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Biomedical subjects

Y Hamashima

Publications and source records attributed to Y Hamashima.

At least 109 records · Page 6Linked to original sources

Detection of IgA class circulating immune complexes bound to anti-C3d antibody in patients with IgA nephropathy.

IgA class circulating immune complexes (CIC) were detected by solid-phase fluorescent enzyme immunoassay of F(ab')2 anti-C3d antibody in the serum of 52 patients with IgA nephropathy. Conglutinin (Kg) binding IgA class CIC were also measured, and results by these assays were compared. Kg binding IgA class CIC and anti-C3d binding IgA class CIC were detected in 27% and 44%, respectively, of the patients with IgA nephropathy. Either or both of the two were found in 65% of the patients. There was no significant correlation between IgA class CIC detected by these methods and serum IgA. Although all samples with a very high level of anti-C3d binding IgA class CIC did not also have a very high level of Kg binding IgA class CIC, there was a slight quantitative correlation between the 2 assays. Ultracentrifugation analysis showed that anti-C3d binding IgA class CIC were of various sizes between polymeric (21 S) and monomeric IgA (7 S), whereas Kg binding IgA class CIC were mostly monomeric IgA (8 S) with a minor component of heavy fractions (14 S). Both IgA class CIC fixed iC3b and IgA class CIC fixed C3d are present in IgA nephropathy. These observations suggest that the different types of complement bound to IgA class CIC have different roles in IgA nephropathy.

Antigen-Antibody Complex↗

Dermatopathological studies on skin lesions of MRL mice.

The MRL-lpr/lpr(MRL/l) mouse is a new animal model for human systemic lupus erythematosus (SLE) and skin lesions with hair loss and scab formation are one of the characteristic manifestations in this mouse. We investigated the histopathology of the skin lesions in MRL/l mice and studied the related autoimmune phenomenon. Light microscopical observations revealed hyperkeratosis, acanthosis, hypergranulosis, liquefaction, vasodilation in the dermis and T-cell infiltration into the dermis at the age of 5 months (mo). Immunohistological studies showed the presence of immunoglobulins and/or complement depositions at the dermal-epidermal junction (DEJ). In some mice there was deposition of immunoglobulin at the DEJ at 2 mo and in 90%-100% of MRL/l mice at over 5 mo. Temporal relationship was present among cutaneous immunoglobulin depositions, the occurrence of anti-DNA antibodies and proteinuria. These findings suggest that MRL/l mice might provide a new aid for studying the biological mechanisms of the development of skin lesions in human SLE.

Age Factors↗

Anti-hapten antibodies and autoantibodies in Japanese patients with lepromatous leprosy.

In the sera of patients with lepromatous leprosy anti-DNP antibodies were detected in order to determine the mode of polyclonal B-cell activation. Anti-DNP antibodies were found in 30% of the patients with active lepromatous leprosy and in 8% of those with inactive lepromatous leprosy. The level of anti-DNP antibodies in active patients was significantly higher than the level in inactive patients and control. However, the presence of anti-DNP antibodies was unrelated to the production of circulating immune complexes and antinuclear antibodies. These results suggest that polyclonal B-cell activation might occur but that the B-cell clones stimulated by M. leprae are different from patient to patient.

Adult↗

Ultrastructural observations of skin lesions in MRL mice--dermoepidermal junction.

The MRL-lpr/lpr (MRL/l) mouse, a new animal model for the study of human systemic lupus erythematosus (SLE), shows characteristic skin manifestations in addition to several systemic autoimmune phenomena. The ultrastructural changes observed in the dermoepidermal junction (DEJ) and in the uppermost dermis were: infolding of the DEJ; deformities of the basal lamina--partial disappearance, thickening, hanging down, duplication, and separation from the basal cell membrane; basal laminalike dense material in the uppermost dermis and increased anchoring fibrils; particles composed of circulated half-desmosomes between the basal cells and the basal lamina, and in the uppermost dermis with or without an enclosing basal lamina; cell processes of the basal cells; and invagination of the basal lamina in the basal cells. Most of these findings were similar to the ultrastructural changes observed in the skin lesions of human SLE. The skin eruptions of MRL/l mice might be a new aid in the investigation of the pathogenesis of the skin lesions of human SLE.

Animals↗

Immunopathological correlation between mesangial C3d-deposition and C3d-fixing circulating immune complexes in lupus nephritis.

By a direct immunofluorescent technique, glomerular C3d deposition was examined in a total of 50 renal biopsy specimens from patients with lupus nephritis. C3d deposition was then compared with disease activity, glomerular IgG and C3c deposition, and the levels of circulating immune complexes (CIC) measured by a solid-phase anti-C3d assay. There was a good correlation between disease activity and the positivity of glomerular C3d deposits (P less than 0.001), as well as C3c deposits (P less than 0.001). Even in clinically inactive patients, a relatively high percentage (59%) of C3d deposits were positive compared with C3c deposits (17%). Mesangial C3d deposition correlated with clinical disease activity more significantly (P less than 0.005) than capillary wall C3d deposition (P less than 0.025). C3d deposits were detected in all of the 30 cases with positive C3c deposits, and moreover, in 15 of the 20 (75%) cases with negative C3c deposits. Glomerular IgG deposits were almost always associated with C3d deposits, both in mesangial areas and along capillary walls, with statistical significance (P less than 0.005, P less than 0.001, respectively). The serum levels of C3d-fixing immune complexes (IC) were significantly correlated with the positivity and intensity of mesangial C3d deposits. This study demonstrates glomerular deposition of C3d in patients with lupus nephritis and reveals a significant correlation between mesangial C3d deposition and disease activity.

Antigen-Antibody Complex↗

Lack of synergy between T and B cells in the response to 2-mercaptoethanol in old NZB/W F1 mice.

The responses of NZB X NZW (NZB/W) F1 mice to 2-mercaptoethanol (2-ME) were examined from the viewpoint of T-B cell interaction. Young (1-month-old NZB/W F1 mice responded to 2-ME in an almost similar pattern to that of BALB/c mice, although a slightly higher rate of DNA synthesis was observed in B cell-enriched cultures (75% B cells) containing 2-ME than in those of BALB/c mice. Old (9-mth-old) NZB/W F1 mice showed an absent synergistic effect of T and B cells in the response to 2-ME. These results indicate an abnormality of T-B cell interaction particularly in old NZB/W F1 mice.

Animals↗

Immunoelectron microscopic studies of IgA nephropathy.

Immunoelectron microscopy was used in this study of IgA nephropathy to examine the relationship between immune deposits and electron-dense deposits seen by electron microscopy, and these findings were correlated with the severity of mesangial proliferation. Immunoelectron microscopic studies for antihuman gamma-chain, alpha-chain, mu-chain, C3, and C3d were performed by the method of Nakane in 16 patients with IgA nephropathy. The patients with minimal glomerular involvement and focal proliferative glomerulonephritis showed electron-dense reaction products of IgA in the paramesangial area, while the patients with diffuse proliferative glomerulonephritis showed electron-dense reaction products of IgA throughout the enlarged mesangial matrix. Immunoelectron microscopy showed electron-dense reaction products of IgA at the same locations as the electron-dense deposits seen on electron microscopy. C3 deposits were identified in 15 out of the 16 patients, but were less dense than IgA deposits. Electron-dense reaction products of C3 contained both positive and negative sites in 7 patients. Extensive C3d deposits were found in all cases in association with IgA deposits. The locations of these deposits were the same as those of the IgA deposits. These findings suggest that C3 deposits dissociate from the immune deposits and that the locations of the immune deposits correlate well with the severity of mesangial proliferation.

Biopsy↗

Demonstration of C3d deposits in membranous nephropathy.

An immunoperoxidase technique for light microscopy was carried out in 16 patients with idiopathic membranous nephropathy in order to determine the role of the complement system in glomeruli. Although C3 deposits are found in 50% of the cases, C3d deposits are identified in all cases in association with IgG deposits. This suggests that C3 deposits are degraded and dissociated from immune complexes. Patients with glomerular C3 deposits showed more proteinuria than those without glomerular C3 deposits. The presence of C3 deposits indicates the importance of proteinuria in human membranous nephropathy.

Antigen-Antibody Complex↗

Distribution of IgG subclasses in membranous nephropathy.

The distribution of human IgG subclasses among the glomerular deposits in human membranous nephropathy was examined by immunofluorescence with subclass specific monoclonal antibodies. Large amounts of granular deposits of IgG4 were identified along the capillary loops in all 12 patients, and seven patients had small amounts of IgG1 deposits. Neither IgG2 nor IgG3 deposits were detectable in any of the patients. On the contrary, all four IgG subclasses were detected in membranoproliferative glomerulonephritis and lupus nephritis with a predominance of IgG1 and IgG3. The results indicate that IgG4 is predominant in the glomerular deposits in membranous nephropathy and may play an important role in its pathogenesis.

Complement System Proteins↗

Monostotic fibrous dysplasia in the femoral neck. A clinicopathologic study.

In eight patients with monostotic fibrous dysplasia in the femoral neck, the lesion was virtually limited to the neck region without any extension into the shaft. In one patient with symptoms of 40 years' duration and another with a recurrent lesion, there was a deformity in the neck of the femur. A pathologic fracture, including a minor one, was identified in two patients. Roentgenographically, the lesion should be distinguished from various entities producing a localized central region of rarefaction in the proximal femur. The histologic features of fibrous dysplasia are characteristically diagnostic. Six of the eight patients were successfully treated by curettage and bone graft. There was no evidence of malignant transformation.

Adolescent↗

Correlation of C3d fixing circulating immune complexes with disease activity and clinical parameters in patients with systemic lupus erythematosus.

Using anti-C3d as a solid phase reagent, C3d fixing circulating immune complexes (CIC) were detected in sera from patients with systemic lupus erythematosus (SLE), rheumatoid arthritis, membranous nephropathy and IgA nephropathy. Particularly, sera from SLE showed the highest CIC levels and highest incidence of positivity among these diseases. In the 51 serum samples from 48 patients with SLE we studied, the CIC detected by the anti-C3d assay correlated well (P less than 0.01) with the CIC detected by the solid phase C1q assay, but not with those detected by the conglutinin assay. In addition, the CIC detected by the anti-C3d assay correlated more significantly (P less than 0.001) with disease activity, as well as some clinical parameters (serum anti-dsDNA antibodies, CH50 and C3 levels) than CIC detected by the other two assays of SLE sera. The anti-C3d binding materials were found to be of intermediate (8-19S) and small (7S) sizes in a small number of SLE sera which we analysed.

Antigen-Antibody Complex↗