PubMed Health⌕ Search

Biomedical subjects

Y Aida

Publications and source records attributed to Y Aida.

At least 91 records · Page 5Linked to original sources

Immunopathologic study and characterization of the phenotype of transformed cells in sheep with bovine leukemia virus-induced lymphosarcoma.

We used monoclonal antibodies and immunohistologic examination of lymph nodes, to elucidate the pathogenesis of lymphosarcoma induced by infection with bovine leukemia virus (BLV). The superficial cervical lymph nodes from 3 BLV-infected but apparently healthy sheep and 5 sheep with full-blown lymphosarcoma were examined. We also investigated the integration of bovine leukemia provirus by use of Southern blotting. In lymph nodes from sheep lacking clinical signs of infection, in which the provirus had been integrated at multiple sites in the genome, many large hypertrophic follicles were observed in the cortex. These follicles had germinal centers consisting of CD4+T cells and B cells that expressed surface IgM (sIgM) and major histocompatibility complex (MHC) class-II antigens, but not B cell-specific B2 molecule. The percentage of CD4+T cells in the cortex was significantly (P < 0.05) higher than that of the controls and sheep with lymphosarcoma. In all sheep with lymphosarcoma, the lymph nodes were completely destroyed by proliferating neoplastic cells, and in addition, small atrophic follicles, which consisted of normal B-cell marker-positive cells, were seen near the trabecula and the subcapsule. In these instances, neoplastic cells appeared to be a monoclonal population derived from a single CD5- B-cell lineage and to be classified as 2 types, CD5-CD4-CD8-B2+MHC class-II+sIgM+ and CD5-CD4-CD8-B2+MHC class-II+sIgM-. Moreover, CD8+T cells infiltrated diffusely throughout the tumorous lymph nodes apart from the atrophic follicles, and CD4+ cells were observed around atrophic follicles. Both types of T cells were small-size, normal lymphocytes with round and noncleaved nuclei, and were apparently non-neoplastic cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Identification of tumor-associated antigen that is expressed on bovine leukemia virus-induced lymphosarcoma cells and expression of its human homologue in human T-cell lymphotrophic virus I-infected cell lines.

By using the monoclonal antibody (MAb) c143 against tumor-associated antigen that is expressed in tumor cells of cattle with bovine leukemia virus (BLV)-induced enzootic bovine leukosis (EBL), we found a novel bovine MHC class II-related antigen which consists of alpha chain (36-37 kDa) and beta chain (32 and 34 kDa). The nature of the c143 antigen was different from previously identified class II antigens, such as DR and DQ, as indicated by test for reactivities with mouse L cell transfectants expressing human class II antigens, sequential immunoprecipitation and tryptic peptide mapping. With the progression of EBL, the number of cells carrying the c143 antigen increased, and the beta chain was specifically phosphorylated at serine residue(s) in lymphosarcoma cells and the cell lines derived from them. A marked difference between expression patterns of the c143 antigen and the class II antigens was observed in lymph nodes from BLV-free and -infected animals. Although bovine mixed lymphocyte reaction (MLR) was inhibited by the addition of MAbs against class II antigens, the c143 MAb did not inhibit a lymphoproliferative response of T cells in the MLR, suggesting that the function of this antigen is distinct from those of classical class II molecules. Significantly, although the human homologue of the c143 antigen is expressed little if at all in human T-cell lines, such as CEM, Molt-4, Jurkat and HPB-ALL, its expression become apparent in T-cell lines infected with human T-cell lymphotrophic virus I (HTLV-1).

Animals↗

gp51 of bovine leukemia virus gene expression in hamster cells.

Recombinant pMMEx-bovine leukemia virus env gene DNA fragments were produced and expressed in eukaryotic cells. Clone C4, containing an SmaI-SmaI fragment of the gene coding for gp51, was co-transfected with pSV2neo DNA into Chinese hamster cells. About 800 geneticin-resistant cell clones were isolated and then morphologically and biologically characterized. The presence of gp51 encoding env gene fragments was detected in 17 of them by Southern blotting. The expression of gp51 gene in hamster cells was confirmed by Western blotting of their lysates with monoclonal antibodies (MAbs) directed against different epitopes of gp51 of bovine leukemia virus. The immunoreactivity of the expressed peptides with MAbs directed against neutralizing epitopes of gp51 of bovine leukemia virus was confirmed.

Animals↗

Phenotype and ontogeny of cells carrying a tumor-associated antigen that is expressed on bovine leukemia virus-induced lymphosarcoma.

The phenotype and ontogeny of cells carrying the tumor-associated antigen (TAA), identified in tumors of cattle with enzootic bovine leukosis (EBL) by use of the monoclonal antibody (MAb) c143, were analyzed by flow cytometry and immunohistochemistry. The TAA recognized by the c143 MAb (c143 TAA) was mainly expressed on B-cells, macrophages, reticular cells, and a minor population of BoCD4-positive T-cells in bovine leukemia virus (BLV)-free normal cattle. When the peripheral blood mononuclear cells from normal cattle were activated in vitro, some populations of BoCD8-positive T- and non-T/non-B-cells also showed expression. Moreover, B-cells expressed the c143 TAA until the antigen was lost from cells at the final stage of B-cell differentiation, namely, the plasma cell stage. The c143 MAb-positive cells in blood of BLV-free normal cattle form heterologous subpopulations, and these cells coexpress other surface markers such as BoCD2, BoCD5, BoCD6, and B-cell-specific molecules B1 low, B1 bright, and B2. In BLV-infected cattle, the proportion of peripheral blood mononuclear cells that express the c143 TAA increased with the progression of EBL, and, in addition, BLV-infected cattle that had no lymphosarcomas showed increased proportions of c143 MAb-positive cells that coexpressed surface IgM (sIgM), BoCD5, B1 low, and B2 but not BoCD2, BoCD4, or BoCD6. Furthermore, most of the c143 MAb-positive tumors from all cattle with EBL appeared to be a monoclonal population derived from a single B-cell and to be divided into two types, c143 TAA+BoCD5+B1 low+ B2+ sIgM+ or sIgM-. Collectively, these results show that the c143 TAA is not only a useful surface marker for identification of EBL but also a marker of differentiation of lymphoid cells.

Animals↗

Differentiation and mineralization in osteogenic precursor cells derived from fetal rat mandibular bone.

The process of mineralization in cells prepared either by neutral protease digestion (Pro I) or by collagenase digestion (fifth cycle, Col V) from fetal rat mandible was studied in vitro. Alkaline phosphatase (ALPase) activity of cells in Pro I was low on day 3, increased rapidly from day 8, and reached a maximum on day 16, whereas that in Col V was high on day 2, then declined and thereafter elevated to reach a maximum on day 13. Both cell populations synthesized type I collagen in cell matrix and medium. Type III collagen was observed in cell matrix of Pro I on day 14 and 21. There was alpha 2 band of type V collagen in cell matrix of Pro I on day 21. Calcium deposition could be detected from day 14 in Pro I and from day 19 in Col V. The von Kossa-positive nodules were found on day 17 in Pro I and day 21 in Col V, respectively. The extracellular matrix in Pro I electron-microscopically consisted of well-banded collagen fibrils with a large number of calcified spherules. An elevation of ALPase activity, collagen synthesis, and mineral deposition occurred sequentially with a time lapse in Col V, and almost simultaneously in Pro I. The number of mineralized nodules was correlated with the density of plated cells in Pro I, but not in Col V. Dexamethasone caused an increase in the number of mineralized nodules in Pro I, but not in Col V, suggesting that Pro I contained osteoprogenitor cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗

Antigenic regions defined by monoclonal antibodies on tumor-associated antigens of bovine leukemia virus-induced lymphosarcoma cells.

Tumor-associated antigens (TAAs) expressed on enzootic bovine leukosis tumors were divided previously into three types by use of 13 monoclonal antibodies (MAbs): common TAA, partially common TAA and individually distinct TAA. Since MAb-defined epitopes on the common TAA were conserved on both soluble TAA prepared from bovine B-lymphoma cells and untreated viable same cells, all the MAbs that bound to the soluble TAA also bound to untreated viable cells. By contrast, MAb-defined epitopes on the partially common and individually distinct TAAs varied according to the test systems used. Two of seven MAbs were found to bind to both the soluble TAA and viable cells and one MAb bound to the soluble TAA but not to the viable cells.

Animals↗

Toxicity studies of a synthetic antioxidant, 2,2'-methylenebis (4-ethyl-6-tert-butylphenol) in rats. 2. Uncoupling effect on oxidative phosphorylation of liver mitochondria.

Effects of 2,2'-methylenebis (4-ethyl-6-tert-butylphenol) (MBEBP) on hepatic mitochondrial oxidative phosphorylation in vitro, and on hepatic peroxisomal enzymes activities and microsomal mixed-function oxidase activities were studied. 1. A low concentration of MBEBP, less than 50 microM, increased state 4 respiration and decreased state 3 respiration. However, a higher concentration of MBEBP, greater than 100 microM, acted as a respiratory inhibitor. Therefore, MBEBP was found to act as an uncoupler of oxidative phosphorylation in rat liver mitochondria. 2. MBEBP significantly decreased peroxisomal enzymes, cyanide-insensitive palmitoyl-CoA oxidizing activity and catalase activity in the livers of rats fed 0.2, 1.0 or 5.0% MBEBP for 4 weeks. 3. In microsomal enzyme assay, NADPH cytochrome c reductase activity was significantly increased, however, cytochrome P-450, cytochrome b5 levels, aminopyrine N-demethylase and benzo [a] pyrene hydroxylase activities were not significantly increased in the livers of rats fed 1.0 or 5.0% MBEBP for 4 weeks. The weight loss and the decrease of serum triglyceride level observed in the MBEBP-treated rats seemed to be caused by its uncoupling effects, which might also be the cause of the testicular damage induced by MBEBP.

Animals↗

Tumor-associated M(r) 34,000 and M(r) 32,000 membrane glycoproteins that are serine phosphorylated specifically in bovine leukemia virus-induced lymphosarcoma cells.

Tumor-associated antigens that are expressed in tumor cells of cattle with enzootic bovine leukosis (EBL) were analyzed previously by use of 13 monoclonal antibodies. We biochemically identified one of the tumor-associated antigens, which is recognized by the c143 monoclonal antibody, as two glycoproteins, each having an apparent molecular weight of 32,000 or 34,000. These glycoproteins were found in the plasma membrane of peripheral blood lymphocytes of both bovine leukemia virus (BLV)-free normal and BLV-infected cattle. With the progression of EBL, the proportion and the absolute number of cells positive for the tumor-associated antigen increased. Moreover, the level of the M(r) 34,000 component, which was susceptible to cell-surface labeling, increased over the level of the M(r) 32,000 component. Partial proteolytic peptide mapping with V8 protease and deglycosylation analysis revealed that the two glycoproteins most likely have an identical M(r) 30,000 polypeptide portion but have different N-linked oligosaccharide portions. Both glycoproteins were found to be phosphorylated at serine residue(s) in EBL-derived B-lymphoid cell lines and in tumor cells and peripheral blood lymphocytes from cattle with EBL, but not in peripheral blood lymphocytes from BLV-free normal cattle and BLV-infected cattle without any evidence of tumor, suggesting that the phosphorylation of these glycoproteins is related to the transformed state of the BLV-infected B-lymphoid cells.

Animals↗

Difference in tumor incidence and other tissue responses to polyetherurethanes and polydimethylsiloxane in long-term subcutaneous implantation into rats.

The long-term (1- and 2-year) adverse tissue responses including tumor formation by subcutaneous implantation of polyurethanes (PUs) and silicone (Sil) films into rats were compared. The weight-averaged molecular weights (Mw) of the PUs prepared from 4,4'-diphenylmethanediisocyanate, poly(tetramethyleneglycol) of Mn = 1000 and 1,4-butanediol are 220,000 (U-4), 124,000 (U-6), and 55,600 (U-8). The 50:50 mixed film of U-6 and silicone (U-6/sil) was prepared by roll-mixing of the noncured silicone and the U-6 solution followed by evaporation of the solvent and heat-curing at 70 degrees C. The tissue responses around implants were classified into four groups as follows: (A) tumor, (B) atypical cell proliferation accompanied by preneoplastic changes, (C) cell proliferation without preneoplastic changes, (D) no obvious responses. In both implantation periods, the PUs gave higher incidents of the adverse responses including tumor formation in comparison to Sil. No significant molecular weight-dependent trend was found in a 1-year study using U-4, 6, and 8. Significant PU-dose-dependent trends were found in a 2-year study: the total active incidence (A+B+C), U-6(22/29) greater than U-6/sil(11/29) greater than sil(7/28); tumor incidence (A), U-6(11/29) greater than U-6/sil(2/29) = sil(2/28). No detectable amounts of 4,4'-methylenedianiline (MDA) were found in the PUs. The methanol extracts from the PUs were negative in the mutagenicity tests. These indicate no relationship between the tumor formation by the PU films and the mutagenicities of the chemicals (mainly oligomers) leached from the PUs.

Aniline Compounds↗

Toxicities of microencapsulated tribromomethane, dibromochloromethane and bromodichloromethane administered in the diet to Wistar rats for one month.

The gelatin-starch syrup microencapsulation method was applied to subacute toxicity studies of tribromomethane (TBM), dibromochloromethane (DBCM) and bromodichloromethane (BDCM). Groups of Wistar rats (7 males and 7 females) both sexes were given diet containing microcapsules of each of these trihalomethanes (THMs) at the following concentrations: TBM, 0.068, 0.204 and 0.612% in males, and 0.072, 0.217 and 0.651% in females; DBCM, 0.020, 0.062 and 0.185% in males, and 0.038, 0.113 and 0.338% in females; BDCM, 0.024, 0.072 and 0.215% in males, and 0.024, 0.076 and 0.227% in females. Suppression of body weight gain was seen in each high-dose males fed TBM or BDCM and females fed DBCM or BDCM. Histopathologically, hepatic lesions such as vacuolization and swelling of liver cells were significantly noted in both sexes of all groups fed TBM, in both sexes of the middle- and high-dose groups fed DBCM, and in males of the high-dose group and in females of the middle- and high-dose groups fed BDCM. In addition, single cell necroses were observed in males and females fed DBCM and in males fed BDCM. Hepatic cord abnormalities were also noted in males of the high-dose group fed BDCM. Although no increases in serum transaminase activities (ASAT, ALAT) were evident in either sex fed any of the THMs, decreases in triglyceride content, cholinesterase and lactate dehydrogenase activity were observed. Renal lesions reported to occur in gavage studies were not found in the present feeding study. Lowest-observed-adverse-effect-level (LOAEL) of TBM and no-observed-adverse-effect-level (NOAEL) of DBCM and BDCM were determined to be 56.4 mg/kg, 18.3 mg/kg and 20.6 mg/kg, respectively, under the present experimental conditions.

Administration, Oral↗

Toxicity studies of a synthetic antioxidant, 2,2'-methylenebis (4-ethyl-6-tert-butylphenol) in rats. 1. Acute and subchronic toxicity.

The acute and subchronic toxicity studies on 2,2'-methylenebis (4-ethyl-6-tert-butylphenol) (MBEBP) were conducted using male and female Wistar rats. In acute toxicity test, the LD50 values were estimated to be greater than 10 g/kg BW by oral and intraperitoneal administration in each sex. In subchronic toxicity test, groups of 10 rats of each sex were fed a diet containing 0.2, 1.0 or 5.0% of MBEBP and examined at 4 and 12 weeks. Body weight gain was significantly depressed at doses of 1.0 and 5.0% in both sexes, but the depression in the 1.0% group was severer than that in the 5.0% group in males. Hematological analysis showed slight but significant decrease of hemoglobin in the 1.0 and 5.0% groups of both sexes. Urine analysis showed no remarkable changes in all treated rats of both sexes. In biochemical analysis of serum, decrease of triglyceride level and cholinesterase activity, and increase of amylase activity were observed in treated rats. Histopathologically, testicular atrophy and decrease of spermatogenesis were observed in male rats fed 1.0 or 5.0% MBEBP for 4 and 12 weeks and vacuolization of parathyroid gland cells was observed in female rats fed 1.0 and 5.0% MBEBP for 12 weeks. In subchronic test, the lowest observable adverse effect levels for MBEBP toxicity were estimated to be 171 mg/kg BW/day in male rats and 180 mg/kg BW/day in female rats.

Administration, Oral↗

Chronic toxicity of microencapsulated bromodichloromethane administered in the diet to Wistar rats.

A chronic feeding study was carried out in Wistar rats using microencapsulated bromodichloromethane. The test substance was administered in the diet at doses of 0, 0.014, 0.055 and 0.22% for 24 months. Rats were sacrificed after 6, 12, 18 and 24 months of continuous dosing. The results showed a suppression of body weight gain in the 0.22% group for both males and females. Dose related changes were clearly observed in the liver with histopathological findings including fatty degeneration in the 0.014% or higher dose male groups, and fatty degeneration and granuloma in the 0.055 and 0.22% group females, as well as bile duct proliferation and cholangiofibrosis in the 0.22% group for both males and females. No significant differences in incidences or numbers of neoplastic changes were seen between control and any of the treatment groups. There were no dose-related non-neoplastic lesions in the kidneys of either sex. Lowest-observed-adverse-effect-level was determined to be 6.1 mg/kg/day under the present experimental conditions.

Animal Feed↗

[A study of the relationships between exposure periods and no-effect doses in repeated dose toxicity tests].

In the risk assessment of chemicals to humans, it is a very important step to determine no-observed-adverse-effect-levels (NOAEL) or lowest-observed-adverse-effect-levels (LOAEL) from animal experiments. Recently, short-term screening tests, such as 28-day repeated dose toxicity test, are carried out in accordance with the regulative guidelines for the safety evaluation of chemicals. However, many problems still remain in the risk assessment to human based on short-term toxicity studies. For this reason, we studied the relationships between the exposure periods and NOAELs or LOAELs in repeated dose toxicity tests using available test results of 18 halogenated compounds. The ratios between each NOAEL or LOAEL of short-term tests (14, 28 days, 13 weeks and 6 month) and those of long-term tests (longer than one year) were calculated on the basis of same animal species, route and toxic effect. From this study, it was considered that exposures above 13 weeks were needed to satisfy the present safety factor considerations for setting an acceptable daily intake (ADI).

Administration, Inhalation↗

Cross-reactivity between a monoclonal antibody that recognizes a tumor-associated antigen on bovine lymphosarcoma cells and blood lymphocytes from various mammalian species.

Tumor-associated antigens that are expressed in lymphosarcoma B cells of cattle with enzootic bovine leukosis had been analyzed in terms of their reactivity with 13 monoclonal antibodies (MAB). By use of flow cytometry and radioimmunoprecipitation, 1 of the MAB (c143) that recognized a tumor-associated antigen cross-reacted with blood lymphocytes (BL) from various mammalian species. By use of flow cytometry, the c143 MAB reacted with 10 to 49% of BL derived from human beings, mice, dogs, horses, pigs, llamas, sheep, goats, and cattle. Titer of the c143 MAB with BL from horses, pigs, human beings, and llamas ranged between 1:6.0 x 10(4) and 1:5.3 x 10(5); titer associated with BL of goats and sheep was 1:1.6 x 10(6); and that associated with BL of cattle was 1:4.3 x 10(7). The c143 MAB specifically immunoprecipitated 3 homologous proteins from cell extracts of caprine, ovine, and bovine BL (32-, 34-, and 36- to 37-kDa bovine proteins; 31-, 32-, and 36- to 37-kDa caprine proteins; and 31.5-, 33-, and 36- to 37-kDa ovine proteins), but none was immunoprecipitated from human, murine, canine, porcine, and llama BL. These results indicate that the avidity of the c143 MAB in binding to BL from ruminants (eg, goats, sheep, and cattle) is higher than that to BL from human beings, mice, dogs, horses, pigs, and llamas. In sheep, the c143 MAB could immunoprecipitate the aforementioned proteins from BL of the Suffolk breed, but not BL from the Corriedale breed, whereas the c143 MAB immunoprecipitated apparently identical proteins from BL of 4 breeds of cattle.

Animals↗

Neutrophil responses to lipopolysaccharide. Effect of adherence on triggering and priming of the respiratory burst.

We studied neutrophil responses to LPS using three methodologic refinements: Teflon bags or serum-coated glass tubes that did not directly trigger neutrophils, LPS-free cytochrome c to measure O2- release, and heat-inactivated serum to inhibit inactivation of LPS by neutrophils. Neutrophils incubated in uncoated glass or plastic tubes adhered to the glass and released O2-, but were not primed for enhanced release of O2- in response to triggering by FMLP. Triggering by the glass or plastic surface did not occur if the neutrophils were stirred to prevent adherence. Adherence to glass or plastic and O2- release were not affected by a mAb (IB4) directed against the beta-chain of the leukocyte adhesion family of surface glycoproteins (CD11/CD18). Neutrophils incubated in glass or plastic did not show enhanced expression of alkaline phosphatase on their surface. When neutrophils were incubated in serum-coated glass tubes or in Teflon bags, there was no O2- release. However, adherence, expression of alkaline phosphatase, and release of O2- were triggered by adding 1 ng/ml LPS plus 1% serum, but not by either LPS or serum alone. In the presence of LPS and serum, O2- release was much higher when the cells were unstirred (adherent) rather than stirred. However, both unstirred and stirred cells expressed a similar elevated level of alkaline phosphatase. LPS-triggered O2- release and adherence were inhibited by antibody IB4. In contrast, priming by LPS for enhanced FMLP-triggered O2- release was greater in stirred cells than in unstirred cells. The antibody enhanced priming of unstirred neutrophils. These results suggested that uncoated glass or plastic triggered O2- release without involvement of leukocyte adhesion glycoproteins. However, neutrophils incubated with LPS and serum expressed alkaline phosphatase and IB4-inhibitable adherence glycoproteins that allowed neutrophils to interact with serum-coated glass or Teflon to trigger O2- release. Priming by LPS for enhanced response to FMLP was suppressed in adherent neutrophils, and this suppression was partly released by IB4. Thus, triggering and priming were reciprocally regulated by neutrophil glycoproteins interacting with surfaces.

Alkaline Phosphatase↗

1-Hydroxyethylidene-1,1-bisphosphonate decreases the postovariectomy enhanced interleukin 1 secretion from peritoneal macrophages in adult rats.

Bisphosphonates are potent inhibitors of bone resorption. In previous studies, we have shown that ovariectomy accelerates bone resorption and 1-hydroxyethylidene-1, 1-bisphosphonate (HEBP) inhibits ovariectomy-accelerated bone resorption in female Wistar adult rats. As interleukin 1 (IL-1) stimulates bone resorption in vitro and in vivo, we have investigated the effects of ovariectomy and HEBP administered in vivo on IL-1 secretion from peritoneal macrophages in adult rats. Ovariectomy or sham surgery were performed in female Wistar rats at 40 weeks of age. Ovariectomized and sham-operated rats were administered with HEBP (10 mg) or saline, 10 times in total, from 43 to 46 weeks of age. Paraffin oil-induced peritoneal macrophages at 46 weeks of age were cultured for 24 hours. Lipopolysaccharide (LPS)-stimulated peritoneal macrophages from ovariectomized rats secreted more IL-1 than sham-operated rats. HEBP decreased LPS-stimulated IL-1 secretion from peritoneal macrophages in ovariectomized rats, but not in sham-operated rats. In vivo administration of HEBP decreased IL-1 secretion only in postovariectomy hyperresorptive states. These results suggest that alterations in LPS-stimulated IL-1 secretion from oil-induced peritoneal macrophages may be responsible, at least in part, for the postovariectomy acceleration in bone resorption and its inhibition by HEBP.

Analysis of Variance↗