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Biomedical subjects

R Nishimura

Publications and source records attributed to R Nishimura.

At least 271 records · Page 15Linked to original sources

Sequential assays of hormone receptors and the Tritiated Thymidine Labeling Index in 7,12-dimethylbenz(a)anthracene-induced rat mammary cancers.

This study was carried out to determine whether hormone receptors and the Tritiated Thymidine Labeling Index (TLI) would change with intervening treatment in 7,12-dimethylbenz(a)anthracen-induced rat mammary cancer as well as to evaluate their predictive significance. Forty-eight tumors were studied. TLI significantly correlated inversely with the binding sites of cytoplasmic estrogen receptors (ERC), but not of cytoplasmic progesterone receptors (PRC). From the response to the two treatments ovariectomy or adriamycin, it was demonstrated that ERC was a predictor of the response to ovariectomy and TLI showed a predictive value in the response to adriamycin. Ovariectomy generally induced a marked decrease in ERC level and PRC level, whereas adriamycin led to an increase and decrease in ERC level and PRC level, respectively. TLI showed a remarkable decrease in tumors which were responsive to ovariectomy or adriamycin. Some tumors, which had been the intermediate or ineffective group with a previously given treatment, were evaluated for the first time as being the effective group with another type of treatment. These results suggest that the response to treatment for breast cancer may change over the clinical course and ideal treatment for advanced breast cancer should included concomitant chemo-endocrine therapy.

9,10-Dimethyl-1,2-benzanthracene↗

Measurement of cutaneous blood flow by clearance of hydrogen gas generated by electrolysis.

In an attempt to assess the reliability of a method for measurement of local blood flow-namely, the clearance of electrochemically generated hydrogen gas-a series of experiments were conducted using the skin and skin flap in rats and rabbits. The results showed high accuracy in obtained values, good reproducibility in the repeated measurements, and consistency with the values obtained by the hydrogen gas inhalation method. Histological examination revealed only minimal damage to the tissue resulting from the measurement. Using this method, blood flow was measured at different sites on the flap in rats. The critical point of blood flow as measured by this method was thoroughly consistent with the dye distance as well as with the survival length. No injurious effects of the measurement procedure on flap survival were noticed. The present study suggests a wide potential application of this method in plastic surgery because of its high reliability and because no radioactivity is involved.

Animals↗

Free alpha subunits of glycoprotein hormone with dissimilar carbohydrates produced by pathologically different carcinomas.

The two kinds of glycoprotein hormone alpha subunit ectopically produced by an undifferentiated carcinoma of the left femoral region (TM-alpha) and an adenocarcinoma of the right external genitalia (FS-alpha) were examined for amino acid composition, isoelectric focusing, molecular weight, the ability to combine with standard hCG beta and affinity with lectins (Con A, Ricin and PNA). Both TM-alpha and FS-alpha exhibited immunoantigenicity similar to standard hCG alpha. Furthermore, there were no significant differences in the amino acid compositions of TM-alpha, FS-alpha or standard hCG alpha. In isoelectric focusing, while standard hCG alpha exhibited a neutral charge, both TM-alpha and FS-alpha exhibited strong negative charges. FS-alpha was as sensitive to sialidase as standard hCG alpha, whereas most of the TM-alpha exhibited resistance to sialidase. TM-alpha contains sialidase-insensitive peripheral material with a negative charge. The affinity with Ricin-Sepharose indicated that most of the FS-alpha and some of the TM-alpha may contain terminal sialic acid and the penultimate structure, Gal beta 1----4G1cNAc; the affinity with PNA-Sepharose indicated that both may also contain terminal sialic acid and the penultimate structure, Gal beta 1----3GalNAc. These observations suggest that dissimilar glycosylation processes are present in the carcinoma ectopic biosynthesis of glycoprotein hormone alpha subunit.

Adenocarcinoma↗

Leukocyte migration inhibition in relation to nuclear pleomorphism and lymphoid infiltration in breast cancer.

Leukocyte migration inhibition (LMI) in patients with breast cancer was examined by using 3 M-KCl tissue extracts of breast tumors. Tumor extracts were obtained from 12 breast carcinomas of various histological types. In 20 of 65 (30.8%) leukocyte preparations from 25 patients with breast cancer migration was inhibited by breast cancer tissue extracts. In 26 leukocyte preparations from eight healthy persons and 22 preparations from eight patients with benign diseases of the breast migration was not inhibited by the breast cancer extracts. In only two of 47 (4.3%) leukocyte preparations from 12 patients with other cancers migration was inhibited by the extracts. The occurrence of LMI was the highest in leukocytes from the patients with breast cancer showing marked nuclear pleomorphism (10/19, 52.6%) or showing marked mononuclear cell infiltration (6/12, 50.0%). These results suggest that 3 M-KCl tissue extracts of breast cancer may contain tumor-associated antigens in solubilized form and that there may be a correlation between LMI and nuclear pleomorphism of cancer cells of the leukocyte donor as well as mononuclear cell infiltration in the tumor of the leukocyte donor.

Adenofibroma↗

[Binding of human chorionic gonadotropin with insufficient terminal sugar to peanut agglutinin].

We have studied the binding of human chorionic gonadotropin (hCG) in sera and urine of normal pregnant women and patients with trophoblastic diseases to the lectin from peanut (Arachis hypogaea, PNA). As the basic experiments, purified standard hCG and its alpha and beta subunits were examined for binding to a PNA-Sepharose column. Both standard hCG and hCG-beta adsorbed to the PNA-Sepharose only when they were treated with neuraminidase, whereas hCG-alpha was still not adsorbed even after treatment with neuraminidase. The major proportions of hCG in sera and urine from normal pregnancy and hydatidiform mole were not adsorbed to the PNA-Sepharose column. On the other hand, the proportions of PNA binding fraction in sera and urine from choriocarcinoma were significantly elevated in 4 of 6 cases. The PNA binding fraction was significantly higher in serum than in urine of each individual. The PNA binding fractions were extracted and purified from urine of 2 patients with choriocarcinoma, and were quantitatively found to be asialo-hCG. These results suggest that PNA-Sepharose affinity chromatography is an effective tool to use in detecting incompletely sialylated hCG and hCG-beta and may be a useful index for the clinical diagnosis of choriocarcinoma.

Choriocarcinoma↗

Comparison of carbohydrate structure between human chorionic gonadotropin present in urine of patients with trophoblastic diseases and healthy individuals.

Human chorionic gonadotropin (hCG) highly purified from the urine of patients with trophoblastic diseases (choriocarcinoma and hydatidiform mole) and from healthy pregnant women contains four asparagine-linked sugar chains in one molecule. Comparative studies of the sugar chains released by hydrazinolysis revealed that the structures of the sugar chains of choriocarcinoma hCGs are quite different from those of mole and normal hCGs. The carbohydrate structures of mole hCGs are the same as those of normal hCG, while all choriocarcinoma hCGs examined contain two triantennary, two unusual biantennary, and one monoantennary complex-type sugar chains which are not found in normal hCGs. The triantennary and unusual biantennary sugar chains contain the +/- NeuAc alpha 2----Gal beta 1----4GlcNAc beta 1----4Man alpha 1----3 group in common. The total amounts of fucosylated sugar chains in choriocarcinoma hCGs are twice those found in the hCGs of other groups. Therefore, the appearance of the N-acetylglucosaminyl transferase responsible for the formation of the GlcNAc beta 1----4Man alpha 1----3 group and the increase of the fucosyl transferase responsible for the formation of the Fuc alpha 1----6 GlcNAc----Asn group appear to be specific characteristics of malignant transformation of the trophoblast, and the structural changes of sugar chains could serve as useful markers for the diagnosis of choriocarcinoma.

Carbohydrate Sequence↗

[A clinical observation of genitourinary tract tuberculosis during the last decade].

Altogether, 92 patients were diagnosed as having genitourinary tuberculosis, and were treated at our clinic from 1972 to 1981. These patients form the basis for our statistical study. The incidence of genitourinary tuberculosis among our new outpatients showed a tendency to decrease and was less than 0.4% during the last five years. The mean age of the genitourinary tuberculosis patients was 42.8, rather higher than ten years ago. Of these, 41% had a history of tuberculosis and 54% chiefly complained of bladder-related symptoms. Tubercle bacilli were detected in 87% of the patients. About 45% of the patients with urinary tuberculosis underwent nephrectomy, which was indicated principally in cases of non-functioning kidneys and severe hydronephrosis. A combination of PAS, INH, and RFP was used most often and was administered in 58 cases. Used second most often was a combination of SM, PAS, and INH (administered in 46 cases).

Adolescent↗

[Studies on the mechanism of the estrogen action in human breast cancer].

Only some 50% of estrogen receptor positive breast cancer patients respond to hormone therapy. It is possible that the mechanism of the estrogen action is disturbed in malignant cells. In order to determine which steps of the mechanism are disturbed, cytoplasmic estrogen and progesterone receptor and nuclear estrogen receptor were studied in 217 cases of human breast cancer. Thirty breast cancer tumors were examined for nuclear translocation of estradiol in vitro. The assessment of the translocation experiments showed good correlation to the ERN status by the DCC method. This experiment was considered to be a simple method of assessment of translocative ability.

Breast Neoplasms↗

Detection of incompletely sialylated human chorionic gonadotropin by peanut agglutinin in choriocarcinoma.

Human chorionic gonadotropin (hCG) in normal pregnancy and hydatidiform mole did not bind to the peanut agglutinin (PNA)-Sepharose column, whereas significant amount of hCG in choriocarcinoma adsorbed to the column. Therefore, PNA-Sepharose affinity chromatography is an effective tool for the detection of desialylated hCG and may be useful also for the diagnosis of choriocarcinoma.

Arachis↗

[The determination of the recognition site of an antiserum detecting desialylation on O-glycosidic carbohydrates of hCG and its clinical applications. The relationship between the presence of asialo-hCG and malignant change in trophoblastic disease].

Human chorionic gonadotropin (hCG) is a specific tumor marker glycoprotein hormone for trophoblastic diseases. It contains 4 asparagine-linked and 4 serine-linked carbohydrate units. Recently, variations in the carbohydrate moieties of hCG in chorio-carcinoma have been suggested. However, the immunological method of detecting these malignant transformational changes of carbohydrate units in hCG have not been investigated. We therefore attempted to assess the possibility of establishing a radioimmunoassay system which can detect these transformational changes in serine-O-glycosidically linked carbohydrate units of hCG. HCG-specific hCG beta COOH-terminal portion contains all 4 O-glycosidically linked sugar chains (positions 121, 127, 132 and 138). An antiserum (R141) generated against the enzymatically cleaved, desialylated hCG beta COOH-terminal peptide (residue 123-145) by toepad immunization method was extensively characterized. This antiserum reacts with asialo-hCG better than with native hCG. It does not bind with synthetic COOH-terminal peptides nor monosaccharides such as N-acetyl-D-galactosamine and D-galactose, which are sugar components in O-glycosidic carbohydrate chains. The HF-treated asialo-hCG, in which galactose residues are further removed, still reacts with the antiserum. The antiserum requires both the peptide sequence and N-acetyl-D-galactosamine residues for its binding. Glycophorine and fetuin, which also contain the same O-glycosidic carbohydrate structure, do not react with the antiserum. Beta subunit gains its binding capability to the antiserum only upon desialylation, while native alpha and beta subunits do not react. The antiserum has high specificity toward asialo-hCG in which particularly O-glycosidic carbohydrate units are desialylated. With a specific radioimmunoassay system using this antiserum (R141), urinary hCG preparations from 29 patients with various trophoblastic diseases were analyzed. Asialo-hCG immunoactivity was insignificant in all patients with hydatidiform mole, invasive hydatidiform mole and persisted trophoblastic disease. However, asialo-hCG was found in 2 out of 6 cases of choriocarcinoma. The existence of asialo-hCG may be related to the advancement of disease.(ABSTRACT TRUNCATED AT 400 WORDS)

Asialoglycoproteins↗

Treatment of bladder cancer with a combination of hyperthermia, radiation and bleomycin.

The treatment of urinary bladder cancer with hyperthermia in combination with radiation and bleomycin was investigated. Immediately following a daily course of external bladder irradiation (150-200 rad; total 4 week exposure of 3500-4000 rad), patients diagnosed with transitional cell carcinoma of the bladder were irrigated with a solution of warmed saline (intravesical temperature, 42 degrees C-43 degrees C), containing 30 micrograms/ml bleomycin. Of a total of 33 patients, complete responses were observed in 14 patients, and partial responses were observed in 10. The side effects of the combined treatment were limited to local symptoms of bladder and urethral irritation. These preliminary results suggest that the combined use of hyperthermia, radiation, and bleomycin may represent an effective conservative therapy for the management of bladder cancer in humans.

Adult↗

Muscarinic cholinergic receptors in human gastric mucosa.

Muscarinic cholinergic receptor sites in human gastric mucosa were analyzed directly by using radioligand binding techniques with the specific muscarinic antagonist 3H-quinuclidinyl benzilate (QNB) as ligand. Specific binding of 3H-QNB to membrane preparations from human gastric mucosa was saturable, of high affinity (Kd = 4.17 +/- 1.94 nM, Bmax = 0.37 +/- 0.04 pmol/mg protein) and selectively inhibited by muscarinic antagonists (atropine, scopolamine) and agonists (acetylcholine, pilocarpine). These findings provide direct evidence for the existence of muscarinic cholinergic receptors in human gastric mucosa. The specific 3H-QNB binding to its receptor was blocked by atropine but not by histamine, cimetidine, pentagastrin, or synthetic human gastrin. The muscarine and histamine H2-receptor, or muscarine and gastrin receptor, probably do not share the same locus.

Acetylcholine↗

Structures of the asparagine-linked sugar chains of human chorionic gonadotropin produced in choriocarcinoma. Appearance of triantennary sugar chains and unique biantennary sugar chains.

Human chorionic gonadotropin (hCG) highly purified from urine of the patient with choriocarcinoma contains four asparagine-linked sugar chains in one molecule. The sugar chains were quantitatively liberated as radioactive oligosaccharides from polypeptide portion by hydrazinolysis followed by N-acetylation and NaB3H4 reduction. The structures of these sugar chains were determined by the combination of sequential glycosidase digestion, periodate oxidation, and methylation analysis. As compared with the sugar chains of normal urinary and placental hCG reported previously, they include several prominent structural differences. More than 97% of the sugar chains of choriocarcinoma hCG was free from sialic acid, while the sugar chains of normal hCG were mostly sialylated. Choriocarcinoma hCG contains unusual biantennary complex-type sugar chains in addition to regular tri-, bi-, and monoantennary sugar chains. These sugar chains have two outer chains linked at the C-2 and C-4 positions of the same alpha-mannosyl residue of the trimannosyl core. Since normal hCG does not contain any triantennary sugar chains, occurrence of Gal beta 1 leads to 4GlcNAc beta 1 leads to 4Man alpha 1 leads to group is another characteristic feature of the sugar chains of choriocarcinoma hCG. The evidence that the monoantennary sugar chain of Man alpha 1 leads to 6(Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GlcNAc beta 1 leads to 4(Fuc alpha 1 leads to 6)GlcNAc leads to Asn is not found in normal hCG and the sum total of fucosylated sugar chains is 50%, which is twice as much as normal hCG, indicated that fucosylation is also modified in choriocarcinoma tissue.

Adult↗