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Biomedical subjects

Y Tsukada

Publications and source records attributed to Y Tsukada.

At least 199 records · Page 11Linked to original sources
PubMed1986

Septal deafferentation enhances the neurotrophic effects of rat hippocampus on cultured neural cells from the central nervous system.

Neurotrophic effects (NTEs) of various brain regions of 4-week-old rats were examined in primary culture of rat embryonic cerebral hemispheres. Extracts of the hippocampus, brainstem and septal nucleus highly enhanced the survivability of neuronal cells and the division of non-neuronal cells by 9 days. The septohippocampal tract (fimbria fornix) was cut and the effect on the neurotrophic activity in the hippocampus was examined. The NTEs of hippocampal extracts remained unchanged 3 days after septal deafferentation, was significantly increased by 7 days, peaked at 14 days and returned to the basal level by 21 days.

Animals↗
PubMed1986

Evaluation of a conjugate of purified antibodies against human AFP-dextran-daunorubicin to human AFP-producing yolk sac tumor cell lines.

The anticancer drug, DNR, was conjugated to an affinity-purified horse antibody to human AFP (aAFP) via a dextran bridge. The conjugate (immunoglobulin: DNR molar ratio, 1:50) was twice as potent as free DNR in an in vitro cytotoxicity assay against an AFP-producing human yolk sac tumor. The in vivo effect of aAFP, DNR, and the conjugate was tested against the human yolk sac tumor growing in nude mice. The conjugate, at a concentration of DNR containing the equivalent amount of 20 micrograms or 70 micrograms/mouse significantly retarded tumor growth whereas free aAFP showed only a slight inhibition of tumor growth compared to the PBS-treated control. Mice which received 20 micrograms/mouse of free DNR showed a moderate retardation of tumor growth whereas those which received 70 micrograms/mouse of DNR or a mixture of DNR and aAFP showed emaciation and early death due to acute toxicity of the drug. These results suggest that the anti-body-drug conjugate accumulated preferentially on the AFP-producing tumor cells and that cytotoxicity occurred.

Animals↗
PubMed1986

Selective in vitro and in vivo growth inhibition against human yolk sac tumor cell lines by purified antibody against human alpha-fetoprotein conjugated with mitomycin C via human serum albumin.

The anticancer drug mitomycin C (MMC) was conjugated with an affinity-purified horse antibody to human alpha-fetoprotein (aAFP) with human serum albumin (HSA) as the intermediate drug carrier. The conjugate (aAFP:HSA:MMC molar ratio, 1:1:30) retained full antibody binding activity as determined by a competitive binding radioimmunoassay. In a cytotoxicity test in which the AFP-producing human yolk sac tumor TG-1 cells were preincubated with test materials for 2 h followed by an additional 48-h culture in fresh medium, the conjugate was 20-fold more cytotoxic than free MMC at an equivalent MMC concentration of 100 ng/ml. The in vivo antitumor effect of the conjugate was tested against the human yolk sac tumor JOG-9 growing in athymic nude mice. When the tumor-bearing mice were treated with a total of 6 injections given on 2 consecutive days and then every other day starting 8 days after SC tumor inoculation [2 (equivalent MMC) microgram/head per injection], the conjugate retarded tumor growth more effectively than free MMC and normal horse immunoglobulin conjugate.

Adolescent↗
PubMed1986

Stage III and IV squamous cell carcinoma of the vulva.

From 1957 to 1975, 61 patients with FIGO Stage III and IV vulvar carcinoma underwent primary therapy at Roswell Park Memorial Institute and all have been followed for 5 years or until death. The 5- and 10-year survival for Stage III was 77 and 60%, respectively. The 5- and 10-year survival for Stage IV was only 7.1%. Of the Stage III recurrences, 73.3% occurred within the local operated area: urethra, vagina, anus, or perineum. In contrast, 61% of the recurrences in Stage IV were distant, i.e., outside of the operated area. Because of the high local recurrence rate for Stage III and the low survival and high rate of distant recurrences in Stage IV, new treatment plans are proposed for patients with Stage III or IV vulvar carcinoma.

Adult↗
PubMed1986

Alteration of the primary pattern of central myelin in a chimaeric environment--study of shiverer----wild-type chimaeras.

Using chimaeras produced from the shiverer mutant with a BALB/C background (white coat color) and normal mice of the C57BL/6N strain (black coat color) by the aggregation method, the morphological patterns of the central myelin sheaths were examined by electron microscopy, with special reference to the structure of the myelin lamellae of the one genotype in an environment dominated by the other genotype. The results obtained may be summarized as follows. The oligodendrocytic processes of both genotypes are able to interact independently with the axon unrelated to its genotype. The lamellar structure of the myelin sheath, i.e., whether or not it is composed of alternating major dense and intraperiod lines, is primarily determined by the genotypes of the oligodendrocytes concerned. The processes of shiverer oligodendrocytes can spirally enwrap axons in the chimaeric CNS which shows dominance of the normal genotype. In contrast, in the environment of shiverer dominance, the spiral arrangement of the oligodendrocytic processes of the normal genotype is often disturbed, probably by the oligodendrocytic processes of the shiverer genotype. Thus, the primary pattern of the myelin sheaths can be altered under the chimaeric condition, and the formation of the myelin sheaths depends essentially on the behavior of the oligodendrocytic processes, which is determined by the genetic specificity.

Animals↗
PubMed1986

The effect of arcuate nucleus transplantation on the development of the anterior pituitary in monosodium glutamate-treated rats.

Treatment with monosodium glutamate (MSG) during the neonatal period is known to produce a selective lesion of the arcuate nucleus in rat brain, which is the major site of production of growth hormone releasing-hormone (GRH), followed by a secondary reduction in growth hormone (GH) synthesis in the anterior pituitary. Normal arcuate nuclei from hypothalamic areas of newborn rats were transplanted into the third ventricles of 27-day-old rats which were treated with MSG on alternate days for the first 10 days of life. Ninety days after birth, the anterior pituitaries were examined for GH synthesis by immunohistochemical staining with GH antiserum. The results indicated that the impaired GH synthesis in the anterior pituitary treated with MSG was partially restored in some recipients by grafts of arcuate nuclei in which the GRH-containing neurons were clearly detected by immunohistochemical staining with GRH antiserum.

Animals↗
PubMed1986

Production of monoclonal antibody to 2',3'-cyclic nucleotide 3'-phosphodiesterase from bovine cerebral white matter.

Lewis rats were immunized with partially purified 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) from bovine cerebral white matter and the spleen cells were fused with cell of a mouse myeloma cell line (SP-2). The production of monoclonal antibody was detected by enzyme-linked immunoadsorbent assay, immunohistochemical staining of bovine cerebrum, Western blotting analysis, and CNPase binding assay. Monoclonal antibody that specifically binds CNPase molecules was obtained. However, the antibody did not suppress the enzyme activity. Western blotting analysis demonstrated that the monoclonal antibody binds both CNa (Wla) and CNb (Wlb). The monoclonal antibody was identified as being of the IgG2c subclass. Immunohistochemical examination revealed that the myelin sheath in the CNS was heavily stained with the monoclonal antibody in several species (bovine, mouse, rat, and human). In contrast, peripheral nervous system myelin was not stained even in bovine tissue. These results suggest that the monoclonal antibody obtained in the present study specifically recognizes the CNPase molecules in the CNS.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1986

[Anti-tumor activity of an anti-human alpha-fetoprotein antibody-human serum albumin-mitomycin C conjugate against human yolk sac tumor maintained in vitro and in nude mice in vivo].

The anti-cancer drug, mitomycin C (MMC), was conjugated to an affinity-purified horse antibody to human alpha-fetoprotein (aAFP) via purified human serum albumin (HSA) as an intermediate carrier. The conjugate (aAFP immunoglobulin (IgG): HSA: MMC, molar ratio 1: 1.10:29.8) was 21 or 38 times as cytotoxic as free MMC or PBS at the MMC concentration of 100 ng/ml, respectively, against alpha-fetoprotein-producing human yolk sac tumor in vitro. The in vivo effects of the conjugate and various controls were also tested against human yolk sac tumor growing in nude mice. The conjugate over a total of 6 injections retarded the initial tumor growth at the concentration of MMC, containing equivalent amounts of 2 micrograms/mouse (0.1 mg/kg)/injection in the conjugate, whereas free MMC and normal horse IgG-HSA-MMC showed only slight inhibitory effects alone at non-toxic levels. These results suggest that the specific antibody-conjugate was considerably more effective than free MMC against the tumor maintained in nude mice as well as in vitro cultures.

Animals↗
PubMed1986

Prevention of vaginal recurrence of stage I endometrial adenocarcinoma with postoperative vaginal radiation.

From 1975 to 1982 a prospective study was conducted at Roswell Park in 68 patients (group 1) for surgical stage I endometrial cancer, grade 1 or 2, and less than 50% myometrial invasion. These patients were treated by total abdominal hysterectomy, bilateral salpingo-oophorectomy, and postoperative vaginal radium. With median follow-up of 4.8 years, there has not been a single vaginal recurrence. This treatment plan was based on a prospective study at the same institute from 1958 to 1967, which compared patients with stage I endometrial cancer treated by hysterectomy alone, preoperative radium followed by hysterectomy, and hysterectomy followed by postoperative radium. In addition, 19 patients (group 2) were evaluated as to their initial treatment after their referral to Roswell Park with vaginal recurrence after surgical treatment for stage I endometrial cancer. None of these patients were treated initially with postoperative vaginal radium after hysterectomy. Based on the zero incidence of vaginal recurrence in 117 patients with FIGO stage I endometrial cancer, the estimated five-year survival rate of 97.2% for the group 1 patients, and the actuarial five-year survival of 95% in the 1958 to 1967 prospective study, it is concluded that primary surgery should be followed by postoperative vaginal radium (cesium) in those patients with stage I endometrial cancer, grade 1 or 2, with less than 50% myometrial invasion.

Adenocarcinoma↗
PubMed1985

Hormonal regulation during secretion of alpha-fetoprotein in hepatoma cells grown in synthetic medium.

The variant cell line of H4-II-E-C3 cells derived from the Reuber H-35 hepatoma cells has been established using protein- and lipid-free synthetic medium. This H4-II-E-C3-V line can synthesize and secrete considerable amounts of alpha-fetoprotein (AFP) and albumin. The addition of 5 X 10(-7) M dexamethasone to the medium stimulated the excretion of AFP without increasing total AFP synthesis, whereas 8.7 X 10(-8) M insulin inhibited the excretion of AFP without a significant inhibition of intracellular AFP synthesis. However, neither dexamethasone nor insulin altered either the cellular or secreted levels of albumin. Cells were pulse labeled with [35S]methionine and then chased after addition of excess unlabeled methionine. AFP appeared in the medium after 10 min, and 50% of the protein was secreted after 110 min. The rate of secretion of AFP was much slower than that of albumin, 50% of which was secreted after 25 min. Dexamethasone, 5 X 10(-7) M, caused a marked enhancement in the rate of AFP secretion, with 50% released after 75 min. Insulin, 8.7 X 10(-8) M, by contrast, caused a marked delay in AFP secretion with only 20% released after 180 min and then a plateau was approached. Since the intracellular AFP was excreted 55% after 180 min the remaining 25% of newly made AFP was suggested to be degraded during secretion. The kinetics of movement of AFP during secretion and endoglycosidase H treatment of intracellular and secreted AFP suggested that insulin impeded the transport of AFP from the rough endoplasmic reticulum to the Golgi apparatus.

Animals↗
PubMed1985

An AFP-producing gastric carcinoma with features of hepatic differentiation. A case report.

A patient with primary gastric adenocarcinoma with extremely high serum alpha-fetoprotein (AFP) levels (12,000 ng/ml) is described. Histologically, foci strongly resembling hepatocellular carcinoma with hyaline globules were noted. Within tumor cells, AFP was identified with both light and electron microscopy, showing the production of AFP by tumor cells themselves. Furthermore, 88% of serum AFP combined with Concanavalin A (ConA), revealing that it was hepatic-type AFP and not germ-cell-type. Localization of alpha-1-antitrypsin within tumor cells was also noted. Ultrastructural study showed that there were two types of structures corresponding to periodic acid-Schiff (PAS)-positive globules, one of which, the proteinaceous material in intracytoplasmic lumina, was found to contain AFP. Among gastric adenocarcinomas with a high serum AFP level (several thousand or more ng/ml of AFP), foci resembling hepatocellular carcinomas have been reported by several investigators. Those gastric carcinomas, together with the current case, may constitute a clinicopathologic entity, hepatoid adenocarcinoma of the stomach.

Adenocarcinoma↗
PubMed1985

Immunohistochemical detection of the gene product of Rous sarcoma virus in human brain tumors.

We have studied 108 cases of brain tumors by immunohistochemical staining utilizing an antiserum against the src gene product and GFA protein in order to elucidate the relationship between the brain tumors and the transforming genes. While the normal human brain tissues were not positive with the antiserum against the src gene product, several astrocytomas were clearly positive and other brain tumors were negative with the same. Src-gene product related peptide was detected in some of the human astrocytomas.

Astrocytoma↗
PubMed1985

Immunohistochemical studies on mouse cerebral cortex grafted into the third ventricle of rats treated with cyclosporin A.

Newborn mouse cerebral cortex was transplanted into the third ventricle of an adult rat brain. After the operation, the immunosuppressant cyclosporin A was administered daily for two weeks, and the grafted tissue was examined immunohistochemically at the 4th week. Neurons, astroglias and oligodendroglias were positively stained by antibodies against neurofilament, glial fibrillary acid protein and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), respectively. The CNPase staining indicated that myelination had occurred in the grafted tissue. Thus both neuronal and glial elements in the grafted tissue could survive and mature in the third ventricle of the different species upon administration of cyclosporin A.

Animals↗
PubMed1985

Cyclosporin A enhances the survivability of mouse cerebral cortex grafted into the third ventricle of rat brain.

The effect of the immunosuppressant cyclosporin A on the survivability of newborn mouse cerebral cortex transplanted into the third ventricle of adult rats was investigated. Hematoxylin staining revealed that the transplanted mouse brain tissue was rejected by 4 weeks after the transplantation in the control group. In contrast, a large mass of grafted tissue was clearly detected in the third ventricle even 4 weeks after the transplantation in the cyclosporin A-treated group, and the grafted tissue was heavily stained with Thy-1.2 mouse monoclonal antibody. The results indicate that cyclosporin A is an effective immunosuppressant in neuronal transplantation as well as in transplantation of other organs.

Animals↗
PubMed1985

Distribution and morphology of callosal commissural neurons within the motor cortex of normal and reeler mice.

Retrograde transport of horseradish peroxidase was used to examine the cells of origin of the callosal commissural fibers (CC neurons) in the primary motor cortex of normal and reeler mice. Quantitative analysis of the intracortical, laminar distribution, and dendritic orientation of CC neurons was performed in conjunction with qualitative observation of their morphology. For comparison, similar quantitative data were obtained for the cells of origin of the corticospinal tract (CST) of normal and reeler mice from materials described previously by Terashima et al. ('83). In the normal mouse, CC neurons are distributed in a bilaminar pattern such that the largest number of cells are located in supragranular layers II and III and in infragranular layer V. The majority of CC neurons are normal (upright) pyramids, although a few in the upper zone of layer VI are inverted pyramidal cells. In the reeler mutant, CC neurons are found in all cortical layers, but two-thirds are situated in the lower half of the cortex. On the basis of the celL shape and orientation of the apical dendrite, CC neurons of the reeler were classified into six morphological types: (1) typical pyramidal, (2) inverted pyramidal, (3) tumbled, (4) hook-shaped, (5) polymorphic, and (6) simple. The apical dendrites of the CC neurons in all layers of the cortex of the reeler mouse are randomly oriented; no direct relationship between the intracortical position of the soma and orientation of the apical dendrite was found. In contrast, CST neurons in the reeler mutant are concentrated in the outer third of the cortex, and there is a relationship between the laminar distribution of these cells and the alignment of their dendrites with respect to the pial surface: the apical dendrites of CST neurons lie in superficial layers tend to be oriented obliquely, whereas those of CST neurons in the deeper of cortex most often are oriented vertically, i.e, toward the pial surface. Quantitative analysis revealed that the relative intracortical positions of CC and CST neurons are reversed in the reeler mutant although both populations exhibited greater laminar disposition, and as a consequence, there is more intermingling of the two cell groups in the reeler than in the normal mouse. Thus, the present study suggests that the normal cytoarchitectonics of the primary motor cortex are inverted in the reeler mutant mouse.

Animals↗