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H Hanawa

Publications and source records attributed to H Hanawa.

At least 55 records · Page 3Linked to original sources
PubMed1996

Suppression of fluid accumulation following pericardial inflammation in a patient with primary chylopericardium.

The patient was a 50-year-old woman with primary chylopericardium. Triglyceride rich chyloid fluid was continuously drained from the pericardial space through an indwelling catheter. A surgical procedure was scheduled since a medium chain triglyceride diet was insufficient to control the fluid accumulation. Before the operation, inflammatory signs were apparent around the indwelling catheter and the catheter was removed immediately. The inflammation was easily treated with antibiotics, and the pericardial effusion no longer accumulated during a follow-up period of 10 months. The inflammatory process may have caused fibrin production and tissue adhesion in the pericardial cavity, and these might have prevented an accumulation of chyloid fluid and occluded the connection between the thoracic duct and the pericardial cavity.

Catheters, Indwelling↗
PubMed1995

Synchronous expansion of intermediate TCR cells in the liver and uterus during pregnancy.

The immunophysiology of pregnancy was investigated in relation to how extra- and intrathymic pathways of T cell differentiation are modulated during pregnancy. Pregnancy was produced in syngeneic and allogeneic combinations in mice. In both cases, a prominent decrease in the number of thymocytes and a mild increase in the number of hepatic mononuclear cells (MNC) were induced during the periparturient period. The most striking change was the increase in the number of intermediate TCR cells with extrathymic T cell properties in the liver. When MNC yielded by the uterus were examined, an expansion of intermediate TCR cells was also observed in this organ during pregnancy. The major populations in the pregnant uterus were NK cells and intermediate TCR cells, the latter of which contained double-negative CD4-8- cells and consisted of both alpha beta and gamma delta T cells. All of these properties coincided with those of extrathymic T cells in the liver. Reflecting extrathymic T cell differentiation, MNC in the liver and pregnant uterus expressed mRNA of RAG-1 and RAG-2. To determine the role of hormonal regulation in this phenomenon, the effects of various pregnancy-associated hormones on thymocytes and hepatic MNC were examined in nonpregnant mice. Of the hormones tested, estrogen was found to induce a response similar to that seen in pregnant mice. These results suggest that a local immune response in the uterus during pregnancy is a phenomenon occurring synchronously with systemic immune systems.

Animals↗
PubMed1995

Effects of 15-deoxyspergualin on experimental autoimmune giant cell myocarditis of the rat.

BACKGROUND: The benefits of immunosuppressive therapy for human myocarditis are controversial. The effects of a new immunosuppressant agent, 15-deoxyspergualin (DSG), on rats with experimental autoimmune myocarditis (EAM), an animal model of human giant cell myocarditis, were examined. METHODS AND RESULTS: Lewis rats were immunized with cardiac myosin in Freund's complete adjuvant on day 0. In the first experiment, the effective doses of DSG required to prevent EAM were investigated. Rats were placed into one of five groups: the control group (A) was administered saline from days 1 to 10; group B, 0.3 mg/kg per day of DSG; group C, 1.0 mg/kg per day of DSG; group D, 3.0 mg/kg per day of DSG, and group E, 10.0 mg/kg per day of DSG. Rats were killed on day 28. The heart weight/body weight ratios of the rats of groups D and E were significantly lower than that of the control group. Macroscopic and microscopic scores for myocarditis decreased in groups D and E. In the next experiment, the effects of delayed administration of DSG in preventing autoimmune myocarditis were studied. Two groups of rats received 3.0 and 10.0 mg/kg per day of DSG from days 6 to 15, respectively. Two other groups of rats received the same doses of DSG from days 11 to 20. No preventive effect of delayed DSG treatment was observed. The effects of long-term, delayed initiation therapy then were evaluated. Rats were administered 10.0 mg/kg per day of DSG from days 6 to 25. The heart weight/body weight ratio and macroscopic and microscopic scores of the rats so treated significantly decreased compared with the controls. CONCLUSIONS: It was demonstrated that DSG can prevent the development of cardiac myosin-induced autoimmune myocarditis.

Animals↗
PubMed1995

An ultrastructural study on experimental autoimmune myocarditis with special reference to effector cells.

The previously described animal model of autoimmune myocarditis induced by immunization of Lewis rats with cardiac myosin was investigated pathologically, ultrastructurally and immunohistologically. Cardiac dendritic cells and infiltrating macrophages were dominantly encamped at the front of the myocarditis. The macrophages accompanied by neutrophils infested cardiocytes, forming rosette figures as a sign of active cardiocytolysis. The dendritic cells reached into intact muscle at a short distance from the inflammation. T cells, the most important candidate for effector cells in this animal model, were generally found at a distance from active muscle necrosis.

Animals↗
PubMed1995

Dual rearrangement of immunoglobulin and T-cell receptor genes in a case of splenic lymphoma with villous lymphocytes.

We report here a case of "splenic lymphoma with villous lymphocytes" (SLVL) which exhibited both B- and T-cell phenotypes and genotypes. The patient was a 73-year-old man. Physical examination revealed splenomegaly and lymphadenopathy. The white blood cell count was 55.2 x 10(9)/L with 70.5% atypical lymphocytes, having cytoplasmic villi, characteristic of SLVL. The atypical cells infiltrated both the red and white pulps. Immunological analysis of the peripheral leukocytes showed both B- and T-cell phenotypes (CD5,CD11c,CD19,CD20,HLA-DR, SmIgM and lambda positive). DNA analysis revealed a dual rearrangement of the immunoglobulin heavy chain gene and T-cell receptor beta gene. SLVL has been identified as a B-cell leukemia with a relatively benign clinical course. This case had both B- and T-cell pheno- and genotypes with a progressive course. To the best of our knowledge, no case of SLVL with dual genotypes has ever been reported.

Aged↗
PubMed1995

Localization of porcine cardiac myosin epitopes that induce experimental autoimmune myocarditis.

Porcine cardiac myosin induced severe myocarditis in Lewis rats, similar to that seen after immunization with human or rat cardiac myosin. We investigated the localization of pathogenic epitopes by using porcine cardiac myosin. Subfragment-1 (S-1) and the rod were obtained by alpha-chymotryptic digestion. The rod was further fragmented by using cyanogen bromide cleavage. Three subfragments of S-1 were prepared by tryptic digestion. All Lewis rats immunized with the rod exhibited severe myocarditis, and the immunization of the cyanogen bromide-cleaved peptide equivalent to human beta-cardiac myosin heavy chain RDCB9 (residues 1070 to 1165) induced moderate myocarditis. Although none of the rats immunized with the whole S-1 exhibited any myocardial lesions, moderate inflammatory cardiac lesions were detectable in rats immunized with the tryptic digests of S-1. Our results indicate that the myocardiogenic epitopes in Lewis rats are located in the RDCB9 (residues 1070 to 1165) of the cardiac myosin rod and that a cryptic minor epitope may reside in S-1.

Amino Acid Sequence↗
PubMed1994

Glucocorticoid independence of acute thymic involution induced by lymphotoxin and estrogen.

Acute thymic involution is known to be induced under conditions of physical stress, bacterial infections, and malignancies. It is speculated that glucocorticoids, tumor necrosis factor (TNF), and other factors may act as mediators for the thymic involution under such conditions. It was herein investigated whether either lymphotoxin (TNF beta) or estrogen could induce thymic involution without the help of glucocorticoids. Interestingly, both lymphotoxin or estrogen alone induced profound thymic involution even in adrenalectomized mice. In contrast to glucocorticoids, which induce lymphocytopenia throughout the organs, lymphotoxin and estrogen did not induce lymphocytopenia in the peripheral organs. More importantly, lymphotoxin and estrogen rather stimulated extrathymic T cells in the liver and other organs. These results suggest that lymphotoxin and estrogen per se might be important regulators of immune systems.

Animals↗
PubMed1994

T cell receptor peptide therapy for autoimmune encephalomyelitis: stronger immunization is necessary for effective vaccination.

Although T cell receptor (TCR) peptide therapy was initially reported to be a very effective method for prevention of the development of experimental autoimmune encephalomyelitis (EAE), it was recently demonstrated that the same peptide immunization led to enhanced and chronic EAE in some cases. In the present study, we examined the effect of the TCR peptide (V beta 8.2-39-59) vaccination on the development of EAE by employing several immunization protocols. We found that TCR peptide vaccination effectively prevented EAE development only when the peptide was injected with Mycobacterium tuberculosis-enriched CFA in the vicinity of the challenge site. Under such conditions, a sufficient number of peptide-reactive T cells were generated. Flow cytometry and immunohistochemical analyses using anti-peptide antibody and anti-V beta 8.2 mAb revealed that despite the presence of V beta 8.2+ cells, very few peptide-positive T cells appeared in the lymphoid organs throughout the course of EAE. These findings imply that antibodies that are generated after immunization with V beta 8P are hardly accessible to their specific epitopes in the native protein. Insufficient generation of both T cells and antibodies against V beta 8.2-positive T cells may be attributable to the outcome of the therapy. To establish effective TCR peptide immunotherapy, these disadvantages should be overcome by using other TCR sequences and/or by employing a more suitable adjuvant.

Adjuvants, Immunologic↗
PubMed1994

Anti-alpha beta T cell receptor antibody prevents the progression of experimental autoimmune myocarditis.

We investigated the effects of anti-alpha beta T cell receptor antibody in rat experimental autoimmune myocarditis (EAM), using a new animal model of autoimmune myocarditis characterized by the appearance of multinucleated giant cells. EAM was induced by injecting Lewis rats subcutaneously in the footpads with 1.0 mg of human cardiac myosin in an equal volume of Freund's complete adjuvant (FCA) on days 0 and 7. In experiment 1, we evaluated the effect of long-term anti-alpha beta TCR antibody therapy on prevention of progression of EAM. Long-term administration of anti-alpha beta TCR antibody prevented progression of EAM in a dose-dependent manner. Flow cytometry performed at the time of sacrifice showed that the percentage of alpha beta T cells in lymph nodes and spleen was similar in the control group and the group in which almost no histologic evidence of myocarditis was found. In experiment 2, we examined the effects of short-term therapy. Rats were killed at different stages and pathologic specimens were examined. Short-term therapy delayed the onset of myocarditis. Results of flow cytometry suggested that impairment of antigen recognition or T cell function by occupancy of the TCR rather than depletion of TCR was the mechanism responsible for suppression of EAM.

Animals↗
PubMed1994

Rat dilated cardiomyopathy after autoimmune giant cell myocarditis.

One of the possible causes of dilated cardiomyopathy is considered to be a sequel to myocarditis. Two mechanisms have been proposed in the process of progression of myocarditis into dilated cardiomyopathy: one is a persistent viral infection, and the other is an autoimmune myocardial injury. To clarify the possible part played by the autoimmune mechanism in the process, using an animal model, we investigated whether autoimmune myocarditis, exclusively not related to viral infection, might develop into dilated cardiomyopathy. Experimental autoimmune myocarditis was elicited in Lewis rats by immunization with cardiac myosin fraction. Rats of the control group were immunized with ovalbumin. The clinical course was observed over 4 months. Six rats from the myosin-immunized group died during the acute phase and the healing phase, and all those rats had severe myocarditis. All rats that survived until the end of the study showed enlarged and discolored hearts. Aneurysmal changes were observed in the right ventricle during thoracotomy. The ratio of heart weight to body weight of the myosin-immunized group was significantly higher than that of the control group (3.36 +/- 0.49 versus 2.69 +/- 0.06 g/kg, respectively; P < .005). The lengths of the anterior interventricular fissure and the posterior interventricular fissure of the hearts of the myosin-immunized group were significantly longer than those of the control group. The external diameter of the left ventricle of the myosin-immunized group was also significantly larger than that of the control group. Diffuse myocardial muscle loss and replacement fibrosis were the prominent histological findings of the rats of the myosin-immunized group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Morphological analysis of multinucleated giant cells occurred in experimental autoimmune myocarditis.

Our previous study reported the rich existence of multinucleated giant cells in an autoimmune myocarditis experimentally induced in rats. The present study investigated the histochemical and ultrastructural characteristics of these giant cells. Histochemistry for an acid phosphatase clearly demonstrated multinucleated giant cells dispersed at the inflammatory foci. Ultrastructurally, the giant cells were shown to be single cells, but not clustered cells. Their ultrastructural characteristics were very similar to the basic features of macrophages, except that the giant cells were poor in lysosomes and phagosomes. It was noticeable that some macrophages possessed three or more nuclei, displaying an intermediate form between mononuclear macrophages and multinucleated giant cells. These findings suggest that the giant cell in the experimental autoimmune myocarditis is a single multinucleated cell, and possibly derived from macrophages by cell-to-cell fusion.

Acid Phosphatase↗
PubMed1994

Successful prevention and treatment of autoimmune encephalomyelitis by short-term administration of anti-T-cell receptor alpha beta antibody.

To identify an effective immunotherapy for T-cell-mediated autoimmune diseases, prevention and treatment of experimental autoimmune encephalomyelitis (EAE) induced in Lewis rats was attempted by administering a monoclonal antibody (mAb), R73, which is specific for rat T-cell receptor (TcR) alpha beta. Short-term administration of R73 at relatively low doses before immunization with encephalitogenic antigen, myelin basic protein (MBP), prevented the development of EAE. However, treatment with anti-CD4 and anti-Ia mAb in the same protocol was ineffective. Flow cytometric analysis demonstrated that short-term administration of R73 resulted in transient down-regulation of the TcR molecules, whereas the number of CD2-expressing T cells was well preserved. Furthermore, the response to MBP of T cells isolated from rats that were pretreated with R73 and then immunized with MBP was strongly suppressed. On the other hand, the T-cell response of R73-pretreated rats to a third-party antigen which was immunized at a later period was not inhibited. These findings suggest that in vivo administration of a low dose of R73 protects rats from EAE by inducing anergy of MBP-reactive encephalitogenic T cells. Furthermore, R73 treatment which started on day 10 of the immunization (shortly before the day of onset of clinical signs) completely suppressed the induction of EAE and that which started on day 11 (the day of onset) hastened recovery. Since the phenotypes of the TcR V beta chain of encephalitogenic T cells are not so limited as previously believed, immunotherapy with mAb against the TcR alpha beta framework may be one of the best methods for treatment of T-cell-mediated autoimmune diseases.

Amino Acid Sequence↗
PubMed1994

Identification of CD4- CD8- alpha beta T cells in the subarachnoid space of rats with experimental autoimmune encephalomyelitis. A possible route by which effector cells invade the lesions.

Experimental autoimmune encephalomyelitis (EAE) was induced in Lewis rats to elucidate the origin of effector T cells and the route by which they invade lesions. Since mouse studies have suggested that some autoimmune diseases are induced by extrathymic T cells in the liver, we focused our attention on the properties of mononuclear cells (MNC) isolated from the liver and other organs in rats with EAE. A small but significant proportion of LFA-1+ alpha beta T cells was identified in the liver as early as day 7 after immunization with myelin basic protein (MBP). Such LFA-1+ alpha beta T cells were also abundant among MNC attached to the spinal cord (i.e. subarachnoid space), and MNC infiltrated the spinal cord in rats with EAE (day 12). In electron microscopy, MNC attached to the spinal cord were found to be quite unique in terms of their large cell size with well-developed microvilli. More importantly, they were comprised of a considerably large proportion of double-negative CD4- CD8- T cells as well as single-positive CD4+ T cells. However, the cells which infiltrated the spinal cord were mainly CD4+. The present results raise the possibility that the subarachnoid space might be a major site for the expansion of extrathymic T cells in rats with EAE, and that only a limited population of CD4+ T cells invade the spinal cord directly through the outer layer and elicit EAE.

Animals↗
PubMed1993

Characterization of T cells infiltrating the heart in rats with experimental autoimmune myocarditis. Their similarity to extrathymic T cells in mice and the site of proliferation.

A model of experimental autoimmune myocarditis, which resembles fatal giant cell myocarditis in humans, was previously established in rats immunized by s.c. injection of human cardiac myosin. We characterized herein the surface phenotype of lymphocytes infiltrating the heart and pericardial cavity as well as of mononuclear cells in various organs by using mAb in conjunction with immunofluorescence tests. Since profound thymic atrophy always accompanied the diseased states, attention was focused on characterization of T cells with properties similar to those of extrathymic T cells. In mice, extrathymic T cells were activated in association with thymic atrophy, expressed high levels of LFA-1 and IL-2R beta-chains, and contained a significant proportion of double negative CD4-CD8- T cells. In diseased rats, a large proportion of activated T cells that expressed high levels of LFA-1 and IL-2R was demonstrated in the pericardial effusion and heart tissue. Such T cells were rare in the other organs. Light scatter and microscopic observation revealed that activated lymphoblasts were most abundant in the pericardial effusion. Moreover, one-fourth of such T cells in the pericardial effusion displayed double negative phenotype. These cells in rats might correspond to the extrathymic T cells in mice. However, only a limited population of such activated T cells infiltrated the heart tissue. Concerning the location of such T cells mainly in the outer layer of the heart, it raised the possibility that extrathymic T cell differentiation in these autoimmune rats might occur in the pericardial cavity, and the differentiated cells then migrated to the sites of the cardiac lesion.

Animals↗
PubMed1993

Cardiac contractile proteins and autoimmune myocarditis.

Concerning cardiac contractile proteins, antigenicity and myocardiotogenicity were discussed. In normal states, these proteins are immunologically tolerant, and can not provoke any heart-specific disease. Why the proteins can provoke such lethal autoimmune myocarditis has not been completely elucidated. Shortly after cardiac infection or myocardial ischemia, these proteins may work as the antigen for the autoimmune myocarditis. First of all, the role of cardiac myosin has been strongly emphasized. But, the antigen determinants: epitope proteins remain unclear. Either cross-activity to the streptococcal M protein and/or the alpha-helical coiled-coil protein may be an important factor to determine antigenicity. In this autoimmune myocarditis, the roles of T-lymphocyte and cardiac dendritic cell are noticeable. Through further study on the relation between antigen epitope and the infectious agents in the heart; on cardio-cytotoxicity of the T-lymphocyte and on the precise contribution of cardiac dendritic cells, this autoimmune myocarditis will be more clarified.

Actins↗
PubMed1993

Preferential distribution of V beta 8.2-positive T cells in the central nervous system of rats with myelin basic protein-induced autoimmune encephalomyelitis.

To determine the role of encephalitogenic T cells in the formation of lesions in the central nervous system (CNS), experimental autoimmune encephalomyelitis (EAE) was induced in Lewis rats by immunization with either myelin basic protein (MBP) or the synthetic peptide which corresponds to the 87-100 sequence of guinea pig MBP, and T cells expressing T cell receptor (TcR) V beta 8.2, V beta 8.5, V beta 10 and V beta 16 in the lymphoid organs and CNS were localized and quantified by flow cytometry (FCM) and immunohistochemistry. In normal rats, the percentage of T cells expressing these V beta phenotypes to the total number of TcR alpha beta+ T cells, as determined by FCM, ranged from 5% to 10% in the lymph node. V beta 16+ T cells were the most predominant population among the four V beta subsets tested. Essentially the same findings were obtained from the analysis of the lymphoid organs of rats with EAE which had been induced by immunization with the same two antigens. In sharp contrast, 15-20% of the T cells isolated from lesions of MBP-induced EAE expressed V beta 8.2. Thus, the percentage of V beta 8.2+ T cells in the EAE lesions was threefold higher than that in the lymph node, while the proportions of V beta 8.5+, V beta 10+ and V beta 16+ T cells were about the same in both organs. The predominance of V beta 8.2+ T cells in EAE lesions was confirmed by counts of immunohistochemically stained T cells in the spinal cord. Moreover, it was revealed that (i) the predominance of V beta 8.2+ T cells was greatest during the development of EAE and became less obvious at the recovery state, and (ii) at the peak stage of EAE, approximately 85% of V beta 8.2+ T cells were distributed in the parenchyma while 15% were in the perivascular space of the CNS vessels. These findings indicate that encephalitogenic T cells which express V beta 8.2 infiltrate the CNS at a very early stage of EAE and become the predominant population in infiltrating T cells, and further suggest that encephalitogenic T cells, not only recruit inflammatory cells in the CNS, but also cause neural tissue damage, such as demyelination.

Amino Acid Sequence↗
PubMed1993

Characterization of intermediate TCR cells in the liver of mice with respect to their unique IL-2R expression.

We previously demonstrated that T cells with intermediate TCR intensity (i.e., intermediate TCR cells) which possibly generate extrathymically are preferentially present in the liver of mice. This population was further characterized with respect to the expression of IL-2 receptor (IL-2R) and others. Two-color staining for CD3 (or TCR alpha beta) and IL-2R alpha (and beta) demonstrated that intermediate TCR cells as well as NK cells constitutively expressed IL-2R beta but not IL-2R alpha. A small number of intermediate TCR cells was also identified in other immune organs by using this staining method. In vivo and in vitro stimulation experiments revealed that regular, bright TCR cells, which originally lacked the expression of both IL-2R alpha and beta, acquired the highest expression of IL-2R alpha and beta, while intermediate TCR cells did not. These results suggested, in conjunction with their other properties demonstrated here, that intermediate TCR cells might be more primitive T cells than regular T cells of thymic origin.

Animals↗