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Biomedical subjects

J Yagi

Publications and source records attributed to J Yagi.

At least 55 records · Page 3Linked to original sources
PubMed1989

Prevention of diabetes in NOD mice by injection of autoreactive T-lymphocytes.

The nonobese diabetic (NOD) mouse develops a high incidence of autoimmune diabetes and is believed to be a good model for insulin-dependent diabetes mellitus (IDDM) in humans. We isolated T-lymphocyte lines from islets of newly diabetic NOD mice, some of which are autoreactive to NOD spleen cells. Because autoreactive T-lymphocytes have been implicated in immune suppression, we injected NOD mice with an autoreactive T-lymphocyte line. The injected mice had a marked decrease in incidence of IDDM compared with control mice. Moreover, their islets showed no insulitis at 1 yr of age. We conclude that autoreactive T-lymphocytes can prevent the development of IDDM in NOD mice. This result suggests that 1) islets contain both effector cells capable of damaging pancreatic beta-cells and cells able to regulate this autoimmune response, and 2) development of IDDM depends on the balance between these opposing forces.

Animals↗
PubMed1988

Morphology of the alimentary tract of Trichinella spiralis muscle larvae with emphasis on the esophagus.

This study was designed to provide a comprehensive description of the ultrastructure of the esophagus of Trichinella spiralis muscle larvae. Although the esophagus exhibited basically the same structure throughout its entire length, being composed of a single cell-layered epithelium, the basal lamina, and the cuticle, some morphological diversity was observed, depending on the level of sectioning. The upper esophagus, devoid of a muscular sheath, was equipped with myofilamentous cytoplasm and a thick cuticle. The middle and lower esophagus was surrounded by the muscular sheath on the basal side and thin cuticle on the luminal side. The cytoplasm usually contained glycogen, ribosomes, and mitochondria. The presence of an amorphous substance in the lumen of the esophagus is reported for the first time. It was completely homogeneous or finely granular and always devoid of any substructure.

Animals↗
PubMed1988

Localization of fibronectin and actin in cultured rabbit keratocytes.

Migration of activated keratocytes toward the corneal stromal wound is one of the most important processes of successful healing. To understand the motility of keratocytes and the interaction of fibronectin and intracellular actin filaments, we cultured rabbit corneal keratocytes and studied dynamic movements of the cells by time-lapse cinematography. We also examined the changes in the localization of fibronectin and actin using double staining immunofluorescent microscopy. The cultured keratocytes first attached to the substratum in round globular shape and then spread with many extending processes. In the early stage of the cultivation, fibronectin was observed inside the cells. Later, fibronectin was observed outside the cells, suggesting formation of the extracellular matrix. When keratocytes spread, actin was observed as a stress fiber inside the cells. At the edge of the cellular processes, a close interaction between fibronectin and actin was observed. The present results demonstrated that cultured keratocytes had active motility and that there were close interactions between the extracellular fibronectin and intracellular actin filaments. The organization of fibrillar actin filaments (F-actin) might be affected by the binding of extracellular fibronectin to the cell surface receptor for fibronectin.

Actins↗
PubMed1988

Immune recognition and effector function in subsets of CD4 T cells.

T cells expressing the cell surface differentiation antigen CD4 are involved in most immune responses. Our studies address two issues about CD4 T cell responses to antigen: first, how does the T cell receptor come together with its ligand to generate an immune response, and what is the role of the CD4 molecule in this response? Second, are all CD4 T cells identical in their functional activity, and how does the activating signal determine the functional outcome of a response? Our studies outlined below suggest that the T cell receptor and its peptide: class II major histocompatibility complex (MHC) molecule ligand come together in a defined orientation determined in part by the binding of CD4 to both the T cell receptor and its ligand. Our studies suggest that the V beta chain is involved directly in MHC antigen recognition, binding self MHC with low affinity and non-self MHC with high affinity. The selective effect of the Mls locus on V beta expression is believed to reflect the binding of the Mls protein directly to the V beta region. CD4 is described as a co-receptor, forming an inducible part of the T cell receptor and binding to the same class II MHC molecule as that receptor. Studies with both cloned lines and normal CD4 T cell populations suggest the existence of two separable subsets with definable function. One set appears to be specialized for the activation of the humoral immune response, while the other drives the cell-mediated immune responses, particularly those involving the activation of macrophages. These two subsets of CD4 T cells have differential activation requirements, seen particularly in the requirement for interleukin 1 (IL-1) in the activation and clonal expansion of CD4 T cells involved in humoral immunity. This requirement for IL-1 may also be observed in the priming of this subset of CD4 T cells. These studies demonstrate that the optimal activation of CD4+ T cells involves recognition of peptide fragments presented by class II MHC molecules and accessory signals derived from the antigen presenting cells.

Animals↗
PubMed1987

Epitopes associated with MHC restriction site of T cells. III. I-J epitope on MHC-restricted T helper cells.

I-J epitopes were found to be associated with the functional site of the class II MHC-restricted helper T (Th) cells: Virtually all of the H-2k-restricted Th cell function of H-2kxbF1 T cells was inhibited by the anti-I-Jk mAb, leaving the H-2b-restricted function unaffected. The I-Jk epitope was inducible in Th cells of different genotype origin according to the environmental class II antigens present in the early ontogeny of T cells. Although above results suggested that I-J is the structure reflecting the inducible MHC restriction specificity, further studies revealed some interesting controversies: First, the I-J phenotype did not always correlate with the class II restriction specificity, e.g., I-Ab-restricted Th from 5R was I-Jk-positive, whereas I-Ak-restricted Th of 4R was not. Second, there was no trans expression of parental I-J phenotypes and restriction specificities in F1 Th, e.g., the I-J phenotype was detected only on I-Ab-restricted Th of (4R X 5R)F1, whereas it was absent on I-Ak-restricted Th. This strict linkage between the restriction specificity and I-J phenotype was also found on Th cells developed in bone marrow chimera constructed with intra-H-2-recombinant mice. The expression of I-Jk was always associated with the restriction specificity of the relevant host. Thus, the restriction specificity of Th cells followed the host type, and the I-J expression on Th was exactly the same as that expressed by the host haplotype. These results indicate that I-J is an isomorphic structure adaptively expressed on Th cells that is involved in the unidirectional regulatory cell interactions, and that the polymorphism cannot be explained merely by the restriction specificity of the conventional T cell receptor heterodimer.

Animals↗
PubMed1987

Epitopes associated with the MHC restriction site of T cells. I. Selective expression of Iat epitopes on H-2-restricted helper T cells.

We previously established monoclonal antibodies (mAb) that are putatively directed to the I region of H-2k but are reactive only with T cells. Because of their specificity to the unique epitopes different from class II antigens, they are designated as anti-Iat reagents. The present study demonstrated that these anti-Iat inhibit the H-2k-restricted helper T (Th) cell function by acting on the very H-2 restriction site of both H-2k and H-2kxb F1 T cells. This was determined by both the cytotoxic treatment and blocking of antigen-primed Th cells. In the F1 Th population, only those restricted to H-2k were eliminated, leaving the H-2b-restricted Th cells uninhibited. The inhibition of the response was not due to the induction of suppressor T cells, but to the elimination of the function of radioresistant Lyt-1+,2- Th cells. Iatk epitopes were also found on an H-2k-restricted but not on H-2b-restricted Th cell clone established from the same H-2kxb F1 animal. None of the anti-Iatk were reactive with class II antigens on B cells. These results indicate that Iat epitopes are not directly encoded by the I region genes, but are associated with the H-2 restriction site of T cells, which see the self class II polymorphism. Thus, Iat epitopes are expressed clonally in high frequency on H-2k-restricted Th cells of F1, being excluded from the H-2b-restricted Th population. The relationship between Iat and T cell receptor molecules is unknown.

Animals↗
PubMed1987

Shared idiotopes between anti-class II monoclonal antibodies and major histocompatibility complex recognition site of T cells.

We have raised a number of monoclonal antibodies (mAb) against idiotopes (Id) on monoclonal anti-murine class II (anti-Ak or Ek) antibodies. Two anti-Id mAb among 31 were found to cross-react with some T cells but not with macrophages and B cells of H-2k animals. They were able to block syngeneic mixed lymphocyte reaction (SMLR) and antigen-induced major histocompatibility complex (MHC)-restricted T cell proliferation of H-2k but not of other haplotypes. These results indicated that antibodies were recognizing Id associated with the MHC restriction site of T cells. The injection of these anti-Id mAb into H-2k mice resulted in the stimulation of self-class II-reactive T cell clones as determined by SMLR. They were also able to stimulate in non-H-2k strains to prime H-2k alloreactive T cell clones. Some animals developed anti-class II (anti-Iak) antibodies by the injection of anti-Id. These results indicated that certain anti-Id (anti-anti-class II) antibodies cross-reacted with T cell receptors which carried class II restriction specificity and were involved in allorecognition. These antibodies were found to have an ability to alter the T cell repertoire in vivo by stimulating such MHC-restricted clones.

Animals↗
PubMed1987

Spontaneous persistent epithelial defects after cataract surgery.

The natural course of corneal epithelial erosions was studied retrospectively in patients who had undergone cataract extraction. Postsurgical epithelial defects occurred in 41 of 796 eyes (5.2%). No difference was noted in the incidence of corneal epithelial defects in eyes after intracapsular and extracapsular cataract extraction. Of the 41 eyes with postsurgical corneal erosion, 26 (63.4%) showed corneal epithelial defects by the fourth postoperative day. Two types of healing patterns were noticed: rapid healing, in which there was complete epithelial resurfacing within 4 days after the onset of corneal erosion, and prolonged healing, in which the period for complete epithelial resurfacing ranged from 6 days to 34 days. Since fibronectin has been reported to facilitate corneal epithelial migration and adhesion, we administered autologous fibronectin eyedrops in five cases in which corneal epithelial erosion developed after cataract surgery and epithelial defects persisted more than 7 days (except case 2). In all cases receiving fibronectin treatment, complete epithelial resurfacing occurred. In four of five eyes, fibronectin eye drops were effective in epithelial resurfacing within 3-9 days; in one eye, complete epithelial resurfacing took 23 days. The present results indicate that there are two types of epithelial erosion and that fibronectin eye drops might be one of the possible therapeutic approaches for the treatment of persistent epithelial defects. The weak adhesion of epithelial cells underlying basement membrane may be one of the causes of persistent epithelial defects after cataract surgery.

Adult↗
PubMed1986

Ir gene expression on T cells: effect of a monoclonal antibody directed against I region-controlled determinants on T cells.

A monoclonal antibody directed at an I region-controlled epitope uniquely expressed on T cells (Iat) was studied for its in vivo effect on the antibody response under the control of an Ir gene. The antibody was produced by a hybridoma made from A.TH spleen cells immune to A.TL (anti-Ik), that was selected for its reactivity with T but not B cells and macrophages, and thus was designated as anti-IatK. The injection of this anti-Iatk into H-2k, H-2b and H-2k X bF1 mice resulted in the suppression of antibody response to poly-L-(His,Glu)-poly-D,L-Ala--poly-L-Lys [(H,G)-A--L] in H-2k and F1 mice but not that to poly-L-(Tyr,Glu)-poly-D,L-Ala--poly-L-Lys [(T,G)-A--L] both in H-2b and F1 mice. The adoptive cell transfer of the combinations of anti-Iatk- or normal mouse serum-treated T and B cells into irradiated hosts demonstrated that anti-Iatk primarily affected (H,G)-A--L-specific helper T cells but not B cells and macrophages, resulting in the specific elimination of the antibody response. Suppressor T cells were not induced by the treatment with anti-Iatk. The antibody specifically eliminated the (H,G)-A--L-specific but not (T,G)-A--L-specific helper T cells in F1 spleen cells that had been primed with both (H,G)-A--L and (T,G)-A--L. The results indicated that anti-Iatk affected the H-2k-associated Ir gene function born by T cells but not by antigen-presenting cells, which was expressed on F1 helper T cells with apparent exclusion of the other allele, and implied that the Iat antigen on helper T cells is one of the sites of expression of Ir genes.

Animals↗
PubMed1984

Regulation of allotype-linked NPb idiotype by an idiotype-positive soluble factor derived from a T cell hybridoma. Coupling of the circuit regulation to the network concept.

We reported in this paper genetic requirements for the suppression of anti-4-hydroxy-3-nitrophenylacetyl (NP) antibody response induced by an NP-specific, Igh-1 linked idiotype (NPb) positive T suppressor factor (NPb-TsF) derived from a T cell hybridoma 7C3-13 of B10.BR (Igh-1b, H-2k) mouse origin. NPb-TsF could suppress the responses mounted by primed spleen cells of all IgVH compatible strains regardless of their H-2 haplotypes. The majority of the anti-NP antibody response suppressed by NPb-TsF was idiotype positive (Id+). NPb-TsF was also capable of suppressing the responses of H-2 compatible but Igh incompatible strains where responding cells do not produce NPb idiotype. NPb-TsF was incapable of suppressing the responses of mouse strains who are incompatible both in IgVH and H-2 loci, indicating that the identity in either IgVH or H-2 genes between NPb-TsF and responding cells was necessary for the initiation of the suppression by NPb-TsF. It was further found that the NPb-TsF utilizes anti-idiotypic Lyt-1+2+3+ T cells (transducer cells), which are present only in IgVH compatible strains, to ultimately suppress the Id+ antibody production by B cells. These results indicate that there exists a pathway where an idiotypic NPb-TsF activates a suppressor circuit mediated via the idiotype-antiidiotype interactions apart from the previously described carrier-specific and H-2 restricted suppressor circuit. Both pathways involve the 'transduction' step utilizing Lyt-1+2+3+ intermediary T cells. Our experiments provide important clues for coupling the two major immunological concepts, network and circuit.

Animals↗
PubMed1984

Long-term effect of vasectomy on coronary heart disease.

We investigated the association between coronary heart disease (CHD) and vasectomy in a population of 10,632 men who were under surveillance for multiple CHD risk factors during participation in a university-based exercise testing program. We conducted a mail survey with telephone follow-up to determine the vasectomy status of individuals in the population. Responses were obtained from 6,159 individuals. The 4.944 males on whom information was complete enough to be included in the multivariate analysis comprised the study population. Among the 1,383 (28 per cent) vasectomized males in the study populations, the interval from vasectomy to the time of the survey ranged from less than one year to 37 years with a mean duration of 15 years. Although increased relative risks for CHD were found to be associated with family history of CHD, high blood pressure and smoking in this population, the relative risk of CHD associated with vasectomy was not increased in general, nor was it increased when the vasectomized males were classified by time since vasectomy. Likewise, serum antisperm-antibody titers were not predictive of CHD among vasectomized men. These studies support the findings from previous investigations of populations with shorter average post-vasectomy experience in which vasectomy has been shown to be unassociated with altered risk of CHD in humans.

Adolescent↗
PubMed1983

Zonal distribution of cytochrome P-450s (P-450(11) beta and P-450scc) and their relation to steroidogenesis in bovine adrenal cortex.

Zona glomerulosa and zonae fasciculata-reticularis of bovine adrenal cortex were separated by our improved method using a remodeled microtome. A considerable amount of fresh mitochondria and microsomes was quickly obtained. Specific content of cytochrome P-450 in the mitochondria was higher in zonae fasciculata-reticularis than in zona glomerulosa. When metyrapone was added to the mitochondria and the drug-induced difference spectra were measured, there appeared two phases in the titration curve; the first phase was saturated at a concentration of 3 microM and the second phase appeared at concentrations higher than 10 microM. The first phase seemed to be due to the substrate-free P-450(11) beta and the second phase to the cholesterol-bound P-450scc. From these spectral studies contents of cytochrome P-450scc and P-450(11) beta were estimated, and those were found to be equal for each zone. From similar studies on substrate-induced difference spectra, there seemed to be no difference between two zones in the affinity of cytochrome P-450(11) beta for deoxycorticosterone and 11-deoxycortisol. This was also the case with 11 beta-hydroxylase activity and substrate specificity for deoxycorticosterone and 11-deoxycortisol.

Adrenal Cortex↗
PubMed1976

Mutagenicity and cytotoxicity of benzo(a)pyrene benzo-ring epoxides.

Four benzo-ring epoxides of the environmental carcinogen benzo(a)pyrene (BP) were tested for mutagenic and cytotoxic activity in 3 strains of Salmonella typhimurium (TA1538, TA98, and TA100) and in Chinese hamster V79 cells. Although very unstable in aqueous solution, 7beta,8alpha-dihydroxy-0beta,10beta-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (diol epoxide 1), with the 7-hydroxyl group on the same face of the molecule as the epoxide oxygen, was 1.5 to 4 times as mutagenic in the bacterial strains as was its more stable stereoisomer 7beta,8alpha-dihydroxy-9alpha,10beta-epoxy-7,8,9.10-tetrahydrobenzo(a)pyrene (diol epoxide 2). In V79 cells, diol epoxide 1 had one-third the mutagenic activity of diol epoxide 2 but was at least 10 times more labile than diol epoxide 2 in the tissue culture medium. The half-life of diol epoxide 1 in tissue culture medium was about 30 sec, whereas the half-life of diol epoxide 2 was between 6 and 12 min. 9,10-Epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene, which is saturated in the benzo ring, is also very unstable and has mutagenic activity equal to or greater than diol epoxide 1 in the bacterial and mammalian cells. 7,8-Epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene was more stable in aqueous solution than any of the 9,10-epoxides of BP but was much less mutagenic in both the bacterial and mammalian cells. In v79 cells, diol epoxides 1 and 2 and 9,10-opoxy-7,8,9,10-tetrahydrobenzo(a)pyrene were more than 40 times more cytotoxic than 7,8-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene. The mutagenicity of the 2 tetrahydro epoxides toward strain TA98 of S. typhimurium was readily abolished by purified epoxide hydrase, whereas the mutagenic activity of the 2 diol epoxides was relatively unaffected by coincubation with the enzyme.

Animals↗