Background/aims. We have reported that tubular epithelial cell injury caused by renal ischemia−reperfusion is attenuated in conditional VHL knockout (VHL-KO) mice and also that induction of hypoxia-inducible factor (HIF) suppresses angiotensin II-accelerated Habu snake venom (HV) glomerulonephropathy in rats. However, it remains unknown whether VHL knockdown protects glomerular endothelial cells from endothelium-targeted glomerulonephritis. Methods and results.VHL-KO mice with HV glomerulonephropathy (HV GN) had fewer injured glomeruli, a lower mesangiolysis score and reduced blood urea nitrogen levels. Immunoreactivity of vascular endothelial growth factor (VEGF) in the glomerular capillaries was enhanced by VHL knockdown and was conserved even in VHL-KO mice with HV GN, despite HV-attenuating endothelial VEGF expression in vitro . VHL-KO mice showed enhanced nitric oxide (NO) production in glomerular endothelial cells and tubular cells, associated with activated VEGF expression in the kidney (i.e. an activated NO–VEGF axis). The levels of NO in glomeruli and tubules were conserved even in mice with HV GN. In contrast, suppressing NO production in glomerular endothelial cells by an NO synthase inhibitor, Nϖ -nitro- L -arginase, completely blunted the protection of VHL-KO from HV GN. The activated NO-VEGF axis in the kidney of VHL-KO mice was also associated with an elevation in Flk-1 phosphorylation and increased levels of IL-10 and IP-10. Conclusion. Conditional VHL knockdown may enhance the NO–VEGF axis and protect glomerular endothelial cells from HV GN, thereby providing resistance to injury of tubular epithelial cells and glomerular endothelial cells.
Although epidemiological surveys of paediatric rheumatic diseases in Japan have been conducted, they were single surveys with no continuity. This is the first report of the Pediatric Rheumatology Association of Japan registry database, which was established to continuously collect data for paediatric rheumatic diseases.Pediatric Rheumatology International Collaborate Unit Registry version 2 (PRICUREv2) is a registry database established by the Pediatric Rheumatology Association of Japan. The registry data were analysed for the age of onset, time to diagnosis, sex differences, seasonality, and other factors.Our data showed the same trend regarding rates of paediatric rheumatic diseases reported in Japan and other countries. The age of onset was lower in juvenile idiopathic arthritis (JIA) and juvenile dermatomyositis and higher in systemic lupus erythematosus and Sjögren's syndrome. The time to diagnosis was relatively short in JIA and systemic lupus erythematosus but longer in juvenile dermatomyositis and Sjögren's syndrome. Rheumatoid factor-positive polyarticular JIA showed a seasonality cluster with regard to onset.PRICUREv2 aided the retrieval and evaluation of current epidemiological information on patients with paediatric rheumatic diseases. It is expected that the data collection will be continued and will be useful for expanding research in Japan.
Natural killer (NK) cell activity, OK-432-augmented-NK cell activity, concentrations of interferon-gamma (IFN-gamma) in the culture supernatants of lymphocytes stimulated with OK-432, and subsets of NK cells and memory T cells were analyzed in 42 children with acute lymphoblastic leukemia (ALL) receiving maintenance chemotherapy. Natural killer and augmented-NK cell activities, and concentrations of IFN-gamma in the supernatants of cultured lymphocytes, were significantly lower in the patients with ALL than in age-matched control children. Among the NK cell subsets, proportions of CD57+ cells in the patients with ALL were significantly higher than in the controls, and proportions of a memory T cell subset (CD4+ CD29+ T cells) in the patients were also significantly higher than in the controls. These results suggest that the function of NK cells and memory T cells that are considered as IFN-gamma producing cells, may be defective in ALL, and that CD57+ cells and CD4+ CD29+ cells may be resistant to or recover rapidly from suppression by cytotoxic chemotherapy.
Campylobacter gracilis inhabits the gingival sulcus and has been reported to cause various periodontal diseases; it has rarely been reported to cause bacteremia. We describe a case of a two-year-old boy who presented with a consciousness disorder and was transferred to our hospital for treatment of a brain abscess. Magnetic resonance imaging (MRI) showed a 6-cm brain abscess in the right frontal lobe. Urgent drainage and antibiotic administration resulted in a favorable clinical course, and the patient was discharged on the 34th day of hospitalization. Streptococcus anginosus and C. gracilis were identified in the pus. Brain abscesses caused by C. gracilis have rarely been reported, which makes this a valuable case.
The aim of this study is to establish a monitoring method to prevent Epstein-Barr virus (EBV)-associated symptoms including post-transplant lymphoproliferative disorder (PTLD) that occur after pediatric renal transplantation.Circulating EBV loads were quantified by real-time PCR every 1 - 3 months after grafting in 22 pediatric recipients (13 EBV-seronegative [R(-)] and 9 EBV-seropositive [R(+)] recipients before grafting). The peripheral blood cell populations of non-specific activated killer cells (CD8+HLA-DR+ phenotype) in 13 R(-) recipients and EBV-specific cytotoxic T cells (CTLs) reactive with a tetramer expressing HLA-A24-restricted EBV-specific antigens in 8 of 13 R(-) recipients were determined by flow cytometry.EBV-associated symptoms including PTLD (2 cases) were found in 4 R(-) and none of the R(+) recipients. The maximum of EBV load in the R(-) group was significantly higher that in the R(+) group. In R(-) recipients, 4 symptomatic cases had significantly more EBV genome than asymptomatic cases. EBV-specific CTLs were detected in 6 of the 8 R(-) recipients, but these CTLs could not be detected in 1 of the 2 cases at onset of PTLD. The percentage of CD8+HLA-DR+ cells was significantly higher in asymptomatic recipients than in recipients with EBV-associated symptoms whose EBV loads were over 400 copies/microg DNA.Monitoring of killer T cells and EBV loads may allow assessment of the risk of EBV-associated symptoms, and high EBV loads and low EBV-specific and/or non-specific CTL responses may be predictive for development of EBV-associated symptoms such as PTLD.
Cisplatin and carboplatin cause dose-dependent renal dysfunction. Electrolyte abnormalities such as hypomagnesaemia and hypokalemia are commonly reported adverse effects, in addition to increased serum creatinine and uremia. Cumulative dose, dehydration, hypoalbuminemia, and concurrent use of nephrotoxic drugs have been suggested as risk factors for cisplatin nephrotoxicity. The adverse effects of ifosfamide include proximal tubular damage, and renal wasting of electrolytes, glucose and amino acids, Fanconi syndrome, rickets and osteomalacia have also been reported with ifosfamide treatment. Risk factors for ifosfamide nephrotoxicity include the cumulative dose, young age, previous or concurrent cisplatin treatment, and unilateral nephrectomy. Ifosfamide/Carboplatin/Etoposide (ICE) combination therapy induces hypouricemia, which frequently includes renal wasting of electrolytes, and persistent hypouricemia has been observed in recurrent or chemotherapy-resistant patients. We retrospectively examined the incidence of hypouricemia and clinical findings in pediatric patients treated with an ICE regimen. Twenty of 28 (71.4%) pediatric patients had hypouricemia. The duration of hypouricemia was longer in the non-remission subgroup of patients, which suggests that hypouricemia may be a predictive marker for prognosis of malignant disease and efficacy of drugs such as ifosfamide, carboplatin and cisplatin. Nephrotoxicity induced by these drugs may also be more common in pediatric patients than in adults, but it is unclear why a young age is a risk factor and further research is required regarding the mechanism of antineoplastic drug induced-nephrotoxicity in children.
The diagnosis of infectious mononucleosis (IM) is usually on serologic tests. The responses of anti-Epstein-Barr virus (anti-EBV) antibodies are weak in infants. The authors encountered some IM infants in whom anti-EBV antibodies were undetectable during early stage, although EBV genome was found in their blood. The aim of the present study was therefore to clarify the frequency of anti-EBV-antibody negative IM cases.The EBV serostatus of 104 IM children diagnosed on Sumaya criteria was retrospectively studied. The EBV genome in peripheral blood mononuclear cells was measured.The anti-viral capsid antigen-IgM (anti-VCA-IgM)-positive rate in the acute phase was only 25% in infants but 80% in patients ≥ 4 years of age. Twenty percent of the infants were negative for all anti-EBV antibodies and required repeated serologic tests. For infants, the significant rise in anti-VCA-IgG was the most sensitive marker. Three seronegative infants with IM symptoms, with circulating EBV genome during acute phase, were eventually considered as having IM on anti-VCA-IgG seroconversion thereafter.To diagnose IM in infants the serologic test alone in the acute phase is not sensitive enough. It is proposed that the EBV genome be evaluated in peripheral blood mononuclear cells when infants presenting with IM symptoms are negative for anti-EBV antibodies during the acute phase.
