Capillary permeability is a tightly regulated feature of microcirculation in all organ beds. In sepsis, this feature is fundamentally altered. We have previously reported elevated levels of angiopoietin-2 in patients with septic shock, and have investigated tumor necrosis factor (TNF)-related and weak inducer of apoptosis (TWEAK), which mediates both angiogenesis and inflammation, in those patients. Enzyme-linked immunoassay was used to measure serum TWEAK levels in 20 patients with septic shock, all of whom were treated by direct hemoperfusion with a polymyxin B-immobilized fiber column (DHP-PMX), and in 20 non-septic controls. The TWEAK levels were higher in patients with septic shock (192.8 ± 230.5 pg/mL) than in controls (84.1 ± 28.7 pg/mL, P = 0.043). Between 11 survivors and 10 non-survivors, there was no significant difference in the serum TWEAK levels before the DHP-PMX therapy. During DHP-PMX therapy, however, the serum TWEAK levels were significantly increased in non-survivors (142.2 ± 88.1 pg/mL to 399.0 ± 307.1 pg/mL, P = 0.022). There was a significant correlation between the serum TWEAK levels and white blood cell counts (r = 0.393, P < 0.001), platelet counts (r = 0.418, P < 0.001), or serum CRP levels (r = 0.259, P = 0.029), but there was no correlation between the serum TWEAK levels and blood pressure. The serum TWEAK levels were also correlated with the ratio of angiopoietin-2 to -1 (r = 0.464, P < 0.001). TWEAK may be a suitable marker of disease severity and mortality in septic patients, and TWEAK levels may be associated with vascular permeability via angiopoietin balance.
Sepsis is characterized by a systemic inflammatory response to a microbial pathogen. In sepsis, capillary permeability is a tightly regulated feature of microcirculation in all organ beds and is fundamentally altered. We investigated the vascular endothelial growth factor (VEGF) level as a vascular permeability factor and the soluble fms-like tyrosine kinase-1 (Flt-1) level as an antagonist of the VEGF receptors. Serum VEGF and soluble Flt-1 levels in 21 patients with septic shock, who were treated with direct hemoperfusion with a polymyxin B-immobilized fiber column (DHP-PMX), were measured by enzyme-linked immunoassay. The VEGF and the soluble Flt-1 levels were more elevated in patients with septic shock than in controls. Between 14 survivors and 7 non-survivors, there was no significant difference in VEGF level before the DHP-PMX therapy, but the soluble Flt-1 level of survivors was significantly lower than that of non-survivors. Although there was no significant difference between starting and ending VEGF levels in survivors, in non-survivors the VEGF level at the end of DHP-PMX therapy was significantly lower than that at the start. In survivors, the soluble Flt-1 level at the end of DHP-PMX therapy was significantly lower than that at the start. On the other hand, in non-survivors, there was no significant difference between the ending and starting soluble Flt-1 levels. The soluble Flt-1 level may be a suitable marker of disease severity and mortality.
Fabry disease is a lysosomal storage disorder caused by a deficiency of α-galactosidase A. This disease is classified into two types, namely a classical and variant type. We herein present the case of a 36-year-old man who showed a renal variant of Fabry disease and was diagnosed at an early stage by the presence of mulberry cells. He had no history of general symptoms except for proteinuria. The presence of mulberry cells caused us to suspect Fabry disease and he was thereafter diagnosed to have a renal variant of Fabry disease based on the findings of a renal biopsy, a mutation analysis and a low level of α-galactosidase A activity.
Capillary permeability is a tightly regulated feature of microcirculation in all organ beds; however, in sepsis this feature is fundamentally altered. We previously reported elevated levels of vascular endothelial growth factor and its receptor (fms-like tyrosine kinase-1) in patients with septic shock, then investigated two kinds of angiopoietins in those patients. An enzyme-linked immunoassay was used to measure serum angiopoietin-1 and -2 levels in 12 patients with septic shock who were treated by direct hemoperfusion with a polymyxin B-immobilized fiber column (DHP-PMX). The angiopoietin-1 level was lower in patients with septic shock (7.01 +/- 10.08 ng/mL) than in controls (28.24 +/- 11.61 ng/mL, P < 0.001), but the angiopoietin-2 level was higher in septic shock patients (40.83 +/- 30.13 ng/mL vs. 2.47 +/- 1.78 ng/mL, P < 0.001). Between seven survivors and five non-survivors there was no significant difference in angiopoietin-1 levels before DHP-PMX therapy. During DHP-PMX therapy, however, the angiopoietin-2 level was significantly decreased in survivors (31.52 +/- 26.15 ng/mL vs. 17.32 +/- 22.46 ng/mL, P = 0.035). Moreover, at the end of the therapy, the angiopoietin-1 level was significantly lower in non-survivors (1.14 +/- 1.30 ng/mL vs. 10.43 +/- 13.56 ng/mL, P = 0.042), but the angiopoietin-2 level in non-survivors was significantly higher (70.79 +/- 40.47 ng/mL vs. 17.32 +/- 22.46 ng/mL, P = 0.019). The angiopoietin-2 level may be associated with vascular permeability in septic patients, and angiopoietins may be suitable markers of disease severity and mortality.
Human parvovirus B19 (HPV B19) infection is well known as a cause of erythema infectiosum in children. Acute glomerulonephritis due to HPVB19 infection is rarely observed in adults. Here, we present the case of a 45-year-old female who showed acute glomerulonephritis induced by HPVB19 infection with various autoantibodies. She had proteinuria (175 mg/g creatinine) and hematuria (20-29 erythrocytes per high-power field) in a urinalysis, and various autoantibodies such as antinuclear antibodies, proteinase-3-antineutrophil cytoplasmic antibodies (PR3-ANCA), antiglomerular basement membrane (GBM) antibodies, and anticardiolipin antibodies in a blood examination. A renal biopsy showed that endocapillary proliferative glomerulonephritis comprised of mononuclear cell infiltration. By using immunofluorescence microscopy, IgG, IgA, IgM, C3, C4, and C1q deposits were detected mainly in glomerular capillaries. Electron-dense deposits were detected in the subendothelial area and mesangial area by using electron microscopy. All symptoms and abnormal laboratory data were self-improved. Our patient's case may provide a clue to the etiology of ANCA-associated vasculitis or lupus nephritis.
To investigate the distribution of ghrelin in different regions of stomach in Sprague-Dawley rat, and attempt to compare with those of humans and other mammalian species in this study, the stomach of rats was divided into five sections, cardia, fundus, greater curvature, lesser curvature and pylorus. Immunohistochemistry and Western blotting were performed to investigate the ghrelin-producing cells. The immunolocalization and protein levels of ghrelin differed significantly in different regions of stomach in rats. It was present at a high level in the greater curvature of the pars glandularis, and the lesser curvature. In the fundus and pylorus, no ghrelin immunoreactive cells were detected. In this study, we elucidated the distribution of ghrelin-producing cells in different regions of rat stomach in detail for the first time. It is further considered that the differences of ghrelin distribution in stomach of different species may induce different stimulatory effects on fat accumulation and metabolism.
Interstitial pneumonitis is one of the life-threatening diseases associated with ANCA-associated vasculitis. The measurement of serum levels of KL-6, which is a MUC1 mucin and is expressed on type II alveolar pneumocytes and bronchial epithelial cells [1], may be a good monitoring system for the diagnosis and follow-up of interstitial pneumonitis in ANCA-associated vasculitis patients [2]. Moreover, elevated serum KL-6 levels were reduced during convalescence induced by glucocorticoid therapy [2]. In the present case, the elevated serum KL-6 level was preserved during glucocorticoid therapy, but decreased to within the normal range with additional treatment by mizoribine (MZR).A 65-year-old woman visited our hospital complaining of a dry cough and low-grade fever. Crepitate sounds were heard in her chest, and chest X-rays and computed tomography showed interstitial pneumonitis in both lower lung fields. On urinalysis, mild proteinuria (urinary excretion of protein, 0.5 g/day), hematuria, and cellular casts were revealed. Mild anemia (hemoglobin concentration, 11.5 g/dl) and leukocytosis (11,000/mm 3 ) were observed. Although her serum creatinine level (0.66 mg/dl) was within the normal range, her serum cystatin C level was elevated to 0.87 mg/l. Serology revealed elevated levels of C-reactive protein (8.04 mg/dl), MPO-ANCA (208.5 U/ml), and KL-6 (526 U/ml). The major histological finding of renal biopsy was focal necrotizing glomerulonephritis without deposition of immunoglobulins or complements. She was diagnosed with MPO-ANCAassociated vasculitis and treated with an oral corticosteroid (prednisolone 30 mg/day). Although serum C-reactive protein was promptly normalized and MPO-ANCA titers gradually decreased, her high level of serum KL-6 was preserved (Fig. 1). Moreover, her HbA1c level was elevated to 7.0%, and she had been treated with nateglinide. Eighteen months after the initiation of glucocorticoid therapy, the dose of prednisolone was reduced to 7.5 mg/ day and MZR was additionally started at a dosage of 150 mg once a day. At the start of MZR administration, no new symptoms of vasculitis or signs of relapse were noted, and ANCA titers were preserved within the normal range (below 9.0 U/ml). In the 6 months after the initiation of MZR therapy, her elevated serum KL-6 level gradually fell to within the normal range (below 500 U/ml). Although the extent of interstitial pneumonitis in both lower lung fields on chest X-rays and computed tomography was not changed after KL-6 was decreased to the normal range, that area was not expanded.MZR has an immunosuppressive effect equivalent to that of azathioprine, but shows lower hepatic toxicity and myelosuppression. MZR is useful for preemptive treatment of ANCA-associated renal vasculitis patients with a high risk of relapse [3]. MZR caused the delay in the histological development of peribronchial and perivascular lymphocytic infiltrations in the lungs of MRL/lpr/lpr mice [4]. MZR improved renal tubulointerstitial fibrosis in a rat model of unilateral ureteral obst...
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