Ken Hamasaki

Systemic lupus erythematosus and thrombotic thrombocytopenic purpura: a case report and literature review.

AbstractWe describe a patient with systemic lupus erythematosus (SLE) who developed severe and acute thrombotic thrombocytopenic purpura (TTP). Detection of the fragmentation of peripheral red blood cells (RBC) helped the early diagnosis of TTP and the patient was rescued by extensive plasma exchange started promptly after the diagnosis. Because manifestations of TTP are similar to those in SLE, it is sometimes difficult to make an accurate diagnosis of TTP in SLE patients. We emphasise here the significance of the early diagnosis of TTP by the observation of fragmented RBC and the intensive therapy, including plasma exchange, for this very severe condition.

Glomerular overexpression and increased tyrosine phosphorylation of focal adhesion kinase p125FAK in lupus-prone MRL/MP-lpr/lpr mice.

Much progress has been made in understanding how mammalian cells receive a diverse array of external stimuli and convert them into intracellular biochemical signals. Such efforts have identified a large number of signalling molecules. However, our knowledge is limited as to their pathophysiological role in particular diseases. We demonstrate herein that an integrin‐linked signalling molecule, focal adhesion kinase p125FAK (FAK), is overexpressed in glomeruli of lupus‐prone MRL/MP‐lpr/lpr (MRL‐lpr) mouse as compared to its congeneic MRL‐+/+ strain. Increased expression was specifically demonstrated in glomeruli but not in other tissues examined. The overexpression was observed in 16‐week‐old MRL‐lpr mice with active nephritis, as well as in younger animals at 4 weeks of age. Thus, the upregulation of FAK clearly preceded the clinical onset of nephritis. FAK in MRL‐lpr glomeruli is highly tyrosine phosphorylated and is associated with adapter protein Grb2. Previous in vitro studies have shown that the association of FAK/Grb2 links cell adhesion to the Ras pathway, which ultimately stimulates mitogen‐activated protein (MAP) kinase, an important regulator of cell proliferation. In accordance, we observed constitutive MAP kinase activation in MRL‐lpr glomeruli. Our findings suggest that signalling pathways involving FAK are activated in MRL‐lpr glomeruli, and are likely to play a role in the development and progression of autoimmune‐mediated murine nephritis.

Nephrotic syndrome developed in a patient with acute promyelocytic leukemia treated with daunomycin.

Noritsugu Morino, MD, The Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113 (Japan) Dear Sir, Nephrotic syndrome (NS) is an unusual but well-recognized complication of malignant diseases [1,2]. Among the hematologi-cal neoplasms, lymphocytic leukemia and lymphoma have a known association with NS, while its occurrence in the acute myelog-enous leukemia (AML) appears to be exceedingly rare [2]. To the best of our knowledge, there have been only two reports in the literature [3, 4]. We report here a case of acute promyelocytic leukemia (APL) associated with NS. The development of NS was coincidental with the administration of chemotherapy in this case. A 32-year-old Japanese woman presented at our hospital with progressive fatigue and gingival bleeding which had developed 2 weeks earlier. Until then she had been in excellent health with no history of renal disease or drug exposure. The physical examination was normal except for anemic conjunctiva and purpuric lesions scattered on the upper chest. The hematocrit was 21.4%, WBC 34.1 × 109/1 with 12% blast cells and 70% promyelocytes, and the platelet count was 22 × 109/1. Coagulation studies demonstrated that the patient had disseminated intravascular coagulation (DIC). Urinalysis showed trace amounts of protein, and the sediment was normal. Serum albumin was 4.5 g/dl, urea nitrogen 16.3 mg/dl, and creat-inine 0.6 mg/dl. The bone marrow aspirate showed increased cellularity with 13.2% myeloblasts and 82.4% promyelocytes. The 1⁄8 · · β ‘ Fig. 1. a Ligh micrograph of a glomerulus showing minor abnormalities. HE. × 200. b Electron micrograph showing widespread detachment of epithelial cells from GBM. × 8,000. Serum albumin was 3.0 g/dl on the 15th hospital day. Thus, the patient developed NS during the course of chemotherapy for APL. Anticoagulant therapy had little effect on her severe DIC, and the patient died on the 16th day because of massive hemorrhage into both lungs.

Impaired collagen gel contraction with cultured skin fibroblasts from patients with systemic sclerosis.

We investigated the capacity of skin fibroblasts, derived from 9 patients with systemic sclerosis (SSc), to contract collagen lattices in a three-dimensional culture system. In comparison with control fibroblasts (N = 8), more than 30% of SSc fibroblasts exhibited markedly impaired ability to contract collagen lattices. The expression of alpha2beta1 integrins and integrin-mediated signals were not significantly different between normal and SSc fibroblasts. Although the underlying mechanisms remain to be determined, our present data provide evidence that certain aspects of interaction with collagen are impaired in SSc fibroblasts.We investigated the capacity of skin ®broblasts, derived from 9 patients with systemic sclerosis (SSc), to contract collagen lattices in a threedimensional culture system. In comparison with control ®broblasts (N~8), more than 30% of SSc ®broblasts exhibited markedly impaired ability to contract collagen lattices. The expression of a2b1 integrins and integrin-mediated signals were not signi®cantly different between normal and SSc ®broblasts. Although the underlying mechanisms remain to be determined, our present data provide evidence that certain aspects of interaction with collagen are impaired in SSc ®broblasts.