Yuichiro Maruyama

Electron-Microscopic and Inimunohistochemical Study of Beta-2-Microglobulin-Related Amyloidosis

beta 2-Microglobulin (beta 2-MG)-related amyloidosis has been reported as a complication in long-term hemodialysis patients. We observed beta 2-MG amyloid deposits in synovial sheaths, bone cysts and gastric mucosa. They showed unique ultrastructural features, that is bundles or nodules consisting of curved or linear amyloid fibrils, associated with various cell reactions. The electron-microscopic histochemical study showed that they strongly stained with periodic acid-silver methenamine stain. A similar phenomenon was noticed in the spicules or bundles of amyloid fibrils in primary and secondary renal amyloidosis. With the cationic reagent toluidine blue 0, proteoglycan-like structures were observed around amyloid bundles and nodules, but not on each fibrils. Based on these results, we postulate that there is a close relationship between ultrastructural features and histochemical characteristics in beta 2-MG amyloid fibrils.

Comparative Study of IgA Nephropathy with Acute and Insidious Onset

In order to clarify the difference of clinical and pathological features between the IgA nephropathy patients with acute and insidious onset, 427 patients were examined in this study. Seventy-eight patients with acute onset (group 1) were often associated with mucosal system infections at the abrupt onset. This group revealed macroscopic hematuria, more severe microscopic hematuria (more than 20/hpf), higher glomerular filtration rate (p less than 0.01) and lower serum levels of C3 (p less than 0.01). It had also a significantly higher incidence of exudative lesions (p less than 0.001). On the other hand, the onset of 349 patients (group 2) was noticed to be insidious without preceding infections. This group showed a more severe increase in mesangial cells (p less than 0.01) and a significantly higher incidence of adhesion, arterial sclerosis and tubulointerstitial changes. Deposition of Clq, C4 and IgM and detachment of visceral epithelium from the basement membrane were more frequently seen in group 2. Twenty-seven of 345 patients followed for at least 1 year after the biopsy were on maintenance hemodialysis: 1 patient was in group 1 and 26 were in group 2. These results clarified that there was a difference in clinical, laboratory and histopathological findings between the patients with IgA nephropathy with acute and insidious onset.

No linkage to the COL4A3 gene locus in Japanese thin basement membrane disease families

Summary: Patients with thin basement membrane disease (TBMD) exhibit persistent haematuria with a diffuse thinning of the glomerular basement membrane (GBM), especially of the lamina densa. It appears to be an autosomal dominant trait. It has been reported that the Goodpasture epitope, which is located in the non‐collagenous domain of type IV collagen α 3 chain, may be reduced in patients with TBMD. We speculated that the candidate gene for TBMD could be the type IV collagen α 3 chain gene (COL4A3), which is present closely to type IV collagen α 4 chain gene (COL4A4) on chromosome 2q35–37. We conducted a linkage analysis to investigate the relationship between familial TBMD and COL4A3 gene, using COL4A3 cDNA polymorphism and a (CA)n microsatellite marker located in the COL4A3 gene. We examined 32 individuals from four Japanese families with TBMD. There were no associations between the patients with haematuria and certain alleles of the two markers in the pedigrees of three families. It has been reported that type IV collagen α 1 chain gene (COL4A1) and α 2 chain gene (COL4A2) are not involved in TBMD, and that α 5 chain gene (COL4A5) and a 6 chain gene (COL4A6) map to chromosome X. In conclusion, our findings suggested that familial TBMD is not caused by the genetic abnormalities of type IV collagen genes isolated thus far.

Preservation of fixed anionic sites in the GBM in the acute proteinuric phase of cationic antigen mediated in-situ immune complex glomerulonephritis in the rat

SummaryCationic antigens have been observed to bind with the negatively charged glomerular basement membrane (GBM). Using the cationic reagent polyethyleneimine (PEI), the distribution of glomerular anionic sites was evaluated ultrastructurally in the early stage (2 h-day 7) of cationic antigen mediated in-situ immune complex formation type glomerulonephritis (GN) in the rat. — Renal perfusion via the renal artery with 100 μg of cationized human IgG (pl>9.5), followed by the i.v. injection of specific antibodies, led to an initial increase in urinary albumin excretion, subsequent massive globulinuria and the formation of numerous subepithelial deposits on day 7. — The most striking alteration in glomerular anionic sites was observed on the epithelial cell surface coat; the PEI deposition on the epithelial cell surface was almost identical to that in control glomeruli at 2 and 4 h after the induction of GN; thereafter, on day 7, a broad loss of anionic sites was obseryed on flattened epithelial foot processes. In contrast, fixed anionic sites of the laminae rarae of the GBM showed no apparent alterations in the distribution and number from 2 h to day 7 and did not disappear even in the lamina rara externa adjacent to subepithelial deposits. — These findings not only show that fixed anionic sites of the GBM, in contrast to the rapid decrease in those of the epithelial cell surface, are not completely neutralized or destroyed even in GN, in which cationic antigen participates in the in-situ formation of GBM-deposits. This also indicates that initial impairment of the charge-selective barrier of the GBM by the in-situ interaction between cationic antigen and antibody, is followed by the disfunction of the size-selective permselectivity of the GBM, ultimately causing massive proteinuria.

Clinicopathological study for renal disorders of patients with rheumatoid arthritis.

慢性関節リウマチ(RA)の腎障害を臨床病理学的に検討した.組織検索80例中,微小変化10例,メザンギウム増殖性糸球体腎炎21例(局所性変化7例,び漫性変化14例)は,血尿主体の尿異常を呈し,腎機能は良好であった.膜性腎症は8例で, 3例は特殊薬物の使用がなかった.アミロイドーシス合併は14例で,尿異常,腎機能低下が著明であった.膠原病重複は13例で,抗DNA抗体高値や低補体血症を高頻度に認めた.なお,螢光抗体法で,び漫性増殖性糸球体腎炎を中心に14例がIgA腎炎と診断され,また電顕的に糸球体基底膜のび漫性菲薄化を9例に認め,全例金療法歴を有していた. RAには多彩な腎病変が認められ,関節外症状として重要と思われた.

Clinical problems in chronic hemodialysis patients due to renal amyloidosis

腎不全のため血液透析を行った全身性アミロイドーシス12例 (骨髄腫随伴1例, 原発性4例, 続発性7例) について検討した. 続発性症例の原疾患は, RA 3例, 慢性腸炎1例, 中耳炎1例, 結核1例, ベーチェット病1例であった.初診時主訴は, 蛋白尿が7例と最も多く, 下痢3例, 巨舌1例, しびれ感1例であった. ネフローゼ症候群は8例に認められ, 治療抵抗性であった. 心アミロイドーシスが認められた症例は高窒素血症は軽度であったが, 肺浮腫のため早期の透析導入を余儀なくされたが, いずれも早期に死亡した. 心アミロイドーシスが認められない症例でも, 肺浮腫や全身浮腫のため早期の透析導入が行われた. 臨床的に心アミロイドーシスと診断されない例でも, 心エコー図, 心電図に異常所見が多く, 治療に抵抗性で, 心へのアミロイド物質と沈着が強く疑われた. また, 透析導入後新たに心アミロイドーシスが認められ, 心伝導障害のため死亡した症例もあり心アミロイドーシスは本症透析例の予後を左右する重要な因子と考えられた.腎, 心以外の障害としては, 透析中の血圧低下, 内シャント障害, 下痢, 腹痛などの消化器障害, 皮膚掻痒感, 甲状腺機能低下などが認められた. いずれも難治性であったが, 皮膚掻痒感に対してHDF, 甲状腺機能低下に対して甲状腺ホルモン薬が有効であった.