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Find video protocols related to scientific articles indexed in Pubmed.
[Classification of Diabetic Nephropathy 2014].
Nihon Jinzo Gakkai Shi
PUBLISHED: 08-19-2014
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The Committee on Diabetic Nephropathy revised the classification of diabetic nephropathy in view of the current status of eGFR and CKD in Japan. To make revisions for the classification of diabetic nephropathy 2014, the Committee carefully evaluated the report of the Research Group on Diabetic Nephropathy, Ministry of Health, Labour, and Welfare of Japan. The major revisions made were as follows: 1. eGFR can be used for the evaluation of GFR; 2. In stage 3 (overt nephropathy), A and B were combined; 3. Stage 4 (renal failure) was defined as GFR less than 30 mL/min/1.73 m2, regardless of albuminuria; and 4. The importance of differential diagnosis was stressed in all stages.
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[Molecular epidemiology of the Methicillin-resistant Staphylococcus aureus(MRSA) by the internal transcribed spacer PCR (ITS-PCR) method and the phage open reading frame typing (POT) method].
Rinsho Byori
PUBLISHED: 07-24-2014
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Methicillin-resistant Staphylococcus aureus (MRSA) is the most common causative bacteria of hospital acquired infection, and should be rapidly identified for infection control. For this purpose, in our hospital, the PCR electrophoresis patterns of spacer regions (ITS: internal transcribed spacers) (ITS-PCR) are combined with a toxigenicity assay to establish a strain identification method for outbreak surveillance. In the present study, the usefulness of this method was evaluated in comparison with the POT (phage-open reading frame typing) method. One hundred MRSA strains isolated from inpatients in our hospital between April 2011 and March 2012 were classified into 25 patterns using the ITS-PCR method combined with a toxigenicity assay. The strains could be classified into 46 patterns using the POT method. ITS-PCR type 22 strain producing enterotoxin C and toxic shock syndrome toxin-1 could be further classified into 7 patterns using the POT method. In the outbreak of the type 22 strain, cross-infection could be excluded by additional analysis using the POT method, providing more precise information on strain identification. We identified that some strains of the same POT type consisted of different ITS-PCR types or toxigenicities. Therefore, these results suggest that the combination of ITS-PCR method plus toxigenicity assay with POT method may be a useful technique of MRSA typing.
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[Trends for the etiology of infective endocarditis at our hospital these 5 years].
Rinsho Byori
PUBLISHED: 07-16-2014
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The aim of this study is to evaluate characteristics of infective endocarditis for 5 years at Kanazawa University Hospital. Retrospectively, we investigated 39 patients diagnosed as infective endocarditis at our hospital from 2006 to 2010 based on blood culture and/or rejected cardiac specimens. Of 39 patients with infective endocarditis, 27 were male and 12 were female. Mean age was 55.4 years and 69% patients were older than 50 years. The frequent underlying presumed diseases were cardiac diseases. Vegetation was mainly observed at mitral valve and aortic valve. Streptococcus species [14 cases (36%)] and Staphylococcus species [12 cases (31%)] were common pathogens. In Streptococcus species, the critical cause was mostly presumed to be associated with dental procedure and oral cavity. In Staphylococcus species, intravascular device and soft tissue infection were also frequently presumed. Frequency of chronic kidney disease and infection around valve were higher in Staphylococcus species than those observed in Streptococcus species [12 cases (100%) vs. 7 cases (50%); p < 0.05, 6 cases (50%) vs. 1 case (7%); p < 0.05]. Our results suggested that the etiology of patients with Staphylococcus species infection increased in number among patients suffering from infective endocarditis at our hospital.
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Immediate therapeutic efficacy of low-density lipoprotein apheresis for drug-resistant nephrotic syndrome: evidence from the short-term results from the POLARIS Study.
Clin. Exp. Nephrol.
PUBLISHED: 05-28-2014
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Hyperlipidemia is not merely a complication but a major exacerbating factor in longstanding nephrotic syndrome (NS). Low-density lipoprotein apheresis (LDL-A) has been reported to ameliorate dyslipidemia and induce rapid remission of NS. Several clinical studies have suggested the therapeutic efficacy of LDL-A, but the level of clinical evidence is insufficient. Therefore, a multicenter prospective study, POLARIS (Prospective Observational Survey on the Long-Term Effects of LDL Apheresis on Drug-Resistant Nephrotic Syndrome), was initiated in Japan.
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Classification and characteristics of Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis in a nationwide, prospective, inception cohort study.
Arthritis Res. Ther.
PUBLISHED: 04-09-2014
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We investigated the clinical and serological features of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in Japan using data from a nationwide, prospective, inception cohort study.
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Anti-erythropoietin receptor antibody-associated pure red cell aplasia accompanied by Coombs-negative autoimmune hemolytic anemia in a patient with T cell/histiocyte-rich large B cell lymphoma.
Int. J. Hematol.
PUBLISHED: 03-18-2014
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A 79-year-old female diagnosed with T cell/histiocyte-rich large B cell lymphoma in complete remission after six cycles of rituximab-combined chemotherapy developed severe anemia, reticulocytopenia, and bone marrow erythroid hypoplasia. She was diagnosed with pure red cell aplasia (PRCA) accompanied by Coombs-negative autoimmune hemolytic anemia evidenced by a lack of glycophorin-A-positive cells in the bone marrow, haptoglobin under the detection level, and a high titer of RBC-bound IgG. Anti-erythropoietin receptor (EPOR) antibody was detected in the serum, and oligoclonal ?/? and ?/? T cells were also detected in her peripheral blood by Southern blotting analysis. Parvovirus B19 DNA was not detected by PCR. Although the treatment with rituximab had limited efficacy (specifically, only for hemolysis), subsequent cyclosporine therapy led to prompt recovery of erythropoiesis with the disappearance of anti-EPOR antibody and oligoclonal T cells. This is the first case report of anti-EPOR antibody-associated PRCA in a patient with malignant lymphoma treated successfully with cyclosporine.
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Fatty liver and serum cholinesterase are independently correlated with HbA1c levels: cross-sectional analysis of 5384 people.
J. Int. Med. Res.
PUBLISHED: 03-04-2014
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To examine the association between glycosylated haemoglobin (HbA1c) and fatty liver markers.
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Clinical course after corticosteroid therapy in IgG4-related aortitis/periaortitis and periarteritis: a retrospective multicenter study.
Arthritis Res. Ther.
PUBLISHED: 01-30-2014
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Immunoglobulin G4 (IgG4)-related aortitis/periaortitis and periarteritis are vascular manifestations of IgG4-related disease. In this disease, the affected aneurysmal lesion has been suspected to be at risk of rupture. In this study, we aimed to clarify the clinical course after corticosteroid therapy in IgG4-related aortitis/periaortitis and periarteritis.
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Relapse and its remission in Japanese patients with idiopathic membranous nephropathy.
Clin. Exp. Nephrol.
PUBLISHED: 01-15-2014
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The prognosis in patients with idiopathic membranous nephropathy (IMN) is diverse. However, the prognosis after relapse and factors affecting relapse remain unclear.
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Pro-inflammatory/Th1 gene expression shift in high glucose stimulated mesangial cells and tubular epithelial cells.
Biochem. Biophys. Res. Commun.
PUBLISHED: 11-28-2013
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Diabetic nephropathy (DN) is a major cause of end stage kidney disease and a strong risk factor for cardiovascular diseases. Growing data show chronic inflammation plays an important role for the progression of DN. As for the immune cells, anti-inflammatory leukocytes as well as pro-inflammatory leukocytes play an important role in DN. In addition to leukocytes, renal resident cells contribute to the inflammatory process of DN. However, precise functions, phenotypes and immune balance of renal resident cells remain to be explored. Therefore, we hypothesized that the aberrant immune balance of renal resident cells contributes to the pathogenesis of DN. To explore this possibility, we performed genome-wide transcriptome profiling in mesangial cells and tubular epithelial cells (TECs), which were stimulated by high glucose (HG) and detected the expression of inflammation associated genes. HG increased the mRNA expression of oxidative stress, inflammasome and mammalian target of rapamycin (mTOR) related genes in mesangial cells. Pro-inflammatory/Th1 gene expression was upregulated, but Th2 related gene expression was downregulated in mesangial cells. In TECs, HG stimulation increased pro-inflammatory/Th1/Th2 gene expression. Phosphorylation of signaling proteins shifted towards pro-inflammatory phenotype with suppressed phosphorylation of Th2 related signaling in TECs. The data taken together indicate that HG shifts the immune balance toward pro-inflammatory/Th1 phenotype in mesangial cells and TECs, which might initiate and/or prolong inflammation, thereby resulting in diabetic nephropathy.
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[Chairmens introductory remarks].
Rinsho Byori
PUBLISHED: 11-12-2013
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Recently, mild to moderate renal dysfunction has attracted attention as a new common disease in Japan as well as all over the world. Also, the morbidity of endstage renal disease and progression to dialysis is increasing each year. It is now widely recognized that renal dysfunction is a major risk for cardiovascular disease; therefore, cardio-renal relationships should be investigated. To elucidate the pathophysiology of this relationship and develop new methods for early diagnosis, treatment and prevention can promise a long and healthy life. It is also important to provide high quality data on urinalysis and kidney function.
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Long-term outcomes of Japanese type 2 diabetic patients with biopsy-proven diabetic nephropathy.
Diabetes Care
PUBLISHED: 10-02-2013
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We evaluated the structural-functional relationships and the prognostic factors for renal events, cardiovascular events, and all-cause mortality in type 2 diabetic patients with biopsy-proven diabetic nephropathy.
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Treatment and impact of dyslipidemia in diabetic nephropathy.
Clin. Exp. Nephrol.
PUBLISHED: 09-20-2013
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Recent epidemiological research revealed that dyslipidemia is a risk factor for development and progression of diabetic nephropathy. Results from interventional studies revealed the possibility that anti-hyperlipidemic agents have a better effect on diabetic nephropathy through improvement of albuminuria and loss of renal function. In addition, dyslipidemia may be a consequence of albuminuria and renal dysfunction, thereby perpetuating kidney damage. Today, the proportion of diabetic patients receiving statins is increasing due to their beneficial effect on cardiovascular mortality. However, treatment for patients should be determined based on consideration of the risk and benefit of the treatment. More insight into the pathogenesis of diabetic nephropathy and the effects of life-style changes is required.
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Reversibility of the pulmonary function based on the partial flow-volume curve predicts the efficacy of bronchodilator therapy for treating chronic cough.
Intern. Med.
PUBLISHED: 09-18-2013
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Partial expiratory flow-volume curves have the potential to detect mild bronchoconstriction because they are not affected by the modulatory effects of deep inspiration. The aim of this study was to investigate the relationship between the efficacy of bronchodilator therapy (BDT) in treating the cough and to assess the increase in the expiratory flow of the partial flow-volume curve at 40% above the residual volume level (PEF40) caused by treatment with a short-acting beta-2 agonist (SABA) in patients with chronic nonproductive cough.
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Clinical impact of albuminuria and glomerular filtration rate on renal and cardiovascular events, and all-cause mortality in Japanese patients with type 2 diabetes.
Clin. Exp. Nephrol.
PUBLISHED: 08-03-2013
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The number of patients suffering from diabetic nephropathy resulting in end-stage kidney disease is increasing worldwide. In clinical settings, there are limited data regarding the impact of the urinary albumin-to-creatinine ratio (UACR) and reduced estimated glomerular filtration rate (eGFR) on renal and cardiovascular outcomes and all-cause mortality.
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Impact of kidney function and urinary protein excretion on pulmonary function in Japanese patients with chronic kidney disease.
Clin. Exp. Nephrol.
PUBLISHED: 07-30-2013
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Although the cardiorenal relationship in chronic kidney disease has been investigated, information about the lung-kidney relationship is limited. Here, we investigated the impact of kidney function and urinary protein excretion on pulmonary dysfunction.
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Kidney lesions in diabetic patients with normoalbuminuric renal insufficiency.
Clin. Exp. Nephrol.
PUBLISHED: 07-17-2013
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Diabetic nephropathy is a leading cause of end-stage renal disease in Japan. Microalbuminuria has been considered as the first clinical sign of diabetic nephropathy. However, recent studies demonstrated that normoalbuminuric renal insufficiency is not uncommon for diabetic patients, especially in type 2 diabetes. Although the pathogenesis of normoalbuminuric renal insufficiency in diabetic nephropathy remains to be fully elucidated, distinct clinical and pathological features of diabetic patients with this finding have been reported as compared to those in diabetic patients with a typical clinical course. In type 1 diabetes, more advanced glomerular lesions were found in patients with normoalbuminuric renal insufficiency than in patients with normoalbuminuric preserved renal function. In contrast, disproportionately advanced tubulointerstitial and vascular lesions, despite minor diabetic glomerular lesions, which denote the presence of diabetic kidney lesions as well as nephrosclerosis, were likely to be related to the development of normoalbuminuric renal insufficiency in some type 2 diabetic patients. In addition, long-term outcomes of diabetic patients with normoalbuminuric renal insufficiency remain controversial. Further studies to gain a better understanding of the structural-functional relationships and natural history of diabetic patients with normoalbuminuric renal insufficiency may improve the benefits of therapeutic interventions for diabetic nephropathy.
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Successful delivery in a patient with antineutrophil cytoplasmic antibody-associated glomerulonephritis.
Intern. Med.
PUBLISHED: 07-15-2013
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We herein report a case of spontaneous pregnancy and preterm delivery in a 29-year-old patient with myeloperoxidase-antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis. Her basal serum creatinine level before pregnancy was 1.4 mg/dL and her urinary protein level was approximately 2 g/day. The proteinuria and hematuria increased during pregnancy, and the patient was admitted to our hospital and treated with prednisolone (PSL). At 27 weeks of gestation, she delivered a live infant weighing 848 g via cesarean section. No relapse of ANCA-associated glomerulonephritis occurred.
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Validation of a newly proposed histopathological classification in Japanese patients with anti-neutrophil cytoplasmic antibody-associated glomerulonephritis.
BMC Nephrol
PUBLISHED: 06-12-2013
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BACKGROUND: A new histopathological classification of anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis was recently proposed. We evaluated the predictive value of this classification for renal outcome in Japanese patients. METHODS: We enrolled 122 patients with ANCA-associated glomerulonephritis diagnosed at several institutions in Japan between January 2000 and March 2010. Twenty patients were excluded because of observation durations of <1 year, and/or because their biopsy specimens contained <10 glomeruli. Renal biopsy specimens were categorized into four classes according to the proposed classification. We evaluated the predictive value of immunohistochemical staining for alpha-smooth muscle actin (SMA), Wilms tumor 1 (WT1), CD68, and cytokeratin for end-stage renal disease (ESRD). RESULTS: The study population included 54 men and 48 women. Age, estimated glomerular filtration rate (eGFR), and proteinuria were 66.3 +/- 11.3 years, 21.6 ml/min. and 1.10 g/24 h, respectively. Eighty-six patients were positive for myeloperoxidase-ANCA, five were positive for proteinase 3-ANCA, and 11 were negative for both antibodies. Median follow-up time was 41.0 months. Twenty-three patients (22.5%) developed ESRD during the follow-up period. Twelve patients died during follow up; 7/12 patients developed ESRD before death, and 5/12 patients died without ESRD. The incidence of ESRD increased with sequential categories: focal, 2/46 (4.3%); crescentic, 9/32 (28%); mixed, 8/18 (44%); and sclerotic, 4/6 (67%). The focal class had the best renal survival and the sclerotic class had the worst renal survival (p < 0.001). Kaplan-Meier renal survival analysis was similar to that of the new classification system proposal. In the multivariate analysis, the classification system tended to be a prognostic factor for ESRD (p = 0.0686, crescentic, mixed and sclerotic vs. focal, hazard ratio (HR) [95% confidence interval, CI]; 2.99 [0.61--22.7], 5.04 [1.11--36.4] and 9.93 [1.53--85.7], respectively). alpha-SMA-positivity also tended to be associated with ESRD (p = 0.1074). CONCLUSION: The new histopathological classification was associated with eGFR at 1 year and tended to be associated with ESRD in our Japanese cohort with ANCA-associated glomerulonephritis. alpha-SMA positivity might be an additional prognostic factor for ESRD.
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Adipose tissue-derived stem cells as a regenerative therapy for a mouse steatohepatitis-induced cirrhosis model.
Hepatology
PUBLISHED: 04-15-2013
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Cirrhosis is a chronic liver disease that impairs hepatic function and causes advanced fibrosis. Mesenchymal stem cells have gained recent popularity as a regenerative therapy since they possess immunomodulatory functions. We found that injected adipose tissue-derived stem cells (ADSCs) reside in the liver. Injection of ADSCs also restores albumin expression in hepatic parenchymal cells and ameliorates fibrosis in a nonalcoholic steatohepatitis model of cirrhosis in mice. Gene expression analysis of the liver identifies up- and down-regulation of genes, indicating regeneration/repair and anti-inflammatory processes following ADSC injection. ADSC treatment also decreases the number of intrahepatic infiltrating CD11b(+) and Gr-1(+) cells and reduces the ratio of CD8(+) /CD4(+) cells in hepatic inflammatory cells. This is consistent with down-regulation of genes in hepatic inflammatory cells related to antigen presentation and helper T-cell activation. Conclusion: These results suggest that ADSC therapy is beneficial in cirrhosis, as it can repair and restore the function of the impaired liver.
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Coordinated changes in DNA methylation in antigen-specific memory CD4 T cells.
J. Immunol.
PUBLISHED: 03-18-2013
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Memory CD4(+) T cells are central regulators of both humoral and cellular immune responses. T cell differentiation results in specific changes in chromatin structure and DNA methylation of cytokine genes. Although the methylation status of a limited number of gene loci in T cells has been examined, the genome-wide DNA methylation status of memory CD4(+) T cells remains unexplored. To further elucidate the molecular signature of memory T cells, we conducted methylome and transcriptome analyses of memory CD4(+) T cells generated using T cells from TCR-transgenic mice. The resulting genome-wide DNA methylation profile revealed 1144 differentially methylated regions (DMRs) across the murine genome during the process of T cell differentiation, 552 of which were associated with gene loci. Interestingly, the majority of these DMRs were located in introns. These DMRs included genes such as CXCR6, Tbox21, Chsy1, and Cish, which are associated with cytokine production, homing to bone marrow, and immune responses. Methylation changes in memory T cells exposed to specific Ag appeared to regulate enhancer activity rather than promoter activity of immunologically relevant genes. In addition, methylation profiles differed between memory T cell subsets, demonstrating a link between T cell methylation status and T cell differentiation. By comparing DMRs between naive and Ag-specific memory T cells, this study provides new insights into the functional status of memory T cells.
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Adipose tissue derived stromal stem cell therapy in murine ConA-derived hepatitis is dependent on myeloid-lineage and CD4(+) T-cell suppression.
Eur. J. Immunol.
PUBLISHED: 03-17-2013
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Mesenchymal stromal stem cells (MSCs) are an attractive therapeutic model for regenerative medicine due to their pluripotency. MSCs are used as a treatment for several inflammatory diseases, including hepatitis. However, the detailed immunopathological impact of MSC treatment on liver disease, particularly for adipose tissue derived stromal stem cells (ADSCs), has not been described. Here, we investigated the immuno-modulatory effect of ADSCs on hepatitis using an acute ConA C57BL/6 murine hepatitis model. i.v. administration of ADSCs simultaneously or 3 h post injection prevented and treated ConA-induced hepatitis. Immunohistochemical analysis revealed higher numbers of CD11b(+) , Gr-1(+) , and F4/80(+) cells in the liver of ConA-induced hepatitis mice was ameliorated after the administration of ADSCs. Hepatic expression of genes affected by ADSC administration indicated tissue regeneration-related biological processes, affecting myeloid-lineage immune-mediating Gr-1(+) and CD11b(+) cells. Pathway analysis of the genes expressed in ADSC-treated hepatic inflammatory cells revealed the possible involvement of T cells and macrophages. TNF-? and IFN-? expression was downregulated in hepatic CD4(+) T cells isolated from hepatitis livers co-cultured with ADSCs. Thus, the immunosuppressive effect of ADSCs in a C57BL/6 murine ConA hepatitis model was dependent primarily on the suppression of myeloid-lineage cells and, in part, of CD4(+) T cells.
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Long-term observations of clinicopathological characteristics and outcome of Japanese patients with pauci-immune crescentic glomerulonephritis.
Clin. Exp. Nephrol.
PUBLISHED: 03-11-2013
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The clinicopathological characteristics and outcome with pauci-immune crescentic glomerulonephritis (CreGN) are presumed to vary over time. We examined the characteristics and outcome of Japanese patients with CreGN according to the treatment periods.
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CCL2/CCR2 augments the production of transforming growth factor-beta1, type 1 collagen and CCL2 by human CD45-/collagen 1-positive cells under high glucose concentrations.
Clin. Exp. Nephrol.
PUBLISHED: 03-11-2013
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The migration and activation of circulating profibrotic cells including fibrocytes by the action of the chemokine/chemokine receptor system has been implicated in pathological fibrogenesis. In the present study, the involvement of collagen 1 (Col1)-producing cells, CD45-positive/collagen-1-positive (CD45(+)/Col1(+)) cells originally named as fibrocytes via CC chemokine receptor 2 (CCR2), a cognate receptor of CCL2/monocyte chemoattractant protein, was examined in diabetic conditions.
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ER stress induced impaired TLR signaling and macrophage differentiation of human monocytes.
Cell. Immunol.
PUBLISHED: 02-13-2013
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Endoplasmic reticulum (ER) stress causes impairment of the intracellular protein synthesis machinery, affecting various organ functions and homeostasis systems, including immunity. We found that ER stress induced by the N-linked glycosylation inhibitor, tunicamycin, caused susceptibility to apoptosis in the human monocytic cell line, THP-1 cells. Importantly, prior to tunicamycin-induced apoptosis, the proinflammatory response to toll-like receptor (TLR) 4 ligand lipopolysaccharide (LPS) stimulation was attenuated with respect to the expression of the proinflammatory cytokines. This impaired expression of proinflammatory cytokines was a consequence of the inhibition of NF-?B activation. Moreover, tunicamycin-induced ER stress disturbed the differentiation of THP-1 cells into macrophages induced by phorbol-12-myristate-13-acetate treatment. We also confirmed that ER stress affected the response of primary human monocytes to TLR ligand and their ability to differentiate into macrophages. These data suggest that ER stress imposes an important pathological insult to the immune system, affecting the crucial functions of monocytes.
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Japan Diabetic Nephropathy Cohort Study: study design, methods, and implementation.
Clin. Exp. Nephrol.
PUBLISHED: 01-17-2013
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Diabetic nephropathy, leading to end-stage renal disease, has a considerable impact on public health and the social economy. However, there are few national registries of diabetic nephropathy in Japan. The aims of this prospective cohort study are to obtain clinical data and urine samples for revising the clinical staging of diabetic nephropathy, and developing new diagnostic markers for early diabetic nephropathy.
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LPA1-induced cytoskeleton reorganization drives fibrosis through CTGF-dependent fibroblast proliferation.
FASEB J.
PUBLISHED: 01-15-2013
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There has been much recent interest in lysophosphatidic acid (LPA) signaling through one of its receptors, LPA1, in fibrotic diseases, but the mechanisms by which LPA-LPA1 signaling promotes pathological fibrosis remain to be fully elucidated. Using a mouse peritoneal fibrosis model, we demonstrate central roles for LPA and LPA1 in fibroblast proliferation. Genetic deletion or pharmacological antagonism of LPA1 protected mice from peritoneal fibrosis, blunting the increases in peritoneal collagen by 65.4 and 52.9%, respectively, compared to control animals and demonstrated that peritoneal fibroblast proliferation was highly LPA1 dependent. Activation of LPA1 on mesothelial cells induced these cells to express connective tissue growth factor (CTGF), driving fibroblast proliferation in a paracrine fashion. Activation of mesothelial cell LPA1 induced CTGF expression by inducing cytoskeleton reorganization in these cells, causing nuclear translocation of myocardin-related transcription factor (MRTF)-A and MRTF-B. Pharmacological inhibition of MRTF-induced transcription also diminished CTGF expression and fibrosis in the peritoneal fibrosis model, mitigating the increase in peritoneal collagen content by 57.9% compared to controls. LPA1-induced cytoskeleton reorganization therefore makes a previously unrecognized but critically important contribution to the profibrotic activities of LPA by driving MRTF-dependent CTGF expression, which, in turn, drives fibroblast proliferation.
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The impacts of albuminuria and low eGFR on the risk of cardiovascular death, all-cause mortality, and renal events in diabetic patients: meta-analysis.
PLoS ONE
PUBLISHED: 01-01-2013
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Precise effects of albuminuria and low estimated glomerular filtration rate (eGFR) on cardiovascular mortality, all-cause mortality, and renal events in diabetic patients are uncertain.
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[Circulatory function test for the diagnosis of diabetic complications].
Rinsho Byori
PUBLISHED: 12-23-2011
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Diabetic patients suffer from systemic complications, which are generally characterized by a lack of early symptoms. In the management of diabetes, early diagnosis of complications and preventing progression are of importance. Vascular complications of diabetes are divided into microvascular and macrovascular complications. Circulatory function tests play a major role in diagnosing the presence and severity of macrovascular complications in clinical settings. In this review, we outlined the significance and precautions of each test in the diagnosis of diabetic macrovascular disease. 1) Echocardiography: Diabetic patients are often associated with ischemic heart disease, and some patients present with diffuse wall motion abnormalities due to multivessel disease. Patients with diabetic cardiomyopathy may have signs of left ventricular diastolic dysfunction with normal systolic function. 2) Carotid ultrasonography: Increase in intima-media thickness is associated with the onset of cardiovascular and cerebrovascular disease. Hypoechoic plaque and the thrombus formation have been reported to be closely related with cerebral infarction. 3) Assessment of lower extremity artery: Patients with diabetes are at a higher risk of developing peripheral artery diseases (PAD), which lead to disability. Doppler ultrasonography is widely used for noninvasive diagnosis of PAD. Information of real-time physiological blood flow is useful for disease monitoring. 4) Ankle-brachial index (ABI): ABI is a simple method recommended for screening and evaluating PAD of lower limbs. The limitation of this measurement is that pseudonormalization may occur with severe calcification of artery walls. 5) Pulse wave velocity (PWV), flow-mediated dilatation (FMD): PWV and FMD provide information for the function of blood vessels. Functional changes in peripheral arteries may precede structural changes. In this regard, these tests may play an important role in early diagnosis.
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Risk factors associated with relapse in Japanese patients with microscopic polyangiitis.
J. Rheumatol.
PUBLISHED: 12-15-2011
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We retrospectively studied the risk factors associated with relapse during remission maintenance therapy for myeloperoxidase-antineutrophil cytoplasmic autoantibody (MPO-ANCA)-positive microscopic polyangiitis (MPA).
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[Analysis of brain activity during delayed matching-to-sample test].
Rinsho Byori
PUBLISHED: 09-28-2011
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Despite recent advances in uncovering the neural signature of memory processing in humans, spatiotemporal characteristics of cerebral activity during mental transformation of the visual (color) memory to the visuo-spatial memory has not been studied. The aim of this study was to investigate the electrophysiological correlates of internal memory transformation based on the event-related potential analysis using a root mean square (RMS) and a standardized low resolution electromagnetic tomography (sLORETA). Eleven healthy human subjects completed a modified delayed matching-to-sample test in which the visual(color) short-term memory had to be transformed into the visuo-spatial memory according to the matching probe. In comparison with a non-memory control condition, identifiable RMS peak was observed 352ms after the matching probe presentation in the condition of memory transformation. In this time, sLORETA demonstrated the higher current density in the prefrontal region. Our results suggested that the prefrontal region is associated with the internal memory transformation process depicting a spatiotemporal profile similar to P3b.
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[Usefulness of reticulocyte hemoglobin equivalent for the safety of pre-operative autologous blood donation].
Rinsho Byori
PUBLISHED: 08-06-2011
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Pre-operative autologous blood donation (PABD) provides safe blood for patients at the expense of the risk of iron deficiency anemia that may compromise the patients. The reticulocyte hemoglobin equivalent (RET-He) is an indirect measure of the functional iron available for the erythropoiesis over the previous 2-3 days. The aim of this study was to evaluate the clinical usefulness of RET-He quickly measured by the automated hematology analyzer Sysmex XE-2100 in patients undergoing PABD at our hospital. Receiver-operating characteristic curve analysis revealed that RET-He was reliable in the diagnosis of iron deficiency anemia. Two of 14 patients in the absence of post-PABD iron replacement developed marked anemia with low RET-He levels after PABD, suggesting that this anemia was due to iron deficiency. Of 26 patients receiving post-PABD iron replacement, 8 who had already showed low RET-He levels at PABD developed statistically significant reduction in hemoglobin levels after PABD despite adequate iron replacement, indicating that the 8 patients had iron deficiency prior to PABD. These findings suggest that automated measurement of RET-He may contribute to improve the safety of PABD.
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Activation of p38 mitogen-activated protein kinase promotes peritoneal fibrosis by regulating fibrocytes.
Perit Dial Int
PUBLISHED: 06-30-2011
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Peritoneal fibrosis is a serious complication of long-term peritoneal dialysis, and yet the precise pathogenic mechanisms of peritoneal fibrosis remain unknown. Fibrocytes participate in tissue fibrosis and express chemokine receptors that are necessary for migration. The p38 mitogen-activated protein kinase (MAPK) pathway regulates the production of chemokines and has been demonstrated to contribute to the pathogenesis of various fibrotic conditions. Accordingly, we used an experimental mouse model of peritoneal fibrosis to examine the dependency of fibrocytes on p38MAPK signaling.
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[Clinical evaluation of rapid identification of bacteria from positive-testing blood culture bottles by internal transcribed spacer PCR].
Rinsho Byori
PUBLISHED: 06-29-2011
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Delays in diagnosis and initiation of treatment of severe infections such as sepsis greatly influence patient prognosis. Our laboratory introduced rapid identification of bacterial species by PCR for positive blood culture samples as a routine laboratory test since April 2008. We extracted DNA directly from positive blood culture bottles and amplified the internal transcribed spacer (ITS) region of pathogenic microorganisms by PCR in order to identify bacterial species from electrophoretic patterns of PCR products. Of 167 strains from 167 samples excluding three samples with polymicrobial organisms, 144 strains (86.2%) were correctly identified at species level and 17 strains (10.2%) at genus level. The time required between DNA extraction and bacterial identification was about one and one-half hours. In patients with MRSA sepsis, the time of initiation of treatments such as administration of anti-MRSA drugs and intravascular catheter removal has clearly become earlier with the introduction of ITS-PCR, resulting decreased mortality from 35.0% to 16.0%. Rapid identification of pathogens directly from blood culture bottles by ITS-PCR seems to be useful for appropriate treatment of severe infectious diseases.
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Three cases of pneumatosis intestinalis presenting in autoimmune diseases.
Mod Rheumatol
PUBLISHED: 06-15-2011
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Pneumatosis intestinalis (PI) is a comparatively rare disease characterized by the presence of intramural gas in the gastrointestinal tract. PI is known to be associated with several clinical conditions, such as pulmonary diseases, gastrointestinal diseases, and traumatic injury, as well as autoimmune disorders. In particular, PI is commonly seen in systemic sclerosis (SSc) but rarely in systemic lupus erythematosus and dermatomyositis (DM). In this report, we present three cases of PI presenting in autoimmune diseases, including DM, Sjögrens syndrome, and limited SSc, and further discuss its background characteristics.
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Crystal structure of the eukaryotic light-driven proton-pumping rhodopsin, Acetabularia rhodopsin II, from marine alga.
J. Mol. Biol.
PUBLISHED: 06-06-2011
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Acetabularia rhodopsin (AR) is a rhodopsin from the marine plant Acetabularia acetabulum. The opsin-encoding gene from A. acetabulum, ARII, was cloned and found to be novel but homologous to that reported previously. ARII is a light-driven proton pump, as demonstrated by the existence of a photo-induced current through Xenopus oocytes expressing ARII. The photochemical reaction of ARII prepared by cell-free protein synthesis was similar to that of bacteriorhodopsin (BR), except for the lack of light-dark adaptation and the different proton release and uptake sequence. The crystal structure determined at 3.2 Å resolution is the first structure of a eukaryotic member of the microbial rhodopsin family. The structure of ARII is similar to that of BR. From the cytoplasmic side to the extracellular side of the proton transfer pathway in ARII, Asp92, a Schiff base, Asp207, Asp81, Arg78, Glu199, and Ser189 are arranged in positions similar to those of the corresponding residues directly involved in proton transfer by BR. The side-chain carboxyl group of Asp92 appears to interact with the sulfhydryl group of Cys218, which is unique to ARII and corresponds to Leu223 of BR and to Asp217 of Anabaena sensory rhodopsin. The orientation of the Arg78 side chain is opposite to the corresponding Arg82 of BR. The putative absence of water molecules around Glu199 and Arg78 may disrupt the formation of the low-barrier hydrogen bond at Glu199, resulting in the "late proton release".
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The role of cytokine in the lupus nephritis.
J. Biomed. Biotechnol.
PUBLISHED: 05-26-2011
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Lupus nephritis (LN) is a major clinical manifestation of systemic lupus erythematosus (SLE). Although numerous abnormalities of immune system have been proposed, cytokine overexpression plays an essential role in the pathogenesis of LN. In the initial phase of the disease, the immune deposits and/or autoantibodies induce cytokine production in renal resident cells, leading to further inflammatory cytokine/chemokine expression and leukocyte infiltration and activation. Then, infiltrate leukocytes, such as macrophages (M?) and dendritic cells (DCs), secrete a variety of cytokines and activate naïve T cells, leading the cytokine profile towards T helper (Th)1, Th2, and/or Th17. Recent studies revealed these inflammatory processes in experimental animal models as well as human LN. The cytokine targeted intervention may have the therapeutic potentials for LN. This paper focuses on the expression of cytokine and its functional role in the pathogenesis of LN.
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Clinical impact of albuminuria in diabetic nephropathy.
Clin. Exp. Nephrol.
PUBLISHED: 05-10-2011
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Patients suffering from diabetic nephropathy, resulting in end-stage renal failure, are increasing in number. The pathophysiology of diabetic nephropathy remains to be fully investigated. In the clinical setting, the presence of albuminuria/overt proteinuria and a low glomerular filtration rate may predict poor renal prognosis, but the prognosis of the normoalbuminuric renally insufficient diabetic patient remains controversial. In addition to the measurement of urinary albumin excretion, biomarker studies to detect diabetic nephropathy more specifically at the early stage have been performed worldwide. There is a growing body of evidence for remission and/or regression of diabetic nephropathy, which may be an indicator for cardiovascular and renal risk reduction. Deeper insights into the pathological characteristics as well as the clinical impact of albuminuria on renal and cardiovascular outcome are required.
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A superagonistic monoclonal antibody for CD28 ameliorates crescentic glomerulonephritis in wistar-kyoto rats.
Mol. Med.
PUBLISHED: 04-07-2011
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Regulatory T (Treg) cells play an important role in the resolution of crescentic glomerulonephritis, where a T helper 1 (Th1)-predominant immune response promotes crescent formation. Therefore, agents that increase Treg cells appear to be ideal for suppressing T-cell-mediated renal pathology. We hypothesized that a superagonistic monoclonal antibody for CD28 (JJ316), which has been known to preferentially expand Treg cells in vivo, could prevent nephrotoxic serum-induced nephritis in Wistar-Kyoto rats, one of the experimental models of crescentic glomerulonephritis. Administration of JJ316 attenuated crescent formation, proteinuria and glomerular accumulation of macrophages and CD8(+) T cells. These changes were accompanied by increased infiltration of Treg cells. Among glomerular macrophages, the CD163(+) subset was significantly increased after treatment, suggesting that Treg cells may modulate the phenotype of macrophages leading to resolution of glomerulonephritis. In an adoptive transfer experiment, two T-cell subsets (CD4(+)CD25(+) and CD4(+)CD25(-) T cells) purified from spleens and lymph nodes of donor rats primed with JJ316 3 d before were inoculated into nephritic recipient rats, which recapitulated the beneficial effects of in vivo administration of JJ316. Furthermore, a single injection of JJ316 administered 3 d after disease induction completely protected nephritic rats from death for 2 months. In conclusion, we demonstrated that treatment with JJ316 has a dramatic therapeutic effect on an experimental crescentic glomerulonephritis, possibly due to expansion and activation of Treg cells.
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Fractalkine and its receptor, CX3CR1, promote hypertensive interstitial fibrosis in the kidney.
Hypertens. Res.
PUBLISHED: 03-31-2011
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Hypertension promotes and escalates kidney injury, including kidney fibrosis. Fractalkine/CX3CL1 is a unique chemokine that works as a leukocyte chemoattractant and an adhesion molecule. Recently, fractalkine/CX3CL1 has been reported to promote tissue fibrosis via its cognate receptor, CX3CR1. However, the involvement of the fractalkine-CX3CR1 axis in the pathogenesis of hypertensive kidney fibrosis remains unclear. The impacts of the fractalkine-CX3CR1 axis on hypertensive kidney fibrosis were investigated in a deoxycorticosterone acetate (DOCA)-salt hypertensive model in CX3CR1-deficient mice, which were sacrificed on day 28. The blood pressure levels were similarly elevated in both CX3CR1-/- C57BL/6 and wild-type C57BL/6 mice. Fractalkine and CX3CR1 were upregulated in kidneys that were damaged by hypertension. Deficiency in CX3CR1 inhibited kidney fibrosis, as evidenced by a decrease in the presence of interstitial fibrotic area detected by type I collagen in Mallory-Azan staining, concomitant with the downregulation of transforming growth factor (TGF)-?(1) and type I procollagen mRNA expression in damaged kidneys. The CX3CR1 blockade also decreased the number of infiltrating F4/80-positive macrophages in damaged kidneys. These results suggest that the fractalkine-CX3CR1 axis contributes to kidney fibrosis in a hypertensive mouse model, possibly by the upregulation of macrophage infiltration and the expression of TGF-?(1) and type I collagen.
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Matrix metalloproteinase-2 (MMP-2) and membrane-type 1 MMP (MT1-MMP) affect the remodeling of glomerulosclerosis in diabetic OLETF rats.
Nephrol. Dial. Transplant.
PUBLISHED: 03-17-2011
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We reported previously that diabetic glomerular nodular-like lesions were formed during the reconstruction process of mesangiolysis. However, the precise mechanism has yet to be elucidated. Here, we investigated the roles of matrix metalloproteinase (MMP)-2, which is activated from proMMP-2 by membrane-type (MT)-MMP in the sclerotic and endothelial cell injury process of a type II diabetic model, Otsuka Long-Evans Tokushima Fatty (OLETF) rats.
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Nucleotide excision repair gene polymorphisms may predict acute toxicity in patients treated with chemoradiotherapy for bladder cancer.
Pharmacogenomics
PUBLISHED: 11-05-2010
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Platinum-based chemoradiotherapy (CRT) as bladder conservation therapy has shown promising results for muscle-invasive bladder cancer. However, treatment-related toxicity remains a major consideration in therapeutic planning. Some common polymorphisms in genes involved in DNA repair (encoding enzymes that repair DNA damaged by platinum agents and ionizing radiation) are reported to result in modulation of the repair capacity. We investigated associations between functional genetic polymorphisms involved in DNA repair and acute toxicity of CRT to determine the predictive value of these polymorphisms for toxicity.
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[A case of bronchiolitis obliterans caused by allogeneic hematopoietic stem cell transplantation diagnosed with a body plethysmograph].
Rinsho Byori
PUBLISHED: 10-23-2010
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A 19-year-old woman with acute myeloid leukemia (M1) was treated with allogeneic hematopoietic stem cell transplantation. She was diagnosed with skin graft-versus-host disease 27 days after the transplantation. She was admitted to the Dept. of Respiratory Medicine at Kanazawa University Hospital, because she complained of progressive obstructive ventilatory impairment. A high-resolution computed tomography (CT) scan showed centrilobular small nodules. A chest CT scan (inspiratory phase and expiratory phase) revealed hyperlucent areas forming a mosaic pattern. A ventilation-perfusion scan showed matched unequal distribution. The pathological diagnosis made using biopsied lung, obtained by a right lower partial lobectomy, was constrictive bronchiolitis. Pulmonary function tests on admission showed mixed ventilatory impairment. %Residual volume(RV)/total lung capacity(TLC) was measured by the closed-circuit helium dilution method and was within the upper limit of the normal range. However, %RV/TLC measured by a body plethysmograph indicated a value of 258.1%. We believe that the difference in the %RV/TLC values reflected air trapping caused by bronchiolitis obliterans. Thus, the lung volume fraction measured by body plethysmograph was useful for diagnosing bronchiolitis obliterans in this case. [Rinsho Byori 58 : 906-911, 2010].
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Two cases of mycosis fungoides treated by reduced-intensity cord blood transplantation.
J. Dermatol.
PUBLISHED: 09-28-2010
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Mycosis fungoides is a cutaneous T-cell lymphoma, which is clinically divided into three stages: patch, plaque and tumor. Despite a variety of treatments the prognosis is poor in advanced mycosis fungoides. Recently, allogeneic hematopoietic stem cell transplantation has been successfully applied for such cases. We performed reduced-intensity umbilical cord blood transplantation for two advanced mycosis fungoides patients. Case 1 was a 56-year-old man and case 2 was a 30-year-old woman. Tumors of each case were refractory to conventional chemotherapy. Although radiation therapy was considerably effective, tumors relapsed after several months. Reduced-intensity umbilical cord blood transplantation was performed because case 1 had no human leukocyte antigen-identical siblings and the sibling of case 2 did not agree to be the donor. The male patient died of pulmonary failure 23 days after reduced-intensity umbilical cord blood transplantation. The case 2 patient succeeded in reduced-intensity umbilical cord blood transplantation and remained in complete/partial remission for 13 months. However, chemotherapy-resistant tumors relapsed, and allogeneic hematopoietic stem cell transplantation was performed at 17 months. She died of cerebral hemorrhage 23 days after the procedure. Reduced-intensity umbilical cord blood transplantation may be included in the treatments for advanced mycosis fungoides, where graft-versus-lymphoma effect seems to be a significant factor for the success of the treatment.
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Involvement of bone-marrow-derived cells in kidney fibrosis.
Clin. Exp. Nephrol.
PUBLISHED: 08-30-2010
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Cellular mechanisms have been proposed in the pathogenesis of fibrotic processes in the kidney. In this setting, cell sources underlying the generation of matrix-producing cells in diseased kidneys have been categorized as activated resident stromal cells (e.g., fibroblasts, pericytes), infiltrating bone-marrow-derived cells (e.g., fibrocytes, T cells, macrophages), and cells derived from epithelial-mesenchymal transition/endothelial-mesenchymal transition. Among these cell sources, accumulating evidence has shed light on the involvement of bone-marrow-derived cells, including monocytes/macrophages, and a circulating mesenchymal progenitor cell, fibrocyte, in the progression of fibrosis in kidney. Bone-marrow-derived cells positive for CD45 or CD34, and type 1 (pro)collagen dependent on the chemokine and renin-angiotensin systems migrate into diseased kidneys and enhance synthesis matrix protein, cytokines/chemokines, and profibrotic growth factors, which may promote and escalate chronic inflammatory processes and possible interaction with resident stromal cells, thereby perpetuating kidney fibrosis.
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Involvement of CD11b+ GR-1 low cells in autoimmune disorder in MRL-Fas lpr mouse.
Clin. Exp. Nephrol.
PUBLISHED: 06-03-2010
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Myeloid-derived suppressor cells (MDSCs) have been identified as immunosuppressive cells in tumor-related inflammation. However, the pathogenesis of MDSCs for autoimmune disease has not been investigated as yet. The aim of this study was to address whether MDSCs contribute to autoimmune organ injury in lupus-prone mice.
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A case of microscopic polyangiitis following mycoplasma infection in a patient with MPO-ANCA positive pulmonary fibrosis.
Allergol Int
PUBLISHED: 04-15-2010
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Microscopic polyangiitis is a vasculitic disease that may result in a pulmonary renal syndrome. Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis is strongly associated with infection.
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A case of neurosarcoidosis with necrotizing granuloma expressing angiotensin-converting enzyme.
Mod Rheumatol
PUBLISHED: 03-25-2010
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We described a case of neurosarcoidosis with necrotizing sarcoid granulomatosis in a 22-year-old man. Contrast-enhanced brain computed tomography scan and magnetic resonance imaging showed intracerebral multiple nodular lesions. Noncaseating and partial necrotizing granulomas were detected in the specimen resected by neurosurgery. In addition, immunohistochemical examination revealed the expression of angiotensin-converting enzyme in necrotizing granuloma. Thus, these findings were consistent with neurosarcoidosis. Clinical and pathological presentation, immunological features, and treatment modalities of neurosarcoidosis are discussed.
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The absence of interleukin-6 enhanced arsenite-induced renal injury by promoting autophagy of tubular epithelial cells with aberrant extracellular signal-regulated kinase activation.
Am. J. Pathol.
PUBLISHED: 12-11-2009
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Sodium arsenite (NaAs)-induced autophagic cell death (ACD) of a mouse renal tubular epithelial cell line (mProx24), which expresses enhanced levels of interleukin-6 (IL-6), was reduced by the suppression of autophagy by 3-methyladenine or Atg7 knockdown. The inhibition of the IL-6/signal transducer and activator of transcription 3 (STAT3) signal pathway by anti-IL-6 antibody or a Jak2 inhibitor (AG490) exaggerated ACD of mProx24 cells after NaAs challenge, attenuating STAT3 activation and reciprocally enhancing extracellular signal-regulated kinase (ERK) phosphorylation. In contrast, an ERK inhibitor, PD98059, reduced NaAs-induced ACD in mProx24 cells. Subcutaneous injection of NaAs (12.5 mg/kg) into BALB/c (wild-type) mice enhanced intrarenal expression of IL-6, mainly produced by tubular cells, and caused severe renal injury characterized by hemorrhages, acute tubular necrosis, cast formation, and brush border disappearance, with increases in serum urea nitrogen (blood urea nitrogen) and creatinine levels. In addition, IL-6-deficient (IL-6(-/-)) mice exhibited exaggerated histopathological changes with higher blood urea nitrogen and creatinine levels. Moreover, in IL-6(-/-) mice treated with NaAs, ACD in renal tubular cells was significantly augmented, along with diminished STAT3 activation and reciprocal enhancement of ERK signaling, compared with wild-type mice. Finally, the administration of exogenous IL-6 into wild-type mice significantly reduced NaAs-induced ACD along with diminished ERK activation and eventually alleviated acute renal dysfunction. Thus, IL-6/STAT3 signal pathway could inhibit ERK activation, a crucial step for ACD, eventually attenuating NaAs-induced renal dysfunction.
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Blockade of a chemokine, CCL2, reduces chronic colitis-associated carcinogenesis in mice.
Cancer Res.
PUBLISHED: 09-22-2009
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Accumulating evidence indicates the crucial contribution of chronic inflammation to various types of carcinogenesis, including colon carcinoma associated with ulcerative colitis and asbestosis-induced malignant mesothelioma. Ulcerative colitis-associated colon carcinogenesis can be recapitulated in mice by azoxymethane administration followed by repetitive dextran sulfate sodium ingestion. In the course of this carcinogenesis process, the expression of a macrophage-tropic chemokine, CCL2, was enhanced together with intracolonic massive infiltration of macrophages, which were a major source of cyclooxygenase (COX)-2, a crucial mediator of colon carcinogenesis. Mice deficient in CCL2-specific receptor, CCR2, exhibited less macrophage infiltration and lower tumor numbers with attenuated COX-2 expression. Moreover, CCL2 antagonists decreased intracolonic macrophage infiltration and COX-2 expression, attenuated neovascularization, and eventually reduced the numbers and size of colon tumors, even when given after multiple colon tumors have developed. These observations identify CCL2 as a crucial mediator of the initiation and progression of chronic colitis-associated colon carcinogenesis and suggest that targeting CCL2 may be useful in treating colon cancers, particularly those associated with chronic inflammation.
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Fibrocytes are involved in the pathogenesis of human chronic kidney disease.
Hum. Pathol.
PUBLISHED: 08-05-2009
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The presence of chronic kidney disease in humans is associated with a risk of kidney function loss as well as the development of cardiovascular disease. Fibrocytes have been shown to contribute to organ fibrosis. In this study, the presence of fibrocytes was investigated immunohistochemically in kidney biopsy specimens from 100 patients with chronic kidney disease. In addition, 6 patients with thin basement membrane disease were studied as a disease control. In patients with chronic kidney disease, the infiltration of fibrocytes was observed mainly in the interstitium. The number of interstitial fibrocytes in patients with chronic kidney disease was higher than that in patients with thin basement membrane disease. The number of infiltrated fibrocytes in the interstitium correlated well with the severity of tubulointerstitial lesions, such as interstitial fibrosis, in patients with chronic kidney disease. In addition, there were significant correlations between the number of interstitial fibrocytes and the number of CD68-positive macrophages in the interstitium as well as urinary monocyte chemoattractant protein-1/CCL2 levels. In particular, there was an inverse correlation between the number of interstitial fibrocytes and kidney function at the time of biopsy. Finally, the numbers of interstitial fibrocytes and macrophages as well as urinary CCL2 levels were significantly decreased during convalescence induced by glucocorticoid therapy. These results suggest that fibrocytes may be involved in the pathogenesis of chronic kidney disease through the interaction with macrophages as well as CCL2.
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Physiological response to low temperature in the freshwater apple snail, Pomacea canaliculata (Gastropoda: Ampullariidae).
J. Exp. Biol.
PUBLISHED: 08-04-2009
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Cold hardiness of the freshwater apple snail, Pomacea canaliculata, varies seasonally. We investigated lethal factors and physiological changes arising from exposure of P. canaliculata to low temperatures. Snails did not survive freezing. The supercooling point of cold-acclimated (cold tolerant) snails (-6.6+/-0.8 degrees C) did not differ significantly from that of non-acclimated ones (-7.1+/-1.5 degrees C) under laboratory conditions. Furthermore, snails died even under more moderately low temperatures approaching 0 degrees C. These results indicate that indirect chilling injury is a factor in the death of P. canaliculata at low temperatures. Regardless of whether the snails were acclimated to low temperatures, all of the dead, and even some of the snails still alive at 0 degrees C, had injured mantles, indicating that the mantle may be the organ most susceptible to the effects of low temperatures. The concentration of glucose in the posterior chamber of the kidney and concentration of glycerol in the digestive gland were significantly higher in cold-acclimated snails than in non-acclimated ones, suggesting carbohydrate metabolic pathways are altered in snails during cold acclimation.
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[Deep vein thrombosis in Noto Peninsula earthquake victims].
Rinsho Byori
PUBLISHED: 06-16-2009
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The earthquake occurred in the Noto Peninsula in the northern part of Ishikawa prefecture, Japan, at 9:25 a.m. on March 25th 2007. Medical activities for prevention of deep vein thrombosis (DVT), early detection of DVT, and early treatment of DVT were performed immediately after the earthquake on the basis of a previous report regarding earthquake disasters. This report described the conditions involved in the development of DVT. General inhabitants in shelters were examined by questionnaires, venous ultrasonography of lower limb, and blood tests. The DVT-positive rate was 10.6% (21 cases/198 cases), and the soleal vein was the most common location of DVT accounting for 71.4% of cases(20 lower limbs/28 lower limbs). Plasma levels of fibrin/fibrinogen degradation products and D-dimer in the DVT-positive group (20 cases) were significantly higher than those in the DVT-negative group(162 cases) (P<0.03). No deaths or cases of serious illness caused by DVT were reported in the earthquake. The medical activities described here were effective due to the past experience and the cooperation of many people.
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Design and methods of a strategic outcome study for chronic kidney disease: Frontier of Renal Outcome Modifications in Japan.
Clin. Exp. Nephrol.
PUBLISHED: 06-11-2009
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The continuous increase in the number of people requiring dialysis is a major clinical and socioeconomical issue in Japan and other countries. This study was designed to encourage chronic kidney disease (CKD) patients to consult a physician, enhance cooperation between nephrologists and general practices, and prevent the progression of kidney disease.
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Of the three classifications of healthy lifestyle habits, which one is the most closely associated with the prevention of metabolic syndrome in Japanese?
Intern. Med.
PUBLISHED: 05-01-2009
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Metabolic syndrome is associated with a high risk of cardiovascular morbidity and mortality. The predominant cause of metabolic syndrome is an unhealthy lifestyle. Healthy habits are represented by Breslows 7 healthy practices, Morimotos 8 items and Ikedas 6 healthy habits. This study was done to determine which set of healthy habits was most likely to result in a reduced risk of developing the metabolic syndrome.
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[Lung age in smokers, past smokers anid non second-hand smoke].
Rinsho Byori
PUBLISHED: 04-20-2009
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"Lung age" calculated from the height, sex, and 1-second forced expiratory volume is a new index to express the respiratory function. We assessed the differences in the lung age among smokers, past smokers, and non-smokers. The subjects comprised 886 Japanese who visited the Shimbashi Medical Checkup Office at Jikei University Hospital. The smokers (n=215), past smokers (n=300), and non-smokers (n=371) were classified. In the smokers, the number of cigarettes smoked per day was 19.7+/-9.8, and the period of smoking was 27.5+/-9.4 years. The non-smokers were divided into those in the presence or absence of second-hand smoke. The lung age added to the calendar age was 9.8+/-14.7 years in smokers, 4.8+/-17.8 years in past smokers, and -0.8+/-14.0 years in non-smokers. These data showed significant differences(p= 0.0003). The smoking index was calculated from smoking years multiplied by the cigarette number per day. The lung age with a smoking index >or=600 was 13.2+/-14.9 years, being significantly higher than that (7.2 +/-14.0 years) with a smoking index <600 (p=0.003). In the non-smokers, the lung age was -0.5+/-12.8 years in the presence and -1.0+/-14.1 in the absence of second-hand smoke. In conclusion, smoking increases the lung age.
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Chemokine/chemokine receptor-mediated inflammation regulates pathologic changes from acute kidney injury to chronic kidney disease.
Clin. Exp. Nephrol.
PUBLISHED: 03-27-2009
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Ischemia-reperfusion injury is a main cause of acute kidney injury. Tubular necrosis and interstitial inflammatory cell infiltration are characteristic pathologic changes of acute kidney injury. The main necrotic area should be repaired with new tubular epithelial cells after the injury. On the other hand, some parts of the injured kidney progress to interstitial fibrosis, a characteristic pathologic change in chronic kidney disease. We hypothesized that interstitial infiltrating leukocytes, that are attracted and activated by chemokines, are key mediators in the pathogenesis of tubular necrosis, regeneration of the necrotic area, or interstitial fibrosis. A large number of chemokines were upregulated after ischemic injury, and chemokine receptor-expressing inflammatory cells were attracted by these chemokines. Genetic or molecular modulating experiments in the mouse model have begun to reveal the key participants and their specific roles at the levels of inflammation, regeneration, and fibrosis. Among these chemokines/chemokine receptors, our data indicated CCR2-mediated macrophage infiltration mainly affected tubular necrosis after ischemic acute kidney injury, interferon-gamma-inducible protein (IP)-10-producing macrophages participate in regeneration of tubular epithelial cells, and CX3CR1-mediated macrophages and platelet infiltration and aggregation play roles in interstitial fibrosis in chronic kidney disease. These chemokines and chemokine receptors on infiltrating inflammatory cells would be novel clinical markers or targets for therapeutic intervention.
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CSF-1 signals directly to renal tubular epithelial cells to mediate repair in mice.
J. Clin. Invest.
PUBLISHED: 03-03-2009
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Tubular damage following ischemic renal injury is often reversible, and tubular epithelial cell (TEC) proliferation is a hallmark of tubular repair. Macrophages have been implicated in tissue repair, and CSF-1, the principal macrophage growth factor, is expressed by TECs. We therefore tested the hypothesis that CSF-1 is central to tubular repair using an acute renal injury and repair model, ischemia/reperfusion (I/R). Mice injected with CSF-1 following I/R exhibited hastened healing, as evidenced by decreased tubular pathology, reduced fibrosis, and improved renal function. Notably, CSF-1 treatment increased TEC proliferation and reduced TEC apoptosis. Moreover, administration of a CSF-1 receptor-specific (CSF-1R-specific) antibody after I/R increased tubular pathology and fibrosis, suppressed TEC proliferation, and heightened TEC apoptosis. To determine the contribution of macrophages to CSF-1-dependent renal repair, we assessed the effect of CSF-1 on I/R in mice in which CD11b+ cells were genetically ablated and determined that macrophages only partially accounted for CSF-1-dependent tubular repair. We found that TECs expressed the CSF-1R and that this receptor was upregulated and coexpressed with CSF-1 in TECs following renal injury in mice and humans. Furthermore, signaling via the CSF-1R stimulated proliferation and reduced apoptosis in human and mouse TECs. Taken together, these data suggest that CSF-1 mediates renal repair by both a macrophage-dependent mechanism and direct autocrine/paracrine action on TECs.
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Relationship between the three kinds of healthy habits and the metabolic syndrome.
Obes Res Clin Pract
PUBLISHED: 02-06-2009
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Summary: Objectives: In 2005, the diagnostic criteria for Japan-specific metabolic syndrome were published. The representative health habits are Breslows seven healthy practices, Morimotos eight items and Ikedas six healthy habits. We investigated the prevalence of metabolic syndrome related with life-style strongly among these three sets of healthy habit.Methods: Cross-sectional study was conducted for the prevalence of metabolic syndrome by practicing these healthy habits. 20,776 Japanese individuals visited the Health Science Center at Jikei University Hospital in Japan for medical check-ups. Subjects were divided into 8 groups based on gender and age (females in their 30s, 40s, 50s and 60s, and males in their 30s, 40s, 50s and 60s). Participants completed a simple, self-administered lifestyle questionnaire based on the three sets of healthy habits. Subjects were divided into three groups (poor, moderate and favorable) according to each of the healthy habit criteria.Results: Significant differences were observed among 10 groups for Breslows seven healthy practices, 4 groups for Morimotos eight items, and 13 groups for Ikedas six healthy habits. Ikedas six healthy habits showed the most significant differences among the three sets of habits.Conclusions: Among the three methods tested, to practice more Ikedas healthy habits were the most useful for metabolic syndrome.
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Dendritic cells contribute to autoimmune kidney injury in MRL-Faslpr mice.
J. Rheumatol.
PUBLISHED: 01-22-2009
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Dendritic cells (DC) contribute to autoimmune disease progression and pathogenesis. Mature DC have been reported to secrete high mobility group box protein (HMGB-1), a novel inflammatory cytokine, via p38 mitogen-activated protein kinase (MAPK) activation. We investigated whether DC are involved in progression of autoimmune diseases followed by secretion of HMGB-1 via p38 MAPK activation in a lupus-prone mouse model.
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A nationwide survey of rapidly progressive glomerulonephritis in Japan: etiology, prognosis and treatment diversity.
Clin. Exp. Nephrol.
PUBLISHED: 01-02-2009
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The etiology, prevalence, and prognosis of rapidly progressive glomerulonephritis (RPGN) including renal vasculitis vary among races and periods.
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Clinical findings on ANCA-associated renal vasculitis from the Japan RPGN registry obtained via a questionnaire survey.
Clin. Exp. Nephrol.
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Renal involvement with significant organ damage is common in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). As a result, it is independently referred to ANCA-associated renal vasculitis. Clinically, ANCA-associated renal vasculitis is characterized by rapidly progressive glomerulonephritis. Pathologically, it is defined by pauci-immune type necrotizing and crescentic glomerulonephritis. According to previous reports from all over the world, the etiology, prevalence, and prognosis of RPGN including ANCA-associated renal vasculitis varies among races and periods. To elucidate the clinical characteristics of Japanese RPGN patients, a registry derived from a questionnaire survey was established in 1999 and maintained until 2006. As a result, 1,772 cases were collected, analyzed, and reported previously. In this mini-review, we outline the characteristic clinical findings of Japanese patients (Asian) with ANCA-associated renal vasculitis, based on the registry data.
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Prediction formula for interrupter respiratory resistance in healthy Japanese adults.
Rinsho Byori
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Interrupter respiratory resistance (Rint) measurement is useful for evaluating lung function in patients who cannot perform traditional pulmonary function tests. However, data on the prediction formulas for Rint in healthy Japanese adults are lacking. Our aims were to examine the relationship between Rint and sex, age, height, and weight, to establish prediction formulas, and to evaluate our new prediction formula (%Rint) in patients with asthma. Rint measurement was performed in 1,536 healthy adult subjects aged 21-80 years. This study was conducted according to ATS guidelines, which recommend obtaining 10 measurements to ensure a minimum of 5 technically acceptable interruptions (Am J Respir Crit Care Med 2007). Stepwise multiple linear regression analysis indicated that height was the most significant variable independently correlating with Rint. The Rint prediction formulas for our cohort based on height were: RintE = -0.03168 x height + 8.204084 and Rinti = -0.02985 x height + 7.920835. Both %RintE and %Rinti were significantly higher in patients with asthma than in normal subjects (%RintE; 135.2 +/- 26.4 vs. 98.6 +/- 25.5, %RintI; 142.4 +/- 30.4 vs. 98.6 +/- 27.4; p < 0.0001). We established prediction formulas of Rint for healthy Japanese adults. %Rint is useful in screening for asthma.
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Autoantibodies to erythropoietin receptor in patients with immune-mediated diseases: relationship to anaemia with erythroid hypoplasia.
Br. J. Haematol.
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The prevalence, clinical associations and pathogenic role of newly identified autoantibodies to the erythropoietin receptor (EPOR) in patients with anaemia were investigated. Sera from 203 patients with immune-related or chronic kidney diseases were screened for anti-EPOR antibodies by enzyme-linked immunosorbent assay, and antibody specificity was evaluated by immunoprecipitating EPOR from AS-E2 cells using purified immunoglobulin (Ig) fractions. In addition, the pathogenic role of anti-EPOR antibodies was determined by examining their inhibitory effects on AS-E2 cell proliferation. Clinical findings were compared between patients with and without anti-EPOR antibodies, in all patients and those with systemic lupus erythematosus (SLE). Serum anti-EPOR antibodies were detected in 52 patients. Purified IgG or IgM fractions from anti-EPOR antibody-positive sera immunoprecipitated EPOR and inhibited the EPO-dependent proliferation of AS-E2 cells in a dose-dependent manner. Anti-EPOR antibodies were associated with low haemoglobin concentrations and reticulocytopenia in all patients enrolled and those with SLE. Further, there was a negative correlation between the levels of anti-EPOR antibodies and the number of bone marrow erythroblasts in patients who underwent bone marrow examinations. These findings suggest that EPOR autoantibodies are present in a subset of patients with anaemia and that impaired erythropoiesis can be mediated by anti-EPOR antibodies, which functionally neutralize EPO activity.
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Nodular lesions and mesangiolysis in diabetic nephropathy.
Clin. Exp. Nephrol.
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Diabetic nephropathy is a leading cause of end-stage renal failure all over the world. Advanced human diabetic nephropathy is characterized by the presence of specific lesions including nodular lesions, doughnut lesions, and exudative lesions. Thus far, animal models precisely mimicking advanced human diabetic nephropathy, especially nodular lesions, remain to be fully established. Animal models with spontaneous diabetic kidney diseases or with inducible kidney lesions may be useful for investigating the pathogenesis of diabetic nephropathy. Based on pathological features, we previously reported that diabetic glomerular nodular-like lesions were formed during the reconstruction process of mesangiolysis. Recently, we established nodular-like lesions resembling those seen in advanced human diabetic nephropathy through vascular endothelial injury and mesangiolysis by administration of monocrotaline. Here, in this review, we discuss diabetic nodular lesions and its animal models resembling human diabetic kidney lesions, with our hypothesis that endothelial cell injury and mesangiolysis might be required for nodular lesions.
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Association of changes in the gene expression profile of blood cells with the local tumor inflammatory response in a murine tumor model.
Biochem. Biophys. Res. Commun.
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Cancer tissue is frequently associated with the host inflammatory response, which involves blood cells. Using DNA microarrays, we examined the gene expression profiles of blood and tumors in a murine subcutaneous hepatocellular carcinoma model, in which tumors develop during the initial 10 days and then diminish and disappear by day 25 after implantation. Immunohistochemical and gene expression analysis indicated that tumor tissues were associated with an active immune response, particularly the CD4+ T cell-mediated immune response, on day 10. The genes commonly up-regulated in blood and the fraction enriched with tumor-associated inflammatory cells on day 10 also suggested the involvement of CD4+ T cells. Unsupervised hierarchical clustering analysis of gene expression of peripheral blood cells on days 0, 10, 15, 20, and 25 indicated two major clusters: the tumor-existence cluster on days 10, 15, and 20, and the tumor-free cluster on days 0 and 25. Additionally, sub-clusters were detected on each day. These results suggest that the gene expression profile of whole blood cells is affected by the local tumor condition, and is associated with the local host immune response. Its analysis will facilitate exploration of the underlying important features of the host immune response to tumors.
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Cytokine profiles of patients with enterohemorrhagic Escherichia coli O111-induced hemolytic-uremic syndrome.
Cytokine
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Proinflammatory cytokines are related to the pathogenesis of enterohemorrhagic Escherichia coli (EHEC) infection and hemolytic-uremic syndrome (HUS). We assessed the kinetics of the release of cytokines such as neopterin, interleukin (IL)-6, IL-8 and tumour necrosis factor (TNF)-? and the soluble forms of type I and II TNF receptors during EHEC O111-induced HUS (EHEC O111/HUS). Fourteen patients with EHEC O111/HUS were enrolled in this study. Serum concentrations of all cytokines other than TNF-? were significantly elevated in patients with severe HUS compared with those in patients with mild HUS. Although serum concentrations of TNF-? were not significantly higher in patients with severe HUS, most patients with acute encephalopathy showed elevated TNF-? levels. Serum concentrations of these cytokines rapidly and markedly increased, and massive hypercytokinaemia developed 1 day before the diagnosis of HUS in patients with severe HUS. Changes in the number of white blood cells and concentration of serum lactate dehydrogenase were significantly larger between the onset of hemorrhagic colitis and the time of the diagnosis of HUS in patients with severe HUS compared with those in patients with mild HUS. Proinflammatory cytokines play an important role in the pathogenesis of EHEC infection and development of severe complications, including HUS and encephalopathy. Monitoring the cytokine profile may be useful for assessing disease activity of EHEC O111 infections.
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[Recognition of the importance of reversed CPC in CPC].
Rinsho Byori
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Clinicopathological conferences (CPC) are one of the most important clinical conferences, and processes of both diagnosis and treatment performed in an autopsy case are retrospectively and finely checked to offer better medical treatment in the future. In CPC, the medical history, physical findings, laboratory data, image findings, diagnosis and treatment are discussed in the order that a physician examines a patient. Differential diagnoses usually decrease and several important diagnoses remain as the CPC discussion progresses. Medical treatment is also reexamined to identify a better approach. In this CPC, several medical doctors in various special fields try to understand the detailed state of the patient from each standpoint, and such a CPC is called an Expert CPC at Shinshu University School of Medicine. This CPC is carried out followed by reversed-CPC (R-CPC) of the same case. The purpose of this CPC is to understand the importance of R-CPC and to understand the correct interpretation of routine laboratory data.
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Fas Ligand Has a Greater Impact than TNF-? on Apoptosis and Inflammation in Ischemic Acute Kidney Injury.
Nephron Extra
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Fas ligand (FasL) and tumor necrosis factor (TNF)-? are major pro-apoptotic molecules and also induce inflammation through cytokine and chemokine production. Although precise intracellular mechanisms of action have been reported for each molecule, the differential impact of these molecules on kidney injury in vivo still requires clarification.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.