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Biomedical subjects

Y Tsukada

Publications and source records attributed to Y Tsukada.

At least 235 records · Page 13Linked to original sources
PubMed1985

Radiation associated hyperthyroidism in patients with gynecological malignancies.

To determine the effect of abdominal and/or pelvic irradiation for gynecological malignancies on the later development of hyperthyroidism, 1,884 medical records of the patients diagnoses as carcinomas of cervix and corpus uteri, and of ovary were reviewed. Among 1,269 patients with radiation therapy, 5 patients developed hyperthyroidism after irradiation to the abdomen and/or pelvis. This is a statistically significant increase when compared with an epidemiological study. Radiation dose to the thyroid was estimated to be 30 to 200 rads. Two other patients who were irradiated to the nose or supraclavicular region in addition to the abdomen also developed hyperthyroidism. However, none of 581 patients without radiation therapy became hyperthyroid. The results indicate that radiation therapy for treatment of gynecological malignancy gives a significant radiation exposure with an increase in the incidence of subsequent hyperthyroidism.

Adolescent↗
PubMed1985

Immunoperoxidase localization of a high-molecular-weight mucin recognized by monoclonal antibody 1D3.

The distribution of an antigen recognized by murine monoclonal antibody 1D3 (Bhattacharya, M., Chatterjee, S.K., Barlow, J. J., and Fuji, H. Cancer Res., 42: 1650-1654, 1982) was investigated in various types of human malignant and normal adult tissues by indirect immunoperoxidase assay in fixed paraffin-embedded sections. One hundred percent of ovarian mucinous cystadenocarcinomas expressed high levels of the antigen with intense staining of 80 to 100% of the tumoral area, thus confirming our previous finding with radioimmunoassay and absorption analyses. About 51% of colonic carcinomas, 33% of gastric carcinomas, and 22% of pancreatic carcinomas were also positive for this high-molecular-weight mucoprotein antigen. All other ovarian and nonovarian carcinomas tested including carcinoma of lung, breast, endometrium, cervix, and prostate were not stained by 1D3. In addition, sarcomas, melanomas, and lymphomas also did not express any detectable level of the antigen. When surveyed against various normal adult tissues, 1D3 had reactivity limited to the colon. Normal colon, however, exhibited reduced staining intensities compared to tumors or to the apparently normal colon adjacent to tumors. The antigen thus appears to be a colorectal tissue-specific antigen showing increased levels in ovarian mucinous cystadenocarcinomas and in some gastrointestinal tumors. 1D3 antigen is a potential tumor marker for mucinous ovarian and colonic tumors.

Animals↗
PubMed1984

Observations on the brainstem-spinal descending systems of normal and reeler mutant mice by the retrograde HRP method.

Brainstem neurons which project to the lumbar spinal level were identified in both reeler mutant mice and normal controls (Balb/c mice) by the retrograde horseradish peroxidase (HRP) technique. In normal controls after HRP injection into the lumbar cord, retrogradely labelled neurons were observed in (1) the lateral vestibular nucleus, (2) the pontine and medullary reticular formations including the nucleus centralis caudalis pontis, nucleus gigantocellularis, nucleus paragigantocellularis, nucleus raphe magnus et pallidus, and nucleus centralis medullae oblongatae pars ventralis et dorsalis, and (3) the dorsal column nuclei, i.e., the nucleus gracilis and nucleus cuneatus medialis. In reeler mutant mice, labelled neurons were again seen in the nuclei referred to above, and their cellular type and distribution patterns within the corresponding nuclei were similar to those of the normal controls. These observations suggest that (1) the brainstem nuclei of reeler mutant mice which project to the lumbar spinal cord are cytoarchitecturally normal, (2) the reeler genetic locus (rl) does not affect the nonlaminated structures in the brainstem, at least those referred to above, and (3) the motor dysfunctions observed in the reeler, such as action tremor, dystonic posture, and reeling ataxic gait, are not attributable to the brainstem-spinal descending systems.

Animals↗
PubMed1984

The inhibitory effects of horse anti-rat AFP antiserum on the uptake of 2-deoxy-D-glucose by AFP-producing rat hepatoma cells.

The inhibitory effects of horse antiserum against rat alpha-fetoprotein (AFP) on the uptake of 2-deoxy-D-glucose (2dG) by the AFP-producing rat ascites hepatoma AH66 cells was studied. AH66 cells cultured in medium containing 20% heat-inactivated antiserum had a 1.5-fold lower rate of sugar uptake than did AH66 cells which were cultured in medium containing 20% heat inactivated normal horse serum. The inhibition of 2dG uptake by antiserum was dependent on both the concentration and the exposure time of antiserum. Preincubation of AH66 tumor cells for 2 and 6 h with antiserum prior to the measurement of 2dG uptake resulted in a 70.1% and 58.2% decrease in 2dG uptake compared to control cells. Antiserum did not inhibit the rate of phosphorylation of 2dG by tumor cells. Kinetic constants for the uptake of 2dG in both AH66 cells treated with antiserum to AFP and in control cells were calculated from Lineweaver-Burk plots. The Km remained constant at approximately 1.2 mM, but the Vmax was twice as small for the cells treated with antiserum as for the control cells (571 vs 923 nanomoles/2 X 10(5) cells/min). These studies suggest that the inhibition of 2dG uptake by treatment with antiserum was the result of a decrease in the number of transport sites, or a decrease in the amount of carrier protein for the sugar which was present on the surface of the plasma membrane of the AH66 cells.

Animals↗
PubMed1984

Daunomycin-arachidonic acid complex as a potential new antitumor agent.

A daunomycin-arachidonic acid complex (DM-C20:4) administered IV had a marked antitumor effect on the intraperitoneal growth of the AFP-producing hepatoma cell line, AH66. However, the daunomycin-arachidic acid (DM-C20:0) saturated fatty acid complex showed only the same antitumor effect on the AH66 cells as free daunomycin. It was demonstrated that the DM-C20:4 preparation maintained its chemical properties for some time in both plasma and liver homogenate.

Animals↗
PubMed1984

2',3'-Cyclic nucleotide 3'-phosphodiesterase activity in the cerebrospinal fluid of patients with demyelinating diseases.

We aimed to study the level of CNPase activity in the cerebrospinal fluid of patients with demyelinating diseases and other neurological diseases, particularly multiple sclerosis, with reference to CSF myelin basic protein content. CNPase activity was measured paper chromatographically using radioactive 2',3'-cAMP as a substrate. Myelin basic protein content was measured with a radioimmunoassay. The mean level of CNPase activity was significantly higher for multiple sclerosis than for nonneurological controls. Dividing the disease phases of multiple sclerosis into the three periods, the CNPase activity was found to be significantly elevated in the worsening period and reduced in the improving period and the inactive period. The level of CNPase activity in the cerebrospinal fluid of multiple sclerosis coincided with the clinical activity of the disease. The level of CNPase activity correlated well (r = 0.84) with the level of myelin basic protein content in cerebrospinal fluid. The ratio for CNPase activity and myelin basic protein content in cerebrospinal fluid was almost the same as that in human central nerve myelin. We concluded that CNPase activity in the cerebrospinal fluid from neurological patients is an indicator of destruction of myelin in the central nervous system, and the measurement of CNPase activity in the cerebrospinal fluid of multiple sclerosis could be useful in the clinical management.

2',3'-Cyclic Nucleotide 3'-Phosphodiesterase↗
PubMed1984

Stimulation of Snell dwarf mouse neuronal growth by GH and T4.

An investigation of the Snell dwarf motor cortex, area 6 of Caviness, was carried out by means of a modified Golgi silver impregnation method. The pyramidal neurons located in layer V were found to have small perikarya, short primary dendrites with sparse branchings. Following administration of bovine growth hormone (bGH) and thyroxine (T4) during the first 20 d of postnatal life, this retarded neuronal growth was restored to normal: neuronal perikarya were enlarged, and the dentrites were thicker with denser branchings. These results were confirmed in the sections stained for neuron specific enolase (NSE). These findings demonstrate that exogenous GH and T4, will enhance neuronal growth in the Snell dwarf cerebrum, and restore neuronal arborization to normal.

Animals↗
PubMed1984

Cell lineage analysis of Schwann cells in the PNS determined by shiverer-normal mouse chimeras.

The myelin of the peripheral nervous system from the shiverer mutant mice is characterized by the absence of myelin basic protein, while the other myelin protein components are present at normal levels. Myelin lamella formation is normal in the shiverer mutant. Therefore, by using antiserum against myelin basic protein, we can distinguish the shiverer from the wild-type control myelin immunohistochemically. To study the cell lineage of Schwann cells, chimeras produced by the aggregation of eight-cell embryos from wild-type mice and shiverer mice have been used. Using myelin basic protein as a marker, it was observed that Schwann cells in the sciatic nerve existed as patches of cells with like-genotype. The patches occurred in a linear array along the axons with some intermingling of Schwann cells. Complete randomization by intermingling of Schwann cells was not observed and clones of Schwann cells may persist as contiguous groups throughout peripheral nerve development.

Animals↗
PubMed1984

Development of a highly sensitive enzyme-immunoassay for serum carbonic anhydrase-III.

A highly sensitive sandwich enzyme-immunoassay (EIA) for human muscle carbonic anhydrase isozyme III (CA-III) has been developed using microplate as a solid-phase and peroxidase as a labelled enzyme. The assay can detect levels as low as 2 ng/ml when 20 microliter of sample sera were used. Sera from patients with various neurological diseases were studied using this method, and elevated serum CA-III levels were found in patients with Duchenne muscular dystrophy, limb-girdle dystrophy, fascioscapulohumeral dystrophy, polymyositis and amyotrophic lateral sclerosis. The values correlated well with the results of radioimmunoassay (RIA), with a correlation coefficient of 0.92 (P less than 0.001). We feel EIA is preferable to RIA for its simple methodology.

Carbonic Anhydrases↗
PubMed1984

Effect of anti-alpha-fetoprotein serum on human hepatoblastoma.

There is no definitive treatment of hepatoblastoma. Except for radical resection, the prognosis of unresectable cases remains pessimistic. Therefore, the development of new anticancer drugs for this tumor is urgently needed. Using the human hepatoblastoma cell line (c-HB-3) we demonstrated that horse anti-alpha-fetoprotein containing serum suppressed proliferation of the hepatoblastoma cells. This effect was dependent on the duration of exposure and the concentration of anti-alpha-fetoprotein serum.

Animals↗
PubMed1984

A novel method of conjugation of daunomycin with antibody with a poly-L-glutamic acid derivative as intermediate drug carrier. An anti-alpha-fetoprotein antibody-daunomycin conjugate.

In studies on antitumor antibody-cytotoxic drug conjugates as potential antitumor agents with improved tumor specificity, daunomycin (DM) was first linked to a poly-L-glutamic acid (PLGA) derivative having a single masked thiol group. At the thiol group, DM-linked PLGA was bound to horse anti-rat alpha-fetoprotein (AFP) antibody. The anti-AFP antibody-PLGA-DM conjugate (anti-AFP conjugate, DM/PLGA/Ig molar binding ratio, 7.5/1.2/1.0) retained most of the antigen-binding activity of the parent antibody and was more potent than either unconjugated DM, a conjugate similarity prepared with normal horse immunoglobulin (normal conjugate), or an unconjugated mixture of anti-AFP antibody and DM in an in vitro cytotoxicity assay against the AFP-producing rat ascites hepatoma cell line AH66. Anti-AFP conjugate tended to be less cytotoxic than DM against the AFP-nonproducing rat ascites hepatoma AH272 cells, and in this case there was no difference between the cytotoxicities of anti-AFP conjugate and of normal conjugate.

Animals↗
PubMed1984

Purification and properties of N-acetylneuraminate lyase from Escherichia coli.

N-Acetylneuraminate lyase [N-acetylneuraminic acid aldolase EC 4.1.3.3] from Escherichia coli was purified by protamine sulfate treatment, fractionation with ammonium sulfate, column chromatography on DEAE-Sephacel, gel filtration on Ultrogel AcA 44, and preparative polyacrylamide gel electrophoresis. The purified enzyme preparation was homogeneous on analytical polyacrylamide gel electrophoresis, and was free from contaminating enzymes including NADH oxidase and NADH dehydrogenase. The enzyme catalyzed the cleavage of N-acetylneuraminic acid to N-acetylmannosamine and pyruvate in a reversible reaction. Both cleavage and synthesis of N-acetylneuraminic acid had the same pH optimum around 7.7. The enzyme was stable between pH 6.0 to 9.0, and was thermostable up to 60 degrees C. The thermal stability increased up to 75 degrees C in the presence of pyruvate. No metal ion was required for the enzyme activity, but heavy metal ions such as Ag+ and Hg2+ were potent inhibitors. Oxidizing agents such as N-bromosuccinimide, iodine, and hydrogen peroxide, and SH-inhibitors such as p-chloromercuribenzoic acid and mercuric chloride were also potent inhibitors. The Km values for N-acetylneuraminic acid and N-glycolylneuraminic acid were 3.6 mM and 4.3 mM, respectively. Pyruvate inhibited the cleavage reaction competitively; Ki was calculated to be 1.0 mM. In the condensation reaction, N-acetylglucosamine, N-acetylgalactosamine, glucosamine, and galactosamine could not replace N-acetylmannosamine as substrate, and phosphoenolpyruvate, lactate, beta-hydroxypyruvate, and other pyruvate derivatives could not replace pyruvate as substrate. The molecular weight of the native enzyme was estimated to be 98,000 by gel filtration methods. After denaturation in sodium dodecyl sulfate or in 6 M guanidine-HCl, the molecular weight was reduced to 33,000, indicating the existence of 3 identical subunits. The enzyme could be used for the enzymatic determination of sialic acid; reaction conditions were devised for determining the bound form of sialic acid by coupling neuraminidase from Arthrobacter ureafaciens, lactate dehydrogenase, and NADH.

Escherichia coli↗
PubMed1984

Partial purification and properties of the inhibitors of Na, K-ATPase and ouabain-binding in bovine central nervous system.

Endogenous inhibitors of Na,K-ATPase and ouabain-binding were partially purified from bovine central nervous system, and some of their properties were studied. They were eluted as low-molecular-weight fractions by gel filtration. They could be adsorbed by both Amberlite IR 120 and Amberlite IRA 400 at acidic and basic pH, respectively, indicating that they could act as both anions and cations at different pH. These inhibitors of ouabain-binding appeared to affect specific binding of ouabin, and Scatchard plot analysis showed that the inhibition was competitive, suggesting that they could bind to the same site as ouabain, presumably to Na,K-ATPase itself. The inhibitory activities were heat stable, but charring inactivated them completely.

Animals↗
PubMed1984

Immunohistochemical study on oxytocin-like substance in the human placenta.

Our previous studies have demonstrated that a large quantity of oxytocin (OT)-like substance exists in human placental tissue. In the present study, the localization of the OT-like substance in the human placenta was investigated by the PAP (peroxidase and antiperoxidase complex) immunohistochemical method. The results demonstrated that the site of syncytiotrophoblast was positively stained by specific antiserum to OT, whereas the tissue was not significantly stained by normal rabbit serum (NRS). These results suggest that the OT-like substance might be localized in syncytiotrophoblast of the placental tissue.

Cross Reactions↗
PubMed1984

[Effect of antibody to rat alpha-fetoprotein (AFP) on protein and DNA synthesis of rat ascites hepatoma AH66 cells].

Effects of horse antibody (purified IgG) to rat AFP on synthesis with both protein and DNA of rat ascites hepatoma cells were examined. The addition of antibody to the cultures showed a decrease in protein synthesis within several hours; whereas, it showed a transient increase in the incorporation of thymidine into tumor cells approximately in 6-12 hours both in vitro and in vivo. Eventually within 24-48 hours, more than 50% of the cells in culture were killed and inhibited the synthesis of DNA by the antibody treatment. The stimulatory effect of antibody on the synthesis of DNA in the tumor cells was more obviously observed in synchronized cells which were capable to obtain by the treatment with thymidine followed by hydroxyurea. The synchronized tumor cells cultivated with antibody containing medium also exhibited the shortening of the cell cycle from 22 to 12-20 hours. Based on these effects of antibody on tumor cell growth, sequential administration of antibody followed by an anticancer drug (carboquone) was proven to be the most effective immunochemotherapeutic schedule for tumor bearing rats, showing 25-33% long-term survival in comparison with any other controls.

Amino Acids↗
PubMed1984

An anti-alpha-fetoprotein antibody-daunorubicin conjugate with a novel poly-L-glutamic acid derivative as intermediate drug carrier.

In studies on antitumor antibody-cytotoxic drug conjugates as potential antitumor agents with improved tumor specificity, daunorubicin [(DM) daunomycin] was conjugated with an affinity-purified horse antibody to rat alpha-fetoprotein (AFP) with a novel derivative of poly-L-glutamic acid (PLGA) as the intermediate drug carrier. A single masked thiol group first was introduced by PLGA, and the thiol group was generated from it after the linking of DM to PLGA at the carboxyl groups of PLGA. The thiol group was used selectively for binding PLGA-DM to antibody that had been modified so as to have the maleimide groups. The conjugates (DM:PLGA:immunoglobulin molar ratio, 19.6:2.8:1 or 11.8:1.1:1) were more potent than DM in in vitro cytotoxicity against the AFP-producing rat ascites hepatoma cell line AH66. In therapeutic experiments, the conjugates were more efficacious in prolonging the lives of AH66 hepatoma-bearing DONRYU rats than DM, antibody, a mixture of DM and antibody, or a conjugate similarly prepared with normal horse immunoglobulin.

Animals↗
PubMed1984

[Preparation of conjugates of adriamycin with antibodies to alpha-fetoprotein and their properties].

For its selective accumulation into tumor cells, the antitumor drug adriamycin (ADM) was attached to specific antibodies reactive against alpha-fetoprotein, a carcinoembryonic protein, and the antibody and antitumor activities of the resulting conjugate were investigated. Using the glutaraldehyde or carbodiimide binding methods, preparations containing 4-5 moles of ADM per mole of antibody were obtained. They retained 60-75% of the original antibody activity. Upon incubation of AH-66 ascites hepatoma cells with the conjugates, an increased number of dead cells and inhibited uptake of 3H-thymidine by the cells were observed. The conjugates were more effective against tumor cells than the free drug, and it was further presumed that the cytotoxic action of ADM on normal cells could be reduced by binding it to a macromolecular protein.

Animals↗