fast repair of potentially lethal damage, and pulmonary toxicity due to damage in endothelium of pulmonary capillary caused by high blood concentration of bleomycin, continuous intravenous administration seems to be a useful method to prevent pulmonary toxicity and to enhance antitumor effect. In case of adriamycin, according to its cardiotoxicity due to damage in cardiac muscle cell caused by high blood concentration on adriamycin, drip infusion or weekly low dose schedule is a safe, effective therapy to prevent cardiomyopathy. In case of aclacinomycin A, based on the mechanism of action of its marked inhibition in RNA synthesis compared to adriamycin, daily administration for certain days is an effective method.

Aclarubicin↗

Argyrophil cell carcinoma of the uterine cervix with ectopic production of ACTH, beta-MSH, serotonin, histamine, and amylase.

The case of a 38-year-old female with primary argyrophil cell carcinoma of the uterine cervix is reported. Two years after operation the patient developed widespread metastases with typical Cushing's syndrome. Microscopically, the tumor consisted of solid anaplastic cells, adenocarcinoma, and squamous cells. The plasma levels of ACTH and cortisol were elevated. Many cells of both the primary and metastatic tumors showed argyrophilia. Almost all the cells of the metastases contained numerous round secretory granules measuring about 117 micrometers in diameter. Small rod-shaped or larger round secretory granules, measuring 250 and 430 micrometers respectively, were also found in a few of these cells. The tumors in the right lung, pancreas, and kidney contained high levels of ACTH, beta-MSH, serotonin, histamine, and amylase. This is the first report of ectopic production of these five substances from argyrophil cell carcinoma of the uterine cervix.

Adrenocorticotropic Hormone↗