Severe hypersensitivity to mosquito bites (HMB) is characterized by intense local skin reactions and systemic symptoms such as high fever, lymphadenopathy, and hepatosplenomegaly. Patients with HMB often have natural killer (NK) cell lymphocytosis associated with Epstein-Barr virus (EBV) infection. Here we investigated whether mosquito bites have any influence on the oncogenesis of EBV-infected NK cells. We examined six HMB patients with EBV-infected NK cell lymphocytosis. We first demonstrated that CD4+ T cells, but not NK cells, proliferated well in response to mosquito salivary gland extracts (SGE), especially to SGE of Aedes albopictus. When NK cells were cocultured with autologous CD4+ T cells stimulated by mosquito SGE, the expression of viral oncogene latent membrane protein 1 (LMP1) was remarkably enhanced. Next, we stimulated mononuclear cells of the patients with mosquito SGE, and NK cell counts were monitored for 28 d. The counts changed little from initial levels in the culture with mosquito SGE, whereas they decreased steadily in the culture without the extracts. Furthermore, we detected LMP1 mRNA in the skin lesion induced by mosquito SGE. These results suggest that mosquito bites can induce expression of the viral oncogene LMP1 in NK cells via mosquito antigen-specific CD4+ T cells, which is involved in the oncogenesis of NK cells in vivo.

Surrogate light chains (lambda 5/VpreB) are selectively expressed in early precursors of B cells. B-cell defects in X-linked agammaglobulinemia (XLA) are caused by mutations in the gene for Bruton's tyrosine kinase. To elucidate the nature of early B-lineage cells in bone marrow (BM), samples from 13 XLA patients and 24 healthy controls of different ages were comparatively analyzed using an antihuman VpreB monoclonal antibody. Expression of surrogate light (SL) and mu-heavy chains were examined after cell membrane permeabilization because they are mainly expressed in the cytoplasm of early B-lineage cells. A flow cytometric analysis of normal BM identified 5 discrete cell types of B cells: mu(-)SL(++) (pro-B [B-cell progenitor]), mu(low)SL(++) (pre-B1a), mu(low)SL(+) (pre-B1b), mu(low)SL(- )(pre-B2), and mu(high)SL(- )(B). The large cells, presumably in cycling states, were enriched in pre-B1a cells. The frequencies of B-lineage cells in BM were higher in young children, and declined with advancing age. In contrast, XLA showed a profound reduction in BM B-lineage cells. In XLA BM, an expansion of pro-B cells with some small pre-B1a cells was marked, but other cells were negligible. These observations illustrate a B-cell maturation defect in XLA as well as a normal human B-cell differentiation pathway. The results suggest that the genetic defect in XLA may impede the evolution of pro-B cells beyond the earlier pre-B stage into the later stage of pre-B cells in B-cell development. (Blood. 2000;96:610-617)

Although idiopathic membranous nephropathy (IMN) is thought to represent a diffuse glomerulopathy, it was found that three of 31 children histologically diagnosed as IMN showed focal and segmental deposition of immunoglobulin G (IgG) and C3 on the glomerular capillary walls. The present study attempted to comparatively investigate clinical and pathological features of the diffuse group and the focal segmental group in 31 IMN children. Immunofluorescence study revealed that 28 of 31 IMN exhibited diffuse granular deposition of IgG along glomerular capillary walls. In contrast, focal and segmental deposition of IgG and C3 was noted in three children with IMN. In addition, focal and segmental electron-dense deposits were identified in these cases. In two children of the focal segmental group, immunofluorescent patterns of IgG deposition were unchanged even at the second biopsy. The focal segmental form of IMN tended to occur in younger children than diffuse IMN. However, other clinical parameters such as the range of proteinuria, hematuria, serum albumin and prognosis did not show any significant differences between both groups. Electrophoretic profiles of urinary proteins on sodium dodecylsulfate-polyacrylamide gel electrophoresis were not different between both groups. It is proposed that the focal segmental form of IMN may have a distinctive glomerulopathy from the typical form of IMN.

We studied the contributions of glomerular hypertrophy in renal disease. The patients were 20 cases of IgA nephropathy with prolonged proteinuria, 13 cases of Alport syndrome and 12 cases of focal glomerular sclerosis (FGS). All patients had a normal creatinine level on renal biopsy. We determined the mean glomerular tuft area in the equatorial region of five glomeruli that showed no sclerotic change in each patient using an image analyzer and compared the value with the mean value in normal controls. Glomerular hypertrophy was defined as a value over the mean glomerular tuft area +1SD of normal controls. Glomerular hypertrophy was found in 14 IgA nephropathy cases (70.0%), 4 Alport syndrome cases (30.7%) and 8 FGS cases (66.7%). The incidence of glomerular hypertrophy was significantly higher in IgA nephropathy than in Alport syndrome and FGS showed a higher tendency compared with Alport syndrome. Of the patients with renal insufficiency, 4 of 6 IgA nephropathy cases (66.6%), 0 of 5 Alport syndrome cases (0%) and 1 of 3 FGS cases (33.3%) showed glomerular hypertrophy, IgA nephropathy patients showed the highest incidence of glomerular hypertrophy. The interval between the final biopsy and renal insufficiency showed no significant difference in this study. In IgA nephropathy, obsolescent glomeruli were significantly increased in the group in which the glomerular tuft area was over the mean +2SD compared with the group with an area less than the mean +2SD. FGS cases showed no relationship between the ratio of obsolescent glomeruli to whole glomeruli and glomerular hypertrophy. This study suggested that glomerular hypertrophy may cause declining renal function in IgA nephropathy, but not in Alport syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Cells from 203 childhood leukemia patients were analyzed using a broad panel of markers, such as immunological marker studies and Southern blot and Northern blot analyses to define the lineage-specific classification of childhood leukemia. Phenotypically, they were divided into B lineage (62.6

We analyzed the usage of the 6 recombining element (6Rec) and six V6 genes in cell samples from 15 patients with CD3- and 10 patients with CD3' T-cell acute lymphoblastic leuke- mia in an attempt to define the hierarchy of genetic events that is associated with the T-cell receptor (TCR) a/6 gene complex during T-cell ontogeny. Based on the deletion patterns of these genes, we surmised their relative order on chromosome 14 to be as follows: 5'-V64, V66, V61, V65. GRec, V62, D61-3, J61-3, C6, W63-3'. In agreement with previous reports, V6l was found to be preferentially rearranged in CD3' samples. In CD3- samples, V62 and V63 rearrange- ments were observed at a high frequency. Incomplete V6D6 rearrangements using V62 or V63, which are closest to C6,