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Biomedical subjects

S Kodama

Publications and source records attributed to S Kodama.

At least 19 recordsLinked to original sources
PubMed1992

Changes of DNA methylation in protooncogenes in the process of radiation-induced transformation of mouse m5S/1M cells in vitro.

To assess the importance of changes in DNA methylation in an X-ray-induced cellular transformation process, methylation patterns of five nuclear protooncogenes in fifteen transformant clones were studied and compared to that of the parental non-transformed cell line m5S/1M. All transformants examined revealed an alteration in DNA methylation in some of the genes, although these changes were variable among them. A comparison of cellular characteristics with corresponding DNA methylation changes in different clones suggested that the loss of contact inhibition and the gain of anchorage independency were associated with increases of methylation in many genes, whereas the acquisition of tumorigenicity was often accompanied by a decrease of methylation in the N-myc and c-myc genes. Resultant data indicate that the alteration of DNA methylation is closely related to transformation process, yet how this involvement occurs is complex and remains unclear.

Animals↗
PubMed1992

Suppression of X-ray-induced chromosome aberrations in ataxia telangiectasia cells by introduction of a normal human chromosome 11.

We studied X-ray-induced chromosome aberrations in ataxia telangiectasia (AT) cells containing an introduced chromosome 11 or 12 derived from normal human fibroblasts. We used microcell-mediated chromosome transfer to introduce the normal chromosomes into AT cells belonging to complementation group D. Cells were irradiated with 1 Gy of X-rays in the G2 phase. All 5 hybrid clones with an introduced chromosome 11 showed a reduction in the frequency of chromatid-type aberrations to normal levels, whereas all 4 hybrid clones with an introduced chromosome 12 failed to show this reduction. This finding, taken together with our previous report that chromosome 11 can restore radioresistant cell killing in AT cells, indicates that a defective gene on chromosome 11 in AT cells is responsible for the hypersensitivity to not only cell killing but also chromosome aberrations. Our results suggest that a putative AT gene on chromosome 11 plays an important role in the repair process of radiation-induced DNA damage that leads to chromosome aberrations.

Animals↗
PubMed1992

Characterization of recombinant murine interleukin 5 expressed in Chinese hamster ovary cells.

We have purified recombinant murine interleukin 5 (rmIL-5) from the supernatant of Chinese hamster ovary cells. Each peptide fragment of the purified rmIL-5 generated by Achromobacter protease I digestion was characterized and glycosylation sites were determined. Although rmIL-5 contains three potential sites of N-linked glycosylation (Asn-26, Asn-55 and Asn-69), Asn-69 is not glycosylated. The oligosaccharides released from the protein by hydrazinolysis were fractionated by paper electrophoresis, lectin column chromatography and gel permeation chromatography, and their structures were analysed by sequential exoglycosidase digestion in combination with methylation analysis. The results indicated that they are a mixture of bi-, tri- and tetraantennary complex-type sugar chains with and without a fucose at the C-6 position of the proximal N-acetylglucosamine residue and high-mannose-type sugar chains. Although > 80% of the sugar chains are neutral oligosaccharides similar to recombinant human IL-5 (rhIL-5; Kodama, S., Endo, T., Tsuroka, N., Tsujimoto, M. and Kobata, A. (1991) J. Biochem., 110, 693-701), rmIL-5 has more tetraantennary oligosaccharides than rhIL-5. A site differential study revealed that Asn-55 has more tetraantennary oligosaccharides than Asn-26.

Amino Acid Sequence↗
PubMed1992

Hepatic resection is not enough for hepatocellular carcinoma. A follow-up study of 92 patients.

We followed up 92 patients who underwent curative hepatic resection for hepatocellular carcinoma between 1982 and 1991. The long-term survival rates for these 92 patients for 1, 3, and 5 years were 98.8, 81.6, and 57.3%, respectively. As of May 1991, the carcinoma had recurred in 52 patients (56.5%). Recurrent tumors usually occurred in the residual liver within 3 years after surgery but were not always located near the primary lesion. The biologic characteristics of the primary tumors, such as serum alpha-fetoprotein, tumor size, number of tumors, and portal involvement, were closely related to recurrence and long-term survival. However, the type of hepatectomy performed on the primary tumor had little influence on recurrence or long-term survival. We conclude that recurrence cannot be avoided by hepatic resection alone, much less with limited resection; postoperative positive adjuvant therapy is required to prevent recurrence for patients with satellite nodule and/or portal involvement.

Adolescent↗
PubMed1992

Solid-phase anti-CD3 antibody activation and cryopreservation of human tumor-infiltrating lymphocytes derived from epithelial ovarian cancer.

The effect of solid-phase anti-CD3 antibody activation and cryopreservation was evaluated on thirteen samples of tumor-infiltrating lymphocytes (TILs) derived from epithelial ovarian cancer. Seven preparations of TILs were cultured with or without solid-phase anti-CD3 antibody in addition to 100 units/ml of recombinant interleukin-2 (rIL-2). The proliferation rate of all of the seven TIL preparations stimulated by anti-CD3 antibody on the fourth or fifth day of culture was 3.4 to 9.8 times greater than that of lymphocytes cultured with rIL-2 alone. Furthermore, in an experiment with five TIL samples activated with anti-CD3 antibody, three of them showed augmented cytotoxic activity against autologous fresh tumor cells. The population of CD3+/CD8+ TILs was increased after 4-5 weeks of cultivation and CD8+ lymphocytes amounted to over 70% in all of seven preparations tested, whereas two of seven preparations not activated by anti-CD3 antibody were CD3+/CD4(+)-dominant. In addition, nine preparations of TILs cultured with rIL-2 were cryopreserved for several weeks; after recovery from cryopreservation, no major change was observed in cell surface markers, in growth rate or in cytotoxic activity. These results suggest that cryopreserved and/or anti-CD3 antibody-activated lymphocytes could conveniently be employed in a clinical trial of adoptive immunotherapy employing TIL.

Antibodies↗
PubMed1992

[Serum eosinophil cationic protein (ECP) and major basic protein (MBP) levels in patients prepared for asthma attack].

Serum ECP levels, serum MBP levels and blood eosinophil counts (Eo) were studied in patients prepared for asthma attack. Five severely asthmatic children were studied. Samples were taken just before their 33 times of home stay loading test. Serum ECP levels were significantly higher in the patients who suffered asthma attacks during their home-stay period than in those who did not. In addition, serum ECP levels were higher in the patients whose asthma attack started less than 12 hours after they returned home. However, there was no significant correlation either in serum MBP levels or peripheral eosinophil counts between these groups. These findings suggested that serum ECP levels increased in patients prepared for asthma attack.

Adult↗
PubMed1992

Marinesco-Sjögren syndrome with reduced cytochrome c oxidase in muscle.

The present study deals with the sisters of Marinesco-sjögren syndrome without parental consanguinity. Cranial MRI of sisters in a 0.5T superconducting magnet revealed the cerebellar hypoplasia or atrophy, especially in vermis and tonsils with dilatation of IVth ventricle. Microscopic findings of muscle biopsy indicated moderate variation of fibers with phagocytosis, rimmed vacuoles and no ragged red fibers with markedly decreased cytochrome C oxidase activity. 1H-NMR study of urine indicates the secondary decreased turnover rate in urea cycle due to high concentration of 3-hydroxy-n-butyrate.

Biopsy↗
PubMed1992

Thyroid function in premature infants.

The present study was performed using the simultaneous assays of free T4 and TSH levels in dried blood spots of filter paper for mass-screening of inborn errors of metabolism in order to clarify the thyroid function of premature infants. The subjects were divided in three groups: A group infants less than 1500 g at birth (n = 34, 27.4 +/- 2.6 weeks of gestational age), B group infants from 1500 to 2500 g at birth (n = 104, 35.6 +/- 2.4 weeks) and C group infants over 2500 g at birth (n = 490, 39.0 +/- 1.2 weeks). TSH levels were 4.51 +/- 3.03, 2.62 +/- 2.24 and 2.84 +/- 2.06 microU/ml in A, B and C group respectively and significant difference was recognized in group A and C. Free T4 levels were 0.71 +/- 0.42, 1.81 +/- 0.96 and 2.15 +/- 0.67 ng/dl, in group A, B and C respectively, and significant differences were recognized in all three groups. There was positive correlation between free T4 levels and gestational ages (Y = -2.413 +/- 0.11725X, r = 0.206, p less than 0.05).

Humans↗
PubMed1992

[The study of ovarian metastasis in uterine cancer].

The correlation between histological ovarian metastasis and histologic cell type, clinical stage, depth of invasion, lymph node metastasis, and menstrual activity were analyzed in 566 patients who underwent surgery for uterine cancer at the hospital of Niigata University between January, 1971 and May, 1990. Ovarian metastasis was studied in 456 patients with stage Ib or more advanced cervical cancer and 110 patients with stage Ia or more advanced endometrial cancer. The following results were obtained: 1. The incidence of ovarian metastasis of cervical cancer by histologic cell type was 18.6% (8/43) for adenocarcinoma, 6.7% (1/15) for mixed type adenocarcinoma and squamous cell carcinoma, and 0% (0/398) for squamous cell carcinoma. The metastasis rate in patients with endometrial carcinoma was 10.8% (10/93) for adenocarcinoma, but there was no metastasis of 2 squamous cell carcinoma, 13 mixed type of adenocarcinoma and squamous cell carcinoma or 2 undifferentiated carcinoma. 2. The incidence of metastasis of cervical adenocarcinoma by stage was 5.3% (1/19) for stage Ib and 29.2% (7/24) for stage II. The metastasis rate of mixed type of adenocarcinoma and squamous cell carcinoma was 0% (0/6) for stage Ib and 11.1% (1/9) for stage II. The incidence of metastasis of endometrial carcinoma was 2.1% (1/47) for stage Ia, 15.0% (3/20) for stage Ib, 15.0% (6/40) for stage II and 0% (0/3) for stage III. 3. All the patients with ovarian metastases of uterine cervical cancer had invasion to a depth of more than 2/3 of the uterine cervix, while the incidence of ovarian metastasis of endometrial carcinoma was increased with deep invasion of the uterine muscular layer, and metastasis was present even in shallow invasion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1991

Age as a prognostic factor in patients with squamous cell carcinoma of the uterine cervix.

Correlations between age and several prognostic factors, such as histologic cell type, depth of invasion, intravascular invasion, and lymph node metastases (LNM), were analyzed in squamous cell carcinoma of the cervix (SCC). A total of 380 patients with Stage IB or more advanced SCC underwent radical hysterectomy at the authors' institution from 1971 to 1987. The cases were divided into four age groups: 30 to 39 years, 40 to 49 years, 50 to 59 years, and 60 to 69 years. The depth of invasion was classified in four categories according to pathologic examination of surgical specimens. The only significant factor was the frequency of LNM with deeper invasion, which was less in the 60-to-69-year age group than in the younger age groups. The 5-year survival rates of the patients with LNM also were higher in the 60-to-69-year group. Thus, age 60 or older can be considered a prognostic factor correlating to LNM in squamous cell carcinoma of the cervix.

Adult↗
PubMed1991

Role of the C-terminus in the biological activity of human interleukin 5.

Alterations of the C-terminal amino acid sequence of recombinant human interleukin 5 (rhIL-5) caused significant changes in its biological activity. Removal of eight amino acids from the C-terminus of rhIL-5 by CNBr treatment led to a complete loss of biological activity as determined by the BCL1 cell IgM-inducing assay. Oxidation of Met residue located at C-terminus also resulted in a loss of activity. These results suggest that the C-terminal amino acids of rhIL-5 are crucial for its biological actions.

Animals↗
PubMed1991

Use of adoptive transfer of tumor-infiltrating lymphocytes alone or in combination with cisplatin-containing chemotherapy in patients with epithelial ovarian cancer.

Lymphocytes isolated from fresh human epithelial ovarian tumors can be expanded in the presence of recombinant interleukin-2, and some CD8 antigen-positive lymphocytes can lyse autologous fresh tumor cells. We treated 7 patients with advanced or recurrent epithelial ovarian cancers, using the adoptive transfer of these tumor-infiltrating lymphocytes (TILs) following a single i.v. injection of cyclophosphamide. One case of disappearance (complete response) and 4 cases of greater than 50% decrease of tumor (partial response) were reported (14.3 and 57.1%, respectively). Regression of tumors in the ovary, liver, lung, and lymph node, both primaries and metastases, lasted for 3-5 months. Furthermore, 10 patients were treated alternately with a cisplatin-containing chemotherapeutic regimen and the adoptive transfer of TILs. Seven cases of complete regression and 2 cases of partial regression of cancer were reported. Four of the 7 patients with a complete response have had no recurrence for greater than 15 months of follow-up. It appears that this experimental technique of adoptive transfer of TILs achieves high response rates even without recombinant interleukin-2 administration and that the prospect of combined therapy using TILs and cisplatin offers hope for increasing the cure rate and long-term survival.

Adult↗
PubMed1991

Immunohistochemical study on tissue inhibitors of metalloproteinases in normal and pathological human livers.

The localization of tissue inhibitor of metalloproteinases (TIMP) in normal and pathological livers was examined by immunohistochemistry using monoclonal antibodies at the light microscopic level. In normal liver, immunoreactive TIMP was detected in smooth muscle cells and endothelial cells of blood vessels, fibroblasts, bile duct cells and Kupffer cells, indicating that TIMP is likely to be a general element of the liver. Immunoreactivity was observed in newly-formed blood vessels, proliferating bile ductules, and fibroblasts in the expanded portal area and fibrous septa of chronic active hepatitis and cirrhosis. TIMP was strongly stained in the capsule of hepatocellular carcinoma. The intensity of the immunoreaction in the capsule was generally greater than that in cirrhotic liver apart from the tumor mass. In three of five cases with hepatocellular carcinoma, endothelial walls in contact with tumor cells were positive.

Antibodies, Monoclonal↗
PubMed1991

Appearance and evolution of the specific chromosomal rearrangements associated with malignant transformation of mouse m5S cells.

Chromosomal alterations were studied during the acquisition of malignant phenotypes in two karyotypically distinct cells isolated from transformed foci induced by x-irradiation in mouse m5S cells. Because the transformants, despite foci origin, showed low ability to grow in agar, they were cultured in vitro with serial transfer schedules to allow further cell generations and assayed for anchorage independence (AI) at each passage level. The AI frequency increased with the cell doubling numbers. Chromosome analysis showed that a focus was one cell origin, but the transformants showed karyotypic instability during cell proliferation, giving rise to the rearrangements clustered in the distal region of the specific chromosomes. These rearrangements appeared to be directed toward the acquisition of malignant phenotypes. Analysis of the types and sites of rearrangements indicated that a mechanism exists that induces frequent rearrangements of the specific region of a chromosome during the process of transformation into the malignant state.

Animals↗
PubMed1991

Carbohydrate structures of human interleukin 5 expressed in Chinese hamster ovary cells.

The asparagine-linked sugar chains of recombinant human interleukin 5 produced by Chinese hamster ovary cells were released quantitatively as oligosaccharides by hydrazinolysis. After N-acetylation followed by NaB3H4 reduction, each oligosaccharide was isolated by paper electrophoresis and serial lectin column chromatography. Study of their structures by sequential exoglycosidase digestion in combination with methylation analysis, revealed that they are bi-, tri-, and tetraantennary complex-type with fucosylated and non-fucosylated trimannosyl cores and high mannose type sugar chains. More than 80% of the sugar chains occur as biantennary complex-type sugar chains. Although acidic oligosaccharides amount to only 14% of the total oligosaccharides, their sialic acid residues occur exclusively as the Sia alpha 2----3Gal group. Removal of the sugar moiety from intact recombinant human interleukin 5 produced a 2.5-fold increase of its activity to induce IgM secretion.

Animals↗