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Biomedical subjects

I Kawabata

Publications and source records attributed to I Kawabata.

At least 55 records · Page 3Linked to original sources

Alleviation of autoimmunity in BXSB mice by monoclonal alloantibody to Ly-5 (CD45).

One of the hallmarks of immunological abnormalities in mice that are prone to syndromes resembling systemic lupus erythematosus is polyclonal activation of B cells and a switch of serum immunoglobulins or autoantibodies from IgM to IgG that coincides with onset of autoimmune disease. Therefore, we investigated whether the development of autoimmunity can be alleviated in such mice by administration of monoclonal alloantibody directed against Ly-5, because this was known to reduce levels of polyclonal IgG antibody without affecting other immunoglobulin isotypes. Our results indicate that at least some forms of autoimmune disease may be effectively treated by thus reducing the concentration of IgG autoantibody in this manner.

Animals↗

Successful pregnancy in a patient with paroxysmal nocturnal hemoglobinuria: case report.

In this report, the maternal and fetal risks in a patient with paroxysmal nocturnal hemoglobinuria (PNH) were evaluated. A patient with PNH carried a pregnancy to successful delivery, with a healthy male infant, and suffered from postpartum cerebral subcortical thrombosis followed by recovery. An elevated level of serum lactate dehydrogenase isoenzyme (alpha-hydroxybutyrate dehydrogenase) was observed during pregnancy; the level returned to normal by delivery. However, the hemoglobin concentration during pregnancy and post-partum was kept at 8 g/dl. This is the first report of a relation between the onset of hemolysis and pregnancy. The management of pregnancy in such patients is discussed.

Adult↗

Antenatal evaluation of upper gastrointestinal dilatation complicated by non-immune hydrops fetalis and polyhydramnios.

A case of upper gastrointestinal dilatation associated with fluid collection in the peritoneal cavity is reported where the prenatal diagnosis was made sonographically in a non-immunologic hydrops fetalis. Neither generalized edema nor pleural effusion were detected. Polyhydramnios was complicated. Almost complete drainage of the abdominal fluid was accomplished with rapid re-accumulation of fetal ascites and no resolution of intestinal dilatation. After delivery by Cesarean section, the male infant died the next day due to respiratory distress syndrome. Postmortem histologic examination failed to confirm the ultrasonographic findings including ileal obstruction and subsequent hypoplasia in the colon. Despite the discrepancy between clinical and pathologic findings, the findings of this case would improve the etiology of hydrops where no possible cause is found.

Adult↗

A good outcome pregnancy in a patient with paroxysmal nocturnal hemoglobinuria.

In this report, the maternal and fetal risks in a patient with paroxysmal nocturnal hemoglobinuria (PNH) were evaluated. A patient with PNH carried a pregnancy to successful delivery, with a healthy male infant, and suffered from postpartum cerebral subcortical, but not hepatic, thrombosis followed by recovery. An elevation of serum levels of lactate dehydrogenase isoenzyme, alpha-hydroxybutyrate dehydrogenase, was observed during pregnancy. The level was ameliorated to the non-pregnant level by delivery. However, hemoglobin concentrations during pregnancy and post-partum were at least 8 g/dl. This is a first report that shows tight coupling between an onset of intravenous hemolysis and pregnancy. The management of pregnancies in such patients is also discussed.

Adult↗

[Functional and structural analysis of the Lyb-2 system].

The Lyb-2 system of the mouse is a B cell-specific cell surface molecule encoded by a gene on chromosome 4. We have previously reported that Lyb-2 is involved in an early phase of B cell differentiation, specifically a process mediated by B cell stimulatory factor-1 (BSF-1) or-interleukin 4. It is thus very important to define the functional role and structural features of Lyb-2 molecule for the understanding of the regulatory mechanisms of B cell activation initiated by BSF-1. In our attempt to resolve these issues, we found that Lyb-2 antibody inhibits activation processes mediated by BSF-1 such as induction of Ia antigen on the B cell surface and of IgG1 production in lipopolysaccharide-activated B cells, suggesting that Lyb-2 molecule participates in a signaling event triggered by the binding of BSF-1 to its receptor. In the structural analysis, we found that in contrast to previous reports, Lyb-2 is not a monomer of 45 kilodaltons (kDa) but is composed of two components with molecular weight of 45 kDa and 105 kDa. Reduced and nonreduced two-dimensional electrophoresis analysis further revealed that Lyb-2 molecules are present on the B cell surface in two forms, a disulfide-bonded heterodimer of 45 kDa and 105 kDa chains and a 45 kDa homatrimer. How the structural uniqueness of Lyb-2 is related to its functional expression remains to be determined.

Animals↗

Differential regulation by Ly-5 and Lyb-2 of IgG production induced by lipopolysaccharide and B cell stimulatory factor-1 (IL-4).

We have previously shown that mAb Ly-5 which on B cells recognizes a 220,000-Da (B220) molecule, inhibits LPS-induced IgG responses without affecting IgM or proliferative responses, whereas mAb Lyb-2 which modulates B cell activation processes induced by B cell stimulatory factor-1 (BSF-1) or IL-4, has no effect on LPS-induced B cell responses. In this report we further examined the cellular mechanisms of Ly-5 antibody action and the effect of Lyb-2 antibody in IgG responses induced by LPS and BSF-1. The results presented demonstrated that the inhibitory effect of Ly-5 antibody seems to be restricted to the IgG class and is observed in all IgG subclasses induced by LPS. Limiting dilution analysis showed that the Ly-5 antibody reduces primarily the precursor frequency of IgG-secreting cells and that the effect on the clone size is partial. Lyb-2 antibody, on the other hand, greatly inhibited IgG1 induction initiated by LPS and BSF-1 by the action on processes triggered by BSF-1, although it could not reverse the reduced IgG2b or IgG3 responses. Limiting dilution analysis revealed that Lyb-2 antibody reduces the precursor frequency but not the clone size of BSF-1-induced IgG1-producing cells, supporting our previous proposition that Lyb-2 plays a critical role in the B cell differentiation mediated by BSF-1. Taken together, these results indicate that both Ly-5 and Lyb-2 are important molecules in IgG subclass regulation, each acting on a distinct activation step.

Animals↗

Computerized three-dimensional reconstruction of the crypt system of the palatine tonsil.

The purpose of the present study is to note the three-dimensional structure of the tonsillar crypt using computer graphics methods. The tonsils used herein were human tonsils obtained from the surgical operation, and were cut in serial sections according to ordinary procedures. The crypt contours obtained from the serial sections were used as inputs to the computer (PC-9801 VM) through the image-scanner (PC-IN 502). The three-dimensional structure of the human tonsillar crypt revealed by computer graphics, showed that the crypts had not only branches but also anastomosis, and that they could divide into two types, a simple unbranched crypt and a complicated branched one. Generally, the simple type of crypt was located in the peripheral zone of the tonsils and the complicated type in the central zone. These findings are discussed briefly and with reference to previous reports.

Child↗

[Induction of thymocyte proliferation with B cell stimulatory factor-1].

Murine B cell stimulatory factor (BSF)-1 or interleukin 4 has been shown to regulate various aspects of B cell activation and differentiation. More recently it has been shown that this lymphokine is also involved in the regulation of T cell and mast cell proliferation. In this study we purified BSF-1 activity from supernatants of T cell hybridoma FS6-14. 13 and tested its activity on a variety of in vitro assays. It was found that the purified BSF-1 material has various activities previously ascribed to BSF-1, and interestingly enough it also induces strong proliferation of thymocytes in collaboration with phytohemagglutinin. These results strongly suggest that BSF-1 plays a regulatory role in thymocyte differentiation and further support the notion that lymphokines generally have a broad spectrum of activity.

Animals↗

A role for Lyb-2 in B cell activation mediated by a B cell stimulatory factor.

The Lyb-2 system of the mouse is involved in regulation of a proliferative step in the differentiation of B cells responding to T-dependent antigen. The present study concerns the role of Lyb-2 in an early phase of B cell activation with respect to B cell receptor functions for activation factors. It is shown that interaction of monoclonal anti (alpha)-Lyb-2 antibody with Lyb-2 on the B cell surface induces B cell proliferation by synergistic action with B cell growth factor II-containing factor or interleukin 1. In contrast, alpha-Lyb-2 antibody could not synergize with the Con A-induced culture supernatant of T cell hybridoma FS6-14.13 (FS6) containing B cell stimulatory factor-1 (BSF-1; formerly called BCGF I), and the effect of combining the two was only additive on B cell proliferation. Absorption studies showed that BSF-1 in FS6 could be absorbed by unstimulated B cells, about 95% of which were at Go phase of the cell cycle, but not by thymocytes, and more importantly that alpha-Lyb-2 antibody blocked the absorption in an Lyb-2-specific manner, possibly by competing with BSF-1. It is thus likely that alpha-Lyb-2 antibody may interact with a BSF-1 receptor on B cells or a molecule closely associated with it. Interestingly, alpha-Lyb-2 antibody mimicked the action of BSF-1 in a costimulator assay with affinity-purified goat alpha-mouse IgM antibody, but could not replace all the activities ascribed to BSF-1. Possible mechanisms involved are discussed.

Animals↗

Selective inhibition of lipopolysaccharide-induced polyclonal IgG response by monoclonal Ly-5 antibody.

We have identified two important molecules involved in the regulation of B cell differentiation, namely Lyb-2 and Ly-5. To gain further insight into the function of these two molecules, we examined the effect of monoclonal Lyb-2 and Ly-5 antibodies on lipopolysaccharide (LPS)-induced B cell growth and maturation. We found that Lyb-2 antibody does not have any effect on LPS-induced proliferation and on polyclonal IgM or total IgG responses. On the other hand, although Ly-5 antibody did not affect proliferation and polyclonal IgM responses, it strongly inhibited polyclonal IgG responses, presumably by direct action on B cells. This inhibition was not caused by direct suppressive effect of Ly-5 antibody or Fc receptor-mediated negative signaling. To exert maximal inhibitory effect, Ly-5 antibody had to be added to the culture during the initial 48 hr. However, the presence of Ly-5 antibody during the first 2 days did not cause a significant inhibition. It is thus likely that Ly-5 plays a critical role in the regulation of LPS-induced B cell maturation into IgG-secreting cells at a phase starting within 48 hr after LPS stimulation and continuing thereafter.

Animals↗

[Clinical evaluation of the TMS-19-Q.GC tablet in acute tonsillitis. A comparative double blind study with josamycin].

In order to compare the clinical efficacy and safety of TMS-19-Q.GC tablet (TMS) with josamycin tablet (JM) in acute tonsillitis, the double blind trial was carried out with the daily dosage of 200 mg X 3 in TMS and 400 mg X 3 in JM. Number of cases evaluated for clinical efficacy were 154 cases (73 treated with TMS and 81 treated with JM). The effective rating of TMS and JM were 89.0% and 88.9% judged by doctors in charge, and 82.2% and 85.2% judged by committee respectively. Bacteriological effects were satisfactory to yield the eradication rates of 93.8% in TMS and 94.7% in JM. Number of cases evaluated for safety were 199 cases (101 treated with TMS and 98 treated with JM). The incidence of side effect was 4.0% (4/101) in TMS and 5.1% (5/98) in JM and most of them were mild gastro-intestinal disorders. Number of cases evaluated for utility were 156 cases (74 treated with TMS and 82 treated with JM). The usefulness rates were 85.1% in TMS and 86.6% in JM. There was no significant difference between TMS and JM, in clinical effect, bacteriological effect, safety and utility. From these results, daily 600 mg dosage of TMS was as useful as daily 1,200 mg dosage of JM in the treatment for acute tonsillitis.

Acute Disease↗

Detection of delayed endolymphatic hydrops by the furosemide test.

Delayed endolymphatic hydrops, an entity which can be differentiated from Meniere's disease, was first reported simultaneously by Nadol et al. (1975) and Wolfson & Leiberman (1975) and specified by Schuknecht (1978). They diagnosed it from the anamnesis of patients and confirmed the hydropic condition of the labyrinth solely by evidence obtained from surgical procedures such as labyrinthectomy. The aim of the present study was to emphasize the usefulness of the furosemide test for distinguishing this entity before surgery by detecting the hydropic condition in the labyrinth. In these 3 years, we encountered 11 cases of endolymphatic hydrops, 9 ipsilateral and 2 contralateral, in our clinic (Univ. of Tokyo Hospital). Among the ipsilateral cases, the estimated genesis of pre-existing hearing loss was most frequent in mumps (44%). The result of the furosemide test in this group was 89% positive. On the basis of this result, we have been able to choose the method of treatment, i.e. 4 cases treated by epidural shunt operation on the endolymphatic sac, 2 by labyrinthectomy, one by cochleosacculotomy and 2 by medication with steroids and diuretics. In the 2 contralateral cases, one was treated by epidural shunt and the other by medication. The authors are therefore able to confirm the usefulness of the furosemide test for detecting delayed endolymphatic hydrops.

Adult↗