Kogo Onodera

Glomerular deposition of hepatitis C virus in membranoproliferative glomerulonephritis.

Hideaki Yamabe, MD, Second Department of Internal Medicine, Hirosaki University School of Medicine, 5 Zaifucho, Hirosaki 036 (Japan) References Johnson RJ, Gretch DR, Yamabe H, et al: Membranoproliferative glomerulonephritis associated with hepatitis C virus infection. N Engl JMed 1993;28:465-470. Yamabe H, Johnson RJ, Gretch DR, et al: Hepatitis C virus infection and membranoproliferative glomerulonephritis in Japan. J Am SocNephrol 1995;6:220-223. Doutrelepont JM, Adler M, Willems M, et al: Hepatitis C infection and membranoproliferative glomerulonephritis. Lancet 1993;341:317. Misiani R, Vicari O, Bellavita P, et al: Hepatitis C virus in renal tissue of patients with glomerulonephritis. Nephron 1994;68:400. Dear Sir, Membranoproliferative glomerulonephritis (MPGN) associated with hepatits C virus (HCV) infection has been recently reported [1] and its prevalence may be very high in primary MPGN [2]. This disease is clinically characterized by nephrotic syndrome, active HCV infection, frequent existence of cryoglobulinemia and hypocomple-mentemia and its pathogenesis is assumed to be caused by immune complex including HCV [1,2]. However, the glomerular deposition of HCV has not yet been demonstrated because the amount of HCV may be very small. We tried to detect the glomerular HCV deposition in this disease. Freezed kidney specimens obtained by renal biopsy in 6 patients were examined for glomerular HCV detection. Polyclonal rabbit antibody to HCV core antigen, which was provided by Dr. K. Shimotohno (National Cancer Center, Tokyo, Japan), was used as first antibody in the indirect immunofluorescence techniques. FITC-conjugated goat anti-rabbit IgG (Organon Teknika Co., Durham, N.C., USA) was used as second antibody. Negative control consisted of staining with normal rabbit serum or antibody to HCV absorbed with HCV core antigen, followed by FITCconjugated goat anti-rabbit IgG. Glomerular HCV deposition was observed in 2 of 6 patients with granular manner along the capillary wall and in the mesangium (fig. 1). Doutrelepont et al.

IgA Nephropathy and Henoch-Schönlein Purpura Nephritis with Anterior Uveitis

Two patients with IgA nephropathy and a patient with Henoch-Schönlein purpura nephritis each associated with anterior uveitis are described. As anterior uveitis accompanying IgA nephropathy improved, renal manifestations were relieved. The patient with Henoch-Schönlein purpura nephritis suffered from not only anterior uveitis but also keratitis. It is suggested that immune mechanisms which induce IgA nephropathy may play a role in the development of anterior uveitis and keratitis.

A case of sjögren's syndrome associated with sweet's syndrome

SummaryWe report a case of Sjögrens syndrome whose clinical course had been indolent until the patient presented with Sweets syndrome (acute febrile neutrophilic dermatosis). This patient showed renal failure and renal tubular acidosis. Sweets syndrome resolved within 3 weeks without corticosteroid therapy. Renal biopsy findings were consistent with interstitial nephritis. His renal manifestations responded to corticosteroid therapy and the renal function remained stable during 6 years follow-up without recurrence of Sweets syndrome. Although close association of both syndromes is already known, in our case Sjögrens syndrome may have been exacerbated by occurrence of Sweets syndrome.

Case Report of Amyloidosis-Like Glomerulopathy with Hepatic Involvement

A few cases of nephrotic syndrome with the glomerular deposition of an amyloid-like material which did not stain with Congo red have been documented. But extrarenal deposits have not been previously reported in this disease. We describe here a case of nephrotic syndrome associated with the deposition of an amyloid-like material in the liver as well as in the renal glomeruli. The deposits were made up of fibrillar structures which resembled those of amyloid when viewed through the electron microscope but they did not stain with Congo red. This is the first report of amyloidosis-like glomerulopathy with extrarenal deposits.

Glomerular Deposition of Hageman Factor in IgA Nephropathy

Glomerular localization of Hageman factor and fibrin-related antigen (FRA) was examined in 31 cases of IgA nephropathy by immunofluorescent techniques. Hageman factor was observed in 21 cases (68%) and FRA in 24 cases (77%). It is suggested that blood coagulation occurs and fibrin is formed in the glomerulus of IgA nephropathy.

Elevated serum secretory IgA in patients with IgA nephropathy.

Serum secretory IgA was measured to elucidate the significance of secretory IgA in patients with IgA nephropathy. The levels of serum secretory IgA and IgA were, respectively, 6.8 +/- 3.5 micrograms/ml and 231.0 +/- 69.2 mg/dl in the controls and 11.8 +/- 3.2 micrograms/ml and 385.3 +/- 78.7 mg/dl in the patients. The levels of serum secretory IgA and IgA in the patients were significantly higher than those in controls (p less than 0.01). Elevated serum secretory IgA may reflect the excessive state of the IgA-secreting system in IgA nephropathy patients.

Mechanism of Urinary Erythrocyte Deformity in Patients with Glomerular Disease

Hiroharu Kubota, MD, Second Department of Internal Medicine, Hirosaki University, School of Medicine, 5 Zaifucho, Hirosaki 036 (Japan) Dear Sir, Birch and Fairley [1,2] and Birch et al. [3] described glomerular bleeding giving rise to a wide range of morphological alterations in red cells such as dysmorphic red cells. In these alterations, we suspect that the doughnut type of deformity is the most characteristic (fig. 1). The mechanism of urinary erythrocyte deformity in patients with glomerular disease is considered to be the result of continuous changes in osmotic pressure and urinary pH in tubuli [2, 3]. However, in our experiments no doughnut-type erythrocytes were seen under osmotic pressure changes and there were no differences in urinary pH between the dysmorphic group (48 cases) and isomor-phic group (35 cases). In glomerular hematuria, another important factor was the passage of erythrocytes through the glomerular capillary wall composed of endothelium, basement membrane and foot process of epithelium [4, 5]. In view of the important finding that erythrocytes were distorted by passage through the ruptured glomerular capillary wall, we carried out further experiments as follows. 1 ml venous blood in 100 ml saline was incubated at 38 ¤C for 30 min. About 50 mm Hg pressure was applied to the suspended erythrocytes filtered by 3 kinds of membrane filters (pore size: 5 and 3 μm, fibrin-coated 5-μm narrowing in size). The filtrates were examined by phasecontrast microscopy and scanning electron microscopy. In this experiment, doughnut-type erythrocytes were seen in the fibrin-coated 5-μm membrane filter group and

Evaluation of Oxidized Low-Density Lipoprotein and Large Molecular Size Low-Density Lipoproteins in Atherosclerosis

To study the roles of modified low-density lipoprotein (LDL) and the molecular size of LDL in atherogenesis, the following studies were carried out. Eight white male rabbits fed a standard oriental diet with 1% cholesterol were used to isolate LDL and to observe changes in the molecular size of LDL due to cholesterol feeding. The tissue LDLs in the aorta were analyzed to confirm the existence of modified LDL (namely, LDL with peroxidized cholesteryl ester) by thin-layer chromatography. In addition, plasma LDLs were isolated from 18 patients with myocardial infarction and 11 patients with angina pectoris to confirm the existence of LDL with peroxidized cholesteryl ester. Each LDL separated consisted of 3 fractions; namely, IDL (1.006-1.018), LDL1 (1.019-1.052) and LDL2 (1.053-1.063) by sequential ultracentrifugation. The molecular sizes of LDL were measured by a planimeter from electron microscopic photographs, with negative staining. The estimation of peroxidized cholesteryl linoleate in LDL was performed using our method. The modified LDLs with peroxidized cholesteryl ester were poorly estimated in the LDL separated from the plasma of cholesterol-fed rabbits and from the aorta extraction after 16 weeks of feeding. The peroxidized cholesteryl ester was clearly identified in the plasma LDLs of the patients with myocardial infarction and angina pectoris, and in whole extracts from human aortic atheroma, although it was not clearly identified in the tissue LDL fraction. The molecular sizes of LDL1 enlarged week by week with cholesterol feeding, but two fractions of IDL and LDL2 did not change in size. The infusion of cholesterol-rich LDL of large molecular size or LDL with peroxidized cholesteryl ester into the vessels led to fixation, on the surface of the arteries of many platelets, red cells, and white cells, and to marked irregularities in the endothelial folds. The evidence suggests that atheromas, formed in a short period in rabbits with cholesterol feeding, are caused mainly by the increase in LDL1 of large molecular size, and that foam cells, formed in human atheromas, are caused mainly by the production of modified LDL with peroxidized cholesteryl ester.

Acceleration of platelet aggregability due to modulation of native LDL.

The aim of this experiment was to clarify whether low density lipoprotein (LDL) causes an acceleration of platelet aggregability. Native LDL was separated into two fractions by filtered tap-water dialysis, namely, water-soluble LDL (WS-LDL) and non-water-soluble LDL. Although native LDL did not enhance the platelet aggregability, WS-LDL made it markedly increased. WS-LDL consisted of the lipid constituents that were not found in native LDL. Namely, in thin-layer chromatography of WS-LDL, an unknown spot between triolein and free fatty acid was clearly stained. This unknown spot in the WS-LDL was produced by the peroxidation of cholesteryl ester in native LDL. It was confirmed that the spot has the same Rf value as the peroxidate of cholesteryl linolate in thin-layer chromatography. If native LDL is modulated by divalent metal ions and oxygen in the fluids, LDL with biological activity such as an increase of platelet aggregability is produced.

Elevated Salivary IgA in Patients with IgA Nephropathy

Elevated Salivary IgA in Patients with IgA Nephropathy H. Yamabe K. Ozawa K. Fukushi H. Ohsawa N. Chiba K. Onodera 2 Department of Internal Medicine, Hirosaki University School of Medicine, Hirosaki, Japan H. Yamabe, 2 Department of Internal Medicine, Hirosaki University School of Medicine, Hirosaki 036 (Japan) Dear Sir, Secretory IgA, which exists in mucosal surfaces of respiratory and digestive tracts, provides the primary defense mechanism against some local infections owing to its abundance in saliva, tears, bronchial secretions and mucous secretions of the small intestine [1]. It is well known that many patients with IgA nephropathy show deteriorated urinary findings when they have an upper respiratory tract infection. But there has been little interest in secretory IgA because it was not detected in the glomeruli [2, 3]. We examined salivary IgA to elucidate the significance of secretory IgA in IgA nephropathy patients. Saliva was obtained without any stimulus from 21 patients with IgA nephropathy and 16 normal controls. Salivary IgA and serum IgA were measured simultaneously by single radial immunodiffusion. The mean levels of salivary IgA and serum IgA were 24.1 ± 10.4 and 266.9 ± 100.9 mg/dl in the controls, 40.0 ± 16.1 and 414.6 ± 98.1 mg/dl in the patients. The levels of salivary IgA and serum IgA were significantly higher in the patients than in the controls (p < 0.001). There was a positive correlation between salivary IgA and serum IgA (r = 0.44, p < 0.01; fig. 1). All salivary IgA is secretory IgA. Secretory IgA is different from serum IgA in its origin, molecular weight and immunological property. It is widely recognized that the patients with IgA nephropathy often have elevated serum IgA, the causes of which remain unexplained. The reason of elevated salivary IgA is also unknown. Bene et al. [4] reported an imbalance in the IgAproducing system of patients with IgA nephropathy. They mentioned that the number of tonsillar IgA-secreting cells was higher than that of IgG-secreting cells in the patients, while the opposite was observed in the controls. Elevated salivary IgA may be caused by the change of the IgAsecreting system in IgA nephropathy.