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Biomedical subjects

H Kaneshima

Publications and source records attributed to H Kaneshima.

At least 91 records · Page 5Linked to original sources

Developmental expression of C3 receptor on murine epidermal Langerhans cells during ontogeny.

The developmental expression of C3 receptor, an important surface marker of murine epidermal Langerhans cells (LCs), was quantitatively studied using an immunohistochemical technique on epidermal sheets and then compared with developmental expression of Ia antigen and membrane ATPase. Anti-Mac-1 monoclonal antibody associated with CR3 was used for detecting C3 receptor and proved positive for LCs by immunoelectron microscopy. Mac-1 positive (Mac-1+) cells showed quite a different distribution from those of ATPase+ and Ia+ cells. Almost the same number of Mac-1+ and ATPase+ cells were present during the embryonic period. The number of Mac-1+ cells gradually decreased from day 1 to day 5 of postnatal life, after which they increased again. Using the double-labeling technique on epidermal sheets at day 1 of postnatal life, it was shown that Ia+ cells possessed membrane ATPase activity and some Mac-1+ cells expressed Ia antigen. On days 4 and 7 of postnatal life all Mac-1+ cells expressed Ia antigen. These findings suggest that Mac-1 antigen observed during the embryonic period gradually fades after birth and is re-expressed after day 5 of postnatal life.

Adenosine Triphosphatases↗

Chlorination of Irgasan DP300 and formation of dioxins from its chlorinated derivatives.

Irgasan DP300 (2,4,4'-trichloro-2'-hydroxydiphenyl ether) (I), an antimicrobial agent for use with fabrics, was easily chlorinated with sodium hypochlorite to give 2',3,4,4'-tetrachloro-2-hydroxydiphenyl ether (II), 2',4,4',5-tetrachloro-2-hydroxydiphenyl ether (III) and 2',3,4,4',5-pentachloro-2-hydroxydiphenyl ether (IV). Irgasan DP300 and its chlorinated derivatives were readily converted into polychlorinated dibenzo-p-dioxins (PCDDs) by heating: Irgasan DP300 was converted into dichlorodibenzo-p-dioxin(s) (di-CDD, 42%); II into two trichlorodibenzo-p-dioxins (tri-CDDs, 22%) and three tetrachlorodibenzo-p-dioxins (tetra-CDDs, 46%); III into two tri-CDDs (44%), more than two tetra-CDDs (25%) and pentachlorodibenzo-p-dioxin(s) (penta-CDD, 1%); and IV into two tetra-CDDs (16%), trace amounts of penta-CDD(s) and four hexachlorodibenzo-p-dioxins (hexa-CDDs, 40%). Although UV irradiation of Irgasan DP300, II and III gave PCDDs, the amounts of PCDDs formed were much smaller than those obtained by heating. Moreover, PCDD was not detected in the UV irradiation of IV. The identified products suggested that disproportionation of chlorine atom(s) occurred in the photolysis.

Anti-Infective Agents↗

Thymic epithelial reticular cell subpopulations in mice defined by monoclonal antibodies.

Thymic epithelial reticular cells (TER) are heterogeneous cell populations. Of 14 rat monoclonal antibodies (moAbs) raised against established cell lines of mouse thymic stromal cells (TSC), two were found to recognize TER subpopulations that exhibited distinct intrathymic distributions. MoAb B6TS-1 (IgG2a) recognized the cell-surface determinant mB6TS-1 on TSC in the subcapsular zone, cortico-medullary junction, and medulla. Double staining with antikeratin antiserum showed that, except in the cortex, the distribution of mB6TS-1 bearing cells highly corresponded with that of keratin-positive TER indicating that mB6TS-1 within the thymus was selectively expressed in a particular subpopulation of epithelial cells. Immunoelectronmicroscopy revealed clear polarity in the expression of mB6TS-1 on TER. In the subcapsular zone. TER adherent to fibrous capsule expressed mB6TS-1 on the cell surface that faced the lymphocytes. In the cortico-medullary junction, mB6TS-1 also was found on the side of the TER closely associated with the small blood vessels. The mB6TS-1-bearing cells in the medulla characteristically had cytoplasmic infoldings containing collagen fibrils and amorphous material but did not exhibit the polarity of mB6TS-1-bearing cells. The mB6TS-1-bearing TER were interconnected by desmosomes and tonofilaments, therefore, were easily distinguished from macrophages, dendritic cells, and other components of thymic stroma. In contrast, another moAb AKTS-1 (IgM) stained the keratin-positive TER localized in the subcapsular zone and cortex forming a fine meshwork but did not stain those in the medulla. MoAb B6TS-1 stained thymic nurse cells but not the central cells of thymic rosettes, whereas moAB AKTS-1 did neither. Formation of lymphoid-stromal cell complexes in vitro was not affected by either antibody.

Animals↗

Reorganization of thymic microenvironments during development and lymphomagenesis.

Modulation of thymic microenvironments during ontogeny and lymphomagenesis in mice was studied with two rat monoclonal antibodies (moAb) which recognized distinct subpopulations of thymic epithelial reticular cells (TER). In adult thymus, the TER subpopulation stained by moAb B6TS-1 was localized in the subcapsular zone, cortico-medullary junction, and medulla. In fetal thymus, it was initially distributed throughout the rudiment, but after day 16 of gestation, it was rapidly redistributed to the locations seen in adult thymus. From an early stage of thymic lymphomagenesis, the TER bearing mB6TS-1 (epitope defined by moAb B6TS-1) in the cortico-medullary junction, in particular those associating with small blood vessels, proliferated and formed a characteristic network throughout the thymus, in which numerous growing lymphoma cells were entrapped. On the other hand, moAb AKTS-1 stained another TER subpopulation that was localized in the cortex in both fetal and adult thymus. Unlike mB6TS-1+ TER, mAKTS-1+ TER became increasingly sparser during lymphomagenesis. Selective proliferation of the mB6TS-1+ TER subpopulation in the cortico-medullary junction was seen in spontaneous, radiation-induced, and chemical-induced mouse thymic lymphomas. The possible biological significance of such modulation of thymic microenvironments in the natural history of lymphomagenesis is discussed.

Animals↗

Action of cobra venom cardiotoxin on chick embryonal fibroblasts transformed with a temperature-sensitive mutant of Rous sarcoma virus.

The cytolytic action of cardiotoxin analogue III from the venom of the Formosan cobra on chick embryonal fibroblasts transformed with a temperature-sensitive mutant of Rous sarcoma virus was investigated. The 50% effective dose of the toxin for the cells cultured at a non-permissive temperature (41 degrees C) or for noninfected normal cells was about 8 micrograms/ml whereas the value was 2 micrograms/ml for the cells cultured at a permissive temperature (36 degrees C). This indicates that the transformed cells became more susceptible to the cytolytic action of the toxin than the non-transformed cells.

Animals↗

Thymic lymphoid-stromal cell complexes in mice: in vitro assay and mechanism of the complex formation.

A quantitative assay was established to analyze in vitro thymic lymphoid-stromal cell complex formation. Major parameters of this assay were the number of thymic lymphocytes, incubation time, the age of the thymocyte donor, and the source and amount of serum used. The majority of complex-forming lymphocytes from normal young adult mice were found to have a blastlike morphology, indicating their possible origin from the subcapsular zone of the thymus. Changes of complex-forming cells during thymus development seemed to support this concept. The complex formation occurred in two steps: adherence of the lymphocytes to stromal cells and subsequent crawling of the lymphocytes under stromal cell cytoplasm. The first step was competitively inhibited by a serum activity and the second was noncompetitively inhibited by chemicals affecting cytoskeleton. In this assay, the behavior of normal complex-forming thymocytes was shown to be similar to that previously demonstrated for leukemia thymocytes with respect to morphology of the complex as well as the effects of certain inhibitors. This assay should provide the means both to analyze the nature of this cell interaction and to explore the relationship between thymocyte differentiation and a step in thymic leukemogenesis.

Animals↗

[Effectiveness of ceftizoxime on various infections in patients with underlying diseases].

Ceftizoxime (CZX), a parenteral cephalosporin derivative belonging to the so-called third generation cephalosporin is reported to have a broad antibacterial activity, particularly against Gram-negative aerobic bacilli and some anaerobes, such as Bacteroides fragilis and a good stability to beta-lactamases. Clinical study was performed on a total of 20 cases, 9 females (1 case had urinary tract infection 3 times) and 11 males, aged from 27 to 82 years. All patients had the underlying diseases. They were bronchial asthma in 3 cases, influenza in 1, chronic pulmonary emphysema in 1, pulmonary fibrosis in 1, chronic bronchitis with strongyloidiasis in 1, lung cancer in 3, esophagus cancer in 2, stomach cancer in 1, hepatoma with urolithiasis in 1, liver cirrhosis with diabetes mellitus in 1, alcoholism with strongyloidiasis in 1, cholelithiasis in 1 and congestive heart failure in 1, respectively. Clinical diagnoses for infections were 2-acute bronchitis, 2-exacerbation of chronic bronchitis, 2-broncho-pneumonia, 2-pneumonia including one suspected case, 1-obstructive pneumonia, 2-secondary pulmonary infection, 1-pulmonary infection, 3-urinary tract infection (UTI), 1-UTI with sepsis, 1-sepsis, 1-sepsis with purulent meningitis, 1-biliary tract infection and 1-infected bronchoesophageal fistula. CZX was given by intravenous drip infusion, at a dose of 1 to 2 g, twice daily for 3 to 15 days. Because of severity in infections and underlying diseases, some cases were treated either steroid, gamma-globulin preparations or other antibiotics in combination with CZX. Twelve out of 15 cases assessed clinically responded satisfactorily to the treatment and efficacy rate was 80.0%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Teleocidin-induced modulation of growth and cell interaction in microenvironment-dependent mouse leukemias.

Teleocidin is a new tumor-promoting substance chemically unrelated to phorbol groups. Its biological effects on thymic microenvironment-dependent leukemias derived from AKR spontaneous leukemias were studied in vitro in comparison with 12-O-tetradecanoylphorbol 13-acetate (TPA), a representative tumor promoter of the phorbol group. Teleocidin stimulated the in vitro growth of 21 out of 31 symbiotic cell lines in the absence of growth-supporting stromal cells. All the responders to teleocidin were responsive also to TPA and the degree of growth stimulation in each cell line was comparable. Both promoters could inhibit the symbiotic complex formation with thymic epithelial cells probably by affecting the cytoskeleton. All symbiotically cultured AKR leukemia cells expressed Thy-1.1 antigen, but their expression of Lyt-1.2 and Lyt-2.1 was heterogenous. There was no direct correlation between teleocidin-responsiveness and Lyt-phenotypes of the leukemia cells.

Alkaloids↗

Progression of mouse thymic leukemias in thymic microenvironments.

Mouse thymic leukemogenesis has been assumed to occur in multiple steps corresponding to the stages of normal T-cell lineage development. One of the roles of the thymus in leukemogenesis is to provide permissive microenvironments for the progression of developing leukemias from thymus-dependent to independent growth. We have devised a method to consistently isolate the symbiotic complex of leukemia cells and thymic epithelium-like stromal cells from primary leukemic thymuses. In such complexes, leukemia cells were able to proliferate in close association with thymic stromal cells in pseudoemperipolesis, i.e., a unique form of cell interaction which we defined. In normal thymus, subcapsular zone blasts, mitotically active early thymic lymphocytes, were able to form similar complexes with thymic stromal cells, but this property was lost as they differentiated into cortical small lymphocytes. These observations indicate that the stage of intrathymic progression of leukemias is critically linked with the stage of subcapsular zone blasts of normal thymic lymphopoiesis. Mechanism and regulation of the complex formation was analyzed by an in vitro assay. We found that many thymic microenvironment-dependent leukemia cells were reversibly stimulated to proliferate by various tumor-promoters sharing a cellular receptor for phorbol esters. Without support by adequate stromal cells or a tumor promoter, leukemia cells rapidly ceased to grow and died. The degree of growth stimulation was well correlated with their tumor-promoting activity in mouse skin. Action of tumor promoters on microenvironment-dependent leukemias seemed to be direct rather than mediated by lymphokines. Another remarkable effect of tumor promoters was their inhibition of complex formation, presumably by affecting the cytoskeleton.

Animals↗

Tumor promoter-dependent mouse leukemia cell line.

From a spontaneous AKR/Ms thymic leukemia symbiotically cultured with thymic epithelial reticular cells, a tumor promoter-dependent cell line A65T was established by passaging the cells in medium containing 12-O-tetradecanoylphorbol-13-acetate (10 ng/ml). The in vitro growth of A65T was strictly dependent on the presence of active tumor promoters. Their action was reversible, since withdrawal of 12-O-tetradecanoylphorbol-13-acetate resulted in rapid decrease in viability of the cells. Three classes of chemically unrelated compounds sharing tumor-promoting activity in mouse skin could support the in vitro growth of A65T: plant diterpene esters; indole alkaloids; and polyacetates. Their growth effect on A65T cells quantitatively correlated well with the tumor-promoting activity in mouse skin. However, other growth stimulators of epidermal cells such as cholera toxin and epidermal growth factor failed to support the growth of A65T. It is suggested that lymphokines such as interleukin-2 and interleukin-3 were not responsible for 12-O-tetradecanoylphorbol-13-acetate-stimulated growth of A65T because concanavalin A-stimulated spleen cell-conditioned medium containing both interleukin-2 and interleukin-3 activities as well as WEHI-3 cell culture supernatant containing potent interleukin-3 activity did not stimulate the proliferation of A65T cells. Furthermore, 12-O-tetradecanoylphorbol-13-acetate did not induce production of any significant amount of either activity in A65T cells. This cell line is useful for the screening of tumor promoters in environments although, so far, all the compounds capable of stimulating A65T growth have been limited to those competing with phorbol esters for the cellular receptor. Also, the cell line provides a potential model for analyzing growth requirements of developing mouse thymic leukemias.

Acetates↗

Unusually early and high rate of spontaneous occurrence of nonthymic leukemias in SL/Kh mice, a subline of SL strain.

Extremely early and high rate of spontaneous occurrence of nonthymic leukemias was observed in SL/Kh mice, a subline of SL mice. In a cohort of 68 females and 21 males, the cumulative incidence at 6 months of age was 88% in females and 48% in males, and at 12 months it was 100% in females and 94% in males. There were two types of leukemias with distinct in vivo homing behavior: the major type (72/86) proliferated in lymph nodes and the spleen, and the minor type (14/86) proliferated predominantly in the bone marrow cavity. In the minor type, paraplegia due to spinal compression by growing leukemia cells in vertebrae was a characteristic clinical manifestation and this was faithfully reproduced by intravenous injection of the leukemia cells from bone marrow. Both types of leukemias were histologically poorly differentiated lymphoblastic leukemias of null cell type, since none of 8 immunocytological and 4 cytochemical differentiation markers allowed either positive identification of their normal derivation or distinction between them. In contrast to AKR mice with a high incidence of thymic leukemias, spontaneous expression of xenotropic virus was observed not only in the thymus but also in the spleen and bone marrow. In addition to the high level of expression of eco- and xenotropic viruses, viruses with dual-tropic host range were isolated sporadically from preleukemic and leukemic lymphoid tissues. Possible factors determining the type of leukemias in SL/Kh mice are discussed.

Age Factors↗