Bone marrow transplantation attenuates murine IgA nephropathy: role of a stem cell disorder

BACKGROUND: The pathogenesis of IgA nephropathy is still obscure. The aim of this study was to investigate whether the fundamental pathogenesis of IgA nephropathy lies in bone marrow stem cells (BMCs). METHODS: We used donors of two different strains for bone marrow transplantation (BMT) into mice with a high content of serum IgA (ddY strain, HIGA mice), a murine model of IgA nephropathy. One group (B6-->HIGA, N = 5) received BMCs of C57BL/6j (B6) mice, and the other (HIGA-->HIGA, N = 8) were reconstituted with BMCs of HIGA mice. RESULTS: Twenty-six weeks after BMT, in B6-->HIGA mice, mesangial deposits of IgA and C3 were statistically milder than those in HIGA-->HIGA mice. Light microscopic observations disclosed that glomerular sclerosis and mesangial matrix expansion in B6-->HIGA mice were decreased compared with those in HIGA-->HIGA mice. These B6-->HIGA mice also excreted less urinary albumin than HIGA-->HIGA mice. Furthermore, serum levels of IgA in B6-->HIGA mice were markedly lower than those in HIGA-->HIGA mice. Size analysis of serum IgA revealed that macromolecular IgA were notably lower in B6-->HIGA mice than in HIGA-->HIGA mice. CONCLUSIONS: Our results suggest that qualitative and quantitative changes of serum IgA are determined at the level of stem cells, and that BMT from normal donors can attenuate glomerular lesions in HIGA mice. This approach may offer a new avenue to study the pathogenesis of IgA nephropathy.     

Immunocytochemical localization of aromaticl-amino acid decarboxylase and catechol-O-methyltransferase in blood vessel wall of the human dental pulp

Relatively large amounts of DOPA as compared with the concentration of norepinephrine are found in human dental pulp. AADC and COMT are localized in blood vessel walls of human dental pulp. This localization suggests a functional relationship between COMT and AADC with regard to the metabolism of DOPA.     

Increased levels of urinary interleukin-6 in Kawasaki disease

Kawasaki disease (KD) often presents with abnormal urinary findings, such as aseptic pyuria, mild proteinuria and microscopic haematuria. In this study, we measured urinary interleukin-6 (IL-6) by a sensitive sandwich ELISA assay using mouse monoclonal antibodies against recombinant IL-6 to elucidate the role of IL-6 in the pathogenesis of renal lesions in KD. Serum IL-6 levels were increased in acute KD as well as in febrile controls. Importantly, urinary IL-6 levels were consistently elevated in patients with acute KD, but much lower in febrile controls. Urinary IL-6 levels returned steadily to normal during the convalescent phase. In addition to IL-6, urinary levels ofN-acetyl--d-glucosaminidase (NAG) and ₂-microglobulin (₂-mg) were also elevated during the acute phase of this disease. Eosinophils and macrophages were identifiable in urinary sediments from these patients. The increased levels of urinary IL-6 in combination with increased NAG and ₂-mg seemed to suggest the presence of certain renal parenchymal lesions with cellular infiltration during the acute phase of the disease. IL-6 may serve as clinically useful parameter for the detection and monitoring of the renal involvement in KD.     

Phospholamban p.Arg14del Cardiomyopathy: A Japanese Case Series

Phospholamban p.Arg14del is reported to cause hereditary cardiomyopathy with malignant ventricular tachycardia (VT) and advanced heart failure. However, the clinical courses of Japanese cardiomyopathy patients with phospholamban p.Arg14del remain uncharacterized. We identified five patients with this variant. All patients were diagnosed with dilated cardiomyopathy (DCM), developed end-stage heart failure and experienced VT requiring implantable cardioverter defibrillator discharge. Four patients survived after implantation of a left ventricular assist device (LVAD), while one patient who refused LVAD implantation died of heart failure. Based on the severe course of the disease, we propose genetic screening for phospholamban p.Arg14del in DCM patients.     

Impact of Dietitian-Led Nutrition Therapy of Food Order on 5-Year Glycemic Control in Outpatients with Type 2 Diabetes at Primary Care Clinic: Retrospective Cohort Study

The aim of this retrospective cohort study was to evaluate the effect of 5-year follow-up of dietitian-led medical nutrition therapy (eating vegetables before carbohydrates) on glycemic control in outpatients with type 2 diabetes (T2DM) at a primary care clinic. A total of 138 patients with dietitian-led medical nutrition therapy (intervention group) and 104 patients without dietitian-led nutrition therapy (control group) were compared for glycemic control, serum lipid, blood pressure, and diabetic complications for 5 years. Each patient in the intervention group received dietary education focused on food order (eating vegetables before carbohydrates) by dietitians. A significant improvement in HbA1c after 5 years in the intervention group [8.5 ± 1.7% (69 mmol/mol) to 7.6 ± 1.1% (59 mmol/mol), p < 0.001] was observed, whereas no change was observed in the control group [7.9 ± 1.2% (62 mmol/mol) to 8.0 ± 1.2% (63 mmol/mol)]. Dietary intake of protein, fat, carbohydrates, cholesterol, and salt in the intervention group demonstrated significant reduction, while the intake of dietary fiber significantly increased after the dietary education. Simple dietary education of ‘eating vegetables before carbohydrates’ presented by dietitians achieved good glycemic control after a 5-year period in outpatients with T2DM at primary care clinic.     

" color="" timer"="" mice:="" visualization="" of="" neuronal="" differentiation="" with="" fluorescent="" proteins"="

Synaptic transmission and long-term potentiation (LTP) in the CA1 region of hippocampal slices have been studied during ageing of a double transgenic mouse strain relevant to early-onset familial Alzheimer's disease (AD). This strain, which over-expresses both the 695 amino acid isoform of human amyloid precursor protein (APP) with K670N and M671L mutations and presenilin 1 with the A246E mutation, has accelerated amyloidosis and plaque formation. There was a decrease in synaptic transmission in both wildtype and transgenic mice between 2 and 9 months of age. However, preparing slices from 14 month old animals in kynurenic acid (1 mM) counteracted this age-related deficit. Basal transmission and paired-pulse facilitation was similar between the two groups at all ages (2, 6, 9 and 14 months) tested. Similarly, at all ages LTP, induced either by theta burst stimulation or by multiple tetani, was normal. These data show that a prolonged, substantially elevated level of Aβ are not sufficient to cause deficits in the induction or expression of LTP in the CA1 hippocampal region.     

Secondary erythrocytosis associated with distal renal tubular acidosis

AIMS: Diagnosis and classification of renal tubular acidosis (RTA) have traditionally been made on the basis of functional studies. Despite recent expanding knowledge about the molecular abnormalities involved in renal bicarbonate (HCO3-) and H+ transport, the pathophysiology of secondary erythrocytosis in association with distal RTA remains obscure. CASE HISTORY: A 2-month-old boy with severe hyperchloremic metabolic acidosis with positive urine anion gap was diagnosed with distal RTA. Replacement therapy with sodium bicarbonate and potassium citrate succeeded in improving his metabolic acidosis and growth. His renal function remained normal. He had persistent erythrocytosis. CONCLUSION: Secondary erythrocytosis is a rarely reported association of distal RTA. It may increase the risk of thromboembolism.