[Phenotypic analysis of cells infiltrating rat liver allograft: preliminary report].
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Animals↗
Biomedical subjects
T Oka
Publications and source records attributed to T Oka.
[Osteosarcoma developing after radiation and chemotherapy for primary mediastinal seminoma].
This report presented an osteosarcoma arising from the same field after radiation and chemotherapy without surgery for primary mediastinal seminoma. A 45-year-old man had received from June 1979 to August 1981 irradiation and chemotherapy for the anterior-mediastinal seminoma. Since then he was been without evidence of disease for five years. In March 1987, he had suffered from an advanced tumor extending from the neck and the mediastinum to the right anterior chest wall. Further irradiation combined with thermotherapy were performed but without improvement. He was thereafter seen and admitted July 23 1987 to our hospital with complaint of back pain. Needle biopsy specimen revealed chondrosarcoma. Despite chemotherapy with CDDP, he died four months later after admission. Pathological finding of his autopsy revealed a widely invading osteosarcoma extending to extra- and intrathorax and the neck without evidence of germ cell component. To explain the pathogenesis of the secondarily developing osteosarcoma, two hypotheses are offered; 1. Malignancy of mesenchymal component in germ cell tumor. 2. Radiation-induced osteosarcoma. The latter hypothesis appears to be the most probable pathogenesis from his autopsy. These findings suggest that a long survival patient with malignant germ cell tumor after therapy should be never considered as being free from a potential risk of secondarily developing malignancy.
Combined Modality Therapy↗
[Biopsy diagnosis of amyloidosis].
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Amyloid↗
In vitro and in vivo hematopoietic effect of mutant human granulocyte colony-stimulating factor.
About 100 derivatives of human recombinant granulocyte colony-stimulating factor (rhG-CSF) were created by various gene-mutagenic techniques, and KW-2228, in which amino acids were replaced at five positions of N-terminal region of intact rhG-CSF, was picked up and evaluated for its biologic and physicochemical properties in comparison with intact rhG-CSF. KW-2228 showed two to four times higher specific activity than that of intact rhG-CSF in mouse and/or human bone marrow progenitor cells by colony-forming unit assay in soft agar, and by cell-proliferation assay in liquid culture. KW-2228 showed a potency to increase peripheral neutrophil counts when it was administered to normal C3H/He mice by single intravenous injection. Increase of total leukocyte count and neutrophils was observed, with peak level at 8 to 12 hours at low doses (0.5 to 1.0 micrograms/mouse), and the highest level was maintained for 24 to 30 hours at high doses (5 to 10 micrograms/mouse). The granulopoietic effect of KW-2228 was examined by several doses of single course (once daily for 10 days) or multiple courses (twice daily injection for 5 days followed by cessation for 9 days on one cycle, 3 cycles in total) of treatment. KW-2228 showed higher activity than that of rhG-CSF, especially at sub-optimal doses of multiple courses of treatment. Furthermore, KW-2228 was found to be more stable physicochemically and biologically than intact rhG-CSF, especially under thermal conditions at 56 degrees C and in the human plasma at 37 degrees C, suggesting a protease resistancy. Pharmacokinetic study showed that plasma concentration of KW-2228 assayed for its bioactivity maintained a higher level than that of intact rhG-CSF for 60 minutes after intravenous injection of this protein to normal mice. Those results suggest that KW-2228 might show a superior in vivo hematopoietic effect to intact rhG-CSF due to its high specific activity to progenitor cells, and also due to its improved physicochemical, biologic, and pharmacokinetic stability in host animals.
Animals↗
Complete nucleotide sequence of cDNA for the cytotoxin alpha sarcin.
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Amino Acid Sequence↗
[A case of obstructive jaundice due to inflammatory pseudotumor-like granuloma].
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Adult↗
Molecular cloning of the Bombyx mori prothoracicotropic hormone.
Prothoracicotropic hormone (PTTH), a brain secretory polypeptide of insects, stimulates the prothoracic glands to produce and release ecdysone, the steroid essential to insect development. The complementary DNAs encoding PTTH of the silkmoth Bombyx mori were cloned and characterized, and the complete amino acid sequence was deduced. The data indicated that PTTH is first synthesized as a 224-amino acid polypeptide precursor containing three proteolytic cleavage signals. The carboxyl-terminal component (109 amino acids) that follows the last cleavage signal represents one PTTH subunit. Two PTTH subunits are linked together by disulfide bonds, before or after cleavage from prepro-PTTH, to form a homodimeric PTTH. When introduced into Escherichia coli cells, the complementary DNA directed the expression of an active substance that was functionally indistinguishable from natural PTTH. In situ hybridization showed the localization of the prepro-PTTH mRNA to two dorsolateral neurosecretory cells of the Bombyx brain.
Amino Acid Sequence↗
Effect of gastric distention on RNA synthesis in neonatal chick liver.
RNA synthesis in the nuclei of liver from newly hatched chicks was enhanced 1.25 fold at 10 min after intragastric administration of water. Differential inhibition of RNA synthesis by alpha-amanitin indicated that the enhancement mainly represented rRNA synthesis; the synthesis of mRNA and tRNA was scarcely affected. Enhanced RNA synthesis was accompanied by greater susceptibility of nuclei to digestion by micrococcal nuclease, indicating that the chromatin structure was modified. It was further shown that the "water effect" was mimicked by distention of the stomach by raising the pressure in the intragastric balloon. Since the prior administration of atropine abolished the "water effect", the enhancement of hepatic RNA synthesis may be mediated by hepatic nervous system.
Age Factors↗
Characterization of flat revertants isolated from cells transformed by Abelson murine leukemia virus (Ab-MuLV).
Transformed Fisher rat fibroblast cell lines by Abelson murine leukemia virus frequently revert to the normal phenotype in usual culture conditions. Molecular biological analysis of three revertant clones isolated from the transformants showed that their morphological reversions were due to inactivation of the v-abl oncogene at multiple steps including transcription, translation or v-abl protein kinase activity itself without any change in structural gene expression of helper virus. These findings suggest the existence of a specific mechanism(s) for elimination of the v-abl oncogene by segregation, mutation, or gene rearrangement in these cells.
Abelson murine leukemia virus↗
Distribution of fibronectin in adenocarcinoma of the lung: classification and prognostic significance.
Fibronectin (FN) was investigated in 75 stroma from lung adenocarcinoma patients. Distribution of FN was classified into three patterns based on immunohistochemical evidence: dense, moderate, and sparse distribution. The incidence of the sparse pattern in both stage I and stage III disease was significantly greater in the infiltrating than in the noninfiltrating areas. The patients were divided into two groups, long-term survivors and short-term survivors. In the group with stage I disease, the incidence of the sparse pattern was significantly greater in the infiltrating than in the non-infiltrating areas. In both areas, the incidence of sparse pattern was greater in the short-term than in the long-term survivors. These data suggest that the disappearance of FN reflects the aggressiveness of the tumor and presumably plays an important role in the prognosis of adenocarcinoma of the lung.
Adenocarcinoma↗
Prognostic significance of laminin in adenocarcinoma of the lung.
The distribution of laminin in tumor-associated basement membrane was immunohistochemically investigated in 115 cases of adenocarcinoma of the lung. The distribution of laminin was classified into continuous and discontinuous staining patterns. The incidence of the discontinuous pattern was less in early-stage disease than that in advanced stages (P less than 0.01). In patients with stage I, the incidence of discontinuous patterns was greater in short-term survivors than in long-term survivors (P less than 0.05). By contrast, in patients with stage III, the discontinuous pattern of laminin was frequently seen in both long-term survivors and short-term survivors, with no difference between the two groups. These data suggest that the discontinuous pattern of laminin in tumor-associated basement membrane reflects the spread and dissemination of tumor, hence a close relationship to the prognosis.
Adenocarcinoma↗
Suppressive effects of interferons on the production and release of human T-lymphotropic virus type-I (HTLV-I).
The effects of human alpha-, beta-, or gamma-interferon (IFN) on the replication and production of human T-lymphotrophic virus type-I (HTLV-I) were investigated in a human T-cell line, MT-2. Virus transmission and production estimated by syncytium formation and HTLV-I-associated reverse transcriptase (RT) activity were strongly suppressed in the presence of alpha- and beta-IFN, but not gamma-IFN. However, the expression of virus specific proteins gp46 but not p19, p24, p28, p36, and gp68 was affected with IFNs as revealed by Western blotting analysis. Electron microscopic observations showed that some of the HTLV-I particles were trapped in the intracellular vacuoles in the presence of high doses of alpha- or beta-IFN. Continuous supply of IFNs appeared to be essential for the constant suppression of RT activity. These results suggest that alpha- and beta-IFN do not inhibit HTLV-I gene expression strikingly but suppress processing or assembly of virus proteins and/or releasing of virions in the late phase of maturation.
Blotting, Western↗
Diagnosis of cardiac allograft rejection by the detection of circulating plasma cardiac myosin light chains.
Twenty adult male Japanese monkeys of the species Macaca fuscata were randomly paired and subjected to heterotopic cardiac transplantation performed by the Ono-Lyndsey method. Without immunosuppression, graft survival ranged between 8 and 27 days, with a mean survival of 14 days. Plasma cardiac myosin light chains were measured by radioimmunoassay, which showed transient increases in myosin levels just following transplantation. Three hearts showed high values at this period and stopped beating when the myosin levels decreased (type 1). The other 7 hearts showed low myosin values after transient increases and 5 of them were rejected with a preceding reincrease in the myosin levels (type 2). Pathological study revealed myocardial necrosis, perivascular cuffing of mononuclear cells and/or neutrophils and/or plasma cells in the type 1 hearts. Measurement of the plasma myosin light chain level was therefore revealed to be of great value in the monitoring of cardiac allograft rejection.
Animals↗
The effect of adjuvant therapy with or without tamoxifen on the endocrine function of patients with breast cancer.
The ovarian and pituitary functions of 64 operable breast cancer patients undergoing adjuvant therapy with cytotoxic chemotherapy and/or tamoxifen were investigated. The post menopausal patients, divided into 3 treatment groups, one with tamoxifen alone, one with tamoxifen and chemotherapy and the other with chemotherapy alone had serum estradiol 17-beta (E2) and progesterone levels lower than the evaluable limits. Although there was no significant difference in the level of estrone sulfate (E1-S) between these three groups, the level of lutainizing hormone (LH) and follicle stimulating hormone (FSH) in the patients treated with tamoxifen alone and tamoxifen and chemotherapy were significantly lower than those treated with chemotherapy alone. The decrease in gonadotropin levels induced by tamoxifen treatment was reversible as it appeared after the initiation of tamoxifen and recovered after its cessation. In the premenopausal patients, a group treated with tamoxifen and chemotherapy had significantly higher E1-S, E2 and progesterone levels and significantly lower gonadotropin levels than a group treated with chemotherapy alone or one treated with a cyclophosphamide regimen. These increases in the levels of estrogen and progesterone were also reversible, and induced by tamoxifen. Thus, adjuvant endocrinochemotherapy causes profound alteration in the hypothalamo-pituitary-ovarian axis and therefore, monitoring a variety of hormonal levels is thought to be necessary for assessing the consequences of adjuvant therapy in breast cancer patients, especially in premenopausal patients using tamoxifen.
Aged↗
Primary culture of normal rat mammary epithelial cells within a basement membrane matrix. II. Functional differentiation under serum-free conditions.
A serum-free primary culture system is described which allows normal rat mammary epithelial cells (RMECs) embedded within a reconstituted basement membrane to undergo extensive growth and functional differentiation as detected by synthesis and secretion of the milk products casein and lipid. RMECs isolated from mammary glands of immature virgin rats were seeded within an extracellular matrix preparation derived from the Engelbreth-Holm-Swarm sarcoma and cultured in a serum-free medium consisting of Dulbecco's modified Eagle's medium-F12 containing insulin, prolactin, progesterone, hydrocortisone, epidermal growth factor, bovine serum albumin, transferrin, and ascorbic acid. Casein synthesis and secretion were documented at the electron microscopic level as well as by an enzyme-linked immunosorbent assay (ELISA) assay using a polyclonal antibody against total rat caseins. Numerous secretory vesicles with casein micelles were noted near the apical surface of the RMECs, and secreted casein was observed in the lumen. These ultrastructural data were confirmed by the ELISA assay which showed that microgram amounts of casein per well were synthesized by the RMECs and that the amount of casein increased with time in culture. Using immunoblot analysis it was demonstrated that the full complement of casein proteins was synthesized. In addition to casein protein, beta-casein mRNA levels were shown to increase with time. Synthesized lipid was detected at both the light and electron microscopic levels. Phase contrast photomicrographs demonstrated extensive intracellular lipid accumulation within the ductal and lobuloalveolarlike colonies, and at the electron micrograph level, lipid droplets were predominantly localized near the apical surface of the RMECs. The lipid nature of these droplets was verified by oil red O staining. Results from this study demonstrate that RMECs from immature virgin rats proliferate extensively and rapidly develop the capacity to synthesize and secrete casein and lipid when grown within a reconstituted basement membrane under defined serum-free conditions. This unique system should thus serve as an excellent model in which the regulation of mammary development and gene expression can be investigated.
Animals↗
Energetic recovery from hypothermic preservation in the rat liver.
Changes in energy metabolism induced by norepinephrine were observed in liver perfused immediately after dissection and in liver stored in Euro-Collins solution at 0 degrees C for 24 hr. Oxygen consumption, glucose output, ATP content, and tissue pH were measured in isolated perfused rat liver at 37 degrees C. In fresh liver, a two-fold increase in glucose output and oxygen consumption was induced by norepinephrine (1 microM), while changes in ATP content and tissue pH were minimal. In stored liver, the cumulative increments in glucose output and oxygen consumption induced by norepinephrine were 30 and 27% those of fresh liver, respectively. ATP content of the unstimulated liver was 76% that of the fresh liver, then decreased to 50% during stimulation. A transient decrease in tissue pH (0.14 pH unit) was significant compared with that of fresh liver. These results suggest that norepinephrine stimulation is useful for assessing energetic and functional recovery of reperfused liver following hypothermic storage.
Adenosine Triphosphate↗
Influenza vaccine: enhancement of immune response by application of carboxy-vinylpolymer.
We evaluated the possibility of application of carboxy vinylpolymer (CVP) to influenza vaccine for the improvement of immune response. Our result shows that CVP induces good immune responses after inoculation of vaccines to mice both subcutaneously, intraperitoneally, and intranasally. Considering the efficacy and safety, intranasal administration of the CVP-coupled vaccine may be the best route of immunization.
Administration, Intranasal↗
Development of a new type of influenza subunit vaccine made by muramyldipeptide-liposome: enhancement of humoral and cellular immune responses.
The muramyldipeptide (MDP), [6-O-(2-tetradecyl-hexa-decanoyl)-N-acetylmuramyl-L-isoglutamine] can be incorporated into liposomes with haemagglutinin and neuraminidase subunits were attached to the inner and outer surfaces of lamellar structures of the liposomes, probably through their hydrophobic ends. The addition of cholesterol resulted in much more stable liposomes, which were similar in size and shape to native influenza virus particles. These liposomes enhanced the immunogenicity of haemagglutinin in mice, such that the levels of antibody induced were about 16-fold higher than those of subunit haemagglutinin vaccine alone. Results of proliferation tests with spleen cells from mice and guinea-pigs were consistent with the immunopotentiation of haemagglutinin by liposomes. In addition, the higher antibody levels produced in mice, immunized with the haemagglutinin and MDP-containing liposomes (MDP-virosomes), were maintained for at least 6 months. Enhancement of the cellular immune response, measured by delayed type hypersensitivity reactions, was also observed in the guinea-pigs immunized with MDP-virosome vaccine. Preliminary tests with splenocytes from mice immunized with different vaccines also indicated that the MDP-virosome vaccine induced cytotoxic T-cell activity in these mice. This study revealed that the formation of liposomes with muramyldipeptide enhanced the level and persistence of circulating antibody, and enhanced cellular immunity in guinea-pigs and mice.
Acetylmuramyl-Alanyl-Isoglutamine↗