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Biomedical subjects

Y Kodama

Publications and source records attributed to Y Kodama.

At least 271 records · Page 15Linked to original sources

Cloning of phenotypically different human lymphocytes originating from a single stem cell.

By using hypoxanthine guanine phosphoribosyltransferase (hprt) gene alterations and chromosome aberrations as in vivo cellular markers, human T, NK, and B cells originating from a single stem cell have been successfully cloned from the peripheral blood of an atomic bomb survivor from Hiroshima. These mutant lymphocytes were selectively cloned, taking advantage of their resistance to a purine analogue, 6-thioguanine. The cloned lymphocytes possessed the same hprt gene alterations and the same chromosome aberration (20q-), but exhibited different surface or functional phenotypes and different rearrangements of TCR or Ig genes. The chromosome aberration patterns strongly suggested that the original stem cell initiated differentiation into each cell type after exposure to atomic bomb radiation. Since the person studied here was exposed to the bomb at 17 yr age, the results suggested that common stem cells exist in adults for at least T, NK, and B cells. The use of hprt gene alterations as specific cellular markers provides a novel method for identifying stem cells in the lymphocyte lineage and for studying lymphocyte differentiation in humans.

Antigens, Surface↗

Cytogenetic analysis of spontaneous and 2-cyanoethylene oxide-induced tk-/- mutants in TK6 human lymphoblastoid cultures.

Two phenotypic classes of selectable tk-/- mutants have been isolated from the TK6 human lymphoblast cell line; one has a normal growth rate (tkn) relative to the parental cell line; the other has a slow growth rate (tks). Complete karyotypes of metaphase chromosomes were prepared and analyzed from 16 tks mutants (eight spontaneous and eight 2-cyanoethylene oxide [CNEtO]-induced), two spontaneous tkn mutants, and the parental TK6 cell line. Southern blot analysis of these tk-/- mutants indicated that all had lost a 14.8 kb polymorphic band corresponding to the active tk allele. No chromosome abnormalities with respect to the parental cell line TK6 were observed in eight spontaneous tks mutants. Chromosome abnormalities that may have been related to CNEtO treatment were observed in four of eight CNEtO mutants. However, chromosome 17, containing the tk locus in man, was cytologically normal with respect to the parental TK6 cell line in 15 of 16 tks mutants. A visible abnormality of chromosome 17 was present in one CNEtO-induced tks mutant. The abnormality was a duplication of the long arm of the chromosome 17, with break points at q11 and q21. The latter break point is close to the site of the tk locus, suggesting that the aberration observed may be associated with tk-/- phenotype. These observations contrast with the relatively high incidence (greater than or equal to 59%) of chromosome 11 abnormalities reported in tks (small colony) mouse lymphoma L5178Y/TK +/- mutants.

Cell Division↗

Copper deficiency in the mitochondria of cultured skin fibroblasts from patients with Menkes syndrome.

The mitochondrial copper concentrations and cytochrome C oxidase activity of the fibroblasts from the patients with Menkes syndrome were investigated. Both the mitochondrial copper concentrations and cytochrome C oxidase activity of fibroblasts from patients with Menkes syndrome were lower than those of the control fibroblasts. These data indicate that the mitochondria of fibroblasts from patients with Menkes syndrome are in a state of copper deficiency. The activity decline of cytochrome C oxidase, a mitochondrial cuproenzyme, seems to be caused by copper deficiency in the mitochondria.

Brain Diseases, Metabolic↗

Micronucleus test with 1-beta-D-arabinofuranosylcytosine administered by intraperitoneal injection and oral gavage.

The effect of route of administration on the outcome of the micronucleus test was evaluated in 2 laboratories by administering the model chemical, 1-beta-D-arabinofuranosylcytosine (Ara-C), by intraperitoneal injection (i.p.) and oral gavage (p.o.) to 2 mouse strains, MS/Ae and CD-1. On the basis of a small-scale acute toxicity study and a pilot experiment for the micronucleus test, a full-scale test was performed with a 24-h sampling time at doses of 12.5, 25, 50, and 100 mg/kg i.p. and 25, 50, 100, and 200 mg/kg p.o. In both strains, MNPCEs were induced at lower dose levels by the i.p. treatment, as determined not only on the basis of mg/kg but also as a ratio of the LD50. When compared with other chemicals tested in this collaborative study, the effective dose levels of this chemical based on the LD50s were exceptionally low by both routes and in both strains, e.g., less than 0.3% of the LD50 by the i.p. treatment. The maximum frequencies of MNPCEs induced were, however, identical (MS/Ae) or even higher (CD-1) by the p.o. treatment.

Administration, Oral↗

A chromosome study of 6-thioguanine-resistant mutants in T lymphocytes of Hiroshima atomic bomb survivors.

Cytogenetic characterizations were made of lymphocyte colonies established from somatic mutation assays for 6-thioguanine (TG) resistance in Hiroshima atomic bomb survivors. G-banded chromosomes were analyzed in both TG-resistant (TGr) and wild-type colonies. Included were 45 TGr and 19 wild-type colonies derived from proximally exposed A-bomb survivors, as well as colonies from distally exposed control individuals who did not receive a significant amount of A-bomb radiation (18 TGr and 9-wild type colonies). Various structural and numerical chromosome abnormalities were observed in both TGr and wild-type colonies. Aberrations of the X chromosome, on which the hypoxanthine guanine phosphoribosyl transferase (HPRT) locus is present, were found in 6 colonies: 2 resistant colonies from controls (45,X/46,XX; 46,X,ins(X)), 3 resistant colonies (45,X/46,XX/46,X, + mar; 46,X,t(Xq +;14q-); 46,Y,t(Xq-;5q +)), and 1 wild-type colony (45,X/47,XXX) from proximally exposed persons. In cases with exchange aberrations, each of the break points on the X chromosome was situated proximally to band q26 where the HPRT locus is known to be assigned. DNA-replicating patterns were also studied, and it was found that abnormal X chromosomes showed early replicating patterns, while normal X chromosomes showed late replicating patterns.

Aneuploidy↗

Dose-response carcinogenicity in rats on low-dose levels of N-ethyl-N-nitrosourethane.

A dose-response study on the carcinogenicity of N-ethyl-N-nitrosourethane (ENUR) was undertaken to examine its effect at low doses. Six-week-old female F344 rats were divided into 5 groups, each consisting of 40 animals. ENUR was dissolved in distilled water at dose levels of 0 (control), 0.15, 0.6, 2.5 and 10 ppm, and rats were given these solutions ad libitum for 2 years. Significant increase of the total tumor incidences and shortening of the mean survival times were observed in groups given 2.5 and 10 ppm ENUR. In groups given 0.6 ppm or more ENUR, digestive tract tumors were induced dose-dependently. They were restricted to the upper digestive tract from the oral cavity to the forestomach, and were histologically squamous cell papillomas or carcinomas. Dose-related differences in the location and incidence of these tumors were found. The virtually safe doses (VSDs) calculated by using the Weibull, Logit and Probit models were 0.365 x 10(-2), 0.110 x 10(-1) and 0.779 x 10(-1) ppm, respectively. The VSDs estimated in the present study are discussed in comparison with those of other carcinogens.

Administration, Oral↗

Novel phase-shift marker in cell surface proteins of Bordetella bronchiseptica.

Cell surface proteins of phase I cultures of Bordetella bronchiseptica strains from various species of animals were compared with those of isogenic phase III cultures by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A protein band with a molecular mass of 74 kilodaltons was found only in various phase I cultures. This protein disappeared in parallel with antigenic modulation and had strong antigenicity. We found it to be an appropriate phase-shift marker for two reasons: it was readily extracted and recognized, and it was specifically identified by its distinct antigenicity.

Animals↗

Primary irritant reactions in the skin of the pika, Ochotona rufescens rufescens.

The skin of the pika (Ochotona rufescens rufescens) was found to be remarkably sensitive to the primary irritation of sodium hydroxide, as compared with the skin of the rabbit. After exposure to 0.1 N sodium hydroxide for 24 hr, the pika skin showed severe erosion, ulceration and necrosis as well as crust formation and hyperkeratosis with vascular dilation, and cell infiltration. The changes appeared already within 1 hr after 1 N or 3 hr after 0.1 N sodium hydroxide application. After application of acetic acid, changes were apparent while less remarkable.

Animals↗

[Metastatic malignant lymphoma of the skull with extradural and extracranial extension. Case report].

A 72-year-old male was hospitalized because of a steadily growing mass (4 x 4 x 2 cm) in the frontal region, noticed following head injury. Six months earlier, he had declined treatment for malignant lymphoma (small non-cleaved cell type), discovered upon evaluation of a subcutaneous mass in his forearm. Neurological examination on admission was negative. Plain skull films revealed a large, osteolytic lesion with an irregular margin. Bone scintigraphy disclosed no uptake other than in the frontal bone. Computed tomography (CT) showed a large, homogeneously enhanced mass with both extradural and extracranial extension, which had destroyed the left frontal bone. The skull tumor was totally resected, and the diagnosis was malignant lymphoma, large cell, immunoblastic and plasmacytoid type. Postoperative combined chemotherapy with vincristine, cyclophosphamide, prednisolone, and adriamycin resulted in the complete disappearance of liver metastases. The patient was readmitted 2 months later, however, because of headache and gradually progressive impairment of consciousness. A CT scan disclosed brain metastasis in the paraventricular region. Radiation therapy (20 Gy) was administered but no further treatment was given. Skull metastasis is not uncommon in cases of malignant lymphoma, but a large mass with both extradural and extracranial extension is rare. Although aggressive chemotherapy was effective, prophylactic irradiation of the brain should have been considered in this case.

Aged↗

[A case report of advanced malignant mixed germ cell tumor of parasellar origin indicating marked efficacy of a salvage combined chemotherapy of CDDP and etoposide and subsequent chemotherapy using oral etoposide].

A case of a 13-year-old boy with malignant mixed germ cell tumor of parasellar origin was reported. After partial removal of the tumor, combined chemotherapy (using cisplatin, vinblastine and bleomycin: PVB therapy) and irradiation were performed, and the tumor was reduced to under one tenth. In spite of PVB maintenance chemotherapy, it became refractory later. The patient was then treated with both CDDP 20 mg/m2 daily for 5 days and etoposide 100 mg/m2 for 1, 3, 5 days. After this one course, the tumor was diminished. Oral etoposide was administered at our outpatient department, and the boy was free of disease for six months.

Administration, Oral↗

Effect of OK-432 on the lymphnode metastasis of MCA-sarcoma cell lines: a new therapeutic approach.

The two unique highly metastatic MCA-sarcoma cell lines have been established by the present authors. The inoculation of 1153Ln, one of the cell lines, either into footpad or subcutaneously on the back of syngeneic mice resulted in the development of metastasis exclusively in almost all lymphnodes of the body. We evaluated the therapeutic effect of a streptococcal preparation, OK-432, on the lymphnode metastasis. Two KE per mouse of OK-432 were injected intratumorally (it) at 4, 7 or 10 days after the footpad inoculation of 1153Ln. OK-432 injected it at 7 days after tumor inoculation showed an inhibition of the lymphnode metastasis. Histological findings indicated that the proliferation of lymphoid cells in the drainage node was most prominent in mice treated with OK-432 at 7 days after the tumor inoculation. A combined treatment of it and intraperitoneal (ip) injections of OK-432 significantly reduced lymphnode metastasis as compared with that of ip injection alone. This can be attributed to the fact that the activated lymphocytes induced by it-injected OK-432 exhibited a potent antimetastatic activity together with general administration (ip) of OK-432 given after surgical removal of the tumor. Low dose of total-body irradiation (TBI), known to augment the antitumor potential of tumor-bearing animals together with general application of OK-432, showed synergistic action in inhibiting tumor growth. Overall results suggest that the better antitumor effect of OK-432 can be anticipated by combination of the agent itself and with other means.

Animals↗

[Experimental study of superior vena caval's reconstruction with ringed E-PTFE grafts].

For evaluating whether 2 types of expanded polytetrafluoroethylene, ringed E-PTFE graft can be utilized for venous reconstruction, especially, for superior vena caval reconstruction or not, the ringed E-PTFE grafts which had 10-15 micron fibril length and 30 micron fibril length were implanted between the innominate vein and the right atrium of the 20 dogs. The grafts were removed for histological and scanning electromicroscopic evaluation at intervals varying from one to twelve postoperative months. Overall patency rate was 62% and severe stenosis at the site of anastomosis was seen in 2 grafts. More than half of the graft showed mild to moderate intimal hyperplasia at the anastomotic sites and the early stage of thrombosis at the middle of the grafts. Mesenchymal cell infiltration was occurred in 46% of the grafts.

Animals↗

Evaluation of thyroid calcification using computed radiography with image plate.

The value of lateral magnification soft x-ray roentgenography using a Computed Radiography (CR) system was studied. ROC curve analysis revealed that a CR system has virtually the same, or a better ability than a screen-film system for detecting thyroid calcification. According to our criteria the CR system an accuracy rate of 77.1% in malignant/benign diagnosis was obtained.

Calcinosis↗

Specular microscopic studies of the corneal endothelia of Japanese diabetics.

We did a specular microscopic study with computer-assisted morphometric analysis of individual cells on the corneal endothelia of 69 Japanese diabetics and 53 age-matched nondiabetics. No statistically significant differences were seen in the mean cell areas of diabetics and nondiabetics. However, the coefficient of variation of cell area was significantly higher and the percentage of hexagonal cells was significantly lower in diabetics than in nondiabetics. Although racial differences of the corneal endothelia exist between Japanese and Americans, diabetic changes are quite similar in the two populations.

Adult↗

Lung burden of green nickel oxide aerosol and histopathological findings in rats after continuous inhalation.

There are few inhalation studies of nickel carcinogenesis. In this study, Wistar male rats were exposed to green nickel oxide (NiO(G)) aerosols (mass median aerodynamic diameter, 0.6 microns) for 7 h/d, 5 d/wk for up to 12 mo. The average exposure concentration was controlled at 0.3 and 1.2 mg/m3 during the exposure. For histopathological examination and measurement of the nickel concentration in rat organs, the rats were sacrificed at 3, 6, and 12 mo of exposure and 8 mo clearance period following 12 mo of exposure. The nickel content in rat lungs that was observed up to 2.6 mg after 12 mo exposure, was proportional to the exposure concentration during the exposure. The clearance of the nickel from the lungs was very slow and the biological half time was determined 7.7 mo. Although the rats were exposed continuously to NiO(G) for 12 mo and kept for 8 mo clearance period, there were no malignant tumors in any of the exposed animals.

Aerosols↗