Search PubMed⌕ Search

Biomedical subjects

Y Tsukada

Publications and source records attributed to Y Tsukada.

At least 289 records · Page 16Linked to original sources
PubMed1982

Comparative studies on nucleoside diphosphatase of rat ascites hepatoma and rat liver: activity level, purification and properties.

1. The activities of nucleoside diphosphatase in various rat ascites cells of hepatoma, and fetal and neonatal rat liver were much lower than that of normal adult rat liver. 2. The enzyme was purified from ascites hepatoma (AH-66 cell lines) to an apparently homogeneous state and the enzymatic properties were studied in comparison with the enzyme from rat liver microsomes. 3. The hepatoma enzyme had less stability based on the results of heat-inactivation experiments. 4. However, the other properties of hepatoma enzyme; Km value, molecular weight, optimal pH, isoelectric point, substrate specificity and antigenicity, were similar to those of rat liver enzyme.

Acid Anhydride Hydrolases↗
PubMed1982

Effect of a conjugate of daunomycin and antibodies to rat alpha-fetoprotein on the growth of alpha-fetoprotein-producing tumor cells.

Daunomycin was covalently attached via a dextran bridge to specific antibodies against rat alpha-fetoprotein produced in a horse. The effect of this conjugate on an alpha-fetoprotein-producing tumor was investigated in terms of cytotoxicity and inhibition or retardation of tumor development. Under the experimental conditions used, the covalent conjugate was by both criteria more efficient than either daunomycin alone or a mixture of daunomycin and specific antibodies or a conjugate of daunomycin with horse immunoglobulin. These results show that the conjugate may be useful as a specific cytotoxic agent against alpha-fetoprotein-producing tumors.

Animals↗
PubMed1982

Chemotherapy by intravenous administration of conjugates of daunomycin with monoclonal and conventional anti-rat alpha-fetoprotein antibodies.

Monoclonal antibodies to rat alpha-fetoprotein (AFP) were produced by hybridization of mouse myeloma cells with spleen cells from mice immunized with rat AFP. The monoclonal antibodies as well as horse anti-rat AFP were coupled via a dextran bridge to daunomycin. Both types of conjugates were tested in vitro and in vivo for their anti-tumor activity. They were equally cytotoxic to rat AH66 hepatoma cell line in culture. Rats challenged with hepatoma cells were treated with the conjugates either by intraperitoneal or intravenous injections. Daunomycin conjugates with horse anti-AFP and monoclonal mouse anti-AFP were capable of delaying the tumor development more efficiently than the controls of antibodies or free drug, mixtures of drug with antibodies, and a conjugate of drug and normal immunoglobulin. The specific conjugates were considerably more effective when the treatments were given intravenously. The specific conjugates produced 60% long-term survival, whereas the controls delayed only slightly tumor development.

Animals↗
PubMed1982

Factors contributing to the poor myelination in the brain of the Snell dwarf mouse.

Conventional histological examination of the pituitary does not distinguish Snell dwarf mutants (dw/dw) from their normal littermates (+/?) in the neonatal stage. However, immunohistochemical examination of pituitaries of litters born to heterozygous Snell parents revealed that in approximately 25% of the glands examined, the number of positive cells was very low in the neonatal stage. We attempted to delineate the events resulting in the poor myelination in the brain of the Snell dwarf mouse, and to devise an immunohistochemical method for identifying the mutant neonate. Differences in the brain weights of the dw/dw and +/? mice first became apparent on the 10th day of age, and from this time on no further increase in the weight of the dwarf mouse brain was recorded. Increase in CNPase activity was found to be suppressed in the cerebrum and brain stem throughout the developmental stage, but not in the other parts of the brain. The yield of isolated myelin decreased by 58% in the mutant mouse, but CNPase activity was equivalent to that of control myelin. Differences in DNA content per cerebrum from the dw/dw and +/? mice first became apparent on the 10th day of age. Henceforth, the dw/dw mice showed no further increase, although the +/? mice continued to increase. [3H]Thymidine incorporation into the DNA fraction in vivo on the 7th day of age, when glial cell proliferation in the cerebrum is most active, was suppressed to about 50% of the control level in all parts of the dwarf brain. These findings indicate that the poor myelination found in the mutant cerebrum is a hypomyelination due to reduce oligodendroglial proliferation caused by lack of circulating growth hormone.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1982

Effects of bovine growth hormone on the retarded cerebral development induced by neonatal hydrocortisone intoxication.

In comparison with normal controls, hydrocortisone-intoxicated rats (HC rats) had smaller cerebra, lowered 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNPase) activity, and greatly reduced learning ability. The reduction in cerebral weight and DNA content was considered to be caused by a decrease in the number of proliferating glial cells, because the usual postnatal elevation of thymidine kinase (TK) activity was found to be suppressed in the cerebra from the HC rats. Electron microscopic observation of the pituitary gland revealed that the 5-day-old HC rat contained growth hormone (GH) secretory cells which were fully packed with GH granules, suggesting a disorder in the system which releases GH. In an attempt to promote cerebral development in the HC rats, we administered bovine GH (bGH) to some of the HC rats daily from the day of birth until weaning (HC + bGH rats). In the HC + bGH rats, the cerebral DNA was restored to normal levels and a concomitant increase in TK and CNPase activity was noted. Furthermore, in the brightness discrimination test, whereas the HC + bGH rats attained the learning ability of the normal controls after only 10 sessions, the HC rats were unable to reach an equivalent level even after 25 sessions.

Animals↗
PubMed1982

Postnatal action of growth and thyroid hormones on the retarded cerebral myelinogenesis of Snell dwarf mice (dw).

Snell dwarf mice (dw) showed a lower CNPase activity (59% of the normal controls) only in the cerebrum among different parts of the CNS, and a strikingly reduced level of spontaneous locomotion activity with an indistinct diurnal periodicity in a 24-h record at 40 days of age. Daily administration of bGH and T4 to the dwarfs during the first 40 days of postnatal life restored CNPase activity to the level of the normal controls, and was accompanied by normalization of the pattern of spontaneous locomotion activity. Daily administration of bGH alone also restored CNPase activity and spontaneous locomotion, but to a lesser extent. The daily administration of thyroid stimulating hormone (TSH) alone, however, failed to restore CNPase activity, in spite of the fact that the thyroid glands of the TSH-treated dwarfs were indistinguishable from the normal controls in organization and appearance. These results indicate that the restoration of both the retarded myelinogenesis and abnormal behavior of the Snell dwarf mice might essentially depend upon GH levels and the synergistic effects of T4.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1982

Neurochemical studies on the cerebellar hypoplasia of Gunn rat (hereditary hyperbilirubinemic rat).

The cerebellar hypoplasia induced by hereditary hyperbilirubinemia in the Gunn rat was analyzed neurochemically and immunohistochemically. The antiserum against myelin basic protein was used to visualize the arborization of the fibers in the cerebellum. Arborization was very scarce in the affected lobes of the homozygous (jj) cerebellum. Na,K-ATPase activity did not show significant differences between the jj and the control (Jj) cerebellum. The concentration of norepinephrine in the jj cerebellum was about 1.5 times that of the control. However, the activation ratio of the Na,K-ATPase by norepinephrine and other catecholamines such as dopamine and isoproterenol was about twice as high as the basal activity, and no significant difference was observed between the jj and the Jj cerebella. The glutamic acid decarboxylase activity of the jj cerebellum did not differ significantly from that of the control.

Animals↗
PubMed1982

Dysmyelination of shiverer mutant mice in vivo and in vitro.

Demyelination in the CNS of shiverer mutant mice was studied in vivo and in vitro. By immunohistochemical reaction with glial fibrillary acidic protein antibody, hypertrophy of the fibrous astrocytes was observed in the white matter of shiverer cerebella. The cerebella of shiverer mice in primary culture from the day of birth showed very poor myelination under optical microscopy. Axons of Purkinje cells are thought to be the main myelinated axons in the primary culture of the cerebellum. Purkinje cells from shiverer appeared normal with regard to Bodian silver impregnation, hematoxylin and eosin staining, and P400 protein characterization of Purkinje cells. Addition of the conditioned culture medium of shiverer to the control culture did not interfere with myelination. We concluded that the demyelination in the CNS of shiverer could be caused by an intrinsic defect of the oligodendrocyte rather than by hypertrophy of the astrocytes or by diffusible factors.

Animals↗
PubMed1982

Chimeric analysis of the pathogenesis of dysmyelination of shiverer mutant mice. Presence of patches of MBP-positive and negative sites in white matter indicating the absence of humoral factors for dysmyelination.

Shiverer is an autosomal recessive mutant mouse characterized by abnormal and poor myelin formation of the central nervous system. Chimera mice were produced from wild-type control (C57BL/6N) and the shiverer mutant mice (BALB/C) by the aggregation technique in order to analyze the pathogenesis of the shiverer mutation. The coat color was a mosaic of both strains. Immunohistochemically we have examined sections of cerebellar white matter of the chimera using antiserum against myelin basic protein (MBP), since MBP is absent in the myelin of the shiverer. Patches of MBP-negative and positive sites were observed in cerebellar white matter. The myelin sheaths, both positive and negative to MBP staining, were well mixed in the white matter but each stained myelin sheath was clearly visible, even in the mixed part. The possibility that humoral factors caused dysmyelination could be eliminated, and it is suggested that the shiverer mutation occurs intrinsic to the cells themselves.

Animals↗
PubMed1982

Phenotypic diversity of gamma-glutamyltranspeptidase activity and protein secretion in hepatoma cell lines.

Characteristic and patterns of gamma-glutamyltranspeptidase (GGT) expression were studied in four rat and three human hepatoma cell lines. Phenotypic diversity of GGT expression was demonstrated by the following findings. (a) GGT specific activity increased rapidly in three of four rat lines during the first 72 hr after subculture. (b) GGT activity was detected in the fourth rat cell line only from 96 to 120 hr after subculture. (c) In late log or stationary cultures, each of the four rat lines assumed a unique and characteristic level of GGT specific activity. (d) The intracellular GGT distribution pattern was markedly varied in rat and human cell lines. (e) GGT activity was confined to isolated cell clusters in one human line in vitro and one rat line both in vivo and in vitro. And (f) there was poor correlation between GGT specific activity and several liver-associated and hepatoma-associated properties. In contrast to evidence of diversity in GGT expression, GGT was shown to be a nonsecreted protein in all four rat cell lines. The constitutive or autogenous nature of the GGT phenotype in rat hepatoma cells was demonstrated by the retention of the GGT-positive and GGT-negative phenotypes of two strains grown in mixed culture; the lack of change in GGT activity when cells were cultured on different substrata, in different media, or in media containing hormones (insulin, dexamethasone, triiodothyronine, or glucagon); and the assumption of nearly constant levels of GGT specific activity in late log or stationary cultures. The results suggest that GGT activity is expressed in hepatomas as a result of disturbed differentiation and that this expression is not necessarily linked to cell proliferation.

Animals↗
PubMed1982

Antithymic antibodies in schizophrenic sera.

Sera from normal controls and schizophrenics were examined for antithymic activity, employing a cytotoxicity test with C3H mouse thymocytes. The average level of antithymic activity in schizophrenics was considerably higher than that of controls, i.e., 50.3 +/- 27.1 (n = 54) and 35.3 +/- 19.5 (n = 33), respectively (p less than 0.01), in a fourfold serum dilution. The antithymic activity in newly admitted unmedicated patients was not statistically different from that of hospitalized medical patients. There was no difference in antithymic activity within the subdivisions of schizophrenia, such as hebephrenic, catatonic, and paranoid types. The antithymic titer also did not correlate with the psychopathological status as assessed by the BPRS total score. The antithymic activity against C3H mouse thymocytes in both the schizophrenic and control sera was completely adsorbed with mouse brain tissue homogenate (where Thy-1 antigen was present) and liver homogenate (where Thy-1 was absent), but not with human brain and liver. It seems unlikely therefore that antithymic factor in human sera contains antibodies against Thy-1 (brain-associated thymic) antigen. Antithymic activity is not considered specific for schizophrenic illness, and the high antithymic activity found in schizophrenics might be produced against unknown xenoantigens, probably as a result of a nonspecific dysfunction of the immunological system in such patients.

Adolescent↗
PubMed1982

gamma-Glutamyl transpeptidase and alpha-fetoprotein expression during alpha-naphthylisothiocyanate-induced hepatotoxicity in rats.

Continuous feeding of alpha-naphthylisothiocyanate to young male Sprague-Dawley rats was shown to produce a concentration-dependent increase in the number of hepatic ductular cells and a concentration- and time-dependent elevation of serum and liver gamma-glutamyl transpeptidase and alpha-fetoprotein. In liver, the increased gamma-glutamyltranspeptidase and alpha-fetoprotein were predominantly confined to the proliferative ductular cell population. It is concluded that early stages of intoxication by the noncarcinogen alpha-naphthylisothiocyanate resemble early stages in induction of liver neoplasia by carcinogens that evoke ductular proliferation. Elevation of gamma-glutamyltranspeptidase and alpha-fetoprotein expression by an expanding ductular cell population characterizes both processes. However, the increase is rapidly reversed after alpha-naphthylisothiocyanate is discontinued, in contrast to the persistence that has been reported when acetylaminofluorene was administered.

1-Naphthylisothiocyanate↗
PubMed1982

Characterization of serum protein components from Donryu rats which were immune to hepatoma AH-66 tumor cells.

Immune serum from Donryu rats which resisted rechallenge with 5 X 10(6) AH-66 tumor cells (1000 X Threshold) was examined for reactivity with these cells using three assays: 1) tumor cell agglutination 2) immunofluorescence and 3) complement mediated cytotoxicity. Whole immune serum and its components had different levels of activities in the various assays and differences in their antigenic specificities were also observed. Whole immune serum showed some activity in all assays to AH-66 tumor cells. Its specificity and that of the IgG "enriched" fraction (insoluble in 40% sat. AmSO4) was studied using the agglutination assay. A general cross-reactivity was seen with all tumor cell lines. These reactions could be eliminated by absorption of the serum or serum fraction with tumor lines other than AH-66 or with embryonic tissue. An IgG "free" derived from the 40% sat. AmSO4 precipitate showed only agglutinin activity but this reactivity, even to AH-66 tumor cells, was abrogated by absorption with embryonic tissue. Incubation of the IgG "free" fraction with tumor target cells blocked the complement mediated cytotoxicity and the immunofluorescence reactivities of the whole immune serum. The alpha 2 macroglobulin component of the IgG "free" fraction appeared to be responsible for its agglutinin activity.

Agglutination Tests↗
PubMed1982

Metachronous ovarian metastases from adenocarcinoma of the colon and rectum.

Our observations indicate that the menopausal status of a patient, the anatomic location or the histologic differentiation of a primary adenocarcinoma of the colorectal area does not seem to affect the incidence of ovarian metastases. Tumors initially classified as Dukes' B2 and, later, associated with ovarian metastases have consistently poorer prognosis. The reason that ovarian metastases attain a relatively large size, while other metastatic foci remain small, is unknown. Regardless of the surgical findings, patients with ovarian metastases from a primary adenocarcinoma of the colorectal area tend to have short survival with widespread distribution of the tumors at death. This would suggest that these metastases occur primarily by the hematogenous route rather than by an orderly invasion to contiguous structures and draining lymph nodes. Patients with resectable solitary ovarian metastases and prospectives of cure must be a rare event in carcinoma of the colon and rectum.

Adenocarcinoma↗
PubMed1981

Purification of specific antibody to alpha-foetoprotein and its immunological effect on cancer cells.

Human of rat alpha-foetoprotein (AFP) was highly purified from ascitic fluid or serum of hepatoma bearers. The purification was carried out mainly by means of immunoadsorbent chromatography using Sepharose coupled to specific anti-AFP antibody with BrCN activation, and by Sephadex gel filtration. Horses were immunized with the purified AFP and the specific antibody was isolated from the antiserum by means of an immunoadsorbent coupled to purified AFP. The specific antibody was found to bind specifically with AFP-producing tumour cells. The antibody was applied for radio immunodetection of the tumour. 125I-labelled antibody was administered to patients or rats with hepatoma, and radioactivity localized in the tumours was scintiscanned with a scintillation camera. In this way, the location of the tumour was detected in about 50% of the hepatoma bearers. The cytotoxicity of the antibody was clearly demonstrated both in vitro and in vivo in animal experiments. The antibody was administered to patients with advanced hepatoma. Although no improvement of the disease was demonstrated, serum AFP levels decreased greatly and in some cases low AFP levels were maintained for long periods suggesting that the antibody suppressed AFP-producing hepatoma cells. No significant side effects were observed in patients who had been administered with the horse antibody.

Animals↗
PubMed1981

Fine structure of the central myelin sheath in the myelin deficient mutant Shiverer mouse, with special reference to the pattern of myelin formation by oligodendroglia.

The central myelin sheaths of the recessive autosomal mutant mouse, Shiverer, were investigated by electron microscopy with special reference to the pattern of myelin formation. The results obtained may be summarized as follows: (1) the major dense line of myelin lamellae generally failed to be formed, but the axons were enclosed by tri-lamellar structures of about 14 nm in width, which were composed of one central membrane formed by fusion of outer leaflets of adjacent cytoplasmic sheets of oligodendroglia, corresponding to the intraperiod line, and two outer membranes which were identical with inner leaflets of adjacent cytoplasmic sheets and became highly electron-dense. However, major dense lines were sporadically observed; (2) the myelin sheath was not generally formed by spiralling of one cytoplasmic process of the oligodendroglia, but by enclosing an axon with several stratified layers of cytoplasmic sheets, some of which were certainly formed by the splitting of one process; and (3) aberrant myelination frequently occurred around the soma of oligodendroglia, not related to any axons.

Animals↗