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Biomedical subjects

R Nishimura

Publications and source records attributed to R Nishimura.

At least 289 records · Page 16Linked to original sources
PubMed1983

Heterogeneity of free alpha-subunit in term placenta.

Free alpha-subunit in normal term placenta was examined for molecular weight, electric charge and ability to combine with standard hCG-beta in comparison with extracellular free alpha-subunit and standard hCG-alpha dissociated from urinary hCG in vitro. The gel chromatography on Sephadex G-100 of the placental extract revealed three major immunoreactive hCG-alpha peaks, designated as P alpha-A (Kav = 0.32-0.46), P alpha-B (0.47-0.58) and P alpha-C (0.59-0.70), near the position of standard hCG-alpha. In the isoelectric focusing, while P alpha-A was mainly distributed over the acidic region, the major components of P alpha-B and P alpha-C were distributed over the basic region. Furthermore, in the combination study with standard hCG-beta, such a alpha-subunit with acidic pI scarcely showed any combining activity whereas alpha-subunit with basic pI revealed significant combining activity. These results suggest the following possibilities: that 1) the various size species of placental alpha-subunit may be responsible for the progressive glycosylation; 2) the small alpha-subunit with basic pI may combine with beta-subunit to form immunoreactive hCG; 3) the alpha-subunit, which has not associated with beta-subunit, may be converted to a large and incombinative form with acidic pI by further glycosylation, followed by secretion as a free alpha-subunit.

Chorionic Gonadotropin↗
PubMed1983

Discordant pregnancy tests in detection of alpha-subunit--producing tumors.

Ectopic production of isolated alpha-subunit of glycoprotein hormones was detected in a 32-year-old Japanese woman with metastatic lung tumor by a discordance in the immunologic pregnancy tests for native human chorionic gonadotropin (hCG) assays. Quantitative discrepancy of titrations among different types of pregnancy tests, ie, competitive (hemagglutination or latexagglutination inhibition) and noncompetitive (hemagglutination or latexagglutination) reactions, was also confirmed experimentally using a highly purified ectopic alpha-subunit from the patient's urine. Thus the discrepancy between the 2 types of assay systems was due, at least partly, to a cross-reaction of high concentrations (20,000 ng/ml) of ectopically secreted free alpha-subunit of glycoprotein hormones.

Adult↗
PubMed1983

[Radiolysis of acrinol in radio-sterilization of acrinol pharmaceuticals].

Acrinol in dry solid state after gamma irradiation with 80 kGy (8 Mrad) undergoes 8% decomposition, with G(-M)=30, and in wet solid state (10% moisture content) undergoes 15% decomposition, with G(-M)=56, as shown by absorbed spectrometric measurement. From these results, it is estimated that the irradiation dose of 25 kGy (2.5 Mrad) prefered by many countries as sterilization dose will achieve the radiolysis rate of 2.8% or 4.7% for dry solid state or wet solid state acrinol, respectively. The stickiness power of plaster tape made of raw rubber and polyterpene resin don't decrease with irradiation dose of less than 40 kGy (4 Mrad). Then, the radio-sterilization on the dose of 25 kGy (2.5 Mrad) may be applied to solid pharmaceuticals such as commercial rubber adhesive plaster with acrinol pad. Besides, acrinol in 0.1% aqueous solution after irradiation of 10 kGy (1 Mrad) at room temperature undergoes 20% decomposition, with G(-M)=0.5. The radiolysis rate in this state is estimated 45% with the dose of 25 kGy (2.5 Mrad). Then, the radio-sterilization with this dose must not be applied to liquid pharmaceuticals such as 0.1% acrinol aqueous solution. While, it was reported by Hosobuchi and Sato that the antimicrobial effect of irradiated acrinol to Staphlococcus aureus increased with irradiation dose. Then, it is expectable that some materials with antimicrobial activity are prodused by gamma irradiation.

Acridines↗
PubMed1983

Concentration-dependent differential effect of retinoic acid on intercellular metabolic cooperation.

A vitamin A analog, 13-cis-retinoic acid (13-cis-RA), was tested for effect on intercellular metabolic cooperation between 6-thioguanine-resistant and -sensitive V79 Chinese hamster cells. Most typical tumor promoters have been reported to inhibit metabolic cooperation. 13-cis-RA was found to enhance metabolic cooperation of cells treated with a potent tumor promoter, 12-O-tetradecanoyl-phorbol-13-acetate. However, inhibition of metabolic cooperation was noticed when 13-cis-RA was used at higher concentrations.

Animals↗
PubMed1983

[Biological and clinical analysis of breast cancer in relation to hormone receptors].

We examined whether or not the presence of hormone receptors (ERC, PRC, and ERN) were related to morphological and functional features in breast cancers. Well-differentiated tumors were more frequently receptor positive while poorly differentiated tumors were generally receptor negative. And labelling index and receptor contents were negatively correlated. There was a significant inverse correlation between the receptor contents and numbers of intracellular organellas in ultrastructural features of breast cancer cells. In LMI tests by 3-M KCl cancer extracts, migration of leucocyte from patients with poorly differentiated tumors were more frequently inhibited than those well differentiated tumors. Patients with receptor positive tumors were more endocrine sensitive and had better prognosis.

Breast Neoplasms↗
PubMed1982

[The response of free alpha-subunit of glycoprotein hormones to LH-RH administration (author's transl)].

The responses of immunoreactive free alpha-subunit of glycoprotein hormones to LH-RH administration were studied in normal men and women, and in patients with hypergonadotropic hypogonadism, hypogonadotropic hypogonadism, trophoblastic disease and isolated ectopic alpha-subunit producing tumor. In patients with hypergonadotropic hypergonadism, basal levels of serum alpha-subunit were elevated and the responses to LH-RH were also excessive compared to those of normal men and women. Conversely, in hypogonadotropic hypogonadism, basal levels of alpha-subunit were significantly low and its response to LH-RH was barely detectable. The response of alpha-subunit to constant intravenous infusion of LH-RH (1 microgram/kg/h) was studied in 4 normal men. Both LH and alpha-subunit revealed biphasic patterns of elevation. Its releasing pattern suggests the possibility that two pools of gonadotropin are involved in the production and secretion of alpha-subunit. In patients with trophoblastic disease secreting low levels of hCG (18 mIU/ml), the responses of alpha-subunit as well as pituitary gonadotropin to LH-RH were normal. However, in cases of high concentrations of hCG (1000 mIU/ml), the responses of alpha-subunit and gonadotropin were suppressed. After the administration of LH-RH to a patient with an isolated ectopic alpha-subunit producing tumor, the serum concentration of pituitary gonadotropin increased within the normal range, although that of alpha-subunit did not show a significant change. These results suggest that the production of alpha-subunit by tumors may be autonomous in contrast with a regulatory production in the pituitary.

Adult↗
PubMed1982

[Studies on the regulatory mechanism of ovarian hCG receptors and placental luteotropin in rats (author's transl)].

The influences of exogenous hCG on rat (pseudopregnant and pregnant) ovarian hCG receptors and the presence of hCG-like material in the rat placenta were investigated. Ovarian hCG receptors in immature rats induced by PMS-hCG priming maintained a binding activity for about 20 days after hCG injection. The administration of hCG to pseudopregnant rats caused time and dose related changes in ovarian 125I-hCG binding percentage and the concentration of serum progesterone. The injection of hCG produced a slight decrease in the binding percentage and was followed by a marked decrease. The measurement of ovarian tissue hCG concentration by radioimmunoassay suggested that the initial loss of binding percentage was associated with the occupancy of receptors by the exogenous hCG, but the major loss of binding percentage might not be attributed to the receptor occupancy. The active process might be involved in the mechanism of receptor loss. The progesterone concentration in sera had a tendency to increase after the injection of 25IU hCG, while it decreased after the injection of 125IU hCG. The 125I-hCG binding percentage to ovaries and the serum concentration of progesterone reached their maximal values from mid to late pregnancy and declined as parturition approached. After the injection of hCG into pregnant rats, the binding percentage rapidly decreased and the serum concentration of progesterone increased. Thereafter the binding percentage recovered on the 4th day after the injection of hCG. On that day, though the concentration of hCG in ovarian tissue was barely detectable, the binding percentage was significantly low compared to the control level. The rat placenta (8th to 21st day of pregnancy) contained hCG-like activities, but they could not be detected in peripheral blood. In the treatment of hCG-antibody in pregnant rats, the binding percentage did not change but the serum concentration of progesterone showed a tendency to decrease to the control level. These studies show that hCG receptors exist as free sites in pregnant and pseudopregnant rat ovaries and may be regulated by down regulation after the treatment of large amounts of exogenous hCG. We found that hCG-like material in rat placenta determined by radioimmunoassay might serve as a luteotropin during pregnancy.

Animals↗
PubMed1982

Relationship between the content of estrogen and progesterone receptors and the pathological characteristics in human breast cancer.

Assays of estrogen receptors (ER) and progesterone receptors (PgR) were performed by using the dextran-coated charcoal (DCC) method in 124 cases of invasive breast cancer. The results were correlated with clinical and pathological characteristics. There was no correlation between steroid hormone receptor contents and menopausal status, size of tumor, axillary lymph node status, or histological type. The presences of ER and PgR were significantly correlated with histological grade and its mitotic component. 78.3% of well-differentiated (Grade I) tumors were ER positive. Of this number, 61.1% were also PgR positive. In contrast, 69.0% of poorly differentiated (Grade III) tumors were ER and PgR negative. Tumors with a prominent lymphoid infiltration demonstrated a low frequency of positive ER and PgR. There was a significant inverse correlation between the degree of lymphoid infiltration and histological grade. These results suggest that the ER and PgR status of tumors may indicate a malignancy, and prognostic information can thus be obtained independently of other known factors such as size of the tumor and axillary lymph node status.

Adenocarcinoma↗
PubMed1982

The characterization of alpha-subunit of glycoprotein hormone produced by undifferentiated carcinoma.

The glycoprotein hormone alpha-subunit was extracted and purified from the urine of a patient with undifferentiated carcinoma producing isolated alpha-subunit. Its final specific immunoactivity was 0.92 (mg alpha-subunit/mg protein). The alpha-subunit exhibited virtually identical immunoantigenicity to hCG-alpha antiserum with standard hCG-alpha. The molecular weight of the alpha-subunit determined by gel chromatography on Sephadex G-100 was greater than that of standard hCG-alpha dissociated by urea in vitro. By SDS disc electrophoresis, however, the alpha-subunit moved faster than hCG-alpha separated by mercaptoethanol reduction. The amino acid composition of the alpha-subunit was quite similar to that of standard hCG-alpha. In the isoelectric focusing, the major components of the alpha-subunit from undifferentiated carcinoma and the alpha-subunit from urine of normal pregnant women (third trimester) were distributed over the range from pH 3.5 to 6.0, while standard hCG-alpha was distributed in the fractions ranging from pH 6.0 to 8.0. The result of a combination study in vitro indicated that both alpha-subunits from undifferentiated carcinoma and from urine of normal pregnant women did not actively combine with hCG-beta. These results suggest that the alpha-subunit secreted by undifferentiated carcinoma is virtually identical with standard hCG-alpha as the protein moiety but differs in regard to carbohydrate moiety, and also suggest that the excess of alpha-subunit, which is not associated with beta-subunit, may have undergone some intracellular modification, and consequently, the electric charge of the freely secreted alpha-subunit changes and it no longer has the ability to combine with the beta-subunit.

Adult↗
PubMed1982

[Discordance of competitive and non-competitive pregnancy tests for human chorionic gonadotropin, as related to alpha subunit producing tumor (author's transl)].

Ectopic production of isolated alpha subunit of glycoprotein hormones(s) in 32-year-old woman with metastatic lung tumor was first detected by a discordance in the immunological pregnancy tests for native human chorionic gonadotropin (hCG). Quantitative discrepancy of titrations among different types of pregnancy test kit, that i, competitive (hemagglutination or latex agglutination inhibition) and non-competitive (hemagglutination or latex agglutination) reactions, was also confirmed by the experimental study using highly purified ectopic alpha-subunit from the patient's urine. Thus, the discrepancy among the two types of assay systems was due by crossreaction of high concentrations (20,000 ng/ml) of ectopically secreted alpha-subunit of glycoprotein hormone(s). We report herein the typical behavior of immunological assay systems for native hCG in determining immunoreactive free hCG-alpha and stress the diagnostic value of the discordance observed in these assay systems.

Adult↗
PubMed1982

Measurement of nuclear estrogen receptors by charcoal adsorption: relationships of cytoplasmic and nuclear estrogen receptors and progesterone receptors in human breast cancer.

Nuclear estrogen receptors (ERN) were measured in human breast cancer and 7,12-dimethylbenz[a]anthracene-induced mammary carcinoma using the dextran-coated charcoal method without addition of an adsorbing material such as hydroxyapatite. Cytoplasmic estrogen receptors (ERC), cytoplasmic progesterone receptors (PgR), and ERN were measured in 111 primary and 11 locally recurrent breast cancers. ERC were found in 52%, PgR in 35%, and ERN in 40%. ERN and PgR were more frequent in tumors with a higher level of ERC. PgR were more frequent in ERN-positive tumors, and ERN were more frequent in PgR-positive tumors. The addition of an ERN assay to both ERC and PgR assay may be more informative for prediction of estrogen dependency than the mere determination of the existence of receptors in the cytoplasm.

Adsorption↗
PubMed1981

[Biological and biochemical properties of human chorionic gonadotropin from urine of patients with hydatidiform mole and its radioimmunoassay (author's transl)].

Human chorionic gonadotropin (hCG) was extracted and purified from the urine of four patients with hydatidiform mole. The immunological activities of the hCG-hydatidiform mole by hCG radioimmunoassay (RIA) ranged from 9,380 to 9,700 IU/mg, and the biological activities measured by the immature rat ovarian weight method ranged from 7,250 to 7,780 IU/mg. The results of the amino acid compositions of all the hCG-hydatidiform moles were practically identical with those of hCG-normal pregnancies. The carbohydrate moiety of the hCG-hydatidiform mole was also suspected to be almost similar to that of hCG-normal pregnancies by the results of their in vitro and in vivo biological activities. It was demonstrated that hCG-hydatidiform mole was composed of alpha and beta subunits (similar to a hCG-normal pregnancy) when hCG-hydatidiform mole was separated into subunits by SDS disc electrophoresis after treatment with mercaptoethanol. The RIA system of hCG-hydatidiform mole can be established. The concentrations of hCG in sera of normal pregnant women and patients with trophoblastic diseases assayed by hCG-hydatidiform mole RIA were equivalent to those obtained by a standard hCG RIA. Hence, a standard hCG-immunoassay method used in the management of hCG is concerned.

Adult↗
PubMed1981

High-performance liquid chromatographic analysis of a new beta-lactam antibiotic, 6059-S (moxalactam).

Reversed-phase high-performance liquid chromatography was applied to the quantitative determination of a new beta-lactam antibiotic, 6059-S, ant its R- and S-epimers were resolved. The procedure was also applied to pharmaceuticals and human urine samples. Chromatographic separation was effected on a bonded hydrophobic stationary phase with two mobile phases: methanol-phosphate butter for the resolution of the epimers and methanol-tetra-n-butylammonium phosphate for the quantitation of 6059-S. For the determination of 6059-S in human urine, the latter mobile phase was used successfully without interference by the other urine components. An in vivo experiment was conducted by administering intravenously 1 g of 6059-S to seven volunteers and analysing their urine by chromatographic and microbiological assays, and a comparison of the results gave a correlation coefficient of 0.9954. One-compartment model analysis of the time-course data revealed that 6059-S was excreted in urine intact with a rate constant of 0.433h-1.

Cephalosporins↗
PubMed1981

Antiandrogenic therapy for the treatment of early stage prostatic cancer.

The goal of this study was to achieve clinical application of antiandrogens for the treatment of carcinoma of the prostate. Based on the results obtained from animal experiments and from a pilot clinical trial on prostatic cancer patients using various antiandrogenic compounds, chlormadinone acetate (CMA) was selected for a clinical trial in patients with carcinoma of the prostate. With nine universities and their affiliated hospitals participating, the therapeutic effect of CMA for carcinoma of the prostate was investigated nationwide. Highly satisfactory antitumor effects with CMA were observed in stage A and B patients of the primary treatment group. For stage C patients in the primary treatment group, good antitumor effects were obtained with CMA treatment. For stage D patients, however, results were poor. No serious side effects were observed in spite of the long period (as long as 6.3 years) and relatively large doses (100 mg daily) of CMA. Therefore, it was concluded that CMA can be recommended as a first choice drug for patients with carcinoma of the prostate.

Androgen Antagonists↗
PubMed1981

Release of human chorionic gonadotropin (hCG) and its alpha-subunit (hCG-alpha) from perifused human placenta.

The release of human chorionic gonadotropin (hCG) and its alpha-subunit (hCG-alpha) from the normal human placenta and the effect of some stimulatory agents on their release were studied in vitro using a perfusion system. Each perfusate was assayed for hCG and hCG-alpha in its own homologous radioimmunoassay systems. Both hCG and hCG-alpha were released from the placenta at any stage of gestation in our perfusion system. Much more hCG than hCG-alpha was released from the placenta in early gestation. By comparison, however, hCG-alpha increased gradually with the gestational age. The amount of hCG-alpha released was almost equal to that of hCG in the placenta in the 17th gestational week. After the 22nd gestational week, hCG-alpha was released in larger quantities than hCG, and about 10 times more hCG-alpha than hCG was released from the term placenta. These results were also confirmed by gel filtration of perfusates on a Sephadex G-100 column. hCG-alpha, compared with hCG, was present in excess in gel filtrated perfusates in the last two trimesters. By adding 1 mM dibutyryl cyclic AMP to the perifusion medium, the release of both hCG and hCG-alpha was stimulated significantly. Synthetic luteinizing hormone releasing hormone (LH-RH) at concentrations of 10 ng/ml and 100 ng/ml had no effect, but at a high concentration (1 microgram/ml), LH-RH stimulated the release of them. Moreover, mouse epidermal growth factor (EGF) stimulated not only the release of hCG and hCG-alpha but also their production, because both hCG and hCG-alpha levels rose progressively with the time course in the presence of EGF. The present studies demonstrate that the perifusion system of chorionic tissues is a useful method for investigating the release of hCG and its subunits in vitro.

Bucladesine↗