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Biomedical subjects

H Mizutani

Publications and source records attributed to H Mizutani.

At least 19 recordsLinked to original sources

Effects of splenectomy on immune thrombocytopenic purpura in (NZW x BXSB) F1 mice: analyses of platelet kinetics and anti-platelet antibody production.

Effects of splenectomy on platelet kinetics and production of anti-platelet antibodies were studied in male (NZW x BXSB) F1 (W/B F1) mice, which are known as the animal model of immune thrombocytopenic purpura (ITP). Studies on organ localization of radiolabeled platelets revealed that splenic uptake significantly increases in W/B F1 mice in comparison with that of normal controls. W/B F1 mice showed a significant increase in platelet counts and, in contrast with sham-operated controls, high levels of platelet counts were maintained up to 6 weeks after splenectomy. Platelet lifespans (PLSs) did not reach normal levels, although prolonged PLSs were observed. In addition, platelet-associated antibody (PAA) values showed a tendency towards transient decrease, but there was no change in platelet-bindable serum antibodies (PBAs). These findings indicate that the suppression of anti-platelet antibody production is essential to the treatment of ITP; splenectomy may not be effective in treating severely affected ITP patients because, although the spleen is one of the major sites of platelet sequestration and antibody production, reticulo-endothelial systems (RESs) (liver, bone marrow, lymphnodes, etc.) other than the spleen are also responsible for the destruction of platelets. We therefore consider the W/B F1 mouse to be a useful model of human ITP, and believe that it provides valuable information for the development of new therapeutic agents in patients with ITP, especially those who do not respond to splenectomy.

Animals

Mechanisms of corticosteroid action in immune thrombocytopenic purpura (ITP): experimental studies using ITP-prone mice, (NZW x BXSB) F1.

To determine the mechanism by which platelet counts increase after corticosteroid therapy for human immune thrombocytopenic purpura (ITP), we studied the platelet kinetics using prednisolone (PDN)-treated ITP-prone mice, (NZW x BXSB) F1 (W/B F1). An increase in platelet counts was observed in W/B F1 mice (n = 10, mean +/- SD, 1,202 +/- 202 x 10(3)/microL) 4 weeks after treatment with PDN (2 mg/kg/d); no increase occurred in nontreated W/B F1 mice (n = 5,651 +/- 126, P less than .005). Prolonged platelet life-spans (PLSs) were observed in treated W/B F1 mice (1.29 +/- 0.40 days), but not in nontreated controls (0.60 +/- 0.24 days, P less than .01). No increase in platelet production (platelet turnover) was found in PDN-treated W/B F1 mice, but significant decreases in platelet-associated antibodies (PAAs) and platelet-bindable serum antibodies (PBAs) were noted. Studies on organ localization of radiolabeled platelets showed that hepatic uptake significantly decreased in the treated W/B F1 mice, but not in nontreated W/B F1 mice. To elucidate the effect of PDN on the reticulo-endothelial phagocytic activity in W/B F1 mice, we studied in vivo clearance of IgG-sensitized, 51Cr-labeled autologous erythrocytes. W/B F1 mice treated with PDN showed a marked impairment of their ability to clear these cells, although PDN had little effect on the number of splenic or hepatic macrophage Fc gamma receptors. These results and our previous findings of splenectomy suggest that PDN improves platelet counts not only by suppressing systemic reticulo-endothelial phagocytic function but also by reducing antibody production.

Animals

Monoclonal antibody to GABA binding protein, a possible GABAB receptor.

A monoclonal antibody has been raised against a partially purified preparation for the GABAB receptor. The antibody recognized a protein of about 80 kDa in bovine brain synaptic membrane. Immunoabsorbent agarose beads conjugated with the antibody were able to remove, without visible changes in electrophoresed profiles of total proteins, over 90% of the baclofen suppressive GABA binding activity (designated herein, GABAB receptor binding activity) in the solubilized synaptic membrane fraction. Moreover, the addition of GB-1 antibody directly inhibited the GABA binding activity in the crude synaptic membrane fraction. These results indicate that the monoclonal antibody obtained here recognizes the GABA binding protein, or more specifically a GABAB receptor.

Animals

Palindromic morphea: multiple recurrence of morphea lesions in a case of systemic sclerosis.

We report an unusual scleroderma case. A 45-year-old woman had recurrent morphea lesions over 10 times in 6 years. She had had preceding inactive systemic scleroderma. New morphea lesions developed cyclically on various portions of her body and improved within 2 years. Interestingly, new lesions have developed on once involved skin as well as uninvolved skin. No exacerbation of systemic scleroderma was induced by outbreaks of new morphea lesions. We could not find a similar case in the literature and named it "Palindromic morphea" because of its unique clinical course. D-penicillamine treatment had a limited effect. Minimal oral prednisolone (5 mg/day) completely suppressed the multiple recurrence of the morphea lesions and enhanced improvement of the sclerosis.

Female

Impaired suppressor function of T cells induced by autologous mixed lymphocyte reaction in patients with idiopathic thrombocytopenic purpura.

Autologous mixed lymphocyte reaction (AMLR)-induced suppressor function was studied in 12 patients with chronic idiopathic thrombocytopenic purpura (ITP). The function was found to be significantly impaired (20 +/- 55%; p less than 0.005) compared with normal subjects (69 +/- 25%). AMLRs in these patients were significantly decreased (p less than 0.05) compared with normal subjects. There was no significant correlation between AMLR-induced suppressor function and platelet counts. Nine patients were studied for AMLR-induced suppressor function before and after splenectomy. The platelet counts increased significantly as a result of splenectomy, but the AMLR-induced suppressor function showed no significant improvement. The results of this study suggest that suppressor dysfunction in ITP may be an immunologic defect irrespective of disease activity. We consider that this abnormality may reflect in vivo failure of the immunoregulatory (feedback) mechanism in ITP.

Adult

Characteristics of the association of brotizolam, a thieno-triazolo diazepine derivative, with the benzodiazepine receptor: a selective and high affinity ligand of the central type I benzodiazepine receptor.

Characteristics of the association of brotizolam, a thieno-triazolo diazepine derivative, to central benzodiazepine receptors were examined. Brotizolam significantly displaced the [3H]flunitrazepam and [3H]beta-carboline carboxylate ethylester bindings to crude synaptic membrane from the rat brain. This agent had the highest affinity for benzodiazepine receptors in the cerebellum, and it was found to be 2.1 times that in the spinal cord. Furthermore, a low concentration of brotizolam potentiated the GABA-stimulated 36Cl- influx into membrane vesicles. In contrast, the bindings of [3H]8-hydroxy-2-(di-n-propylamino)tetralin to 5-hydroxytryptamine1A receptors and [3H]ketanserin to 5-hydroxytryptamine2 receptors were not affected by brotizolam. The present results suggest that brotizolam may be a selective and high affinity ligand for the type I central benzodiazepine receptor. The anxiolytic and hypnotic actions of brotizolam seem to be not due to the association with 5-hydroxytryptamine receptor, but due to the activation of the GABAA receptor complex. Furthermore, the present results suggest that the lower affinity of brotizolam to benzodiazepine receptors in the spinal cord than those in the cerebellum may be related to the low muscle relaxation action of this drug.

Animals

A case of malignant lymphoma accompanied by Klinefelter's syndrome.

A 66-year-old Japanese male with diffuse non-Hodgkin's lymphoma, of the pleomorphic type, complicated with Klinefelter's syndrome is reported. His phisique was characterized by a long arm span, disproportionately longer lower body dimensions and a small sized penis. He had no children. Chromosomal study revealed 47, XXY and hormonal quantification showed hypergonadtropic hypogonadism. Although chemotherapy was administered, his disease took a progressive course and he died. A discussion of chromosomal alteration and oncogenesis and review of the literature are included.

Aged

Positive antinuclear antibody in atopic dermatitis.

Serum samples from atopic dermatitis (AD) patients were examined with two antinuclear antibody-detecting methods, using HEp-2 cells as substrate. 34.0% of 47 AD patients tested with FITC-conjugated polyvalent immunoglobulins (method 1) had positive antinuclear antibody (ANA). 26.3% of 57 AD patients examined with FITC-conjugated anti-IgG (method 2) had positive ANA. We found that AD patients who had facial lesions tended to have positive ANA, whereas severe AD patients tended to have high titres of ANA.

Adolescent

[Clinical significance of antinuclear antibody in patients with idiopathic thrombocytopenic purpura].

The clinical significance of antinuclear antibodies (ANA) in patients with chronic idiopathic thrombocytopenic purpura (ITP) was evaluated. Serum samples of 55 patients with ITP without clinical features of systemic lupus erythematosus (SLE) were examined. The average follow-up period was 5.5 years. Positive ANA was found in 23 of the 55 patients. Twelve of these 23 showed a high-titer of ANA. There was no difference in platelet counts between ANA positive patients and negative patients, and there was no correlation between platelet counts and antibody titers. Ten of the 23 positive sera had precipitating antibodies to nuclear antigens; 7 SS-A and 3 RNP antibodies. The platelet counts of the 7 cases with anti-SS-A antibody positive were slightly low compared with those of the anti-SS-A antibody negative patients. None of the 10 patients developed SLE during the average follow-up period of 8.1 years. These results suggest that ITP patients who have a high-titer of ANA or antibody against SS-A do not always develop SLE. It was concluded that ANA with a high titer or precipitin to nuclear antigens, particularly SS-A, dose not predict a high risk of developing SLE in the future.

Adult

Rapid and specific conversion of precursor interleukin 1 beta (IL-1 beta) to an active IL-1 species by human mast cell chymase.

Secretory granules of human dermal mast cells contain a chymotrypsin-like serine proteinase called chymase. In this study, we demonstrate that the inactive cytokine, 31 kD interleukin 1 beta (IL-1 beta), can be converted rapidly to an 18 kD biologically active species by human mast cell chymase. The product formed is three amino acids longer at the amino terminus than the mature IL-1 beta produced by peripheral blood mononuclear cells and has comparable biological activity. Because chymase is a secretory granule constituent, it is likely to be released into the surrounding tissue when mast cells degranulate. It is also known that non-bone marrow derived cells resident in skin (keratinocytes, fibroblasts) produce but do not process 31 kD IL-1 beta. In this context, chymase may be a potent activator of locally produced 31 kD IL-1 beta. Mast cells lie in close apposition to blood vessels in dermis; therefore, chymase mediated conversion of 31 kD IL-1 beta might be expected to have a critical role in the initiation of the inflammatory response in skin.

Amino Acid Sequence

Two integrin-binding peptides abrogate T cell-mediated immune responses in vivo.

Two VLA proteins (or beta 1 integrins; originally called very late activation antigens) that bind to distinct determinants on fibronectin (FN) are increased on activated immune or memory T cells. VLA-4 binds to the peptide sequence Gly-Pro-Glu-Ile-Leu-Asp-Val-Pro-Ser-Thr (GPEILDVPST in single-letter code) on the alternatively spliced CS-1 form of FN, whereas VLA-5 binds to an Arg-Gly-Asp sequence found on all forms of FN. It has been proposed that the migration of immune T cells out of blood vessels and through connective tissue to a site of antigenic challenge is facilitated by the interaction of such integrins with matrix protein molecules. We have examined directly the role of T-cell integrins in vivo by using the well-characterized, T-cell-mediated contact hypersensitivity (CHS) response to the hapten trinitrochlorobenzene (TNCB). We demonstrate that the cells that transfer CHS to TNCB adhere to FN in the presence of Ca2+/Mg2+, and T-cell populations depleted of FN-adherent cells do not transfer immunity. We further show that TNCB-immune T cells treated with the synthetic peptides GPEILDVPST or Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP in single-letter code), ligands for VLA-4 and VLA-5, respectively, lose their ability to mediate this immune response in a murine model, whereas the control peptides Val-Ile-Pro-Asp-Leu-Thr-Glu-Ser-Pro-Gly and Gly-Arg-Gly-Glu-Ser-Pro have no effect. Neither GPEILDVPST nor GRGDSP significantly inhibited the proliferative response of TNCB-immune T cells in vitro. These data suggest that FN-binding integrins on T cells play a role in the localization of T cells to sites of antigenic challenge in tissue.

Amino Acid Sequence

[MR studies of extension and spread pattern of nasopharyngeal carcinoma].

Seven patients with T2-T4 nasopharyngeal carcinoma were examined by MRI on a 0.5T superconducting system. The obtained MRI images were reviewed focusing on the signal intensity (SI) of tumors, and the extension of tumors into the related spaces from the pharyngeal mucosal space (PMS). Consequently, the SI of tumors demonstrated low on T1 weighted images and high on T2 weighted images. The parapharyngeal space was the first space where the tumors extended from the pharyngeal mucosa. The parapharyngeal space was an intermediate point of extension to the masticator space (MS), the carotid space (CS), the retropharyngeal space (RPS), and the prevertebral space (PVS). The PVS involvement by tumors was not a direct extension from the PMS, because the posterior portion of pharyngobasilar fascia worked as a barrier on MR. Therefore, the longus capitus muscle in the prevertebral space was considered to be involved via the parapharyngeal space (PPS). The masticator space involvement was indicated by slightly high SI of pterygoid muscle on T2 weighted images, and also the effacement of the PPS fat and parapharyngeal venous plexus were considered as a sign of involvement into the masticator space. The retropharyngeal lateral lymph node (Rouviere) metastases were recognized by MR. These metastasized lymph nodes were low on T1 weighted images and high on T2 weighted images.

Adult

Round fingerpad sign: an early sign of scleroderma.

We describe a clinical skin sign in scleroderma termed round fingerpad sign. This term refers to disappearance of the peaked contour on fingerpads and replacement with a hemisphere-like fingertip contour; this change is especially apparent on the ring fingers. A positive round fingerpad sign was found in 72 of 72 ring fingers in 36 patients with progressive systemic sclerosis in 69 of 72 ring fingers in patients with mixed connective tissue disease, and in 24 of 24 ring fingers of patients with Raynaud's phenomenon and sclerodactyly. In contrast, a negative round fingerpad sign was seen in 240 of 240 fingers in normal women (controls). The high sensitivity of this sign is noteworthy. A positive round fingerpad was seen in sign not only typical scleroderma patients but also in groups with less severe skin sclerosis (i.e., in those patients with mixed connective tissue disease or those with Raynaud's phenomenon and sclerodactyly). The sign is a new and useful clinical marker for the early diagnosis of scleroderma.

Adolescent

Simultaneous development of two cases of eosinophilia-myalgia syndrome with the same lot of L-tryptophan in Japan.

A newly recognized and well-described connective tissue disease, eosinophilia-myalgia syndrome, is thought to relate to L-tryptophan ingestion. The suspect L-tryptophan made in Japan has been distributed in Japan and in the United States. Different from many case reports of eosinophilia-myalgia syndrome in the United States, it has not been reported in Japan. We describe the first case reports of two Japanese patients. Eosinophilia-myalgia syndrome developed in these patients simultaneously, during L-tryptophan treatment by the same physician using the same lot of prescribed L-tryptophan. Furthermore, both patients had the following HLA types: HLA-Aw33(w19), -B44(12), and -DR6. These findings implicate the existence of another factor in the development of eosinophilia-myalgia syndrome in addition to the suspect L-tryptophan.

Aged