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Biomedical subjects

K Kakimoto

Publications and source records attributed to K Kakimoto.

At least 55 records · Page 3Linked to original sources
PubMed1993

The suppressive effect of gelatin-conjugated superoxide dismutase on disease development and severity of collagen-induced arthritis in mice.

We studied the effect of superoxide dismutase (SOD) on murine collagen-induced arthritis (CIA), an animal model of human rheumatoid arthritis (RA). Among SOD derivatives studied, only gelatin-SOD conjugate which has prolonged half life in vivo was effective to suppress the development of CIA, while native SOD or gelatin carrier alone was ineffective. Interestingly, pyran polymer-conjugated SOD which also has a long half life showed no suppressive effect on the disease. No significant effect on immune response against type II collagen (CII) was found in any of the experimental groups. In addition, induction of suppressor cells was not detected in spleen or lymph node cells of the gelatin-SOD-treated group. Therefore, these results suggest that oxygen radicals may have an important role in the effector phase of the immune response to manifest this chronic autoimmune polyarthritis. Thus, the use of appropriate antioxidants for the treatment of human RA may be rationalized.

Animals↗
PubMed1992

Expression of a transgenic T cell receptor beta chain enhances collagen-induced arthritis.

SWR/J transgenic (tg) mice were generated expressing the TCR beta chain derived from an anticollagen type II (CII) arthritogenic T cell clone. The SWR/J strain was selected because it is resistant to collagen-induced arthritis (CIA) and lacks the V beta gene segment used by the T cell clone. Expression of the tg beta chain on all thymocytes and peripheral lymph node T cells led to a more efficient anti-CII immune response, but did not confer CIA susceptibility to SWR/J mice. Nevertheless, this tg beta chain enhanced predisposition to CIA as (DBA/1 x SWR) F1 beta tg mice were more susceptible than normal F1 littermates. Our results demonstrate that the expression of the tg beta chain contributes to CIA susceptibility, but by itself it is not sufficient to overcome CIA resistance in the SWR/J strain.

Animals↗
PubMed1992

The effect of anti-adhesion molecule antibody on the development of collagen-induced arthritis.

In order to study how inflammatory cells including autoimmune lymphocytes interact with each other to develop collagen-induced arthritis (CIA), we injected monoclonal antibodies against mouse LFA-1 and ICAM-1 into DBA/1 mice immunized with type II collagen (CII). Both antibodies suppressed the development of CIA. These antibodies showed no effect on anti-CII antibody response, although they both significantly suppressed DTH response. It was suggested that anti-adhesion molecule antibodies suppress CIA mainly through their effect on cell-mediated immunity, without affecting humoral immunity under the conditions used.

Animals↗
PubMed1992

Accessory function of human glioma cells for the induction of CD3-mediated T cell proliferation: a potential role of glial cells in T cell activation in the central nervous system.

Accessory function of human glial cells for the induction of anti-CD3 antibody-mediated proliferation of T cells was investigated by using seven glioma cell lines. Three of them were found to function as accessory cells and one of them, U118, was used for further analysis. U118 cells showed the cell-contact-mediated accessory function for T cell proliferation. It was found that protein synthesis was required to reveal this function, suggesting that some surface molecules are synthesized and expressed on U118 cells during interaction with T cells to mediate effective signals in T cells. Intercellular adhesion molecule-1 seemed to be one of such inducible molecules and was shown to contribute to effective accessory cell-T cell interaction, but necessity of other molecule(s) was also suggested.

Antigen-Presenting Cells↗
PubMed1992

[Mutagenicity studies of prednisolone farnesylate (PNF)].

Prednisolone farnesylate (PNF) was tested for mutagenicity by Ames test using Salmonella typhimurium (TA100, TA1535, TA98, TA1537) and Escherichia coli (WP2 uvrA), for clastogenic activity in vitro by the chromosomal aberration test in a Chinese hamster fibroblast cell line (CHL), and for induction of micronuclei by the micronucleus test in male ICR mice. 1) In Ames test, PNF with and without metabolic activation showed no mutagenicity in any strains at any dose levels (312-5,000 micrograms/plate). 2) In the chromosomal aberration test, PNF with metabolic activation produced a slight increase in the incidence of structural chromosomal aberrations in CHL cells at 1,500 micrograms/ml. 3) In the micronucleus test, a single administration of PNF caused no significant increase of micronucleated polychromatic erythrocytes at any doses (250-2,000 mg/kg).

Animals↗
PubMed1992

[The significance of determination of human herpesvirus-6 (HHV-6) antibody during pregnancy].

HHV-6 which was detected in peripheral blood lymphocytes of lymphocytic patients is now said to be an agent causing exanthema subitum. We investigated the titer of HHV-6 antibody in 100 primigravida and 30 patients with spontaneous abortion by means of the indirect immunofluorescence method (IF method). The positive incidence in which the titer of HHV-6 antibody was more than 10 times in 100 primigravida was 82%. That of HHV-6 IgM antibody was 3% in those who had no complication during pregnancy. This supposes that there may be some women who were infected or were reactivated while they were pregnant. The positive incidence in 30 spontaneous abortion patients was 90%. 3 of them had IgM antibody to HHV-6, and HHV-6 antigen was detected on the epitherium of the chorionic villi by the IF method with HHV-6 monoclonal antibody in two of them. This suggests that the infection or reactivation of HHV-6 may be one of the causes of spontaneous abortions.

Abortion, Spontaneous↗
PubMed1992

Development of the cell contact-mediated accessory function for T-cell proliferation in a human promyelocytic leukaemia cell line, HL-60, by 1,25-dihydroxyvitamin D3.

A human promyelocytic leukaemia cell line, HL-60 cells, did not show accessory cell (AC) function to potentiate the proliferation of human T cells induced by anti-CD3 antibody coupled to latex beads (alpha T3-L). This was found to be at least due to the inability of HL-60 cells to express certain molecules which are inducible with interferon-gamma (IFN-gamma) on mature monocytes and are necessary for interaction with T cells. HL-60 cells acquired the ability to express such surface molecules by stimulation with IFN-gamma when the cells were pretreated with 1,25-dihydroxyvitamin D3 (Vit D). The effect of Vit D was reversible, that is, the AC function of the HL-60 cells was lost when the cells were cultured in Vit D-free medium for 7 days. It was also found that HL-60 cells treated with IFN-gamma and then with Vit D did not show significant AC function. The flow cytometric analysis showed that the expression of HLA-DR and intercellular adhesion molecule-1 (ICAM-1) was highly increased on HL-60 cells when stimulated with IFN-gamma after treatment with Vit D. The expression of ICAM-1 was also induced with IFN-gamma on untreated cells but in lower amounts. Monoclonal antibodies against ICAM-1 and HLA-DR inhibited the alpha T3-L-induced T-cell proliferation, indicating that these molecules are at least required for contact-mediated AC function. Thus our study revealed that HL-60 cells express cell surface interaction molecules necessary for potentiating the T-cell proliferation through two steps, differentiation with Vit D to mature monocyte-like cells followed by stimulation with IFN-gamma.

Antigen-Presenting Cells↗
PubMed1991

Collagen-induced arthritis--characteristics of the animal model and implications for the treatment of autoimmune disease.

Collagen-induced arthritis (CIA) is a chronic polyarthritis induced in mice and rats by immunization with homologous or heterologous type II collagen (CII). In this study, we report on a variety of experiments designed to elucidate the characteristics of CIA and its potential application in the treatment of human disease. The notable results were as follows: Both mouse anti-human-CII monoclonal antibody and a mouse T cell clone reactive to human CII were able to provoke arthritis when i.v. injected into naive mice. When injected together, a synergistic enhancement of the incidence and severity of passive arthritis was seen. However, inoculation with irradiated T cells reactive to human CII could suppress the development of active CIA. Given these results and the fact that CIA closely resembles rheumatoid arthritis both clinically and histologically, we suggest that the CIA animal model provides a good tool for studying the potential of T cell vaccination as a means of treating or preventing human autoimmune diseases.

Animals↗
PubMed1990

Induction of cutaneous mast cell tumors by N-methyl-N'-nitro-N-nitrosoguanidine followed by TPA in female mice of 4 out of 5 strains tested.

Appreciable yields of cutaneous mast cell tumors were induced in a two-stage skin carcinogenesis protocol comprising N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) initiation followed by 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion in 4 of 5 strains of mice. Only female mice of each of the 5 strains were studied. The incidences of benign and/or malignant lesions differed considerably between strains; 27% in DBA/2, 22% in BDF1, 11% in BALB/c, 10% in CDF1 and 0% in C57BL/6 mice and no mast cell tumors were detected in any of the strains when treated with the initiator alone. First found in a DBA/2 mouse at week 50, most tumors were observed after 100 weeks of promotion, and were usually small in size (less than 2 mm in diameter) and predominantly located within the corium, although they occasionally extended into the subcutaneous tissue. Histologically, the benign mast cell tumors were composed of non-encapsulated, well circumscribed densely packed sheets of discrete cuboidal or rhomboid cells. Metachromatic granules were clearly visible in the cytoplasm by Toluidine Blue staining. Two of the tumors induced in DBA/2 mice were diagnosed as malignant mast cell tumors on the twin bases of cellular atypia and deep infiltration into the muscular layer. The cutaneous mast cell tumors were constantly accompanied by subepidermal mast cell aggregations which were also commonly observed in tumor-free skin of mice receiving the initiation-promotion procedure.

Animals↗
PubMed1990

Different types of antigen-presenting cells affect the induction of experimental autoimmune arthritis.

We obtained a type II collagen-specific murine T cell line containing at least two T cell clones, one reacting with only native collagen II and the other with both denatured and native molecules. Only the former could induce arthritis. The arthritogenic T cell clone(s) was preferentially stimulated to grow when epidermal cells were used as antigen-presenting cells. Conversely, the non-arthritogenic T cell clone(s) was mainly stimulated when spleen cells were used. Thus, it is speculated that different types of antigen-presenting cells preferentially present different epitopes on the same antigen, affecting the resulting in vivo immune phenomena.

Animals↗
PubMed1990

Identification of HTLV-I sequence in cord blood mononuclear cells of neonates born to HTLV-I antigen/antibody-positive mothers by polymerase chain reaction.

We developed a polymerase chain reaction (PCR) method which has high sensitivity and simple technique in order to investigate the presence or absence of human T lymphotropic virus type I (HTLV-I) provirus in cord blood mononuclear cells of neonates born to HTLV-I carrier mothers. Out of 40, three subjects were found to contain the HTLV-I provirus genome. These three subjects remained HTLV-I sequence-positive in follow-up study. On the other hand, when examined by a conventional technique for detection of HTLV-I-associated antigen on peripheral mononuclear cells, all 40 neonates were HTLV-I-associated antigen-negative. These results suggest that PCR is more sensitive than the conventional antigen detection method and is useful in early detection of HTLV-I infection in neonates born to HTLV-I carriers.

Base Sequence↗
PubMed1990

p24 protein of a human T-lymphotropic virus type-I (HTLV-I) producing cell line (TCL-Kan) reacts with some normal pregnant women's sera.

Some HTLV-1 antibody carrying pregnant women, who are rated by the gelatin particle agglutination (PA) method, show no expression of HTLV-I antigen in their peripheral blood lymphocytes. Paying attention to this fact, the authors recently studied the reaction of the antibody contained in the PA-positive sera with the antigen protein used for the PA method. This study demonstrated that the protein responsible for non-specific reaction has a molecular weight of 24,000 and that the isoelectric point of this protein differs from that of HTLV-I specific protein.

Agglutination Tests↗
PubMed1990

[Detection of HTLV-I genome in infants born to HTLV-I seropositive mothers by polymerase chain reaction].

We developed a new method to detect human T cell leukemia virus type I (HTLV-I) provirus by amplifying the pX region of the HTLV-I genome by means of the polymerase chain reaction (PCR) method. This new method was used to examine babies delivered by HTLV-I carrier women for HTLV-I vertical transmission. It was found that intra-uterine infection with HTLV-I can occur, though rarely, and some babies carry HTLV-I provirus despite their negative response to HTLV-I antibody, and, noticeably, some of the babies found negative by the conventional antigen detection method may be positive when tested by the PCR method. It was also confirmed with the PCR method that the incidence of vertical transmission of HTLV-I can be reduced to about 1/5 by replacing breast feeding with bottle feeding and frozen mother's milk feeding. It was also found that vertical transmission of HTLV-I can occur at high incidence rates even when the duration of breast feeding is 3 months or less.

Breast Feeding↗
PubMed1989

Requirement for delivery of signals by physical interaction and soluble factors from accessory cells in the induction of receptor-mediated T cell proliferation. Effectiveness of IFN-gamma modulation of accessory cells for physical interaction with T cells.

We analyzed the mechanism by which accessory cells support the induction of the proliferation of human peripheral blood T cells by a monoclonal anti-CD3 antibody, OKT3. Cross-linking of T cell receptor/CD3 complex by anti-CD3 coupled to latex beads and the addition of IL-1 are not enough to induce the IL-2 production and proliferation of T cells extensively depleted of accessory cells, while the addition of both the culture supernatant of macrophages or a monoblastic cell line, U937 cells, and the paraformaldehyde-fixed macrophages or U937 cells which had been precultured with interferon-gamma before fixation into the culture of the T cells with anti-CD3-latex did induce the T cell proliferation. Lack of the addition of either one of these did not induce the response. These results indicate that the signal(s) delivered by soluble factors released from the accessory cells and that delivered by the physical interaction between accessory cells and T cells are both required for the induction of IL 2 production and proliferation of T cells by anti-CD3-latex. Importantly, the macrophages or U937 cells had to be cultured with Con A-stimulated lymphocyte culture supernatant or IFN-gamma prior to fixation with paraformaldehyde, suggesting that a molecule(s) inducible on accessory cells surface by IFN-gamma or other lymphokine is necessary for the effective accessory cell-T cell interaction to induce the T cell response. It was further revealed that the activity of the culture supernatant of accessory cells may be mediated synergistically by IL 1 and a certain other factor(s) and was actually shown to be replaced by the combined addition of rIL-1 and rIL-6 but not by rIL-1 alone. The experimental system described here will be very useful for dissecting the accessory functions for T cell activation.

Adjuvants, Immunologic↗
PubMed1989

T cell line specific for bacterial peptidoglycan subunit: possible role of the COOH-terminal amino acid of the disaccharide tetrapeptide in binding to the T cell receptor.

The T cell line specific for a bacterial cell wall peptidoglycan subunit, disaccharide tetrapeptide of diaminopimelic acid type, was examined for epitope specificity in elicitation of delayed-type hypersensitivity (DTH) in X-irradiated Lewis rats, using pairs of analogs different in optical configuration of the COOH-terminal amino acid. The test cell line induced DTH against analogs with the COOH-terminal D-amino acid but not against those with the L-amino acid at the COOH terminus. A close correlation was found between the T cell line-induced DTH reaction in vivo and the proliferative response in vitro, in terms of clear discrimination of the optical configuration of COOH-terminal amino acid of disaccharide tetrapeptide. The L-isomers (non-stimulatory analogs of T cell proliferation) competitively inhibited the proliferation of the T cell line by the corresponding D-isomers. Thus the L-isomers appear to interact with Ia molecules on antigen-presenting cells. We conclude that COOH-terminal D-amino acid of the disaccharide tetrapeptide could be involved in binding to the T cell receptor, induction of T cell proliferation, and elicitation of DTH.

Amino Acids↗
PubMed1989

Bottle-feeding can prevent transmission of HTLV-I from mothers to their babies.

Breast-feeding is a major factor in the vertical transmission of human T-lymphotropic virus type I (HTLV-I). We studied whether such transmission may be prevented by bottle-feeding. HTLV-I infection was detected by both HTLV-I antigen and antibody tests. Thirty bottle-fed babies were examined 24 months after birth; only one was found to be HTLV-I antigen-positive. This infection rate was lower than that for breast-fed babies in whom HTLV-I antigen was detected in 24 of the 31 24-month-old babies born to HTLV-I positive mothers in a previous study. These results suggest that most vertical transmission of HTLV-I is attributable to breast-feeding and can be prevented by bottle-feeding.

Bottle Feeding↗
PubMed1989

Detection of HTLV-I genome in seronegative infants born to HTLV-I seropositive mothers by polymerase chain reaction.

We applied the polymerase chain reaction (PCR) method to detect gag, env and pX sequences of human T cell leukemia virus type I (HTLV-I) provirus in peripheral blood lymphocytes of seronegative infants born to HTLV-I seropositive mothers. Out of 22, five subjects were found to contain the HTLV-I provirus genome. Two of the five cases were judged to be negative for not only anti-HTLV-I antibodies but also the viral antigens on cultivated lymphocytes by the conventional antibody/antigen detection methods. These results indicate that PCR is of great use as a simple and highly sensitive method detect HTLV-I infection.

Adult↗