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Biomedical subjects

T Isono

Publications and source records attributed to T Isono.

At least 55 records · Page 3Linked to original sources

Infection of inbred rabbits with cell-free HTLV-I.

Inbred rabbits were infected by cell-free HTLV-I to become virus carriers with provirus-carrying cells in the peripheral blood. Repeated injections of cell-free virus into newborn animals led to an increase in the provirus-carrying cells in the peripheral blood and to a lymphocytic infiltration in the portal spaces of the liver, but did not induce an ATL-like disease. Proviral DNA was detected by PCR not only in PBL but also in multiple organs including the brains of such animals. Susceptibility to infection differed between strains, as estimated by the number of provirus-carrying cells in the peripheral blood, with the associated difference in anti-p40tax antibody level in the serum. These results suggest that cell-free HTLV-I could be a potential cause for human HTLV-I infections.

Animals↗

Establishment from Shope carcinoma induced in an inbred rabbit of culture cell lines with various potentials for differentiation and tumorigenicity.

Shope papillomas induced by cottontail rabbit papilloma-virus (CRPV) in domestic rabbits frequently regress spontaneously or, failing to do so, convert into squamous cell carcinomas at a high rate. This papilloma-carcinoma complex in rabbits provides an experimental model for human papillo-mavirus-associated malignancies. The aim of this study was to prepare an experimental system in inbred rabbits by establishing culture cell lines of the tumor. Squamous cell carcinoma developed from a Shope papilloma that had been induced 6 months previously by inoculating CRPV into an inbred B/J rabbit. By in vitro culturing of the tumor cells, cell lines with potentials for terminal differentiation and tumorigenicity were established. Cloning yielded sublines that varied in these potentials and possessed episomal and integrated CRPV genomes as revealed by Southern hybridization in both one- and two-dimensional electrophoresis. Major CRPV-specific transcripts were similarly observed both in well-differentiated and in poorly differentiated sublines. Immunofluorescence with syngeneic rabbit antibody against tumor-specific antigens localized such antigens mainly in the nuclei of the cells of these sublines. This experimental system allows experiments that were not feasible in randomly bred rabbits.

Animals↗

[Hepatic functional evaluation using the galactose tolerance test in patients with obstructive jaundice].

Hepatic functional mass was evaluated in patients with obstructive jaundice using the galactose tolerance test (GaTT), which reflected cytosolic function of hepatocyte. The T-1/2 values as an index on the GaTT were significantly prolonged in patients with obstructive jaundice in comparison with control subjects whether before or after percutaneous transhepatic biliary drainage (PTBD). But in each cases, some showed nearly normal GaTT-T/2 value and others showed severely prolonged value. Patients with obstructive jaundice could be divided into two groups according to the GaTT-T/2 value before PTBD. The decreasing rate of serum bilirubin level "b" after PTBD was significantly fair in the group A patients (good GaTT-T/2 value before PTBD) than the group B (poor GaTT-T/2 value before PTBD) (P less than 0.05). It was that GaTT-T/2 before PTBD which represented hepatic cytosolic functional mass could predict the effect of PTBD in patients with obstructive jaundice.

Aged↗

Antiviral effect of zidovudine in the experimental model of adult T cell leukemia in rabbits.

The antiviral effect of zidovudine was examined in an experimental model of adult T cell leukemia in rabbits. AZT retarded the growth of HTLV-I-transformed rabbit cell line (F647a) and inhibited the transformation of normal peripheral blood lymphocytes in co-culture with the cell line. Inhibition of the transformation was achieved at a much lower concentration of AZT than the suppression of cell growth. Seven newborn F1 hybrids were inoculated intraperitoneally with 1 x 10(7) F647a cells and then were given AZT intraperitoneally, either at a high dose (300 mg/kg/day) or a low dose (30 mg/kg/day) for three weeks. Four newborn animals similarly given F647a cells were left untreated as a control. Examinations carried out three weeks after cell inoculation revealed the following: the HTLV-I provirus was not or hardly detected by the polymerase chain reaction in the peripheral blood lymphocytes of animals given a high dose of AZT, whereas the provirus was detected in all untreated control animals as well as in two animals given a low dose of AZT. In addition, lymphocytic infiltration was not observed in the major organs of the former animals, but was observed in those of the latter animals. These indicate the effectiveness of AZT administration for the prevention of HTLV-I infection and ATL-like disease in rabbits.

Animals↗

[Clinicopathological significance of intrahepatic micrometastases in hepatic metastatic carcinomas].

The micrometastases confirmed only by microscopic examination were investigated in resected liver specimen of hepatic metastatic carcinomas. Twenty three hepatic metastases from gastrointestinal carcinomas were subjected. The micrometastases defined as histologically discontinuous from macroscopic metastatic nodules and less than 1mm in diameter, were found in 8 cases (34.8%). These were 0.2 to 1.0mm (0.52 +/- 0.35, mean +/- SD) in diameter, 1 to 19 (4.1 +/- 6.0) in number and were 2.0 to 29.0 mm distant from the macroscopic metastatic nodules. Histological localization of these metastases were in portal vein in most of cases and rarely in sinusoidal space and hepatic vein. These results suggest that the surgical margin in hepatectomy for hepatic metastases is required more than 3 cm from the tumor and therefore wedge resection is not suitable for the choice of the operative procedure for hepatic metastases because of unsatisfactory surgical margin.

Gastrointestinal Neoplasms↗

Polyclonal increase of HTLV-I provirus-carrying lymphocytes in HTLV-I-carrier rabbits transplanted with Shope carcinoma cells.

Fifteen HTLV-I carrier rabbits of two inbred strains and their F1 hybrid were inoculated with Shope carcinoma cells. The peripheral blood leukocyte counts in all these rabbits increased to 2-4 times the preinoculation level with a concomitant increase in abnormal lymphocytes. Southern blotting analyses of peripheral blood leukocytes revealed the polyclonal integration of HTLV-I proviral genome in all these animals. However, lymphocytic infiltration without any apparent leukemic infiltration was observed in major organs of these animals; a similar but slight lymphocytic infiltration was also observed in non-carrier control animals inoculated with Shope carcinoma cells. These results are interpreted as indicating that the growth of squamous cell carcinoma in HTLV-I carrier rabbits induced the polyclonal expansion of provirus-carrying cells, which may correspond to the intermediate state between healthy carrier and smouldering ATL.

Animals↗

Measurement of sulfidopeptide leukotrienes and their metabolism in human synovial fluid of patients with rheumatoid arthritis.

Leukotriene (LT)C4 in the synovial fluid of patients with osteoarthritis deformans (OA) and rheumatoid arthritis (RA) was measured by radioimmunoassay (RIA) after extraction with Sep-Pak C18 cartridge. The amounts of immunoreactive LTC4 (i-LTC4) in samples from patients with OA and RA were not significantly different, being 0.198 +/- 0.018 pmol/ml (n = 11) and 0.179 +/- 0.016 pmol/ml (n = 12), respectively. After separation by high performance liquid chromatography (HPLC) and measurement by RIA, the levels of other sulfidopeptide LTs, such as LTD4 and LTE4, in synovial fluid from patients with RA were found to be significantly higher than those in fluid from patients with OA. The leukocyte number in synovial fluids did not correlate with the i-LTC4 level. The metabolic activities of these synovial fluids were determined by incubating them with 3H-LTC4 and then separating sulfidopeptide LTs by HPLC. The conversion of LTC4 to LTD4 in synovial fluids of patients with OA and RA were similar, but the dipeptidase activity converting LTD4 to LTE4 was higher in fluid from patients with RA. It is suggested that a high level of LTE4 may contribute to exudation of synovial fluid, since LTE4 increases vascular permeability.

Arthritis, Rheumatoid↗

[Estimation of 1-hexylcarbamoyl-5-fluorouracil (HCFU) and 5-FU concentrations in sera and resected specimens from patients with ovarian tumors].

Concentrations of HCFU and 5-FU in blood and tissues of resected specimens were evaluated in 28 patients with ovarian tumor (pathologically benign 10, malignant 18) preoperatively considered to be malignant. 1) No significant difference of HCFU and 5-FU concentrations in sera, uterus and peritoneum was observed between the benign and cancer groups. 2) No significant difference of HCFU concentration in tissues of ovarian tumor was recognized between the benign and malignant groups, but as for 5-FU concentrations, 0.116 +/- 0.198 micrograms/g tissue in the cancer group was considerably higher than 0.021 +/- 0.144 micrograms/g tissue in the benign group (p = 0.085). Furthermore, the 5-FU level in ovarian cancer tissues was much higher than that in the tissues of the contralateral normal ovary, suggesting that degradation of 5-FU might be delayed in cancer tissue. 3) HCFU concentration in omental tissues from cancer patients was 0.043 +/- 0.061 micrograms/g tissue, significantly higher than that from benign patients, 0.004 +/- 0.008 micrograms/g tissue (p = 0.024). As for 5-FU concentration, no apparent difference was found, suggesting that 5-FU might be quickly eluted or metabolized in omental tissue.

Administration, Oral↗

[Augmentative effects of radiofrequency hyperthermia (RFH) combined with intraperitoneal (IP) administration of CDDP in ovarian cancer].

Radiofrequency hyperthermia (RFH) was applied to 21 adnexal cancer patients in combination with IP administration of CDDP (150 to 200 mg) 2 weeks or more after surgery. The instrument used, an OMR-ON HEH 500C, was shown by rectal temperature monitoring to produce sufficient intraperitoneal temperature elevation up to 40 degrees-41 degrees C. The serum level of filterable CDDP after IP infusion of CDDP (150 mg) followed by sodium thiosulfate rescue was basically the same irrespective of whether RFH was used. It reached a peak level of 2.06 +/- 0.48 micrograms/ml (n = 8) 1h after IP infusion, and gradually declined thereafter. No serious side effect except 3 cases of II- to III-degree burns was recognized. A slight increase in the incidence of prolonged vomiting and diarrhea was found with the RFH combination. This suggests an exacerbating effect of RFH on intestinal damage following CDDP infusion. As for any suppressive effect on reaccumulation of ascites, RFH might have a slight benefit in increasing the antitumor effect of CDDP in 90% of patients.

Body Temperature↗

Subparticles of Anabaena phycobilisomes. II. Molecular assembly of allophycocyanin cores in reference to "anchor" protein.

Entire phycobilisomes (PBS) and two derived particles, whole allophycocyanin (APC) cores and the far-red-emitting fragment of APC cores (14.5 S APC), all containing the 115-kDa polypeptide ("anchor protein"), were compared for the readiness with which the 115-kDa protein could be modified chemically, be degraded by chymotrypsin, and react with the anti-115-kDa serum. The 115 kDa in PBS and the whole APC cores were digested slightly by chymotrypsin and did not react with anti-115-kDa IgG. In contrast, the 115 kDa in 14.5 S APC was digested to 42 kDa and showed a positive reaction with anti-115-kDa IgG. Reconstitution of APC cores from 14.5 S APC and APC trimers was inhibited by the anti-115-kDa IgG, and APC particles with partly digested 115-kDa cannot reconstitute APC cores. These results imply that 115 kDa is embedded mostly inside PBS and is involved more in the maintenance of the molecular assembly of APC cores than in the "anchoring" of PBS to thylakoid. The PBS from Anabaena variabilis (M3) have an APC core larger than those of other PBS and show atypical morphology consisting of five APC discs. They have a polypeptide (115 kDa) that is significantly longer than the corresponding polypeptides (around 95 kDa) of other blue-green algae. This can be interpreted by assuming a relationship between the size of APC cores and the length of the polypeptide.

Bacterial Proteins↗

[Side effects and anti-cancer effects following intraperitoneal (ip) administration of mitomycin C (MMC)].

Nineteen patients with gynecological cancers were initially treated intraperitoneally with MMC at a dose of 20 to 52 mg/body and then intravenously with CAP regimen. The following side effects were observed in patients intraperitoneally administered doses of MMC greater than 25 mg/m2; leucocytopenia 7/12, thrombocytopenia 5/12, liver damage 8/12, renal damage 2/12, ileus 3/12 and severe anorexia 2/12. Sixteen patients were evaluated for their prognoses more than 1 year after treatment. Seven of them are well with no sign of recurrence, but 9 suffered recurrence with or without peritonitis carcinomatosa (PC). The incidence of PC among these 9 cases was not linked with clinical staging, complete or incomplete resection or the dose of MMC administered, but rather with the respective histopathology; mesonephroid 2/2, metastatic 2/2, mucinous 1/1, serous 0/3, endometrial corpus 0/1. The results suggested that the former 3 kinds of cancer did not respond to i.p. infusion of MMC, whereas the latter 2 were sufficiently sensitive to MMC to prevent the occurrence of PC.

Female↗

Measurement of immunoreactive leukotriene C4 in blood of asthmatic children.

Peptide leukotriene (LT) such as LTC4, LTD4, LTE4 have been considered to be major mediators of immediate type hypersensitivity reaction such as asthma. We have developed a rapid and simple extraction method using a Sep-Pak C18 cartridge for the measurement of LTC4 by radioimmunoassay (i-LTC4). In this extraction method, 91% LTC4 was recovered in a final methanol fraction. The identity was confirmed by the recovery test and by the dilution method. The amount of i-LTC4 in plasma from asthmatic patients was determined by radioimmunoassay after the extraction. The order of the plasma level of i-LTC4 was; severe asthma greater than slight or moderate asthma greater than asthmatic patient without attack greater than healthy adult. The highest level of LTC4 was 0.27 +/- 0.11 pmol/ml in severe asthmatic plasma.

Adult↗

Persistence and differentiation of HTLV-I-transformed immature T-cells in HTLV-I carrier rabbits.

Two T-cell lines with immature phenotypes, CD4-8- and CD4+8+, were found among HTLV-I-transformed T-cell lines obtained during experiments using a rabbit model of adult T-cell leukemia. Persistence and differentiation of these clones in vivo were examined by retrospectively analysing a series of cell lines from individual animals and by adoptive transfer of these cells into syngeneic hosts. The double negative cell line did not differentiate and remained double negative in adoptive transfer into neonates and in long-term in vitro culture, while the double positive cell line differentiated both in vivo and in vitro into CD8+ cell, as if the fate of this cell line had been predetermined. Cells of the same clone as this double positive cell line persisted for more than one year in the peripheral blood of the animal. Long-term persistence was not observed for five cell lines of CD4 single positive phenotype, which were obtained from another carrier rabbit. These results suggested that HTLV-I-transformed immature T-cells persist in neonatally infected carriers, continuously giving rise to mature T-cells harboring HTLV-I.

Animals↗