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Biomedical subjects

Y Tsukada

Publications and source records attributed to Y Tsukada.

At least 217 records · Page 12Linked to original sources
PubMed1985

Activation of collagen synthesis in primary culture of rat liver parenchymal cells (hepatocytes).

An increase in collagen synthesis by hepatic parenchymal cells (hepatocytes) was observed during 8 days in primary culture by the quantification of total [3H]hydroxyproline as a marker of total collagen synthesis and the ratio of [3H]hydroxyproline in the high-molecular-weight fraction to total [3H]hydroxyproline as a marker of collagen degradation after incubation of the cells with [3H]proline for 24 h. Type analysis of the collagen produced by the cells after 8 days in culture showed the presence of type I and type III collagens in addition to the components corresponding to type IV and type V (alpha A and alpha B) collagens. Only the latter two types were found in the collagens produced by the cells after 2 days in primary culture. The purity of the hepatocytes inoculated was 97%, and the majority of the contaminating small cells were erythrocytes. The rate of serum albumin synthesis, which is a typical function of the hepatocytes, was constant or increased during the culture period. Immuno-electron microscopic observation indicated the production of type I collagen by the hepatocytes after 8 days in primary culture. These results are explained only by the activation of collagen synthesis in the day-8 hepatocytes in primary culture.

Animals↗
PubMed1985

Univariate and multivariate analyses of 5-year survival, recurrence, and inguinal node metastases in stage I and II vulvar carcinoma.

Ninety-seven patients with FIGO stage I and II vulvar carcinoma were analyzed for 5-year survival, inguinal node metastases (N = 61), and recurrence. Factors analyzed included stage, tumor grade, depth of invasion, presence or absence of tumor cell confluence, presence or absence of lymphatic/vascular space invasion, lesion size, and lymph node metastases. It was concluded that conservative surgery in patients otherwise suitable for surgery should consist of a wide, local excision of the vulvar lesion in conjunction with ipsilateral inguinal node resection if the tumor measured less than or equal to 1 cm in diameter and had a depth of invasion of less than or equal to 1 mm. All other stage I or II patients require radical vulvectomy and bilateral inguinal lymphadenectomy.

Carcinoma↗
PubMed1985

Cerebral myelinogenesis in the Snell dwarf mouse: stimulatory effects of GH and T4 restricted to the first 20 days of postnatal life.

We attempted to define the critical time period during early postnatal life when GH and T4 are essential for myelination. We administered bGH and T4 to Snell dwarf mice during the first and second 20 days after birth. Positive results were obtained only when hormones were given during the first 20 days of postnatal life. We observed a distinct increase in brain weight, DNA content, CNPase activity and a remarkably increased level of spontaneous locomotion activity with a diurnal periodicity. Morphological observations of brain sections stained for myelin basic protein (MBP) correlated the biochemical findings. The later administration of hormones was ineffective. Our interpretation is that the administration of exogenous hormones led to increased myelinogenesis through their stimulatory effects on glial proliferation, as evidenced by the increase in cerebral DNA content.

2',3'-Cyclic Nucleotide 3'-Phosphodiesterase↗
PubMed1985

Effects of glycoprotein synthesis inhibitor on myelination in rat cerebellum.

Effects of a glycoprotein synthesis inhibitor on myelination were investigated in rat cerebellum. The glycoprotein synthesis inhibitor, tunicamycin (TM), was injected intracranially into newborn rats. The activity of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) in the cerebellum was significantly reduced in 2-week-old animals and was restored to the normal level by age 3 weeks. When TM was injected into newborn rats every 3-4 days for a total of 6 times, CNPase activity was still low at 3 and 4 weeks. Immunohistochemical stainings for CNPase and myelin-associated glycoprotein (MAG) were performed on paraffin sections of multiple-TM-injected cerebellum at 3 weeks. The intensity of the staining with MAG antiserum in the white matter was clearly decreased in TM-treated cerebellum compared with the control. The myelin in the granule cell layer was poorly stained with CNPase antiserum in TM-treated cerebellum. Subcellular fractionation was carried out and the CNPase activity in each fraction was measured. The CNPase activity in the myelin fraction (P2A) from the TM-treated cerebellum was significantly lower than that in the control. In contrast, the activity in the synaptosomal (P2B) and microsomal (P3) fractions from the multiple-TM-injected cerebellum was higher than in those from the controls. Polyacrylamide gel electrophoretic patterns of the P2A fractions were analyzed. The P2A fraction from TM-treated cerebellum contained less Wolfgram protein than the control. These results suggest that glycoprotein synthesis plays certain roles in myelination in the central nervous system.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1985

Neurochemical studies on imprinting behavior in chick and duckling.

The effect of lesions in the parts of medial hyperstriatum ventrale (MHV) or lateral neostriatum (LN) on imprinting behavior was examined. Bilateral lesions in MHV severely impaired imprinting behavior in ducklings, but lesions in LN did not impair such behavior. On the other hand, the birds lesioned in MHV still had brightness discriminative learning ability with perfect performance of visuomotor coordination. The neurotransmitter candidates controlling imprinting behavior in MHV were investigated using blockers of neurotransmission. 6-Hydroxydopamine (6-OHDA) and haloperidole injected into MHV did not have specific effect on imprinting behavior although catecholamine contents in MHV was clearly decreased and locomotor activity was strongly suppressed. Atropine injection into MHV caused significant impairment of following behaviour, but locomotor activity was not affected. The injection of atropine into other region did not have any effect. alpha-Bungarotoxin showed no effect on either imprinting or locomotor activity. Kainic acid injection into MHV caused the decrease of glutamate content in the MHV region and it reached maximum at 24 hours after injection. However, imprinting behavior was already impaired at 3 hours after injection, but at 24 hours it had been recovered. A same effect was observed by glutamate injection. The effect of protein synthesis inhibitor on the acquisition process of imprinting was investigated. The acquisition of imprinting was significantly impaired by cycloheximide (CHX) injection into MHV within 2 hours after the first exposure to the imprinting stimulus. When CHX was given 24 hours after, imprinting behavior was not affected.

Animals↗
PubMed1985

Microcephalic cerebrum with hypomyelination in the growth hormone-deficient mouse (lit).

To determine whether GH has an independent action on cerebral development, we examined the central nervous system of the little mouse (lit), a promising model of isolated growth hormone deficiency. Our findings are (A); the weights of two parts of the lit brain were significantly less than those of the normal controls, 81.5% less for the cerebrum, and 81.6% for the cerebellum, (B): the total DNA content was reduced to approximately 80% in the cerebrum and 84% in the cerebellum compared to those of the normal controls, (C); the total RNA content was also reduced in the cerebrum and cerebellum, proportional to the reduction in DNA, (D); CNPase activity was reduced selectively in the cerebrum of the lit mouse (74.4% of the normal control), and (E); the lit mice exhibited a strikingly reduced level of activity with an indistinct diurnal periodicity. These results indicate that GH has independent actions on cerebral development, especially on glial cell proliferation as a precondition of myelin formation.

2',3'-Cyclic Nucleotide 3'-Phosphodiesterase↗
PubMed1985

Disorders in myelination in the twitcher mutant: immunohistochemical and biochemical studies.

The twitcher is an autosomal recessive mutant mouse characterized by absence of galactosylceramidase. The twitcher shows clinical and histological features similar to those of human Krabbe-type leukodystrophy. We here present the results of a neurochemical and immunohistochemical analysis of the twitcher. Electrophoretic analysis revealed that in the particulate fraction of the spinal cord, myelin basic proteins (MBP) and proteolipid protein were decreased, and in the sciatic nerve fibers, PO protein, X, Y and MBP were clearly decreased. 2',3'-Cyclic nucleotide 3'-phosphodiesterase (CNPase) activities of the pallium cerebri, brain stem and spinal cord of the twitcher were about 20% less than those of the control. However, in the sciatic nerve, the activity was half that of the control. Immunohistochemical studies were carried out by means of antisera against MBP and CNPase. There were clear patches indicating both MBP- and CNPase-negative reactions in the white matter of the central nervous system from the twitcher. The reaction on the section of sciatic nerve fibers from the twitcher showed a positive reaction only in a very limited number of fibers with both MBP and CNPase antisera. A clear astrocytic hypertrophy was detected by the antiserum against glial fibrillary acidic protein (GFAP). Even in the grey matter of the cerebral cortex, strong GFAP-positive astrocytes were clearly observed.

2',3'-Cyclic Nucleotide 3'-Phosphodiesterase↗
PubMed1985

Small cell carcinoma of the ovary: a rapidly lethal tumor occurring in the young.

Two patients with metastatic small cell carcinoma of the ovary managed by the Clinical Gynecologic Oncology Service at Roswell Park Memorial Institute are presented. Despite intensive multimodal therapy after extensive cytoreductive surgery, both patients expired from this rare tumor within 6 months of diagnosis. Neither tumor was associated with hypercalcemia, previously reported in the only existing review of the tumor in the world literature. Because of the highly aggressive nature of this cancer, effective combination chemotherapy must be found if the natural history of this tumor is to be altered.

Adolescent↗
PubMed1985

Pleiotropic phenotypic expression in cybrids derived from mouse teratocarcinoma cells fused with rat myoblast cytoplasts.

Cybrid clones were isolated by fusing mouse embryonal carcinoma (PCC4) cells with cytoplasts of rat myoblastic cells (L6TG X CAPr). Although some clones were similar to PCC4 (Type II), a high proportion (88%) were differentiated; the differentiated cells had a mesh-like arrangement (Type I) or were flat with many projections (Type III). Protein patterns of both Type I and Type III cells changed markedly from that of PCC4 cells. Type III cells lacked alkaline phosphatase and expressed endo A and B proteins predominantly. One Type III clone produced alpha-fetoprotein and plasminogen activator (visceral endoderm-like), while another clone consisted of trophectodermal cell-like giant cells. Therefore it was shown that introduction of the somatic cell cytoplasm induces differentiation of teratocarcinoma stem cells, suggesting a cytoplasmic element (or elements) regulating gene expression.

Alkaline Phosphatase↗
PubMed1985

Observations on Golgi epithelial cells and granule cells in the cerebellum of the reeler mutant mouse.

Cerebella of reeler mutant mice at two months of age were studied by the Golgi impregnation method to elucidate the detailed configurations of the Golgi epithelial cells and granule cells. On the basis of configuration of their Bergmann fibers, the Golgi epithelial cells of the reeler were relatively normal, or assumed inverted, swan neck, stellate, bipolar, small, or fan shapes, although their morphological changes were continuous rather than abrupt. Radially ascending Bergmann fibers, as well as disoriented ones, arose from the soma of these varieties of Golgi epithelial cells. In many areas, the granule cells were normally aggregated under the molecular layer and constituted the granular layer, although several granule cells were regionally arrested in migration within the molecular layer in some small areas. The axon of the granule cells ascended sinuously or obliquely, extended horizontally, looped around, or descended. In some cases, the granule cells had no T-like bifurcation of the axon, and assumed a bipolar form.

Animals↗
PubMed1985

Impaired development of rat cerebellum induced by neonatal injection of the glycoprotein synthesis inhibitor, tunicamycin.

The effects of the protein glycosylation inhibitor tunicamycin on the postnatal development of the rat cerebellum were examined in vivo. Tunicamycin (0.2 micrograms) was injected intracranially into 1-day-old rats. Inhibition of glycosylation of the macromolecules in the cerebellum by tunicamycin treatment was suggested by a reduced incorporation of [3H]glucosamine into the trichloroacetic acid (TCA)-insoluble fraction. The tunicamycin treatment did not affect gain in body weight significantly. However the cerebellar weight was significantly reduced by 30-40% compared with that of the controls. Development of GABAergic and cholinergic innervations in the hypoplastic cerebellum was examined by measuring the activities of glutamate decarboxylase (GAD) and choline acetyltransferase (ChAT). The specific activity and the total activity of GAD were significantly reduced in the tunicamycin-treated cerebellum. In contrast the specific activity of ChAT was significantly increased, whereas the total activity of ChAT per cerebellum was identical with that of the controls. These results suggest that the intracranial injection of tunicamycin affects the postnatal development of rat cerebellum, such as GABAergic and cholinergic innervations.

Animals↗
PubMed1985

Immunohistochemical localization of 2',3'-cyclic nucleotide 3'-phosphodiesterase and myelin basic protein in the central nervous system of the jimpy and the normal mouse.

We describe the immunohistochemical localization of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) and myelin basic protein (MBP) in CNS of the jimpy mutant mouse which is characterized by dys- and demyelination. In controls, the CNPase and MBP were localized exclusively in white matter in the CNS. The jimpy mutant mice were severely affected: A very weak reaction was observed in the white matter. Very few CNPase- and MBP-positive myelin sheaths were observed, and some degradation products were also observed after reaction with antisera against both CNPase and MBP. The immunohistochemical reaction in the jimpy mice showed a similar localization in both CNPase and MBP.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1985

P400 protein characteristic to Purkinje cells and related proteins in cerebella from neuropathological mutant mice: autoradiographic study by 14C-leucine and phosphorylation.

P400 protein has been found in the cerebellum and localizes to Purkinje cells. It is a glycoprotein and reacts with plant lectins. Autoradiographic patterns of the protein profiles of mutant mice cerebella after intracranial injections of 14C-leucine were analyzed. P400 protein was one of the dominant proteins labeled in the control cerebellum. No incorporation of 14C-leucine to the position of P400 protein was found in the nervous and pcd mutant mice where no Purkinje cells and no P400 protein are present. P400 protein in weaver cerebellum was labelled more intensely than that in the control. In the staggerer mice, where dendritic arborization of Purkinje cell is poor and no spines are formed on the dendrites, no P400 protein was found and no 14C-leucine incorporation was observed to the position of P400 protein, suggesting that staggerer is a mutation where no P400 protein accumulated in the fractions being studied. P400 protein was phosphorylated independently of the presence of Ca2+. Among the proteins of the isolated Purkinje cells, P400 protein was one of the major proteins phosphorylated.

Animals↗
PubMed1985

Altered myelinated fiber trajectory at various postnatal days in the cerebral cortex of reeler mice by immunohistochemical stain with MBP antiserum.

The cerebral cortex of reeler mutant mice characterized by the derangement of cell position was analyzed by an immunohistochemical staining technique using antiserum against myelin basic protein. All the myelins of the myelinated fibers were stained, so that the fiber trajectories could be clearly traced. In the present study the changes in the fiber trajectories were accompanied by changes in myelination sites. Myelinated fibers were localized in the central white matter and gradually became sparser toward the surface of the normal cerebral cortex, while in the reeler myelinated fibers were observed throughout the cortical plane. From the immunohistochemical analysis of the changes occurring in the myelinated fiber pathways in developmental sequence, it was also shown that the fiber bundle accumulation was thin at the earlier stages (e.g. the 15th postnatal day) and became thick as the animal grew, and the timing of myelination in the reeler was similar to that of the control.

Animals↗
PubMed1985

Auditory brain stem response in neuropathological mutant mice (shiverer and reeler).

Auditory brain stem response (ABR) was investigated in shiverer mice and reeler mice. In shiverer mice, the wave latency after ABR wave III was prolonged and wave V disappeared. Although the interpeak latencies were also prolonged, there were some differences according to the site of the disorder. The threshold was found to be normal. In reeler mice, the findings on the wave latencies were inconsistent. Some of the mice showed no differences from the controls, some showed prolonged latencies, and some showed only wave I. The ABR findings on the shiverer mice were considered to be due to abnormal or poor myelin formation in the central nervous system. Abnormal ABR findings in the reeler mice are probably caused by a secondary change due to the abnormal cell positions resulting from mutation.

Animals↗
PubMed1985

[Chemical modification of anti-cancer drugs to increase their affinity to tumor antigens].

In order to increase the selective localization of anti-cancer drugs to the target tumor cells, polyclonal or monoclonal anti alpha-fetoprotein antibody (aAFP) was conjugated with anti-cancer drugs such as daunomycin (DM), adriamycin (AM) and mitomycin C (MMC) by chemical modification. Dextran (Dex) or poly L-glutamic acid (PLGA) was used to bind aAFP with DM (AM) as an intermediate drug carrier. For the conjugation of aAFP with MMC, a direct binding method through the aziridine ring of the activated MMC derivative or an indirect binding method through serum albumin as an intermediate drug carrier was employed. These conjugates caused greater inhibition of both in vitro and in vivo tumor growth of AFP-producing target tumor cells than did a mixture of aAFP and anti-cancer drugs or a simular conjugate of these drugs with normal horse immunoglobulin. AFP has high affinity to unsaturated fatty acids (UFA) such as arachidonic acid (C20:4) and so on. The antitumor effect of UFA-DM conjugate was also assessed using AFP-producing rat ascites hepatoma cells. It was found that UFA-DM conjugated showed highly selective cytocidal effects against the hepatoma cells.

Animals↗