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Biomedical subjects

M Nonaka

Publications and source records attributed to M Nonaka.

At least 271 records · Page 15Linked to original sources
PubMed1982

Two loci in I-J subregion of the H-2 complex controlling molecules selectively expressed on suppressor and helper T cells.

Different batches of alloantiserum directed at the I-J subregion products of the H-2 major histocompatibility complex (anti-I-J) induced either suppression or augmentation of the in vitro secondary antibody response when added in a minute quantity to the culture of primed spleen cells. The suppressive or augmenting effect of the individual antiserum was found to be determined by its predominant specificity for either one of the two different molecules, both encoded in the I-J subregion, that were selectively expressed on functionally different subsets of T cells, i.e., suppressor (Ts) and helper (Th2) T cells. This was determined by the differential absorption of antiserum with Lyt-1+ and Lyt-2+ T cells as well as with suppressor hybridomas that express an I-Jk product. It was found that the absorption of an anti-I-J antiserum with Lyt-1+ T cells resulted in the loss of activity to eliminate a set of helper T cells (Th2) while leaving the ability to affect antigen-specific suppressor T cells (Ts). The absorption of the same antiserum with either Lyt-2+ T cells or suppressor hybridomas eliminated the activity to kill Ts but not Th2. Thus, the results indicate that the I-J subregion accommodates two or more loci that code for discrete molecules expressed on functionally different subsets of T cells. Because the simple addition of a minute quantity of antisera to the culture resulted in the modulation of antibody response presumably by affecting these two sets of T cells, it is suggested that I-J subregion products act as functional molecules in regulatory cell interactions.

Animals↗
PubMed1981

Stimulation of primary in vitro IgE antibody responses in culture of human peripheral mononuclear cells.

Experiments are presented herein that demonstrate the capacity to stimulate human peripheral mononuclear cells to synthesize and secrete significant quantities of IgE molecules in vitro by exposure to appropriate concentrations of 2,4-dinitrophenyl (DNP)-protein conjugates, pokeweed mitogen (PWM), or a combination of DNP-proteins and PWM. Cultures stimulated in this fashion synthesize increased quantities of both total IgE and DNP-specific IgE antibody molecules. This in vitro human IgE antibody system should provide a useful tool for further exploration of regulatory control of IgE responses in both normal humans and those manifesting various forms of IgE-mediated allergic disorders.

Antibody Specificity↗
PubMed1981

The complement system in rainbow trout (Salmo gairdneri). II. Purification and characterization of the fifth component (C5).

The fifth component of rainbow trout complement was purified to homogeneity using a 4-step purification procedure: 1) 5 to 15% polyethylene glycol precipitation; 2) DEAE-Sepharose column chromatography; 3) gel filtration on Sephadex G-200; and 4) CM-Sepharose column chromatography. A 175-fold purification was attained with 20 to 30% yield of C5 antigen and hemolytic activity. The rainbow trout C5 thus purified was homogeneous as judged by SDS-polyacrylamide gel electrophoresis and immunoelectrophoresis. Rainbow trout C5 was composed of 2 polypeptide chains with m.w. of 133,000 daltons and 86,000 daltons linked by disulfide bonds. The highly purified C5 retained its functional activity. It fully reconstituted the hemolytic titer to C5-depleted rainbow trout serum. Upon activation, this protein was incorporated into a macromolecular complex that closely resembles a membrane attack complex (MAC) of human and guinea pig complement. On the basis of physico-chemical and functional characteristics, we identified this protein as the rainbow trout counterpart of mammalian C5. The identification of C5 in rainbow trout serum strengthened our previous conclusion that the complement system is in a highly developed state already at the phylogenetic level of teleost fish.

Animals↗
PubMed1981

Human IgE antibody synthesis in vitro: stimulation of IgE responses by pokeweed mitogen and selective inhibition of such responses by human suppressive factor of allergy (SFA).

The studies presented herein provide details of an in vitro system in which IgE biosynthesis by human peripheral mononuclear cells can be stimulated by exposure to pokeweed mitogen (PWM). Mononuclear cells of normal donors or patients with hyperimmunoglobulinemia E were cultured in 2 stages, the first stage consisting of exposure of cells to stimulating mitogen; after this first stage incubation, cells were washed and replated in cultures devoid of any additional mitogen for a further 6 days. Under such conditions, human mononuclear cells were shown to synthesize significant quantities of IgE. Both T cells and surface IgE-bearing cells were shown to be necessary in order to obtain an IgE response in this system. Supernatants from 2-way human mixed lymphocyte cultures were shown to contain an IgE class-specific suppressive factor capable of selectively inhibiting in vitro IgE (and not IgG) biosynthesis. This model can be used to compare the regulation of IgE synthesis in normal and atopic donors, and further experiments examining the production and action of this class-specific suppressive factor may have prognostic and therapeutic implications.

Animals↗
PubMed1980

Structural polymorphism of murine C4 and its linkage to H-2.

Heretofore unrecognized structural polymorphism of murine C4(Ss) was demonstrated by using two different techniques: immunofixation electrophoresis and immunofixation isoelectric focusing. By these methods C4 was demonstrated as a broad protein band in freshly bled EDTA-plasma of inbred strains and wild mouse lines. Seven variants of C4(Ss) were identified among a large number of mice tested:C4-v (pI 7.7) exemplified by strain SM/J, C4-B(pI 7.5) exemplified by B10, C4-k (pI 7.3) exemplified by C3H/He, C4-bactrianus (pI 7.2) exemplified by Mus m.bacterianus, C4-d.s(pI 7.0) exemplified by DBA/2 and SJL/J, C4-castaneus (pI 6.6) exemplified by Mus m.castaneus, and C4-NC(pI 6.3) exemplified by NC. F1 hybrid exhibited two C4 bands, each of which corresponds to C4 of a parent. The possibility that the observed polymorphism represents variation of Slp was ruled out because an identical C4 pattern was always observed between male and female mice. The observed structural variation of murine C4 is controlled by a single codominant locus localized within or in the proximity of the S subregion of H-2. This was shown by phenotyping several intra-H-2 recombinant strains and backcross progeny, (B10 X NC)F1 X B10 and (B10 X NC)F1 X NC. An alloantiserum specific for one of the C4 variants (C4-NC) was successfully produced in C3H/He mice by repeated injection of purified C4 of NC mouse. This finding suggests that observed C4 variants or at least some of them represent antigenically distinguishable allotypes of murine C4.

Animals↗
PubMed1979

Suppression of hapten-specific delayed-type hypersensitivity responses in mice by idiotype-specific suppressor T cells after administration of anti-idiotypic antibodies.

Delayed-type hypersensitivity (DTH) responses specific for the phosphorylcholine (PC) hapten were induced in BALB/c mice by immunization with syngeneic peritoneal exudate cells (PEC) coupled with diazotized phenyl-phosphoryl-choline. PC-specific DTH responses were elicited in such immunized mice after footpad challenge with PC-derivatized syngeneic spleen cells. Moreover, PC-immune lymph node cells could passively transfer PC-specific DTH responses to naive BALB/c mice and it was possible to demonstrate that the cells responsible for such passively transferred responses were T lymphocytes. Because the T-15 idiotypic determinant displayed on the TEPC-15 PC-binding myeloma protein is known to be a dominant idiotype associated with anti-PC antibody responses in BALB/c mice, an analysis was made of the effects of anti-T-15 idiotypic antibodies on the induction and expression of murine PC-specific DTH responses. Repeated injections of anti-T-15 idiotypic antiserum, raised in A/J mice by immunization with TEPC-15 myeloma protein, into recipient BALB/c mice both immediately before and after sensitization with PC-PEC virtually abolished the development of PC-specific DTH responses. Although administration of anti-T-15 antiserum effectively inhibited the induction phase of PC-specific DTH responses, these anti-idiotypic antibodies had no suppressive activity at the effector phase of these responses. The inhibition observed with anti-T-15 antibodies was highly specific for the PC hapten, and for PC-specific DTH responses of BALB/c but not A/J mice. Studies were conducted to address the possibility that anti-Id treatment induced suppressor T lymphocytes capable of specifically inhibiting the activity of PC-specific T cells participating in DTH responses. The results demonstrate that idiotype-specific suppressor T cells are, indeed, induced by treatment with anti-Id; moreover, such suppressor T cells, once induced, are highly effective in abrogating both the induction and the effector phases of PC-specific T cell-mediated DTH responses in BALB/c mice.

Animals↗
PubMed1978

Two distinct types of helper T cells involved in the secondary antibody response: independent and synergistic effects of Ia- and Ia+ helper T cells.

We have described here two distinct types of carrier-specific helper T cells which act independently and synergistically to augment the B-cell response to a hapten. They are separable by passage through a nylon wool column. The first type of helper T cell, which we designate as Th1, is nylon nonadherent, and can help the response of hapten-primed B cells only if the haptenic and carrier determinants are present on a single molecule (cognate interaction). The second type of helper T cell, Th2, adheres to the nylon wool column, and can help the B-cell response to a hapten coupled to a heterologous carrier upon stimulation with unconjugated relevant carrier (polyclonal interaction). The addition of a small number of Th2 to the mixture of Th1 and B cells significantly augmented the net response to the hapten carrier conjugate. Both Th1 and Th2 cells belong to the Lyt-1+,2-,3- subclass. Th1 has no detectable Ia antigen, whereas Th2 is killed by certain anti-Ia antisera and complement. The Ia antigen detected on Th2 was found to be controlled by a locus in the I-J subregion. The results clearly established the fact that there are two distinct pathways in the T- and B-cell collaboration, which involves two different subsets of carrier-specific helper T cells.

Animals↗
PubMed1978

Cystic fibrosis of the pancreas in a human fetus.

Postmortem examination of a 26 week old (postmenstrual) human fetus delivered by Cesarean section revealed meconium ileus and many swollen mucus-secreting cells in the gastro-intestinal mucosa. The pancreas showed extensive fibrosis, acinar destruction and dilatation of ducts containing eosinophilic casts. Mucous glands of the lungs also revealed mucous cells swollen and distended with their secretory products. The patient is believed to have cystic fibrosis of the pancreas, suggesting that the pathologic manifestations of the disease may begin early in fetal life.

Cystic Fibrosis↗