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Biomedical subjects

A Seto

Publications and source records attributed to A Seto.

At least 55 records · Page 3Linked to original sources

Sequence and diversity of rabbit T-cell receptor gamma chain genes.

The nucleotide sequences of one constant (C), six variable (V), and two joining (J) gene segments coding for the rabbit T-cell receptor gamma chain (Tcrg) were determined by directly sequencing fragments amplified by the cassette-ligation mediated polymerase chain reaction. The Tcrg-C gene segment did not encode a cysteine residue for connection to the Tcr delta chain in the connecting region, and two variant forms of the Tcrg-C gene segment were generated by alternative splicing, like the human Tcrg-C2 gene. Five of six rabbit Tcrg-V gene segments belonged to the same family and displayed similarity to five productive human Tcrg-V1 family genes as well as the mouse Tcrg-V5 gene. The remaining rabbit Tcrg-V gene segment displayed similarity to the human Tcrg-V3 gene. Both rabbit Tcrg-J gene segments displayed similarity to the human Tcrg-J2.1 and 2.3, respectively. These findings suggested that the genomic organization of rabbit Tcrg genes is more similar to that of human than of mouse Tcrg genes.

Amino Acid Sequence↗

Varied expression of major histocompatibility complex and oncogenes in Shope carcinoma cell lines derived from a single tumor.

The cellular gene expression was compared in four Shope carcinoma cell lines, which were derived from a single tumor and possess various potentials for differentiation and tumorigenicity. The E6 and E7 transforming genes of cottontail rabbit papillomavirus were expressed in all these cell lines, highest level of expression being in the most tumorigenic and undifferentiated cell line, where the major histocompatibility complex (MHC) class I expression was the lowest. The MHC class II antigen, which is not expressed on normal epithelial cells, was detected in all the cell lines, but hardly, if at all, on the surface of these cells. The surface expression of the MHC class II antigen could not be induced by the culture supernatant of phytohaemagglutinin-stimulated splenocytes, which increased the surface expression level of the MHC class I antigen of the same cells. These findings suggest that the aberrant expression of the MHC class II antigen in these cells could not be implicated in the immune response against tumors. The c-fos, c-myc and c-H-ras oncogenes were variably expressed in these cell lines, but there was no correlation with tumorigenicity.

Animals↗

Monoclonal antibody E6G6 recognizes glycolipids as a differentiation antigen in Shope carcinoma cells.

Monoclonal antibody E6G6 preferentially reacted with well differentiated and non-tumorigenic Shope carcinoma cell lines but hardly reacted with undifferentiated and tumorigenic lines as determined by enzyme-linked immunosorbent assay, cytofluorometry and the complement dependent cytotoxicity test. Immunohistochemical analysis of the primary carcinoma tissue revealed that the antibody intensely stained keratinizing carcinoma cells with marked shrinkage whereas it did not stain normal epidermal keratinizing rabbit cells or benign tumor (Shope papilloma) cells, suggesting that the antigen expression in vivo was closely correlated with terminal differentiation of the carcinoma cells. Thin layer chromatography immunostaining revealed that the antigen was comprised of several neutral glycolipids and that differentiated cells contained about ten times more antigen than undifferentiated cells.

Animals↗

Sequence and diversity of variable gene segments coding for rabbit T-cell receptor beta chains.

The nucleotide sequences of 11 variable gene segments coding for rabbit T-cell receptor beta (Tcrb-V) chains were determined by directly sequencing fragments amplified by the cassette-ligation mediated polymerase chain reaction (CLM-PCR) and by modified anchor PCR without the cloning procedure. The nucleotide sequences in two of these 11 rabbit Tcrb-V gene segments coincided with those in two of the four rabbit Tcrb-V gene segments previously reported; the others have not been described. The percentage similarity of each nucleotide sequence of the 11 rabbit Tcrb-V gene segments was analyzed and the segments were divided into nine families, which were homologous to nine human families (Vb 2, 3, 4, 5, 7, 8, 10, 18, and 22), respectively.

Amino Acid Sequence↗

Leukemogenesis-associated antigen in HTLV-I-transformed rabbit cells.

The presence of a leukemogenesis-associated antigen was investigated in an experimental model of adult T-cell leukemia in (B/J x Chbb:HM)F1 rabbits, where adult rabbits develop leukemia within 1-2 weeks following inoculation with HTLV-I-transformed syngeneic cell lines. Leukemogenic activity was found in some but not all HTLV-I-transformed cell lines, and was associated with leukocytosis-inducing activity which was assayed by inoculating these cells into adult rabbits of the parental Chbb:HM strain. The leukemogenic cell line diminished or lost the leukemogenic and leukocytosis-inducing activities during prolonged culture in vitro. A mouse mAb was raised which recognized an antigen uniquely expressed on the cell surface of the leukemogenic cell lines. This antigen was present, however, in all HTLV-I-transformed cells examined and the mAb immunoprecipitated the same 65 kD glycoproteins from both leukemogenic and non-leukemogenic cell lines. Taken together, the antigenic epitope seemed to be expressed on the cell surface in such a manner as to be accessible to the mAb in leukemogenic but not non-leukemogenic cells. The analyses of various cell lines revealed that this antigen was an endogenous antigen and not a viral antigen. The antibody was cytotoxic in vitro against leukemogenic cell lines in the presence of complement, and administration of this antibody to leukemic rabbits resulted in an abrupt decrease in the peripheral blood leukocyte number, leading to remission of the disease.

Animals↗

Aberrant expression of blood group H-antigen in Shope carcinoma cells.

Blood group H-antigen was clearly demonstrated as glycolipids in Shope carcinoma cells and its culture cell lines by thin-layer chromatography immunostaining and immunohistochemical analyses using the anti-H monoclonal antibody. This antigen was not detected in normal epidermal and Shope papilloma cells of rabbits but was present in the outer sheath cells of hair follicles of normal rabbit skin. The H-antigen was also detected by cytofluorometric analysis on Shope carcinoma cell lines and the cells were lysed in vitro by the antibody and complement in a dose-dependent manner. These results suggested that the H-antigen was aberrantly synthesized in epidermal carcinoma cells.

ABO Blood-Group System↗

The effects of impaired liver function on the elimination of antineoplastic agents.

OBJECTIVE: To critically review available data on the disposition of cancer chemotherapy in patients with hepatic dysfunction, and to derive at dose recommendation. DATA SOURCES: All published studies in English. STUDY SELECTION: Both human and animal studies. DATA SYNTHESIS: The available studies were sequentially qualitatively described and critically discussed. CONCLUSIONS: The liver is responsible for the metabolism and elimination of many anticancer agents. Their accumulation during hepatic insufficiency may expose the patient to increased risk of drug toxicity. A variety of clinical methods have been described to estimate the need to decrease doxorubicin dose according to degree of hepatic failure to avoid serious toxicity. In some studies prospective ascertainment of clinical indices such as hepatic enzymes and bilirubin was successful in preventing doxorubicin-induced hepatotoxicity. Liver dysfunction has a major impact on cyclophosphamide pharmacokinetics. However, because such impairment leads to less production of the active aldophosphamide, fewer adverse effects were observed in hepatically impaired patients. Vinca alkaloids are extensively metabolized by the liver and excreted in the bile. Systemic exposure to these drugs is inversely correlated to the degree of hepatic failure measured by serum alkaline phosphatase. Although hepatic metabolism is a major route of elimination of fluorouracil, the kidney also plays an important role in its elimination. It has been suggested to reduce its dose in cirrhotic patients. Available pharmacokinetic data and their clinical implications are also discussed for azathioprine, mercaptopurine, etoposide, epirubicin, amsacrine, cytarabine, and other less-studied drugs. Recommendations for dose adjustments are presented and discussed.

Animals↗

Detection of extraordinary large bio-magnetic field strength from human hand during external Qi emission.

It is generally accepted that more than 10(-6) gauss order magnetism was not detected in normal human condition. However, we detected 10(-3) gauss (mGauss) order bio-magnetic field strength from the palm in special persons who emitted External Qi ("Chi" or "Ki"). This detection was possible by special arranged magnetic field detection system, consisted of a pair of 2 identical coils with 80,000 turns and a high sensitivity amplifier. Each of the coils were rolled 80,000 turns accurately, and were connected in series in opposite direction, actuating as a gradiometer. We measure bio-magnetic field strength in 37 subjects with this detection system. The only 3 subjects of them exhibited strong bio-magnetic field of 2 to 4 mGauss in frequency range of 4 to 10 Hz. This magnetic field strength was greater than that of normal human bio-magnetism by 1,000 times at least. A simultaneous measurement of bio-magnetic field strength and its corresponding bio-electric current was examined in one subject. During exhibiting such strong bio-magnetism, its corresponding electric current was not detectable. Therefore, the extra-ordinary large bio-magnetic field strength can not derive from internal body current alone, hence the origin of the large bio-magnetism is still unknown. We suppose that the extraordinary large bio-magnetic field strength might be originated from "Qi" energy in the oriental medicine or in the oriental traditional philosophy.

Electromagnetic Fields↗

Antitumor effects of vitamin A against Shope carcinoma cells.

The antitumor effects of retinol were tested on three cell lines which were derived from a single Shope carcinoma and differed in their degree of differentiation. Addition of retinol to cultures induced growth retardation and morphological changes of these sublines. On removal of retinol from the culture medium, reversion of the undifferentiated subline was observed, but the two differentiated sublines did not revert. The tumorigenic potential of the differentiated sublines was lost or greatly reduced when they were injected into nude mice after 7 days of culture with retinol, whereas the potential of the undifferentiated subline was only slightly reduced. These results suggest that retinol may be effective against differentiated squamous cell carcinomas, but not against undifferentiated tumors.

Animals↗

Infection without antibody response in mother-to-child transmission of HTLV-I in rabbits.

The presence or absence of the anti-human T-cell leukemia virus type (HTLV-I) antibody and the HTLV-I proviral genome was examined in the offspring of inbred rabbits, which were born to HTLV-I carrier does. The results showed that not all offspring born to the carriers were infected and that not all the infected offspring seroconverted at the age of 10 weeks, which is similar to observations made in human carriers. The anti-HTLV-I antibody was assayed by indirect immunofluorescence in 55 offspring at the age of 10 weeks, which were born to B/J or (B/J x Chbb:HM)F1 seropositive HTLV-I carrier does. Twelve out of 31 offspring born from F1 x F1 mating were seropositive, whereas none of 24 offspring born from B/J x B/J mating, F1 x B/J mating, or F1 x Chbb:HM mating were seropositive. The polymerase chain reaction (PCR) method revealed the presence of the HTLV-I proviral genome in 18 out of 23 offspring born from F1 x F1 mating (F2 hybrids). In these 18 HTLV-I-infected F2 hybrids, 8 were seropositive and 10 were seronegative. The major histocompatibility complex (MHC) of these 23 F2 hybrids was analyzed by restriction fragment length polymorphism (RFLP) in southern hybridization. The results showed no close correlation of MHC with HTLV-I susceptibility or with seroconversion. Natural infection via mother-to-child transmission of virus seems to produce seronegative as well as seropositive carriers. This rabbit model may be useful for the study of seronegative virus carriers via mother-to-child transmission of HTLV-I.

Animals↗

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↗

Killer cell lines against Shope carcinoma cells in rabbits.

Killer cell activity against Shope carcinoma cells was not detected in PBL nor in spleen cells from tumor-bearing B/J rabbits, but was induced by in vitro culture of these cells in the presence of IL-2 and X-irradiated carcinoma cells. HTLV-I-transformed killer cell lines were successfully obtained by the culturing of PBL from an HTLV-I-infected and tumor-bearing Chbb:HM rabbit. These killer cells included large cells with azurophilic granules in the cytoplasm and with a reniform nucleus, thus resembling large granular lymphocytes. The killer activity was similar against the Vx2K cell line from a random-bred rabbit and SCB cell lines from an B/J rabbit, suggesting the absence of MHC restriction.

Animals↗

Selected faecal bacteria and nutrients essential for antagonism of Salmonella typhimurium in anaerobic continuous flow cultures.

As few as five of the species of bacteria commonly found in human faeces--Escherichia coli, Enterobacter aerogenes, Enterococcus faecalis, Bacteroides ovatus and Fusobacterium varium--when grown together in anaerobic continuous flow cultures exerted antagonistic effects on Salmonella typhimurium as great as those given by mixed bacteria from extracts of human faeces. In a single culture, the population of S. typhimurium was c. 10(8) cfu/ml but in mixed cultures with the five antagonistic bacteria or mixed faecal bacteria it was reduced to c. 10(3) cfu/ml. Antagonism appeared to be the result of competition for the growth limiting amino acids, arginine, serine, threonine and aspartic acid. Optimal manifestation of antagonism required the presence of carbon sources fermentable only by antagonistic bacteria, such as lactose 0.1%, w/v, sucrose 0.1% (w/v) and starch 0.2-0.3% w/v. These carbohydrates promoted the growth of the antagonistic bacteria, particularly E. coli and B. ovatus. However, an increase in concentration by several fold of any one of four growth-limiting amino acids in the medium diminished the antagonistic effects and the population of S. typhimurium rose 10(2)-10(3)-fold.

Amino Acids↗

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↗

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↗

Comparison of host responses induced by Salmonella typhimurium infection in genetically resistant and susceptible mice.

A/J and BALB/c mice differ genetically in their resistance to the facultative intracellular bacterium Salmonella typhimurium. We compared the responses of these strains of mice to a virulent S. typhimurium infection. BALB/c mice mobilised more peritoneal exudate cells in response to the infection than did A/J mice 30 h after infection, but the increase in bacterial counts in the livers and spleens of BALB/c mice was 10-fold higher than in A/J mice. The response to Concanavalin A (Con A) of spleen cells from BALB/c mice was depressed, and both L3T4+ and Lyt-2+ T cell subpopulations were decreased following the infection, whereas the response to Con A of A/J mice was increased and the T cell subpopulations were not altered significantly. These results suggest that A/J mice respond more actively to S. typhimurium infection than do BALB/c mice, and this may be related to the natural resistance of mice.

Animals↗