Ken Satoh

Induction and altered localization of 90-kDa heat-shock protein in rat kidneys with cisplatin-induced acute renal failure.

We purified 90-kDa heat-shock protein (HSP90) from murine brains and produced a specific antibody against the protein in a rabbit. This antibody cross-reacted with rat renal HSP90 on immunoblot analysis. Using the antibody, we observed serial immunohistochemical localizations of HSP90 in rat kidneys with cisplatin-induced acute renal failure. In normal kidneys, HSP90 was mainly localized in the cytoplasm of distal tubules and collecting ducts. Twenty-four hours after the cisplatin exposure, a rapid expression of HSP90 was observed in the cytoplasm of epithelial cells in the Henles loops (especially at the luminal side), although there was little change in these cells on light microscopy. Degenerative changes of epithelial cells appeared in the S3 segment of proximal tubules on day 3, and epithelial cell regeneration in this portion was found from day 5. On day 5, HSP90 was markedly expressed in both the cytoplasm and the nucleus of epithelial cells in the S3 segment with a granular pattern. The induced HSP90 was then accumulated in the cytoplasm of these cells on day 7 and disappeared on day 14. Immunoblot analysis of isotonic buffer-extractable renal fractions showed that there was a rapid induction of HSP90 from day 1, and that the maximum induction of HSP90 in the extract at day 5 was 6-fold that of a control. These results suggest that HSP90 plays some role related to functional abnormalities of the Henles loops at the luminal side, and in the regeneration of damaged cells in the S3 segment of proximal tubules, during the course of cisplatin-induced acute tubular injury.

Sclerodermatous Renal Crisis in a Patient With Mixed Connective Tissue Disease

We report a patient with mixed connective tissue disease who developed accelerated hypertension, acute renal insufficiency, and microangiopathic hemolytic anemia. A renal biopsy specimen showed marked vascular changes in small arteries consisting of laminated endothelial cell proliferation and luminal thrombosis, which were similar to those of scleroderma renal crisis. This patient was successfully treated with an angiotensin-converting enzyme inhibitor as well as analogues of prostaglandin E1 and prostaglandin I2. In patients with mixed connective tissue disease, a fatal complication like scleroderma renal crisis should be considered when the blood pressure rapidly increases. The combined administration of angiotensin-converting enzyme inhibitors and analogues of prostaglandin E1 and prostaglandin I2 may be an effective treatment for this complication.

Diffuse Pulmonary Infiltrates as a Roentgenographic Manifestation of Primary Pulmonary Plasmacytoma

5926) is the only yeast that has been tested in doubleblind studies (1). The manufacturer claims that S boulardii is not identical to S cerevisiae (2). However, some authors consider S cerevisiae to be synonymous with S boulardii, and have successfully treated patients with baker’s yeast for C difficile diarrhea (5). Treatment with S boulardii has previously been shown to cause invasive fungal disease in 7 patients (6 –10). All of these cases occurred in debilitated or immunosuppressed patients who had central venous lines. All patients, like ours, recovered with systemic antimycotic treatment.

Pan-nephritis (glomerulonephritis, arteriolitis, and tubulointerstitial nephritis) associated with predominant mesangial C1q deposition and hypocomplementemia: a variant type of C1q nephropathy?

A 35-year-old man showed acute nephritic syndrome manifested as proteinuria, hematuria, and hypocomplementemia after upper respiratory infection. A renal biopsy showed mild to moderate mesangial proliferative glomerulonephritis with an accumulation of mononuclear cells in the capillary loop and with the deposition of C1q (graded as 3+), immunoglobulin (Ig) G, C3 (2+), IgA, IgM, and fibrinogen (weak to 1+), and mononuclear cell infiltration of the glomerular hilus, arterioles, and proximal tubules, which was a peculiar form of renal lesion. The mesangial deposition of C1q has been well documented in lupus nephritis, membranoproliferative glomerulonephritis, and endocapillary glomerulonephritis. The clinical signs and laboratory data in our patient ruled out these diseases. Although an immunofluorescence study showed these similarities to Clq nephropathy, the histopathological features of the peculiar arteriolitis and tubulointerstitial nephritis and laboratory findings of hypocomplementemia, as well as the good response to oral steroid therapy, differed from typical C1q nephropathy. The current patient appears to be a very rare phenotype of nephritis, being the only 1 case in almost 2,800 renal biopsies.

Reversible methotrexate-associated lymphoproliferative disorder resembling advanced gastric cancer in a patient with rheumatoid arthritis.

A 73-year-old woman with rheumatoid arthritis had been treated with weekly low-dose methotrexate (MTX) for 5 years. She suffered from epigastric discomfort. Endoscopic examination revealed a tumor resembling advanced gastric cancer. Biopsy specimens showed atypical lymphoid cell infiltration. Immunohistological studies showed that these cells were positive for CD30 and CD79a, but not for CD15 or CD20. In situ hybridization identified Epstein-Barr virus latency-associated RNA expression in these cells. Clonally rearranged immunoglobulin heavy chain JH gene was not detected by Southern blot analysis. She was diagnosed with Epstein-Barr virus-associated polymorphic lymphoproliferative disorder (LPD) due to immunodeficiency caused by MTX administration. Cessation of MTX therapy led to complete regression of the tumor. To our knowledge, this is the first case of spontaneous remission of MTX-associated gastric LPD after discontinuation of MTX therapy. Increased awareness is needed on the possible occurrence of LPD resembling gastric cancer in rheumatoid arthritis patients treated with MTX.

Analysis of the NPHP genes in two Japanese patients with suspected sporadic juvenile or adolescent nephronophthisis.

BACKGROUND Mutations in 3 genes (NPHP1, NPHP3 and NPHP4) have been identified in patients with juvenile or adolescent nephronophthisis (NPHP) without extrarenal involvement, mainly in patients from western countries. In this study, we analyzed mutations in the NPHP genes of 2 Japanese patients with suspected sporadic juvenile or adolescent NPHP without extrarenal involvement. METHODS A renal biopsy was performed in the 2 patients. Genomic DNA was prepared from peripheral blood mononuclear cells of the patients and their family members. The above NPHP genes were examined by deletion analysis or direct automated sequencing of polymerase chain reaction-amplified DNA products. RESULTS Histological findings in the patients were compatible with those of NPHP. In 1 patient, we identified a novel deletion mutation including about half of exons of the NPHP1 gene. In another patient, there was no mutation in the NPHP genes examined. CONCLUSIONS We found a novel NPHP1 deletion in 1 patient. To our knowledge, this is the second Japanese NPHP case in which genetic diagnosis was made.