A case of dense deposit disease associated with a group A streptococcal infection without the involvement of C3NeF or complement factor H deficiency

A 14-year-old girl presented with acute glomerulonephritis. Tests revealed hypocomplementemia and elevated Antistreptolysin-O titers, and renal biopsy revealed endocapillary and mesangial proliferative glomerulonephritis with double contours of the glomerular basement membrane (GBM). Despite methylprednisolone pulse therapy and the administration of oral prednisolone, overt proteinuria and hypocomplementemia persisted. A second renal biopsy 6 months later confirmed the initial diagnosis of dense deposit disease (DDD) based on electron-dense deposits in the GBM. C3 nephritic factor (C3NeF) and a deficiency of complement factor H (CFH) were not evident. A nephritis-associated plasmin receptor (NAPlr), nephritogenic group A streptococcal antigen, and the plasmin activity by in situ zymography were been in both the first and second biopsy specimens. The patient received combined immunomodulatory therapy with prednisolone and mizoribine, and the urinary protein decreased to a mild level at 27 months after disease onset. These findings suggest that persistent glomerular NAPlr deposition may be associated with the pathogenesis of DDD in some patients without the involvement of C3NeF or CFH mutation and that DDD patients of this type may respond to immunomodulatory treatment.     

Vascular-Resident CD169-Positive Monocytes and Macrophages Control Neutrophil Accumulation in the Kidney with Ischemia-Reperfusion Injury

Monocytes and kidney-resident macrophages are considered to be involved in the pathogenesis of renal ischemia-reperfusion injury (IRI). Several subsets of monocytes and macrophages are localized in the injured tissue, but the pathologic roles of these cells are not fully understood. Here, we show that CD169⁺ monocytes and macrophages have a critical role in preventing excessive inflammation in IRI by downregulating intercellular adhesion molecule-1 (ICAM-1) expression on vascular endothelial cells. Mice depleted of CD169⁺ cells showed enhanced endothelial ICAM-1 expression and developed irreversible renal damage associated with infiltration of a large number of neutrophils. The perivascular localization of CD169⁺ monocytes and macrophages indicated direct interaction with blood vessels, and coculture experiments showed that the direct interaction of CD169⁺ cell-depleted peripheral blood leukocytes augments the expression levels of ICAM-1 on endothelial cells. Notably, the transfer of Ly6C^lo monocytes into CD169⁺ cell-depleted mice rescued the mice from lethal renal injury and normalized renal ICAM-1 expression levels, indicating that the Ly6C^lo subset of CD169⁺ monocytes has a major role in the regulation of inflammation. Our findings highlight the previously unknown role of CD169⁺ monocytes and macrophages in the maintenance of vascular homeostasis and provide new approaches to the treatment of renal IRI.     

The roles of TNFR1 in lipopolysaccharide‐induced bone loss: Dual effects of TNFR1 on bone metabolism via osteoclastogenesis and osteoblast survival

LPS (lipopolysaccharide), a major constituent of Gram‐negative bacteria, regulates proliferation and differentiation of osteoclasts directly or indirectly. This study sought to investigate the functions of the RANK/RANKL pathway in LPS‐induced bone loss in vivo. Wild‐type mice or TNFR1?/? mice were injected LPS with or without osteoprotegerin (OPG) and analyzed histologically. Bone volume was reduced by LPS injection in all groups, and OPG administration prevented the LPS‐induced bone loss regardless of genotypes. LPS‐induced enhancement of osteoclastogenesis in wild‐type mice was blocked by OPG administration. LPS or OPG did not affect osteoclastogenesis in TNFR1?/? mice. Interestingly, osteoblast surface was remarkably reduced in LPS‐treated TNFR1?/? mice as a result of enhanced osteoblast apoptosis. TRAIL, induced by TNF‐α in BMC, triggered apoptosis of primary osteoblast only when TNFR1 signal was ablated in vitro. In conclusion, RANK signaling plays a prominent role in osteoclastogenesis downstream of LPS. Furthermore, TNFR1 regulates bone metabolism through not only the regulation of osteoclast differentiation but also osteoblast survival. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:657–663, 2010     

Intraneural blood flow analysis during an intraoperative Phalen's test in carpal tunnel syndrome

Phalen's test has been one of the most significant of clinical signs when making a clinical diagnosis of idiopathic carpal tunnel syndrome (CTS). However, it is unknown whether intraneural blood flow changes during Phalen's test in patients with CTS. In this study, an intraoperative Phalen's test was conducted in patients with CTS to observe the changes in intraneural blood flow using a laser Doppler flow meter. During Phalen's test, intraneural blood flow showed a sharp decrease, which lasted for 1 min. Intraneural blood flow decreased by 56.7%–100% (average, 78.0%) in the median nerve relative to the blood flow before the test. At 1 min after completing the test, intraneural blood flow returned to the baseline value. After carpal tunnel release, there was no marked decrease in intraneural blood flow. This study demonstrated that the blood flow in the median nerve is reduced when Phalen's test is performed in vivo. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:1022–1025, 2010     

Dissociated pathways for successful memory retrieval from the human parietal cortex: anatomical and functional connectivity analyses

The parietal cortex has traditionally been implicated in spatial attention and eye-movement processes. Recent functional neuroimaging studies have found that activation in the parietal cortex is related to successful recognition memory. The activated regions consistently include the intraparietal sulcus in the lateral parietal cortex and the precuneus in the medial parietal cortex. However, little is known about the functional differences between lateral and medial parietal cortices in the memory retrieval process. In this study, we examined whether the human lateral and medial parietal lobes have differential anatomical and functional connectivity with the temporal lobe. To this end, we used functional magnetic resonance imaging to constrain the analysis of anatomical connectivity obtained by diffusion tensor imaging (DTI). Both DTI tractography and functional connectivity analysis showed that the lateral parietal region has anatomical and functional connections with the lateral temporal lobe, and the medial parietal region has connections with the medial temporal lobe. These results suggest the existence of segregated lateral and medial parieto-temporal pathways in successful memory retrieval.     

Expression of the Prothymosin-α Gene as a Prognostic Factor in Lung Cancer

Prothymosin-α (PTα) is known to play a role in cell proliferation, and the PTα mRNA level may reflect the degree of proliferation of tumor cells. It has been reported that PTα mRNA levels are higher in human colon and liver cancer tissues than in the adjacent normal tissues. We examined the mRNA levels of PTα and c-myc in 20 lung cancers, using Bas 2500Mac systems. The PTα and c-myc mRNA levels in lung cancer tissues were higher than those in normal lung tissues; however, the PTα mRNA levels did not correlate with the stage or pathological subtype of the lung cancer and there was no correlation between the expression of PTα and c-myc. PTα mRNA overexpression in lung cancer was correlated with a poor prognosis. Received: October 13, 2000 / Accepted: May 15, 2001     

Long-Term Outcomes of Immunosuppressed Renal Transplant Recipients with Malignancies

This study analyzes ten cases of malignancy in a cohort of 183 renal transplant recipients, examining surgical management, postoperative immunosuppressive therapy, and long-term outcome. One of these ten patients, who had malignant lymphoma of the jejunum, died of the neoplasm, but the other nine patients did not show any signs of tumor recurrence after removal. All of these nine patients, except for one who had transplant renal cell carcinoma (RCC), received the same dose of immunosuppressive agents after surgery for the malignant disease. Seven patients were still alive at the time of this report, six of whom had good transplant renal function. The findings of this study indicate that even if immunosuppressive agents predispose to the development of cancer, it is not necessary to reduce their dose after removal of the tumor. Received: April 17, 2000 / Accepted: November 20, 2000     

Successful Surgical Treatment of Renal Cell Carcinoma in a Transplanted Kidney from a Cadaveric Donor: Report of a Case

Posttransplant renal cell carcinoma (RCC) usually arises in the native kidneys of renal transplant recipients rather than in the transplanted kidney. This report describes a case of RCC that developed in the transplanted cadaveric kidney in a 37-year-old male recipient 9 months after transplantation. An en bloc radical transplant nephrectomy was performed, and he has subsequently remained stable on hemodialysis for 3 years without any sign of recurrence. Received: March 27, 2000 / Accepted: September 26, 2000     

Gene Expression Profile Prospectively Predicts Peritoneal Relapse After Curative Surgery of Gastric Cancer

Background

Peritoneal relapse is the most common pattern of tumor progression in advanced gastric cancer. Clinicopathological findings are sometimes inadequate for predicting peritoneal relapse. The aim of this study was to identify patients at high risk of peritoneal relapse in a prospective study based on molecular prediction.

Methods

RNA samples from 141 primary gastric cancer tissues after curative surgery were profiled using oligonucleotide microarrays covering 30,000 human probes. Firstly, we constructed a molecular prediction system and validated its robustness and prognostic validity by 500 times multiple validation by repeated random sampling in a retrospective set of 56 (38 relapse-free and 18 peritoneal-relapse) patients. Secondly, we applied this prediction to 85 patients of the prospective set to assess predictive accuracy and prognostic validity.

Results

In the retrospective phase, repeated random validation yielded ~68% predictive accuracy and a 22-gene expression profile associated with peritoneal relapse was identified. The prediction system identified patients with poor prognosis. In the prospective phase, the molecular prediction yielded 76.9% overall accuracy. Kaplan–Meier analysis of peritoneal-relapse-free survival showed a significant difference between the “good signature group” and “poor signature group” (log-rank p = 0.0017). Multivariate analysis by Cox regression hazards model identified the molecular prediction as the only independent prognostic factor for peritoneal relapse.

Conclusions

Gene expression profile inherent to primary gastric cancer tissues can be useful in prospective prediction of peritoneal relapse after curative surgery, potentially allowing individualized postoperative management to improve the prognosis of patients with advanced gastric cancer.     

Easier node dissection after chemoradiotherapy for lung cancer with collagen insertion at mediastinoscopy

Objective: Induction chemoradiotherapy followed by anatomical resection is a current therapeutic strategy for non-small-cell lung cancer with mediastinal node involvement. Dense peritracheal fibrosis and sclerosis after chemoradiotherapy cause difficult mediastinal node dissection. We evaluated a novel technique to make the mediastinal node dissection easier after induction therapy. Methods: At the end of mediastinoscopic node biopsy for staging of lung cancer, cotton-type collagen was inserted anterior and lateral to the trachea in patients with pathologically confirmed mediastinal node involve-ment (n=45). The induction therapy consisted of concurrent use of platinum-based chemotherapy and hyperfractionated radiotherapy. After the chemoradiotherapy all patients underwent a pulmonary resection with complete mediastinal node dissection 7–12 weeks after the collagen insertion. Surgical findings of the mediastinum and the time for node dissection were compared with those without collagen insertion at mediastinoscopy after chemoradiotherapy (n=5). Results: All five patients without collagen insertion showed sclerotic and fibrotic change of mediastinal nodes with severe adhesion to the trachea. In 42 of 45 patients with collagen insertion (93.3%) the collagen remained unabsorbed and separated the mediastinal nodes from the trachea. Mediastinal node dissection was easily accomplished by removing mediastinal tissues lateral and anterior to the collagen. The rate of mediastinal node separation was significantly higher with collagen insertion than without (p< 0.0001). The times for node dissection in patients with and without collagen insertion showed no significant difference. Conclusion: Cotton-type collagen insertion at staging mediastinoscopy for lung cancer separates the mediastinal nodes from the trachea and makes the node dissection easier after induction chemoradiotherapy.