[Regional distribution of sulfatide in human kidney, and anti-sulfatide antibodies in sera from patients with nephritis detected by TLC immunostaining].

Glycolipids were isolated from lipid extract of human kidney. The major neutral glycolipids have been identified as ceramide monohexoside (CMH), ceramide dihexoside (CDH), ceramide trihexoside (CTH), and globoside. As the major acidic glycolipids, Gal Cer sulfate (sulfatide), Lac Cer sulfate, GM3, sialosyl paragloboside, GD3, and disialosyl paragloboside were identified and the most abundant component was sulfatide. Sulfatide was 2 times more concentrated in medulla compared to cortex. In addition, the localization of sulfatide antigen was determined in renal sections by immunoperoxidase staining method. Strong positive staining with sulfatide was observed in distal tubules, limbs of Henle's loop and collecting tubules of normal tissue, whereas glomeruli were negative of staining. However, positive results of glomerular epithelial cells occurred in FSGS and IgA nephropathy so far. Acidic fraction of lipid extract were chromatographed and then tested for antigen by immunostaining. Sera from patients with nephritis contain antibodies to the sulfatides of human kidney as determined by the direct binding of antibody to thin-layer chromatograms. These results suggest that sulfatide antigen may play important role in the occurrence and aggravation of glomerular diseases.

Autosomal recessive polycystic kidney in rats.

We evaluated the characteristics of renal lesions in rat autosomal recessive polycystic kidney (ARPK). In rat ARPK, small cysts appeared primarily in the medulla 2 months after birth and gradually extended to the cortex, forming large cysts involving the entire layer after 8 months. By immunofluorescence microscopy, type IV collagen was more strongly stained in the epithelial basement membrane of the rat ARPK than in the normal rat tubular basement membrane (TBM). Electron microscopy demonstrated a marked thickening, slight splitting and lamination of the TBM in the ARPK. As peroxidase-labeled lectins, dolichos biflorus very strongly stained the cyst epithelium whereas lens culinaris did not. These findings indicate that cysts in rat ARPK originate in the collecting duct.

[A study of an autosomal recessive polycystic kidney disease with facial and skeletal abnormalities in rat].

Clinico-pathological studies were made on rats with polycystic kidney disease (PCK), a congenital renal disorder transmitted as an autosomal recessive trait and characterised by facial and skeletal anomalies, with the results summarised as follows: 1) Affected animals had a poor weight gain and slightly increased urinary excretion of low molecular weight protein from 2 months after birth, and developed polyuria and hypocalciuria 5 months postnatally. They had elevation of serum urea nitrogen, increased urinary excretion of urea nitrogen and hypoproteinemia 8 months postnatally though without showing elevated serum creatinine and died around 10 months of life. 2) Kidneys of chin rats appear granular in surface, enlarge little by little while preserving the entire kidney morphology; a small cyst is formed in the renal medulla 2 months postnatally, then enlarges gradually to encroach upon the cortex and grows to involve all cortical layers by 8 months of life. This cyst was revealed by lectin staining to be derived from the collecting ducts and was assumed to correspond, both morphologically and clinically, to the infantile or juvenile form of PCK in humans. Pathogenetic factors of the characteristic facies and skeletal abnormalities were also investigated.

Portions of basement membrane with decreased negative charge in various glomerulonephritis.

The decrease in negative charge was evaluated in different portions of the basement membrane as well as the lamina rara externa (LRE) and lamina rara interna (LRI). The subjects were nine patients [2 patients with focal segmental glomerulosclerosis (FGS), 2 with membranoproliferative glomerulonephritis (MPGN), 3 with IgA nephropathy, and 2 with Henoch-Schoenlein purpura nephritis (HSPN)] and 2 patients with minor glomerular abnormalities and 1 with tubulo-interstitial nephritis (TIN) as controls. Polyethyleneimine (PEI) was used as a cationic probe. The basement membrane was divided into the peripheral portion (loop basement membrane 7 microns or more from the anchor portion), proximal portion (within 3 microns of the anchor portion), and the paramesangial portion in the paramesangial basement membrane. In each portion, PEI granules per 1 micron of the LRE and LRI were counted. Anionic sites were decreased in the patients with FGS and MPGN, but the damage pattern differed between the two diseases. In the patients with FGS, the decrease in anionic sites was most marked in the peripheral portion with an even greater decrease in the LRI. In the patients with MPGN, the decrease was uniform among the portions. On the other hand, no significant difference was observed in any portion between the patients with IgA nephropathy or HSPN and the controls. The portions with decreased negative charge varied among various glomerular diseases, suggesting different developmental mechanisms.

[Clinicopathological studies of 10 cases with focal segmental glomerulosclerosis].

The clinical picture, histopathological findings, therapy and prognosis of focal segmental glomerulosclerosis (FSGS) were investigated in a retrospective study involving 10 cases. The age of patient at the time of detection ranged from 3 to 19 years, 11 years on the average, being 9 years or above in 6 cases. There was noted a slight tendency toward predominance of males in this series. The disease was detected casually on the occasion of mass survey of urine at school in 6 cases (60%), while by clinical examination on visiting us with nephrotic syndrome in the other 4 (40%). Of the former 6 cases, 5 developed nephrotic syndrome while placed under medical surveillance. Nine of the 10 cases were treated mainly with corticosteroids, to which 5 (50%) were unresponsive and 4 (40%) responsive, with 1 (10%) of these 4 becoming unresponsive since a recurrence. Corticosteroids were not used in 1 case (10%). During follow-up period (which ranged from 1 to 10 years) 6 experienced an elevation of serum creatinine above 2.0 mg/dl, with 5 of them being unresponsive to corticosteroids and 3 begun on hemodialysis therapy. Histologically, cases in which the sum of the proportions of glomeruli affected with segmental sclerosis and with global sclerosis exceeded 30% and, in addition, there were severe tubulointerstitial lesions tended to have a poor prognosis, while those in which sclerosis involved less than 30% of glomeruli and no interstitial damage was discernible had a relatively favorable prognosis and were more frequently responsive to corticosteroids. These findings led us to conclude that FSGS has an ominous prognosis as reported previously and notably, the prognosis is much poorer for the non-steroid-responding type than for the responding type. The study also suggests that the degree of severity of histological changes is determinant of the prognosis of the disease.

Suppressor T-lymphocyte dysfunction in MCNS: role of the H2 histamine receptor-bearing suppressor T lymphocytes.

To evaluate the number and function of suppressor T cells in children with minimal change nephrotic syndrome (MCNS), we performed an inhibition test of rosette formation and measured leukocyte procoagulant activity. The number of histamine H2 receptor-bearing T lymphocytes (histamine H2 R+ lymphocytes) was markedly decreased at the onset of MCNS but gradually increased and was normalized following steroid therapy. The production of leukocyte procoagulant activity by normal T lymphocytes was abolished by incubation with patient's lymphocytes. However, pretreatment of the normal T lymphocytes with cimetidine markedly decreased the suppression. The results suggest an abnormality in the histamine H2 receptors on the patient's suppressor T lymphocytes.

Thyroid antigen-antibody nephritis: possible involvement of fucosyl-GM1 as the antigen.

Hyperthyroidism, microscopic hematuria, and proteinuria developed in an 11-year-old girl. Proteinuria decreased during treatment of hyperthyroidism with an antithyroid drug. On admission, serum anti-thyroglobulin antibody, antimicrosomal antibody, and immune complex were present. The thyrotropin binding inhibitory immunoglobulin (TBII) level was low. On the other hand, an antibody to the ganglioside component (fucosyl-GM1) was detected by an enzyme linked immunosolvent assay (ELISA). A thyroid biopsy specimen showed massive lymphocytic infiltration and interstitial fibrosis. A renal biopsy specimen showed marked proliferation of mesangial cells and increased mesangial matrix with focal segmental capillary wall abnormality. Electron microscopec studies demonstrated mild paramesangial dense deposits. By indirect immunofluorescence, granular glomerular basement membrane and mesangial staining were not detected with rabbit antibody to thyroglobulin, but were detected with rabbit antibody to fucosyl GM1. Fucosyl GM1 was also seen along the basilar aspect of the thyroid follicular epithelial cells. These observation suggests the development of glomerulonephritis mediated by thyroid antigen, particularly ganglioside component.