Case 1: A 27-year-old woman, referred to our hospital because of relapsing fever after travel to Thailand, was given a diagnosis of vivax malaria. Clinical investigation revealed thrombocytopenia, elevated platelet-associated IgG (PAIgG), and negative antibody against Plasmodium vivax antigen. After antimalarial treatment, the levels of both the platelets and PAIgG returned to normal. Case 2: A 28-year-old Sri Lankan man was admitted to our hospital with a complaint of fever. The patient had thrombocytopenia, elevated PAIgG, and positive antibody against Plasmodium vivax antigen. He contracted malaria in Sri Lanka about 6 months prior to this admission. After treatment, the platelet count and PAIgG level returned to normal. In these two cases, high levels of PAIgG may have been involved in the development of the thrombocytopenia. In the first patient, in particular, the thrombocytopenia was thought to be induced by some immunological mechanism prior to the detection of antimaralial antibodies in serum.

It is sometimes reported that the immunological abnormalities in myelodysplastic syndromes (MDS) induce autoimmune disease (i.e., acute systemic vasculitic syndrome, chronic cutaneous vasculitis, polyneuropathy, relapsing polychondritis, and steroid-responsive pulmonary disorders). We investigated the clinical features of patients with MDS accompanied by nephrotic syndrome. We enrolled 125 patients with MDS who were admitted between January 1979 and May 1996 in this study. The renal function was assessed based on the laboratory data and the findings at the physical examination. The diagnoses of nephrotic syndrome and glomerular disease were established when 24-hr urinary excretion was more than 3.5 g and serum total protein was less than 6.0 g/dl, and when the 24-hr protein excretion was more than 1.5 g. Five patients (4%) had glomerular disease, and three (2.4%) had nephrotic syndrome. Of the five patients with glomerular disease, two had refractory anemia (RA), and three had chronic myelomonocytic leukemia (CMMOL). Three of the total 11 patients with CMMOL were diagnosed as having nephrotic syndrome. Among the CMMOL patients, those with nephrotic syndrome showed higher absolute monocyte numbers than did those without nephrotic syndrome (8830 +/- 4677/microl vs. 3061 +/- 2887/microl, P = 0.03). One CMMOL patient was treated with VP-16 and hydroxyurea. As the white blood cell count in this patient decreased, the 24-hr urine protein excretion and the serum tumor necrosis factor alpha level decreased. The relationship between nephrotic syndrome and CMMOL was not clear. High monocyte count and the serum cytokines in MDS patients may play a partial role in the evolution of glomerulonephritis, and CMMOL may be closely related to nephrotic syndrome.

We report three patients with pulmonary disorders associated with myelodysplastic syndromes (MDS). All three patients had symptoms of pyrexia and respiratory discomfort. One patient had pulmonary eosinophilia with bilateral pleural effusion, one had interstitial pneumonia, and one had bilateral pleural effusion caused by systemic vasculitis. Elevated C-reactive protein (CRP) levels, polyclonal hypergammaglobulinemia, and morphological abnormalities in peripheral blood were observed in all three patients. The bone marrow of these patients revealed trilineage dysplasia and eosinophilia. Cytogenetic analysis showed [46,XY,-7,+der(1q;7p)]. Antibiotic treatment was not effective. However, improvement was dramatic after corticosteroid treatment; CRP levels were reduced and the hypergammaglobulinemia was improved. These cases suggest that MDS with [-7,+der(1q;7p)] may be correlated with bone marrow eosinophilia and that an immunologic abnormality may be involved in the pulmonary disorders.

Among 1119 Japanese patients with symptomatic multiple myeloma diagnosed between 1965 and 1981, 38 (3.4%) survived more than 10 years. Younger age, low tumour mass (absence of severe anaemia, hypercalcaemia, renal failure, and multiple bone lesions), low plasma cell percentage in bone marrow, mature and intermediate myeloma according to Greipp's criteria, and a positive response to subsequent treatment, were related to long-term survival according to univariate analysis. Multivariate logistic regression analysis indicated younger age and low tumour mass as pretreatment characteristics to be related to long-term survival. Prognostic factors proposed applicable to myeloma were also related to 10-year survival.

Human induced pluripotent stem (iPS) cells can differentiate into hepatocyte lineages, although the phenotype of the differentiated cells is immature compared to adult hepatocytes. Improvement of cell-cell interactions between epithelium and mesenchyme is a potential approach to address this phenotype issue. In this study, we developed a model system for improving interactions between human iPS-derived hepatic progenitor cells (iPS-HPCs) and human iPS-derived hepatic stellate cell-like cells (iPS-HSCs). The phenotype of iPS-HSCs, including gene and protein expression profiles and vitamin A storage, resembled that of hepatic stellate cells. Direct co-culture of iPS-HSCs with iPS-HPCs significantly improved hepatocytic maturation in iPS-HPCs, such as their capacity for albumin production. Next, we generated iPS cell lines overexpressing LIM homeobox 2 (LHX2), which suppresses myofibroblastic changes in HSCs in mice. Hepatocytic maturation in iPS-HPCs was significantly increased in direct co-culture with iPS-HSCs overexpressing LHX2, but not in co-culture with a human hepatic stellate cell line (LX-2) overexpressing LHX2. LHX2 regulated the expression of extracellular matrices, such as laminin and collagen, in iPS-HSCs. In conclusion, this study provides an evidence that LHX2 upregulation in iPS-HSCs promotes hepatocytic maturation of iPS-HPCs, and indicates that genetically modified iPS-HSCs will be of value for research into cell-cell interactions.