Search PubMed⌕ Search

Biomedical subjects

H Yagi

Publications and source records attributed to H Yagi.

At least 271 records · Page 15Linked to original sources
PubMed1987

The role of lymphokine-activated cell-associated antigen. III. Inhibition of T-cell activation by monoclonal killer-blocking antibody.

The addition of monoclonal killer blocking antibodies (KBA MAb) to cultured T cells resulted in significant inhibition of T-cell responses to concanavalin A (Con A), class I antigen and class II antigen, whereas T-cell responses to phytohemagglutinin are insensitive to KBA MAb. The inhibitory effect of KBA MAb is observed only when KBA MAb is added to the culture at an early time. This indicates that the lymphokine-activated cell-associated antigen (LAA) defined by KBA MAb plays an important role in the early stages of T-cell activation. Con A-induced interleukin 2 (IL-2) receptor acquisition and IL-2 production, both of which are required for the early steps of T-cell activation, were greatly inhibited by KBA MAb. However, KBA MAb did not inhibit the action of IL-2, which is required for later stages of T-cell activation.

Animals↗
PubMed1987

Role of diaxial versus diequatorial hydroxyl groups in the tumorigenic activity of a benzo[a]pyrene bay-region diol epoxide.

Tumorigenic activities of the (7R,8S,9S,10R)-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydro derivatives of benzo[a]pyrene [(+)-B[a]P diol epoxide-2] and 6-fluorobenzo[a]pyrene (6-FB[a]P diol epoxide-2) were evaluated in newborn CD-1 mice. A total dose of 14 nmol of either diol epoxide was administered to preweanling mice, and tumorigenic activity was determined when the mice were 32 to 36 weeks old. At the termination of the study, 13% of solvent-treated control mice had developed lung tumors with an average of 0.19 tumor per mouse. No other tumors were observed in control animals. (+)-B[a]P diol epoxide-2 induced pulmonary tumors in 60% of the mice with an average of 1.9 tumors per mouse, and 14% of the male mice developed hepatic tumors with an average of 0.18 tumor per mouse. In contrast, 6-FB[a]P diol epoxide-2 had no significant tumorigenic activity at the 14-nmol dose. Although both bay-region diol epoxides have the same absolute configuration, (7R,8S,9S,10R), the hydroxyl groups of (+)-B[a]P diol epoxide-2 prefer the pseudoequatorial conformation whereas the hydroxyl groups of 6-FB[a]P diol epoxide-2 prefer the pseudoaxial conformation. The tumorigenicity results reported here are the first direct demonstration that conformation of the hydroxyl groups in a bay-region diol epoxide, in addition to the documented effect of absolute configuration, is an important determinant in the tumorigenic activity of these ultimate carcinogens.

Animals↗
PubMed1987

Cord blood levels of corticotropin-releasing factor.

The levels of corticotropin-releasing factor (CRF) in the cord blood from 34 infants were determined by radioimmunoassay. All infants were born by vaginal delivery after an uneventful pregnancy. Levels of cortisol, dehydroepiandrosterone sulfate and ACTH were high in the cord blood. CRF levels (mean +/- SD) were 100.5 +/- 31.7 and 44.5 +/- 7.8 pg/ml, respectively, in cord blood and in controls (healthy prepubertal children, n = 10). Although the origin of CRF in peripheral circulation has not been clarified, we speculate that the high adrenocortical steroid synthesis of the fetus might be a consequence of high CRF levels in fetal circulation.

Child↗
PubMed1987

Characteristics of mouse thymocyte-derived, interleukin 2-activated killer cells and their precursors.

Culture of hydrocortisone (HC)-resistant C57BL/6 mouse thymocytes with recombinant human interleukin 2 (IL 2) allowed the proliferation of the thymocytes and resulted in the generation of lymphokine-activated killer (LAK) cells cytotoxic to a variety of tumor cells. The cytotoxic activity of the LAK cells was greatly reduced by treatment with anti-Thy 1.2 or anti-Lyt 2.2 monoclonal antibody and complement but not with anti-asialoGM1 antibody plus complement. Fractionation of IL 2-stimulated thymocytes by means of Percoll density gradient centrifugation revealed that both cytotoxic activity and binding capacity to target cells were greater in the cells with lower density and larger size than in the cells with higher density and smaller size. These IL 2-activated thymocytes expressed higher levels of both Thy 1, Lyt 2 and lymphokine-activated cell-associated (LAA) antigens than unstimulated thymocytes, as indicated by a flow cytometric analysis. The frequency of LAK precursor cells was found to be 7.5 times greater in the HC-resistant thymocyte population than in total thymocytes, as determined by means of a limiting dilution method. The LAK precursor cells in HC-resistant thymocytes appeared to be Lyt1- (or dull Lyt 1+), L3T4-, Lyt 2-, asialoGM1-T cells, because elimination of bright Lyt 1+, Lyt 2+ or L3T4+ T cells from HC-resistant thymocytes had no effect on the generation of LAK cells. These results indicate that LAK cells from mouse thymocytes are Lyt 2+ T cells which are inducible from HC-resistant Lyt 2- thymocytes.

Animals↗
PubMed1987

Serum capacity to solubilize immune complexes (ICSC) in patients with insulin-dependent diabetes mellitus.

Immune complex solubilizing capacity (ICSC) of sera obtained from patients with insulin-dependent diabetes mellitus (IDDM) was assayed by the spectrophotometric method. In 17/32 IDDM sera, ICSC was significantly low. The value of ICSC was only weakly correlated with serum CH50 (r = 0.42). Six sera out of 28 showed a high serum immune complex level and low ICSC. The results with these 6 cases suggest the possibility that circulating antigen-antibody complex might be insoluble in vivo. The precise characterization of these 6 patients' autoantibodies was obtained with immunofluorescence tests. Interestingly, 2 of these sera were positive for islet cell surface antibodies (ICSA) and AtT-20 cell (ACTH secreting cell) surface antibodies.

Antibodies↗
PubMed1987

The precursor cells of mouse lymphokine-activated killer (LAK) cells.

Culture of mouse spleen cells with recombinant human interleukin 2 (r-IL 2) resulted in the generation of lymphokine-activated killer (LAK) cells, which could lyse a variety of tumor cells. Negative selection study using various kinds of antibodies and complement indicated that LAK precursor cells existed in both mature spleen lymphocytes and immature spleen null cells. LAK cells were also induced from lymph node cells but not from unfractionated thymocytes. However, hydrocortison (HC)-resistant thymocytes or PNA- thymocyte subpopulations were highly responsive to r-IL 2 and maturated into LAK cells after 5 day-culture with r-IL 2. Moreover, it was demonstrated that r-IL 2 allowed the induction of LAK cells from nude mouse spleen cells, but not from bone marrow cells and fetal liver cells.

Animals↗
PubMed1987

Significance of squamous cell carcinoma (SCC)-related antigens in cutaneous SCC. A preliminary report.

The serum levels of squamous cell carcinoma (SCC)-related antigens (SCC-RAG) were assayed, utilizing the radioimmunoassay kit, in six patients with cutaneous SCC, two patients with Bowen's disease, 18 patients with other benign and malignant dermatoses, and six normal subjects. The SCC-RAG titers were significantly high in three patients with invasive SCC in whom primary tumors were either comparatively large or were associated with metastatic lesions, while they remained within the normal limit in patients with smaller-sized, nonmetastatic SCC, Bowen's disease, other non-SCC dermatoses, and in normal control subjects. The SCC-RAG titers, therefore, provided a useful tumor marker for cutaneous SCC, particularly in advanced stages. In such cases, the values were clearly correlated with tumor behaviors in response to or against treatments and with the development of metastasis.

Aged↗
PubMed1986

Administration of slowly released recombinant interleukin 2. Augmentation of the efficacy of adoptive immunotherapy with lymphokine-activated killer (LAK) cells.

When recombinant human interleukin 2 (r-IL-2) was given to mice by single subcutaneous (s.c.) injection it rapidly disappeared from the blood. However, administration of slowly released r-IL-2 using mini-osmotic pumps caused a significant prolongation of serum levels of IL-2. Using a method for assaying IL-2 in vivo, it was also demonstrated that both the viability and the cytotoxicity of lymphokine-activated killer (LAK) cells could be maintained at a high level in vivo by administration of slowly released r-IL-2 rather than by a single injection of r-IL-2. In addition, we successfully treated EL4-bearing mice by combination therapy consisting of LAK cells and slowly released r-IL-2.

Animals↗
PubMed1986

Stereoselective metabolism of the (+)-(S,S)- and (-)-(R,R)-enantiomers of trans-3,4-dihydroxy-3,4-dihydrobenzo[c]-phenanthrene by rat and mouse liver microsomes and by a purified and reconstituted cytochrome P-450 system.

Metabolism of (+)-, (-)-, and (+/-)-trans-3,4-dihydroxy-3, 4-dihydrobenzo[c]phenanthrenes by liver microsomes from rats and mice and by a purified monooxygenase system reconstituted with cytochrome P-450c has been examined. Bay-region 3,4-diol 1,2-epoxides are minor metabolites of both enantiomers of the 3,4-dihydrodiol with liver microsomes from 3-methylcholanthrene-treated rats or with the reconstituted system (less than 10% of total metabolites). Microsomes from control and phenobarbital-treated rats and from control mice form higher percentages of these diol epoxides (13-36% of total metabolites). Microsomes from 3-methylcholanthrene-treated rats and cytochrome P-450c in the reconstituted system form exclusively the diol expoxide-1 diastereomer, in which the benzylic hydroxyl group and oxirane oxygen are cis to each other, from the (+)-(3S,4S)-dihydrodiol. The same enzymes selectively form the diol expoxide-2 diastereomer, with its oxirane oxygen and benzylic hydroxyl groups trans to each other, from the (-)-(3R,4R)-dihydrodiol (77% of the total diol epoxides). Liver microsomes from control rats show similar stereoselectivity whereas liver microsomes from phenobarbital-treated rats and from control mice are less stereoselective. Three bis-dihydrodiols and three phenolic dihydrodiols are also formed from the enantiomeric 3,4-dihydrodiols of benzo[c]phenanthrene. A single diastereomer of one of these bis-dihydrodiols with the newly introduced dihydrodiol group at the 7,8-position accounts for 79-88% of the total metabolites of the (-)-(3R,4R)-dihydrodiol formed by liver microsomes from 3-methylcholanthrene-treated rats or by the reconstituted system containing epoxide hydrolase. In contrast, the (+)-(3S,4S)-dihydrodiol is metabolized to two diastereomers of this bis-dihydrodiol, a third bis-dihydrodiol, and two phenolic dihydrodiols.

Animals↗
PubMed1986

Reactivity and tumorigenicity of bay-region diol epoxides derived from polycyclic aromatic hydrocarbons.

During the past decade substantial progress has been made in elucidating factors that determine the tumorigenic activity of bay-region diol epoxides, major ultimate carcinogenic metabolites derived from polycyclic aromatic hydrocarbons. Neither high nor low chemical reactivity of the diol epoxides (as measured by rates of uncatalyzed solvolysis) is required for high tumorigenic response. In contrast, aspects of molecular structure such as conformation and absolute configuration strongly influence tumorigenic activity. The role of conformation is illustrated by the observation that those diol epoxides whose hydroxyl groups are pseudoaxial are weak or inactive as tumorigens. Absolute configuration is an important determinant of biological activity of bay-region diol epoxides: in all cases studied to date, the predominantly formed (R,S)-diol-(S,R)-epoxides are generally the most tumorigenic of the four metabolically possible configurational isomers. In the course of investigating the effects of structural factors on tumorigenic activity, we identified the (4R,3S)-diol-(2S,1R)-epoxide of benzo(c)phenanthrene as the most potent tumorigen (in initiation-promotion experiments on mouse skin) of the diol epoxides studied to date. Studies of all four configurationally isomeric diol epoxides derived from benzo(c)phenanthrene led to the striking observation that these diol epoxides exhibit an exceptionally high efficiency of covalent binding, relative to hydrolysis, when allowed to react with calf thymus DNA in aqueous solution. Thus, these diol epoxides should provide an excellent tool for the detailed study of such binding. When the four isomeric benzo(c)phenanthrene diol epoxides are compared, there appears to be no simple correlation between tumorigenic response and either the extent of binding to DNA or the major types of deoxyribonucleoside adducts formed. Deoxyribonucleoside adducts of benzo(c)phenanthrene diol epoxide have also been identified from the DNA of cultured rodent embryo cells after treatment of the cells with tritium-labeled benzo(c)phenanthrene. The distribution of adducts is consistent with predominant metabolic formation of the (4R,3S)-diol-(2S,1R)-epoxide; deoxyadenosine is the major site in the cellular DNA attacked by this epoxide, just as it is in DNA in solution. Further experiments are in progress which we hope will identify more subtle aspects of the DNA binding of benzo(c)phenanthrene diol epoxides that may be uniquely correlated with their tumorigenic activity.

Animals↗
PubMed1986

Augmentation of the therapeutic efficacy of adoptive tumor immunotherapy by in vivo administration of slowly released recombinant interleukin 2.

Immunization of C57BL/6 mice with MMC-treated syngeneic lymphoma cells, MBL-2, caused the generation of antitumor effector cells in vivo and the immunized mice permanently rejected viable MBL-2 lymphoma cells. Both plastic nonadherent T cells and plastic adherent M phi obtained from MBL-2 immunized mouse peritoneal exudate cells revealed strong cytotoxic activity against MBL-2 lymphoma cells, whereas immune spleen cells were not highly active against MBL-2 lymphoma cells in vitro. However, systemic adoptive transfer of immune spleen cells into the MBL-2-bearing mice by i.v. infusion in conjunction with i.p. cyclophosphamide (100 mg/kg) treatment cured the mice of tumor. This therapeutic efficacy of immune spleen cells was reflected by the number of transferred effector cells and over 5 X 10(7) immune spleen cells were required to cure the mice completely. The cells mediating in vivo rejection of MBL-2 lymphoma cells were Thy 1.2+ T cells. This ACIT was specific against MBL-2 lymphoma cells and had no effect on the growth of other syngeneic tumors, B16 melanoma or BMC6A fibrosarcoma. In vivo administration of recombinant interleukin 2 (r-IL2) combined with ACIT greatly modulated the cure rate of tumor-bearing mice. In addition, we found that slowly released r-IL 2 administratered from an ALZET miniosmotic pump was more effective in augmenting the therapeutic efficacy of immune spleen cells in ACIT than a single injection of the same total dose of r-IL 2.

Animals↗
PubMed1986

Generation of lymphokine-activated killer (LAK) cells from tumor-infiltrating lymphocytes.

Culture of tumor-infiltrating lymphocytes (TIL) containing about 20% BMC2 tumor cells with recombinant human interleukin 2 (rIL-2) resulted in the diminish of tumor cells and the growth of lymphocytes. These IL-2-activated lymphocytes showed a strong cytotoxic activity against not only syngeneic tumor cells but also allogeneic tumor cells. Such broad-reactive killer cells, termed lymphokine-activated killer (LAK) cells, are also inducible from spleen cells by in vitro activation with IL-2. However, LAK cells generated from TIL (TIL-LAK) showed higher cytotoxic activity against BMC2 than LAK cells generated from spleen cells (S-LAK). Furthermore, it was demonstrated that TIL-LAK cells revealed marginal cytotoxic activity against normal Con A blasts and YAC-1 cells as opposed to S-LAK. Flow cytometric analysis of TIL-LAK indicated that TIL-LAK cells mainly consisted of Thy 1.2+, Ly 2+, asialo GM1+ cells. TIL-LAK cells displayed not only in vitro cytotoxicity but also in vivo anti-tumor activity. Furthermore, it was also confirmed that TIL-LAK cells could be induced in autochthonous mouse tumor systems and human gastric tumor systems.

Animals↗
PubMed1986

Recombinant interleukin 2 allows the differentiation of Thy 1.2+ LAK cells from nude mouse spleen cells.

Culture of nude mouse spleen cells with recombinant human interleukin 2 (r-IL 2) resulted in the proliferation and generation of lymphokine-activated killer (LAK) cells which could lyse a variety of tumor cells. Flow cytometry study indicated that nude mouse spleen cells contained almost no Thy 1.2+ cells at the initial times of the culture, whereas LAK cells obtained from nude mouse spleen cells by culture with r-IL 2 (nude-LAK cells) expressed high intensity of Thy 1.2 antigen and lymphokine-activated cell-associated (LAA) antigen. The cytotoxic activity of nude-LAK cells was greatly reduced by treatment with anti-Thy 1.2 antibody plus complement but not with anti-Ly 1.2 or Ly 2.2 antibody plus complement treatment. Moreover, nude-LAK cells were resistant to the treatment with anti-asialo GM1 antibody plus complement, in contrast to resident nude natural killer (NK) cells. These data strongly suggested that r-IL 2 allowed the nude mouse spleen cells to differentiate into Thy 1.2+, Ly 1-,2-, asialo GM1- LAK cells which were distinct from Thy 1.2+, Ly 2+, asialo GM1- LAK cells induced from normal mouse spleen cells.

Animals↗
PubMed1986

Adaptive regulation of beta-adrenergic receptors in children with insulin dependent diabetes mellitus.

The beta-adrenergic receptors were investigated in partially purified mononucleal leukocytes (MNL) plasma membranes from 18 patients with IDDM in pediatric period, 9 healthy children and 8 normal adults. The decreased beta-adrenergic receptor number was seen in patients with IDDM (Bmax = 27.6 +/- 8.3 fM (125I) IHYP/mg protein) compared with normal children (Bmax = 40.4 +/- 10.4 fM (125I) IHYP/mg protein) and normal adults (Bmax = 36.9 +/- 6 fM (125I) IHYP/mg protein). MNL beta-receptor binding affinities (apparent Kd = 109.8 +/- 26.1 pM in IDDM, 102.8 +/- 46.6 pM in normal children, 130.0 +/- 43.1 pM in normal adults) did not differ. We divided the patients with IDDM into two groups based on their level of blood glycosylated hemoglobin (HbA1) when samples were taken. Group A IDDM (consisted of 9 diabetic patients with below 10% of HbA1) had markedly decreased beta-receptor numbers compared with group B IDDM (consisted of 9 diabetic patients with more than 10% of HbA1), whereas Kd was not significantly different. Also, there was negative correlation between Bmax and level of blood sugar or HbA1 in IDDM. This is the first report concerning the beta-adrenergic receptor in IDDM in pediatric period. We suggest that decreased Bmax in group B is a homeostatic response to restore the poorly-controlled hyperglycemic state to normoglycemia because the group B patients had high level of HbA1 and blood sugar.

Adolescent↗