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Since propeller flaps are elevated as island flaps and most often nourished by a single perforator nearby the defect, it is challenging to change the flap design intraoperatively when a reliable perforator cannot be found where expected to exist. Thus, accurate preoperative mapping of perforators is essential in the safe planning of propeller flaps. Various methods have been reported so far: (1) handheld acoustic Doppler sonography (ADS), (2) color duplex sonography (CDS), (3) perforator computed tomographic angiography (P-CTA), and (4) magnetic resonance angiography (MRA). To facilitate the preoperative perforator assessment, P-CTA is currently considered as the gold standard imaging tool in revealing the three-dimensional anatomical details of perforators precisely. Nevertheless, ADS remains the most widely used tool due to its low cost, faster learning, and ease of use despite an undesirable number of false-positive results. CDS can provide hemodynamic characteristics of the perforator and is a valid and safer alternative particularly in patients in whom ionizing radiation and/or contrast exposure should be limited. Although MRA is less accurate in detecting smaller perforators of caliber less than 1.0 mm and the intramuscular course of perforators at the present time, MRA is expected to improve in the future due to the recent developments in technology, making it as accurate as P-CTA. Moreover, it provides the advantage of being radiation-free with fewer contrast reactions.

BackgroundThis study compared hand function and the cost effectiveness of treatment between collagenase Clostridium histolyticum (CCH) injection and limited fasciectomy for patients with Dupuytren’s contracture (DC).Materials and MethodsThe CeCORD-J study is a prospective, multicenter, non-randomized controlled, observational study of two parallel groups. Participants were DC patients with multiple affected fingers, including flexion contracture of the proximal interphalangeal (PIP) joint. The primary outcome was the Hand10 score, as a patient-reported outcome measure. We set secondary outcomes of EQ-5D-5L score, degree of extension deficit, and direct cost. Propensity score adjustment was used to balance differences in patient characteristics between groups.ResultsParticipants comprised 52 patients in the Collagenase group and 26 patients in the Surgery group. Hand10 score was significantly better in the Collagenase group at 1 and 2 weeks. EQ-5D-5L score was significantly higher in the Collagenase group at 8 weeks. Mean direct cost was 248,000 yen higher in the Surgery group than in the Collagenase group. Extension deficit angle of the PIP joint was significantly larger in the Collagenase group at 26 weeks.ConclusionsCCH injection provides better short-term hand function and cost effectiveness than surgery.UMIN-CTR (UMIN000029826)

Introduction The safety and efficacy of using artificial collagen nerve conduits filled with collagen filaments to treat nerve defects has not been fully studied in humans. We conducted a multicenter, controlled, open-label study to compare the safety and efficacy of artificial nerve conduit grafts with those of autologous nerve grafts. Methods We included patients with a sensory nerve defect of ≤30 mm, at the level of the wrist or a more distal location, with the first-line surgical methods selected according to a patient’s preference. We compared sensory recovery using static two-point discrimination and adverse events between the artificial collagen nerve conduit and autologous nerve grafting. Results The artificial nerve conduit group included 49 patients, with a mean age of 42 years and nerve defect of 12.6 mm. The autologous nerve graft group included 7 patients, with historical data of an additional 31 patients, with a mean age of 36 years and nerve defect of 18.7 mm. The rate of recovery of sensory function at 12 months was 75% (36/49) for the artificial nerve conduit group and 73.7% (28/38) in the autologous nerve group. No serious adverse events directly associated with use of the artificial nerve conduit were identified. Conclusions The treatment of nerve defects ≤30 mm using artificial collagen nerve conduits was not inferior to treatment using autologous nerve grafts. Based on our data, the new artificial collagen nerve conduit can provide an alternative to autologous nerve for the treatment of peripheral nerve defects.

Ten patients had intrasynovial tendon grafting harvested from the toes for secondary flexor tendon reconstruction in nine fingers and one thumb in our institutes from 2009 to 2014. These patients were followed for a mean of 15 (range: 8–36) months. The ranges of total active motion of the proximal and distal interphalangeal joints of these nine fingers were 143° (range: 108–175°) and of the metacarpophalangeal and interphalangeal joints of one thumb were 110°. In conclusion, this technique is feasible and gives a good result when successful but with a high complication rate.Level of Evidence IV

The vascular anatomy of perforators varies between individuals; thus, accurate preoperative assessment of perforators is essential for safely planning perforator flaps. Perforator computed tomographic angiography (P-CTA) with multidetector-row computed tomography (MDCT) is one of the best available methods to precisely reveal the 3-dimensional anatomic details of perforators. The aim of this report is to describe the authors' experience using P-CTA with MDCT for detecting the perforating vessel preoperatively and a step-by-step approach to harvest perforator flaps based on this technique. This report also provides a comprehensive review of literature on other preoperative assessment tools of perforators.

The authors' strategy for soft-tissue coverage of the hand is presented. The concept of replacing like with like and reconstruction with similar adjacent tissue enhances functional and aesthetic outcomes. In this viewpoint, the pedicle perforator flap is an ideal flap. A decision-making algorithm to select an ideal flap for a particular hand defect is challenging, requiring experiential consideration of functional outcome, appearance, donor-site morbidity, and patient satisfaction. To assist surgeons in determining the most appropriate flap with more evidence, studies are necessary to compare the outcomes of each flap by evaluating hand function, aesthetics, donor site morbidity, and patient satisfaction.

The vascular anatomy of perforators varies between individuals; thus, accurate preoperative assessment of perforators is essential for safely planning perforator flaps. Perforator computed tomographic angiography (P-CTA) with multidetector-row computed tomography (MDCT) is one of the best available methods to precisely reveal the 3-dimensional anatomic details of perforators. The aim of this report is to describe the authors' experience using P-CTA with MDCT for detecting the perforating vessel preoperatively and a step-by-step approach to harvest perforator flaps based on this technique. This report also provides a comprehensive review of literature on other preoperative assessment tools of perforators.

The pathogenic roles of glomerular deposition of components of the complement cascade in IgA nephropathy (IgAN) are not completely clarified. To investigate the pathologic role of complement pathways in IgAN, two IgAN-prone mouse models were examined. Grouped ddY (gddY) mice showed significant high proteinuria, severe glomerular lesions, and extracellular matrix expansion compared with high serum IgA (HIGA) mice but with similar intensity of glomerular IgA deposition. Glomerular activation of the classical, lectin, and alternative pathways was demonstrated by significantly stronger staining for complement (C)3, C5b-9, C1q, C4, mannose-binding lectin (MBL)-A/C, MBL-associated serine protease-2, and factor B and properdin in gddY mice than in HIGA mice. Similarly, the serum levels of IgA-IgG2a/IgM and IgA–MBL-A/C immune complexes and polymeric IgA were significantly higher in gddY mice than in HIGA mice. Moreover, the serum levels of aberrantly glycosylated IgA characterized by the binding of Sambucus nigra bark lectin and Ricinus communis agglutinin I were significantly higher in gddY mice than in HIGA mice. This aberrancy in glycosylation was confirmed by monosaccharide compositional analysis of purified IgA using gas-liquid chromatography. This study is the first to demonstrate that aberrantly glycosylated IgA may influence the formation of macromolecular IgA including IgA-IgG immune complexes and subsequent complement activation, leading to full progression of IgAN.

Background: The Michigan Hand Outcomes Questionnaire (MHQ) has shown reliability, validity and responsiveness and has been used to assess surgical outcomes mainly in North America. We established a Japanese version of the MHQ and evaluated its reliability and validity compared with both the short-form 36 (SF-36) questionnaire and the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire in a Japanese-speaking population. Methods: The MHQ was cross-culturally adapted to a Japanese version according to guidelines. Sixty-eight patients with hand conditions were enrolled in this study and answered the MHQ, DASH questionnaire and SF-36 questionnaire. The MHQ was completed again with an interval of one or two weeks. Reproducibility and internal consistency were statistically assessed by the test-retest method and calculating Cronbach's alpha. Spearman's rank correlation was calculated to assess associations between the MHQ and the SF-36 questionnaire as well as the DASH questionnaire. Results: The intraclass correlation coefficients of MHQ subscales ranged from 0.68 to 0.93. Aesthetics subscale of the left hand showed the lowest intraclass correlation but still a good correlation. Cronbach's alpha values of the MHQ ranged from 0.81 to 0.96 for all subscales. The absolute values of Spearman's rank correlation coefficient between MHQ subscales and DASH function/symptoms scores ranged from 0.49 to 0.82. Spearman's correlation coefficients of the MHQ total score to subscales of the SF-36 questionnaire ranged from 0.42 to 0.68. The strongest correlations were found between work performance of the MHQ and rolephysical of the SF-36 questionnaire. Conclusions: The Japanese version of the MHQ has adequate instrument properties for assessing hand outcomes compared with the SF-36 questionnaire as well as the DASH questionnaire.

Background. The aim of the present study was to explore the significance of extraglomerular (Bowman’s capsule and/or arteriole) C3 (ex-C3) deposits in IgA nephropathy (IgAN). Methods. One hundred and seventy patients with IgAN were divided into two groups: Group A (n = 79), patients who did not have ex-C3 deposits, and Group B (n = 91), patients who had ex-C3 deposits. Results. At the time of renal biopsy, Group B was characterized by a marked increase in diastolic blood pressure, total cholesterol, triglyceride and low-density lipoprotein-cholesterol compared with those of Group A. After 4 years, the estimated glomerular filtration rate (eGFR) in Group B was significantly worse than that of Group A. Upon examination by electron microscopy, the arteriolar dense deposits in Group B were found to occur in significantly higher amounts than in Group A. One hundred and thirty-four patients underwent a 3-year follow-up study after intervention and were re-divided by therapeutic factors as follows: ‘conventional therapy’, treatment with anti-hypertensive drugs and/or anti-platelet drugs, and ‘aggressive therapy’, additional treatment with either tonsillectomy or corticosteroid. Patients treated with conventional therapy in Group B had significantly higher body mass index and levels of C3 and CH50 compared with other Groups. Aggressive therapy was significantly effective in urinary protein reduction in both Group A and Group B. Except for the patients who received aggressive therapy in Group A, the levels of the eGFR gradually declined. Conclusions. It appears that IgAN patients who have ex-C3 deposits have worse clinical outcomes.

A deeper understanding of the mechanism of complement activation may help to elucidate the pathogenesis of IgA nephropathy (IgAN). Traditionally, the activation of an alternative pathway (AP) has been recognized as an enhancer mechanism of glomerular damage. This paper documents contemporary information concerning the possible pathological mechanisms of the lectin pathway (LP) in the circulation and in the glomerulus. The circulating initiator of LP activation is not fully understood. However, ligands for mannose-binding lectin (MBL) which are among the starter molecules of the LP are aberrant glycosylated molecules-containing immune complex. Recent reports have focused onN-glycans on secretory IgA as a candidate ligand. Mesangial deposits of MBL are seen in 25% of patients with IgAN. Mesangial deposits of MBL and C4 and/or C4 breakdown products are implicated as markers for disease progression of IgAN. On the other hand, patients with MBL deficiency tend to show better clinical presentation and lower levels of urinary protein and serum creatinine than MBL-sufficient patients. It is now recognized that involvement of AP and LP constitutes an additional mechanism for explaining the progression of IgAN.

Background. We have recently demonstrated that hemodialysis (HD) patients have significantly higher levels of functional complement activity (FCA) in all three pathways, i.e. the classical pathway, alternative pathway and lectin pathway (LP), than in age-matched controls, though the role of FCA during HD still remains unknown. Methods. Serial plasma or serum samples were obtained from five patients during HD in order to investigate the kinetics of complement components. The levels of the C5b-9 complex, the FCA of the three pathways, a derivative of C3a (C3a desArg) and a derivative of C5a (C5a desArg) in the samples were analyzed. Results. The levels of the C5b-9 complex at 60 min were significantly increased when compared with those at 0 min. Functional activities for all three pathways showed different patterns so the same tendency between pathways was not observed. The levels of C3a desArg and C5a desArg at 60 min were markedly increased when compared with those at 0 min. A Spearman’s rho test showed a strong positive correlation between functional LP activity and C5a desArg. Conclusions. These findings lead to new insights into the FCA during HD and suggest that functional LP activity has an important role in C5 activation.

This guideline was provided by the Japanese Association for Complement Research targeting clinicians for making an accurate diagnosis of hereditary angioedema (HAE), and for prompt treatment of the HAE patient in Japan. This is a 2010 year version and will be updated according to any pertinent medical advancements.

Mannose-binding lectin (MBL), L-ficolin and MBL associated serine protease-2 (MASP-2) are molecules involved in initiation of the lectin pathway (LP) in the complement system. Although MBL deficiency is observed in almost 10% of healthy people, studies of associations between MBL deficiency and end-stage renal disease (ESRD) remain rare. The objective of the present study is to clarify the significance of the LP in maintenance hemodialysis (HD) patients, especially in terms of MBL levels. Two hundred and forty-four HD patients who had been followed up for 74±84months and 199 healthy controls were included in this study. Measurements of serum concentrations of MBL, L-ficolin, and MASP-2 were performed. Low serum MBL levels (

A 59-year-old man was diagnosed with IgG4-related tubulointerstitial nephritis. His symptoms as well as laboratory and imaging findings were improved after initiation of steroid therapy. Serologically, he showed hypocomplementemia (C3 23 mg/dl, C4

We reviewed a series of 62 consecutive patients with dorsally displaced fractures of the distal radius, including 20 extra-articular and 42 intra-articular fractures. All patients were treated with palmar locking plate systems at our institution between 2002 and 2006. After a minimum follow-up time of 12 weeks, the fractures had healed with satisfactory radiographic and functional results. According to the demerit point system of Gartland and Werley, 35 patients were rated excellent, 26 good, and one fair. In the good and fair groups, the demerit points were almost all for ulnar wrist pain. Our results suggest that palmar locking plate systems enable early functional mobilization with good reproducible radiographic and clinical outcomes. Since nine out of 62 patients had residual ulnar wrist pain at the final follow-up evaluation, further investigation of the pathogenesis of ulnar wrist pain is necessary to obtain better functional outcomes.

The aim of this study was to explore the association between the serum concentration of complement component 3 (C3) and a variety of metabolic parameters. The study involved 125 patients in our outpatient clinic. Anthropometric and clinical laboratory data were collected and statistical associations between the serum concentration of C3 and other parameters were evaluated in a cross‐sectional as well as a prospective manner. A group of male patients with metabolic syndrome (Mets, n=35) were characterized by marked increase in serum concentrations of C3, body mass index (BMI), waist circumference, hemoglobin (Hb) A1c, insulin resistance (HOMA‐IR), triglyceride, uric acid, urinary protein, and Hb. In a one‐way analysis of variance of all subjects, the serum concentration of C3 was significantly elevated as the number of items of complying with the Mets diagnostic criteria increased. In 60 of 125 patients who did not have diabetes and were given anti‐lipogenetic medication, the serum concentration of C3 showed significant positive associations with serum levels of CH50, insulin, HOMA‐IR, total cholesterol, hematocrit, LDL‐c, C4, Hb, triglyceride, BMI, and albumin. In a prospective follow‐up evaluation (n=35), there was a significant positive association between ΔC3 (the second concentration of serum C3 minus the first concentration of serum C3)and ΔHOMA‐IR (the second concentration of HOMA‐IR minus the first concentration of HOMA‐IR). In conclusion, in Japanese patients, there is evidence implicating C3 concentration as a marker of Mets coinciding with insulin resistance. J. Clin. Lab. Anal. 24:113–118, 2010. © 2010 Wiley‐Liss, Inc.

A 49-year-old man with pulmonary sarcoidosis was admitted to our hospital because of nephrotic syndrome. Renal biopsy revealed membranous nephropathy and granulomatous interstitial nephritis. DNA and cell membrane constituents of Propionibacterium acnes were detected in the patient’s glomeruli and tubular epithelial cells. Treatment with corticosteroids and an antimicrobial agent resulted in remission of the nephrotic syndrome. This is the second case in which components of P. acnes were found in renal tissue, suggesting latent pathogenesis of P. acnes infection in renal sarcoidosis.

Mannose-binding lectin (MBL), L-ficolin and H-ficolin are human serum lectins, all of which form complexes with MBL-associated serine proteases (MASP). The lectin-MASP complexes bind to the surface of microbes, leading to activation of the lectin pathway of complement. Enzyme-linked immunosorbent assays (ELISA) of the lectin pathway activity reported so far determined the activity via either MBL or L-ficolin, but an assay of activity via plural host defense lectins has not been established. To measure the lectin pathway activation mediated by plural lectins simultaneously, we developed an ELISA system in which N-acetylglucosamine-pentamer conjugated to dipalmitoylphosphatidylethanolamine (GN5-DPPE) was employed as a ligand for the lectins. In our ELISA system, both purified MBL and L-ficolin isolated from serum diluted in a buffer containing high ionic NaCl bound to GN5-DPPE and activated C4. Purified H-ficolin was not capable of binding to GN5-DPPE. MBL and L-ficolin in MBL-sufficient serum also bound to GN5-DPPE and activated C4. Mannose and N-acetylgalactosamine inhibited binding of MBL and L-ficolin to GN5-DPPE, respectively. MBL-deficient serum that had been depleted of L-ficolin did not exhibit C4 activation, but addition of both or either purified MBL and/or L-ficolin to the serum restored the activation in a dose-dependent manner. Thus, C4 cleaving activity could be evaluated with the co-existence of MBL and L-ficolin in vitro. In conclusion, we propose a novel method using GN5-DPPE for investigating the MBL- and L-ficolin-dependent lectin pathway and anticipate that this method will be useful in innate immunity and clinical research.

Background: Erythropoietin in patients under dialysis treatment for renal failure is low which induces anemia. Treatment with recombinant erythropoietin (rEPO) has been used routinely as a supplement treatment for these patients. Immune complexes (IC) react with complement and bind to CR1 on erythrocytes (E-CR1), and are transported to the liver and/or spleen where IC removal and degradation occurs. The erythrocytes then return to circulation where they bind to additional IC. There are some patients whose E-CR1 expression is low with chronic anemia in spite of rEPO treatment. We hypothesized that in hemodialysis (HD) patients altered host defense against infection is associated with low levels of E-CR1. We examined if low E-CR1 in dialysis patients constitutes a risk factor for reduced host defense and poor outcome. Methods: In 95 HD patients, E-CR1 was quantified using a monoclonal E-CR1 antibody and FACS analysis followed by clinical course studies for 5 years. Results: The patients were divided into three groups by E-CR1 level. Percent survival for the low E-CR1 group (53.3%) was significantly lower than the high E-CR1 group (86.4%) (p < 0.01). There were more hepatitis C virus-positive patients within the low E-CR1 group (27.3%) than in the high E-CR1 group (4.7%) (p < 0.05). Furthermore, 10 patients with the lowest E-CR1 levels had severe complications, notably infection at an arteriovenous fistula. Conclusion: A reduced E-CR1 level might be a risk factor for reduced host defense and can be used as a predicting factor for poor prognosis in a HD patient.

Whole-body gamma-irradiation to mice causes thymic atrophy where a population of precancerous cells with mutation can be found. Thus, clonal growth and DNA changes at Bcl11b, Ikaros, Pten, Notch1 and Myc were examined in not only thymic lymphomas but also in atrophic thymuses at various times after irradiation. Clonal expansion was detected from the distinct patterns of rearrangements at the TCRbeta receptor locus in a fraction of atrophic thymuses at as early as 30 days after irradiation. This expansion may be in part owing to the rearranged TCRbeta signaling because the transfer of bone marrow cells with the rearrangement and the wild-type locus into severe-combined immunodeficiency mice showed preferential growth of the rearranged thymocytes in atrophic thymus. Loss of heterozygosity (LOH) at Bcl11b and trisomy of Myc were found at high frequencies in both lymphomas and atrophic thymuses, and in contrast, LOH at Ikaros and Pten were rare in atrophic thymuses but prevalent in lymphomas. Notch1 activation was detected in lymphomas and in atrophic thymuses only at a late stage. Similar patterns of DNA changes were found in atrophic thymuses induced in Bcl11b(+/-) mice. These results suggest the order of genetic changes during lymphomagenesis, Bcl11b and Myc being at the early stage; whereas Ikaros, Pten and Notch1 at the late stage.

IgA nephropathy (IgAN) is the most common form of chronic glomerulonephritis. Although glomerular deposition of complement components is well known, the evidence of serological complement activation in IgAN is inconclusive. We hypothesized that serum levels of complement components and regulatory proteins in patients with IgAN are correlated with its pathogenesis. In the present study we measured complement components in 50 patients with IgAN and 50 healthy volunteers. C5, C1 inhibitor, factor B, C4 binding protein, factor H, and factor I were measured with the use of single radial immunodiffusion. Mannose‐binding lectin (MBL) and properdin (P) were measured by enzyme‐linked immunosorbent assay (ELISA). The correlations among complements in the sera of patients with clinical gradings for IgAN (i.e., the good prognosis group, relatively good prognosis group, relatively poor prognosis group, and poor prognosis group) were evaluated. CH50, C4, factor B, P, factor I, and factor H were significantly higher in IgAN patients than in healthy controls. There were significant correlations between C5 and C4 binding protein, between C3 and C5, or between C4 and factor B in patients with IgAN. In the poor prognosis group, C4 binding protein was significantly higher than in the other groups of IgAN patients. hypercomplementemia occurs in IgAN and is associated with an increase in complement regulatory protein (CRP). C4 binding protein analyses can be used to predict disease prognosis. J. Clin. Lab. Anal. 21:77–84, 2007. © 2007 Wiley‐Liss, Inc.

Background For patients with liver metastases from gastric cancer (LMGC), combination chemotherapy with fluoropyrimidines and platinum agents has been recognized as standard treatment. However, the prognosis of hepatic progression after first-line treatment failure remains poor. When hepatic progression occurs, hepatic arterial infusion (HAI) chemotherapy may be helpful for preventing disease progression. Purpose To retrospectively assess the feasibility and efficacy of HAI chemotherapy using 5-fluorouracil, epirubicin, and mitomycin C (FEM) for patients with LMGC after failure of systemic S-1 plus cisplatin. Material and Methods We reviewed the records of patients who received HAI chemotherapy using FEM for LMGC that progressed during systemic S-1 plus cisplatin treatment while extrahepatic disease was decreased or did not appear. HAI chemotherapy was given as second-line therapy using 5-fluorouracil (330 mg/m2 weekly), epirubicin (30 or 40 mg/m2 every 4 weeks), and mitomycin C (2.7 mg/m2 biweekly). Results Fourteen patients were analyzed. Toxicity of HAI chemotherapy was generally mild. The objective response rate was 42.9%, including a complete response rate of 14.3%. Median times to hepatic and extrahepatic progression were 9.2 and 7.4 months, respectively. Of 12 patients with documented progression after HAI chemotherapy, 10 patients (83.3%) received additional treatment, including irinotecan or taxanes. Overall, median survival was 12.7 months. Conclusion Our findings suggest that HAI chemotherapy using FEM is a feasible and effective treatment for patients with LMGC after failure of systemic S-1 plus cisplatin. HAI chemotherapy employed in the second-line setting is useful for achieving long-term disease control of LMGC.

Background: Complement receptor type 1 on erythrocytes (E-CR1) plays important roles not only in the regulation of complement activation, but also the clearance of immune complexes. Reduced E-CR1 was previously found in patients undergoing hemodialysis (HD). We investigated whether the E-CR1level in HD patients with diabetic nephropathy (DMN) is decreased. The levels of decay accelerating factor (DAF) and CD59 on erythrocytes (E) were also determined to ascertain whether the loss of CR1 is a specific phenomenon or other complement regulatory proteins are also affected. Methods: The levels of CR1, DAF, and CD59 on E were analyzed in 176 HD patients with DMN, 101 HD patients with non-diabetes mellitus renal diseases (non-DMN), and 108 healthy individuals. Hind III restriction fragment length polymorphism of intron 27 of the CR1 gene was analyzed. The serum-soluble CR1 levelwas measured by ELISA. Results: The E-CR1 level was significantly lower in the DMN group than the non-DMN group (p < 0.0001) and healthy individuals (p < 0.05). The E-CR1 level was significantly higher in the non-DMN group than in healthy individuals (p < 0.01). The levels of E-DAF and E-CD59 were significantly lower in the DMN group than non-DMN group (DAF, p < 0.01; CD59, p < 0.0001). Within each genotype of the CR1 gene, the E-CR1 level was significantly lower in the DMN group than in the non-DMN group and healthy individuals (non-DMN, p < 0.01; healthy individuals, p < 0.05). The serum-soluble CR1 level was significantly higher in the DMN group than non-DMN group and control group (p < 0.01 each). However, soluble CR1 did not correlate with E-CR1. Conclusion: Acquired loss of E-CR1 was found among HD patients with DMN. From the viewpoint of host defense, it may be a prognostic factor.

Background/Aims: Mannose-binding lectin (MBL) is characteristic of an acute-phase-reacting protein like C-reactive protein (CRP). However, the prognostic value of the serum MBL level has not been examined. The aim of this study was to evaluate whether the serum MBL level can predict all-cause mortality in hemodialysis (HD) patients. Methods: A total of 131 patients without active infection, who had been on maintenance HD for at least 2 years, were included in this study. The serum MBL, high-sensitivity CRP (hs-CRP) level, nutrition markers, and biochemical parameters were measured in June 1999. The cohort was then followed prospectively for 36 months, and clinical data were recorded. Results: The MBL level of the 131 HD patients was 9.054 ± 5.115 µg/ml (mean ± SD). During the follow-up period, 18 patients (9 males and 9 females) died and 113 (64 males and 49 females) survived. The two leading causes of death were cardiovascular events (n = 6, 33.3%) and infection (n = 4, 22.2%). The serum MBL level was significantly lower among the nonsurvivors (6.596 ± 4.990 µg/ml) than among the survivors (9.445 ± 5.046 µg/ml; p < 0.05). There was a significant, although very weak, correlation between the MBL level and albumin level (p < 0.05), but there was no correlationbetween the MBL level and the hs-CRP level. The patients were divided into two groups according to the serum MBL level (5 µg/ml). Multivariate analysis of factors predicting all-cause mortality in multivariate logistic regression analysis identified a serum MBL level Conclusions: Our findings suggest that the serum MBL level is a significant predictor of outcome in HD patients. HD patients with a low level of serum MBL should be carefully monitored.

A 57-year-old woman with pulmonary sarcoidosis was admitted to the hospital because of an elevation of serum creatinine and blood urea nitrogen. On admission, the laboratory data suggested interstitial nephritis without proteinuria and hematuria, whereas a renal biopsy showed granulomatous interstitial nephritis and mild mesangial proliferative glomerulonephritis. Immunoglobulin and C1q deposits were negative, but mannose-binding lectin, C3, C4d, and C5b-9 deposits were marked in the glomerular mesangial areas. The lectin pathway of complement activation may have contributed to the development of glomerular injury in this patient. DNA of Propionibacterium acnes , which is now strongly suspected as the pathogen of sarcoidosis, was detected in the patient's glomerular mesangial cells; tubular epithelial cells, which were involved in granulomatous inflammation; and mononuclear cells in epithelioid granulomas by in situ hybridization. These findings may add new insights to the pathogenesis of renal sarcoidosis, including its relation to infection, because mannose-binding lectin plays a crucial role in the host defense against various pathogens. From this case of renal sarcoidosis, it is hypothesized that P acnes may be involved in pathogenesis of granulomatous interstitial nephritis and that it plays a role in glomerular complement activation via the lectin pathway.

Background. The level of complement receptor type 1 (CR1) on erythrocytes (E-CR1) is determined by the presence of high (H) or low (L) expression alleles. We investigated whether acquired loss of E-CR1 occurs in haemodialysis patients and, if so, which factors may contribute to acquired loss of E-CR1 in these patients. Methods. The E-CR1 level was determined in 195 Japanese haemodialysis patients, and we selected patients with a high or low E-CR1 level. In patients with low E-CR1 expression, sequence analysis of polymorphic sites (A3650G and C5507G) in the CR1 gene was performed. To assess the effect of the type of dialysis membrane used in the patients with low E-CR1 expression, the dialysis membrane was changed from a cellulose membrane to a biocompatible membrane (to a polyacrylonitrile membrane and then to a polysulfone membrane). To evaluate the susceptibility of E-CR1 to proteolysis, erythrocytes were incubated with various concentrations of trypsin, and the level of remaining CR1 on the erythrocytes was determined. Results. Among patients with high E-CR1 expression (n ¼ 30), 87% had HH alleles and 13% had HL alleles. Among patients with low E-CR1 expression (n ¼ 29), 24% had LL alleles, 45% had HL alleles and 31% had HH alleles. Nucleotides 3650G and 5507G in the CR1 gene were associated with the L allele. Nucleotides 3650A and 5507C were associated with the H allele. Only one patient with HH alleles had nucleotides 3650G and 5507C. Three months after changing the haemodialysis membrane, the E-CR1 level significantly increased (P

A 60-year-old woman who was diagnosed with hereditary angioedema (HAE) developed nephrotic syndrome, with end-stage renal disease (ESRD) occurring about 2.5 years later. During her slide toward ESRD, she experienced three severe episodes of angioedema that each resulted in significant fluid retention. Though the therapeutic administration of C1-inhibitor concentrate was effective in controlling her angioedema, seemed ineffective in preventing her from developing ESRD requiring hemodialysis treatment. We theorized that the patient's low colloid osmolality and glomerular perfusion were important facilitators of her attacks of angioedema.

近年生物学的活性を有するPTH(1-84)=CAP (cyclase activatin PTH) を測定するwhole PTH assayが開発された. 従来区別できなかったPTH(7-84) 等のlarge C-PTH fragments=CIP (cyclase inhibitory PTH) がCAPに対して拮抗作用を有することが注目され, CAP/CIPの変化が無形性骨症の要因として検討されている. 今回ビタミンD経口投与中の維持血液透析患者群においてCAP/CIPが骨回転の指標となりうるか検討してみた. 透析歴4年以上で糖尿病歴, ビタミンDパルス歴のない90名を対象とし1997年1月から2001年3月までの間, 血清Ca, P濃度を毎週, iPTH, β2MGを2か月毎, 右第2中手骨骨密度をDIP法で6か月毎に測定した. さらに2001年4月total PTH=iPTH, CAP, CIP=iPTH-CAP, BAP, BGP, 1CTP等を測定し, iPTHにより低下群 (0-65pg/mL) 25名, 正常群 (65-200pg/mL) 43名, 亢進群 (200-pg/mL) 22名の3群に分け, 骨代謝マーカーとCAP/CIPの関係などを検討した. 透析歴は正常群で有意に短く, 1日あたりのalfacalcidol平均投与量および平均Ca×P積は亢進群で有意に増加していた. iPTHの平均は157.6±152.2pg/mLであり, 低下群でCAP/CIPは1.53±1.63と正常群+亢進群の3.32±2.47に比べて有意に低値を示した. BAP, BGP, 1CTPおよびBGP/1CTPの各骨代謝マーカーも低下群は低値を示し, このビタミンD投与中の患者群でもCAP/CIPが低値を示すことは低回転骨を示唆する可能性が示された. CAP/CIPはPTH分泌低下の指標と考えられたが, さらに骨組織との間に介在する他の要因の検討が必要と思われる.

One of the complications of hemodialysis (HD) therapy is anemia caused by erythropoietin (EPO) deficiency. Recombinant EPO (rEPO) has been used routinely as a supplemental treatment. Erythrocyte expression of the complement regulatory proteins decay accelerating factor (DAF) and CD59 restricts complement activation and inhibits hemolysis. We hypothesized that the efficacy of rEPO treatment may be caused in part by the ability of rEPO to increase erythrocyte expression of DAF and CD59.DAF, CD59, and complement receptor 1 (CR1) levels were analyzed for a group of 95 HD patients and compared with those of a control group. To evaluate effects of discontinuation of rEPO therapy, rEPO therapy was stopped for 12 HD patients until hematocrits decreased to less than 25%. DAF and CD59 levels then were reanalyzed.In the 95 HD patients, three factors correlated significantly: DAF and CD59 (r = 0.642), DAF and CR1 (r = 0.503), and CD59 and CR1 (r = 0.324), whereas no correlations were found in the group of 42 healthy controls. In the experiment in which rEPO therapy was discontinued, 8 of 12 patients reached the defined level of anemia 4 to 7 weeks after rEPO treatment had been withheld. Both DAF and CD59 levels decreased significantly after discontinuation of rEPO therapy (P0.01). DAF and CD59 levels increased in all 8 patients after rEPO treatment was reinitiated (P0.01), and CR1 levels increased in 5 of 8 patients. Four of 12 patients showed no evidence of anemia after discontinuation of rEPO treatment. In these patients, DAF, CD59, and CR1 levels did not change before or after withholding rEPO therapy.One of the mechanisms mediating the efficacy of EPO therapy is increased DAF and CD59 expression.

Background: Thromboembolism is known as a major complication of nephrotic syndrome, but only 4 cases of portal vein thrombosis have been reported as a complication of nephrotic syndrome. All of these 4 cases had acute symptoms, and 3 of 4 were in relapsing phase of nephrotic syndrome when thrombi were found. We describe here a case of 51-year-old woman with fresh nephrotic syndrome that was asymptomatically complicated by portal, splenic and renal vein thrombosis. Conclusion: In the presence of fresh nephrotic syndrome of minimal change, asymptomatic and widely distributed, including portal vein, thrombus formation occurred. If the clinical course shows resistance to therapy, we must consider the complication of venous thrombosis. Anticoagulant therapy with heparin and warfarin was effective and all thrombi disappeared without any other complications.

Serological and histological studies were carried out to explore the role of the lectin complement pathway in the pathogenesis of cryoglobulinemic glomerulonephritis. Sixteen patients with mixed cryoglobulinemia type II with glomerulonephritis (GN) were enrolled. All cases had hepatitis C virus (HCV) infection. The serum concentration of mannose-binding lectin (MBL) was significantly higher in the GN patients than in the normal controls according to ELISA (P < 0.01). IgG, IgM, C1q, C4d, HCV envelope antigen, MBL, and MBL-associated serine protease-1 (MASP-1) could be visualized in the cryoprecipitate of the 16 patients by Dot blot assay. Renal biopsy specimens obtained from 3 patients were examined by immunohistochemistry, and the glomeruli strongly stained for IgG, IgM, MBL, MASP-1, C4d, C3c, and C3d in a fringe-like pattern. The pattern of HCV constituent deposition was partially fringe-like. The complement profiles of the 16 cases were distinctive; briefly, the serum levels of C1q, C2, and C3 were reduced, although the levels of circulating regulatory proteins (C1-inhibitor, factor H, and factor I) were in the normal range. The serum C4 level was significantly reduced. These results indicate that immune complex formation involves molecules of the lectin pathway and leads to organ damage in cryoglobulinemic glomerulonephritis.

The technique of 1-stage elongation of a short third or fourth metacarpal through the palmar approach was devised to avoid the drawbacks of the conventional procedures through the dorsal approach with or without using an external fixator. This technique was used in the treatment of 3 cases and the results and the technique are described.

The function of Epstein-Barr virus (EBV)-specific cytotoxic T cells is disturbed in rheumatoid arthritis (RA) patients but the mechanism for this disturbance has remained unknown. In a recent study searching for the causative gene of X-linked lymphoproliferative syndrome, the gene possibly linked to EBV-specific cytotoxic T cells or NK cell-mediated cytotoxic activity to EBV-infected cells was discovered, and its product is now referred to as signaling lymphocytic-activation molecule-associated protein (SAP) or Src homology 2 domain-containing protein (SH2D1A). In the present study, we attempted to investigate the involvement of the SAP gene in RA using a quantitative real-time PCR; the expression level of SAP transcripts in peripheral leukocytes or T cells was examined for patients with RA. The expression level of SAP transcripts in peripheral leukocytes of 21 RA patients was significantly lower than that of 13 normal individuals (P = 0.0007), four patients with palindromic RA, 11 with inactive systemic lupus erythematosus (SLE) or 17 with chronic renal diseases. The decreased expression of SAP transcripts in RA patients was also observed in peripheral CD2(+) T cells compared with normal individuals. There was no mutation in the coding region of SAP cDNAs derived from peripheral leukocytes of five RA patients. The decreased expression of SAP transcripts in peripheral leukocytes or T cells of RA patients might lead to the failure of the immune system to eliminate the EBV-infected synovial lining cells in joints of RA patients. Our findings have suggested that decreased expression of the SAP gene might be involved in the onset or progress of RA.

It is widely known that glucocorticoids induce and accelerate osteoporosis. High-dose glucocorticoids are administrated daily to patients in the acute phase of nephrotic syndrome. It could be inferred that high-dose glucocorticoids rapidly decrease patients' basal bone mineral density (BMD) and this accelerates the natural progress of osteoporosis associated with aging or menopause. Nine nephrotic patients (male/female: 5/4) without previous prednisolone administration were chosen to measure BMD and the level of the markers for bone turnover before and after treatment for 3 months (total prednisolone administration: 4.5 +/- 0.0 g). Twenty-three patients under remission with prednisolone administration (male/female: 14/9) were included in the long-term treatment group. Patients in this group whose %YAM in the lateral lumbar spine was less than 89% were classified into a low BMD group (n = 10, male/female: 3/7). They were administered etidronate disodium at 200 mg/day for 14 days. BMD and % of young adult mean (YAM) in the lumbar spine (L2-L4 in lateral objection) and other regions were measured by dual-energy X-ray absorptiometry. As markers of bone metabolism, the urinary level of deoxypyridinoline (Dpd) was determined to evaluate osteogenesis, and serum osteocalcin was measured to evaluate bone resorption. BMD of the lumbar spine significantly decreased in the 3-month treatment group (752 +/- 96 mg/cm(2), 7 +/- 4% reduction) compared with the pretreatment group (810 +/- 85 mg/cm(2)). BMD in the long-term treatment group decreased continuously (683 +/- 135 mg/cm(2)). No significant differences were noted in other measurement sites. BMD in the etidronate treatment group increased significantly (597 +/- 55 mg/cm(2)) compared with the pretreatment group (549 +/- 76 mg/cm(2)). Etidronate did not change BMD at the sites with a normal BMD. Among the biochemical markers (BM) examined, the urinary level of Dpd (nMol/liter. Cr) significantly increased in the 3-month treatment group (8.6 +/- 5.1 nMol/liter.Cr) compared with the pretreatment group (5.8 +/- 2.0 nMol/liter. Cr). No significant differences were seen in the BMs measured in the long-term treatment group. The urinary Dpd level of the etidronate treatment group decreased (3.9 +/- 1.4 nMol/liter. Cr) compared with the pretreatment group. These data indicate that etidronate could improve the accelerated bone resorption. In conclusion, high-dose glucocorticoid therapy causes rapid bone resorption and accelerates the natural progress of osteoporosis associated with aging or menopause. Etidronate administration prevents the progress of osteoporosis in nephrotic patients. Preventive treatment should be performed when the estimated BMD in 3 months falls below the baseline by more than 7 +/- 4%, reaching the therapeutic range.

Henoch-Schönlein purpura nephritis (HSPN) is considered a form of systemic vasculitis of the small blood vessels with immune pathogenesis. In this disorder, the complement system is recognized as an important mechanism of glomerular injury. The aim of this study is to determine whether the lectin pathway, a novel pathway of complement activation, is related to the pathogenesis of HSPN. Renal biopsy material from 10 patients with HSPN was studied immunohistochemically and examined for a clinicopathologic correlation. Serum levels of complement components, including mannose-binding lectin (MBL), and plasma levels of complement activation products were also evaluated in these patients and compared with levels in patients with immunoglobulin A (IgA) nephropathy or mesangial proliferative glomerulonephritis (GN) without IgA deposition (non-IgA GN). Glomerular deposition of components of the pathway, MBL and MBL-associated serine protease (MASP-1), as well as C3b/C3c, C5b-9, and C4-binding protein (C4-bp), was detected in 8 of 10 patients. Although no significant correlation was found between glomerular deposition of MBL/MASP-1 and histological or clinical findings, the biopsies on all patients with MBL/MASP-1 deposits were performed within 20 weeks from the onset of disease. Levels of plasma C4d, the activation fragment of C4, and C4-bp, a soluble regulatory protein of the pathway, were greater in patients with HSPN than in those with non-IgA GN. However, there was no difference in serum MBL levels between the three groups of patients (HSPN, IgA nephropathy, and non-IgA GN). These results suggest that complement activation through the lectin pathway was involved at the onset of HSPN, and this mechanism might be important in the disease pathogenesis.