Advanced liver fibrosis is associated with decreased gait speed in older patients with chronic liver disease.

This study investigated whether the progression of liver fibrosis affects the prevalence of sarcopenia and incidence of decreased gait speed in older patients with chronic liver disease (CLD). Patients with CLD aged ≥ 60 years were classified into low, intermediate, and high fibrosis 4 (FIB-4) index groups according to the degree of liver fibrosis. The prevalence of sarcopenia and incidence of decreased gait speed (< 1.0 m/s) were compared among the three groups. Logistic regression analysis was performed to investigate factors affecting the risk of decreased gait speed. No significant difference was observed in the prevalence of sarcopenia among the three groups, but the incidence of decreased gait speed significantly differed (p = 0.029). When analyzed individually, a significant difference in decreased gait speed incidence was observed between the high and low FIB-4 index groups (p = 0.014). In logistic regression analysis, the progression of liver fibrosis (odds ratio: 1.32, 95% confidence interval: 1.13-1.55) and lower extremity muscle strength (LEMS) (odds ratio: 0.92, 95% confidence interval: 0.88-0.97) were significantly associated with decreased gait speed. As liver fibrosis progresses in older patients with CLD, it becomes important to focus on not only skeletal muscle mass and grip strength, but also gait speed and LEMS.

Efficacy of neuromuscular electrical stimulation for thoracic and abdominal surgery: A systematic review and meta-analysis.

This systematic review and meta-analysis examined the efficacy of neuromuscular electrical stimulation (NMES) on lower limb muscle strength and health-related quality of life (HR-QOL) after thoracic and abdominal surgery. We searched the Cochrane Central Register of Controlled Trials, MEDLINE via PubMed, Excerpta Medica Database via Elsevier, Physiotherapy Evidence Database, Cumulative Index to Nursing and Allied Health Literature, World Health Organization International Clinical Trials Registry Platform via their dedicated search portal, and ClinicalTrials.gov on November 2021 and updated in April 2023 to identify randomized controlled trials that examined the effects of NMES after thoracic and abdominal surgery. The primary outcomes were lower limb muscle strength, HR-QOL, and adverse events. We used the Cochrane Risk of Bias Tool and the Grading of Recommendations, Assessment, Development, and Evaluation approach to assess the certainty of evidence. A total of 18 randomized control trials involving 915 participants, including 10 on cardiovascular surgery, two on pulmonary surgery, five on digestive system surgery, and one on other surgery, were included. NMES slightly increased lower limb muscle strength and adverse events in cardiovascular surgery. Adverse events (hypotension, pain, and muscle discomfort) occurred in seven patients. HR-QOL was measured in two studies on cardiovascular surgery, but these were not pooled due to concept heterogeneity. Overall, NMES slightly increases lower limb muscle strength after cardiovascular surgery without serious adverse events. However, higher-quality randomized control trials in thoracic and abdominal surgeries are needed.

Age-specific incidence of joint disease in paediatric patients with haemophilia: A single-centre real-world outcome based on consecutive US examination.

INTRODUCTION: Joint health is one of the most important factors contributing to a healthy life in patients with haemophilia. Recent study revealed that starting early prophylaxis was not enough to prevent joint disease in most paediatric patients with haemophilia. AIM: In this study, we aimed to determine the age-specific incidence of acute joint disease during childhood at single haemophilia treatment centre (HTC). METHOD: The joint health in 48 patients was evaluated based on consecutive US testing for 5 years at annual multidisciplinary comprehensive care. RESULTS: During the study period, 23 patients (47.9%) had no joint disease since the initial examination, whereas 13 patients (27.0%) showed development from negative to positive findings. The incidence of joint disease increased with age: 0% in preschool, 5.3% in elementary school, 14.3% in junior high school and 35% beyond high school age. Among the 13 patients who developed joint disease, two experienced acquired synovitis that resolved during the follow-up period. Statistical analysis revealed that the patients who routinely underwent follow-up by the HTC exhibited a significantly lower incidence of joint disease than did those followed up at other institutions (p < .001). CONCLUSION: These results indicated that close check-up, including routine joint examination using US as well as frequent assessment of pharmacokinetic profile at the HTC, might play an important role in avoiding joint disease among paediatric patients with haemophilia.

A method of determining anaerobic threshold from percutaneous oxygen saturation.

The anaerobic threshold (AT) is the point of the aerobic-to-anaerobic metabolic switch. Despite the many clinical applications of AT, this measurement requires sophisticated equipment and skills. Here, we investigated a simple measurement method for AT using percutaneous oxygen saturation (SpO2) and pulse rate (PR) with a pulse oximeter in a study of exercise stress on healthy volunteers. Twenty individuals (ten men and ten women) were included in the study. Various respiratory parameters, including AT, were measured using conventional analytical methods. The SpO2 threshold (ST) was calculated using the SpO2-Slope method. The mean ± standard deviations SpO2 at ST was 97.8% ± 0.3% in men and 99.0 ± 0.3% in women. The concordance and interchangeability between ST and various five different types of AT, the ventilatory equivalent for oxygen (VE/VO2_AT), V-Slope (V-Slope_AT), ventilatory equivalent (VE_AT), respiratory exchange ratio (R_AT), and partial pressure of end-tidal oxygen (PETO2_AT) were generally high, with positive correlation coefficients in the range of [0.68-0.80]. These findings suggest that the SpO2-Slope method with a pulse oximeter may be a useful and simple method to determine AT compared to conventional methods.

Case-control study of the correlation between the five times sit to stand and 6-min walk distance in patients with pancreatic cancer.

PURPOSE: Cases of pancreatic cancer are increasing, and the risk of developing this disease reportedly increases with age. In recent years, there has been an increasing number of reports on physical function in patients with pancreatic cancer. Methods such as the 6-min walk distance (6 MWD) should be established to evaluate physical function, as a decline in exercise capacity is an important index in these patients. Recently, the 6 MWD has also been used to evaluate physical function in patients with pancreatic cancer. In healthy older adults, a decrease in 6 MWD is reportedly associated with intrinsic capacity and health status. Such factors make assessing 6 MWD important. However, the measurement of 6 MWD requires a sizable measurement environment. The five times sit to stand (FTSTS) test is a simple method that can be performed using a chair. FTSTS is hypothesized to be a useful assessment scale in patients with pancreatic cancer because it is easy to estimate the decline in physical function in clinical practice if the decline in 6 MWD can be estimated by evaluating FTSTS. The study's purpose was to clarify this hypothesis and ascertain the cutoff required to determine the decrease in 6 MWD in clinical practice. METHODS: Sixty consecutive patients with preoperative pancreatic cancer who were assessed for physical function were studied. 6 MWD (< 400 m) was the objective variable, and binary logistic regression analysis was performed, with age, BMI, sex, FTSTS, and HGS as explanatory variables. Receiver-operating characteristic (ROC) curve analysis was performed for the explanatory variables, which were found to be significant based on logistic regression analysis. The area under the curve (AUC) was also calculated. Sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) were evaluated. This study was approved by Hiroshima University Hospital's ethics committee (approval number: E808-1). RESULTS: Fifty-seven of the 60 patients were included in the analysis. Logistic regression analysis showed that FTSTS was a significant explanatory variable; ROC curve analysis showed an AUC of 0.872 and a cutoff value of 8.98 s. The sensitivity, specificity, PPV, and NPV were 82.4%, 80.0%, 63.6%, and 91.4%, respectively. CONCLUSIONS: A decrease in 6 MWD in preoperative pancreatic cancer patients can be identified by performing FTSTS.

Intraocular Pressure Fluctuation during Aerobic Exercise at Different Exercise Intensities.

Few studies have examined the effects of different aerobic-exercise intensities on intraocular-pressure (IOP) changes. This may be important for eye diseases that are impacted by IOP or its fluctuation, including glaucoma, and diabetes that is complicated by diabetic retinopathy. We investigated the effects of low-, moderate-, and high-intensity exercise on IOP in healthy subjects. A submaximal cardiopulmonary exercise test was performed in 18 healthy male subjects, and the maximal oxygen uptake was calculated. The subjects then exercised for 20 min at 30%, 50%, and 70% ·VO2 of maximal oxygen uptake, and their IOP was measured at rest and every 5 min during exercise. Oxygen uptake was monitored using an expiratory gas analyzer during exercise to maintain accurate exercise intensity and adjust exercise load. Oxygen uptake during exercise was significantly higher at all intensities from 5 to 20 min than at rest. IOP was significantly lower at 70% exercise intensity from 5 to 20 min than at rest. A negative correlation existed between IOP and ·VO2. IOP remained unchanged during low- and moderate-intensity exercise but significantly declined during high-intensity exercise compared with that at rest. Although various factors, such as ß-blockers, are involved in IOP decline at rest, a different mechanism is involved in IOP decline during exercise.

Reliability of joint position sense measured in the knee using the level function of the iPhone "Measure" application.

An impaired joint position sense (JPS) causes activity limitations, postural imbalance, and falls. This study compares the reliability of knee JPS measurements between the iPhone's "Measure" application and VICON motion capture system. Eleven healthy participants were recruited for the study. To conduct the study measures, the blindfolded participant, with an iPhone fixed to the lower non-dominant leg, was seated with their lower limbs in a relaxed position. The examiner held the participant's leg at the target angle (30°/60° from initial position) for 5 s before releasing it. The participant was then instructed to move the leg to the same target angle and hold it for 5 s (replicated angle). Absolute angular error (AAE), i.e., the difference between the target and replicated angles, was measured. Intraclass and Pearson correlation coefficients established statistically significant relationships. The study comprised 6 males and 5 females of mean age 27.6±5.6 years, mean height 1.67±0.10 m, and mean body weight 60.7±10.3 kg. Strong correlations existed between iPhone and VICON 30° (ICC = 0.969, r = 0.960, P < 0.001) and 60° AAEs (ICC 0.969, r = 0.960, P < 0.001). Bland-Altman plots showed a mean difference of 0.43° and 0.20° between the AAE measurements at 30° and 60°, respectively. The iPhone's "Measure" application is a simple and reliable method for measuring JPS in clinical practice and sports/fitness settings.

Therapeutic effects of sleeve gastrectomy for non-alcoholic steatohepatitis estimated by paired liver biopsy in morbidly obese Japanese patients.

ABSTRACT: Bariatric surgery has been reported to improve non-alcoholic steatohepatitis (NASH), which is a frequent comorbidity in morbidly obese patients. We performed a retrospective cohort study to estimate the therapeutic effect of sleeve gastrectomy (SG), the most common bariatric surgery in Japan, on obese patients with NASH by comparing the findings of paired liver biopsies.Eleven patients who underwent laparoscopic SG for the treatment of morbid obesity, defined as body mass index (BMI) > 35 kg/m2, from March 2015 to June 2019 at Hiroshima University Hospital, Japan, were enrolled. All patients were diagnosed with NASH by liver biopsy before or during SG and were re-examined with a second liver biopsy 1 year after SG. The clinical and histological characteristics were retrospectively analyzed.One year after SG, body weight and BMI were significantly reduced, with median reductions in body weight and BMI of-22 kg and -7.9 kg/m2, respectively. Body fat was also significantly reduced at a median of 13.7%. Liver-related enzymes were also significantly improved. On re-examination by paired liver biopsy, liver steatosis improved in 9 of the 11 patients (81.8%), ruling out of the pathological diagnosis of NASH. However, fibrosis stage did not significantly improve 1 year after SG. The non-alcoholic fatty liver disease activity score was significantly reduced in 10 of 11 patients (90.9%).Pathological improvement or remission of NASH could be achieved in most morbidly obese Japanese patients 1 year after SG.

Changes in motor function and quality of life after surgery in patients with pancreatic cancer.

OBJECTIVE: To determine the changes in motor function and health-related quality of life after pancreatectomy and identify factors influencing postoperative physical functioning in health-related quality of life. METHODS: This single-centre, prospective, observational study measured 6-min walking distance, grip strength, knee extension strength and health-related quality of life variables in patients with pancreatic cancer, before and after surgery. Paired t- and Wilcoxon signed-rank tests were used to compare pre- and postoperative motor function and health-related quality-of-life variables. Factors associated with postoperative physical functioning scores of health-related quality of life were assessed using multiple regression analysis. RESULTS: Fifty-nine individuals were enrolled. Motor function values decreased significantly postoperatively, including 6-min walking distance (mean ± standard deviation: 402.5 ± 95.4 vs. 497.7 ± 80.4 m, p < 0.001), knee extensor strength (0.42 ± 0.10 vs. 0.47 ± 0.10 kgf/kg, p < 0.001) and grip strength (22.0 ± 8.9 vs. 24.5 ± 9.2 kg, p = 0.001). Multiple regression analysis showed significant association between 6-min walking distance change and postoperative physical functioning scores of health-related quality of life (p = 0.036). CONCLUSION: The results suggest that motor function decreases postoperatively, and a decrease in 6-min walking distance after surgery is associated with postoperative physical functioning in patients with pancreatic cancer.

Effect of the use of passive body trunk exercise equipment on oxygen consumption and self-efficacy for carrying out exercise in patients with type 2 diabetes.

AIMS/INTRODUCTION: Considering the difficulty in inculcating the habit of exercise among patients with type 2 diabetes, devising an easily maintained means of exercise is preferable. Passive body trunk exercise equipment (PBTE) developed for home use might solve several problems related to exercise therapy, both for patients and clinical staff involved in diabetes treatment; however, its efficacy as a therapeutic exercise device for patients with diabetes has not been ascertained. The purpose of this study was to measure the exercise intensity and self-efficacy of PBTE, and to determine whether PBTE is a useful tool for exercise therapy. MATERIALS AND METHODS: The participants were 20 patients with type 2 diabetes, and the duration of exercise using the PBTE was set to 10 min. Oxygen consumption during exercise was measured, and self-efficacy for continuing to exercise using the PBTE and for walking was evaluated after completion of the study. RESULTS: The average exercise intensity using the PBTE was 1.7 metabolic equivalents, whereas the maximum exercise intensity was an average of 2.0 metabolic equivalents; the reported self-efficacy for continuing to exercise using the PBTE was significantly higher than for walking. CONCLUSIONS: Exercise intensity using the PBTE is similar to low-intensity walking, and thus, it might be a useful therapeutic exercise device for patients with type 2 diabetes. Furthermore, it could be an effective exercise device for diabetes patients who do not have regular exercise habits, especially with reduced motor function or lower leg muscle strength.

The Relationship between Knee Biomechanics and Clinical Assessments in ACl Deficient Patients.

The purpose of this study was to clarify the relationship between knee biomechanics and clinical assessments in ACL deficient patients. Subjects included 22 patients with unilateral ACL rupture and 22 healthy controls. Knee kinematics and kinetics during walking and running were examined using a 3-dimensional motion analysis system. The passive knee joint laxity, range of motion of knee joint, and knee muscle strength were also measured. Correlations between the knee kinematic and kinetic data and clinical assessments were evaluated. In the ACL deficient patients, there were no significant relationships between tibial translation during walking and running and passive knee joint laxity. The correlations between knee kinematics and kinetics and range of motion of knee joint were also not significant. Additionally, there were no significant correlations between knee kinematics during walking and knee muscle strength. However, there were several significant correlations between knee kinematics during running and knee muscle strength. The results demonstrate the importance of knee muscle strength for knee kinematics and kinetics during running in ACL deficient patients. Patients with stronger knee muscle strength may demonstrate more nearly normal knee joint movement during dynamic activities such as running.

Knee biomechanics during walking in recurrent lateral patellar dislocation are normalized by 1 year after medial patellofemoral ligament reconstruction.

PURPOSE: Gait kinematics and kinetics of the knee before and after medial patellofemoral ligament (MPFL) reconstruction in patients with recurrent lateral patellar dislocation (RPD) are unknown. The purpose of this study was to measure knee kinematics and kinetics during gait before and 1 year after anatomical MPFL reconstruction in patients with RPD and compare the results to healthy individuals. METHODS: Eleven RPD patients were treated using an anatomical MPFL reconstruction procedure. Gait analysis was conducted before and at 3, 6, and 12 months after surgery. For comparison, 15 healthy volunteers with no history of orthopaedic problems in their lower limbs were included as the control group. Knee kinematics and kinetics were analysed during gait. RESULTS: Before surgery, the internal knee extension moment in RPD patients was significantly lower than in controls (P = 0.025). At 3 months post-operatively, there was an additional decrease in knee extension moment compared to before surgery, and so it was still significantly lower than in the control group (P < 0.01). One year post-operatively, knee extension moment in the RPD group was significantly increased compared to 3 months post-operatively (P < 0.01). The knee flexion angle in the early stance phase in the RPD group at 3 months post-operatively was significantly lower than that of controls (P < 0.01). Knee kinematics and kinetics were similar to that of controls 1 year after surgery. CONCLUSION: Initially, RPD patients had lower knee extension moments during gait compared with controls, but by 1 year after MPFL reconstruction, knee kinematics and kinetics of gait in the RPD patients had returned to normal. These observations indicate that MPFL reconstruction may help to delay prospective knee OA as long as possible by restoring the conformation of the patellofemoral joint and gait biomechanics by surgery.

Courses of change in knee adduction moment and lateral thrust differ up to 1 year after TKA.

PURPOSE: In total knee arthroplasty (TKA), dynamic knee loading may loosen the artificial joint and bone or cause polyethylene wear after prolonged use. TKA decreases knee adduction moment at 6 months, but this effect is lost by 1 year post-operatively. However, lateral thrust after TKA has not been clarified. We hypothesized that like knee adduction moment, lateral thrust would return to baseline levels by 1 year post-operatively. METHODS: Participants were 15 patients who underwent TKA for medial knee OA. Japanese Orthopaedic Association (JOA) score, numeric rating scale, and gait analysis (measurement of peak knee adduction moment, knee varus angle at peak knee adduction moment, lateral thrust, and gait speed) were performed preoperatively (baseline) and 3 weeks, 3 and 6 months, and 1 year post-operatively. RESULTS: JOA score improved from 55 ± 9.8 to 78 ± 12.1 at 1 year post-operatively, and pain decreased significantly from baseline at each follow-up (p < 0.001). Significant increases in gait speed were observed at 6 months and 1 year (p < 0.001). Peak knee adduction moment during stance phase was significantly lower at 3 weeks, 3 months, and 6 months compared to baseline (p < 0.05), but no significant changes were seen at 1 year. Knee varus at peak knee adduction moment did not differ significantly between any measurement points, while lateral thrust was decreased at 6 months and 1 year compared to baseline (p < 0.05). CONCLUSIONS: Temporal courses of changes up to 1 year after TKA differed between knee adduction moment and lateral thrust, so our hypothesis was rejected. LEVEL OF EVIDENCE: IV.

Posterior tibial displacement in the PCL-deficient knee is reduced compared to the normal knee during gait.

PURPOSE: Most individuals with an isolated posterior cruciate ligament (PCL) injury do not complain of disability even if posterior instability is objectively revealed by a static physical examination, such as the posterior drawer test. This suggests it is insufficient to only evaluate posterior instability under static conditions. Therefore, we have investigated the effect of isolated PCL injury on the detailed kinematics of the knee in a dynamic environment such as during gait. METHODS: Eight unilateral PCL-deficient males and eight healthy control volunteers participated in this study. Isolated PCL injury was diagnosed by clinical examination. Stress X-ray imaging showed an average side-to-side difference of 12.7 ± 3.5 mm. Knee kinematics including anteroposterior tibial displacement were analysed during walking using the point cluster technique. RESULTS: Posterior tibial displacement from initial contact was significantly smaller during 9-22 % of the gait cycle by an average of 0.4 cm in the PCL group, compared to controls. In the PCL-deficient knee, the external rotational angle increased by an average of 3.3° at the loading response during 3-11 % of the gait cycle and the varus angle from initial contact increased by an average of 2.0° during 28-52 % of the gait cycle, compared to controls. CONCLUSIONS: Dynamic changes in the rotation and posterior translation patterns were seen after isolated PCL injury, suggesting the kinematics of PCL-deficient knees might be different to normal knees. These factors may contribute to long-term osteoarthritic change. Consequently, when choosing conservative treatment for PCL injury, these changes should be considered to prevent osteoarthritic change. LEVEL OF EVIDENCE: III.

Differences between opening versus closing high tibial osteotomy on clinical outcomes and gait analysis.

BACKGROUND: High tibial osteotomy (HTO) for medial knee osteoarthritis (OA) is mainly performed via two procedures: closing wedge HTO (CW) and opening wedge HTO (OW). In this study, differences between these procedures were assessed by serial clinical evaluation and gait analysis before and after surgery. METHODS: Twenty-one patients underwent HTO for medial knee OA in 2011 and 2012, with 12 patients undergoing CW and nine undergoing OW. The severity of OA was classified according to the Kellgren-Lawrence classification. The Japanese Orthopedic Association score for assessment of knee OA (JOA score), the Numeric Rating Scale (NRS), and the femoral tibial angle (FTA) on X-ray were evaluated. For gait analysis, gait speed, varus moment, varus angle and lateral thrust were calculated. RESULTS: The JOA score and NRS were improved significantly one year postoperatively in both groups. The FTA was maintained in both groups at one year. Varus angle and varus moment were significantly improved in both groups at each postoperative follow-up, when compared preoperatively. Lateral thrust was significantly improved at three months postoperatively in both groups. However, the significant improvement in lateral thrust had disappeared in the CW group six months postoperatively, whereas it was maintained for at least one year in the OW group. CONCLUSIONS: This study found that clinical outcomes were well maintained after HTO. OW reduced knee varus moment and lateral thrust, whereas CW had little effect on reducing lateral thrust. LEVEL OF EVIDENCE: Level IV.

Balance ability and proprioception after single-bundle, single-bundle augmentation, and double-bundle ACL reconstruction.

PURPOSE: The present study sought to determine the influences of single-bundle (SB), single-bundle augmentation (SBA), and double-bundle (DB) reconstructions on balance ability and proprioceptive function. METHODS: 67 patients who underwent a single- or double-bundle ACL reconstruction or a SBA using multistranded autologous hamstring tendons were included in this study with a 1-year follow-up. Body sway and knee kinesthesia (using the threshold to detect passive motion test (TTDPM)) were measured to indicate balance ability and proprioceptive function, respectively. Additionally, within-subject differences in anterior-posterior stability of the tibia and lower extremity muscle strength were evaluated before and after surgery. RESULTS: At 6 and 12 months after surgery, DB reconstruction resulted in better balance and proprioceptive function than SB reconstruction (P < 0.05). Although no significant difference was observed in balance ability or proprioceptive function between the SBA and DB reconstructions, knee stability was significantly better with SBA and DB reconstructions than SB reconstruction (P < 0.05). No significant differences were found in quadriceps and hamstrings strength among the three reconstruction techniques. CONCLUSIONS: Our findings consider that joint stability, proprioceptive function, and balance ability were superior with SBA and DB reconstructions compared to SB reconstruction at 6 and 12 months after surgery.

The role of MASP-1/3 in complement activation.

The complement system, which consists of more than 30 plasma and cell surface proteins, is activated by three pathways: the classical, lectin, and alternative pathways, leading to the generation of opsonins and pathogen destruction. In the lectin pathway, mannose-binding lectin (MBL) and ficolins act as pattern recognition molecules for pathogens, resulting in the activation of MBL-associated serine proteases (MASPs: MASP-1, MASP-2, and MASP-3). Among these proteases, MASP-2 is a key enzyme that cleaves C4 and C2 to assemble a C3 convertase (C4b2a). However, the physiological function of MASP-1 and MASP-3 remains unclear. To investigate the roles of MASP-1 and MASP-3, we generated a MASP-1- and MASP-3-deficient (M1/3 KO) mouse model and found that the deficient mice lacked alternative pathway activation because factor D (Df) remained as a proenzyme in the serum. MASP-1 and MASP-3 were able to convert the proenzyme of Df to an active form in vitro. In addition, MASP-1 was able to activate MASP-2 and MASP-3 as C1r activates C1s. Thus, MASP-1 and MASP-3 seem to be involved in activation of both the lectin and alternative pathways.

Role of complement in a murine model of peanut-induced anaphylaxis.

Peanut allergy is severe and persisting from childhood to adulthood. However, there is no effective prophylaxis or treatment for peanut allergy. Little is known to about the molecular process in the pathogenesis of peanuts allergy, especially in innate immunity. Thus we investigated the role of complement activation in murine peanut anaphylaxis. Complement component C3 deposition on peanut extract (PE) was evaluated using sera from wild-type (WT), mannose-binding lectin associated serine protease (MASP)-1/3 deficient, MASP-2 deficient, and C4 deficient mice. Sera from interferon regulatory factor-4 (IRF-4) deficient mice, which lack serum immunoglobulin, were also used. In anaphylaxis study, mice were pretreated with propranolol and a long-acting form of IL-4, and injected with PE. Mice were then assessed for plasma C3a levels and hypothermia shock by ELISA and rectal temperature measurement, respectively. C3 deposition on PE was abolished in immunoglobulin- and C4-deficient sera. No difference in C3 deposition levels were observed among WT, MASP-1/3 deficient and MASP-2 deficient sera. IgM, IgG2b, IgG3, C1q, and ficolin-A deposits were detected on PE. In anaphylaxis study, MASP-1/3 deficient mice showed elevation of plasma C3a levels similar to WT mice. However, they were significantly reduced in C4- and MASP-2-deficient mice compared to WT mice. Consistently, PE-induced anaphylactic shock was prevented in C4 deficient mice and partially in MASP-2 deficient mice. In conclusion, PE activates complement via both the lectin and classical pathways in vivo, and the complement activation contributes to hypothermia shock in mice.

Mice deficient in ficolin, a lectin complement pathway recognition molecule, are susceptible to Streptococcus pneumoniae infection.

Mannose-binding lectin (MBL) and ficolin are complexed with MBL-associated serine proteases, key enzymes of complement activation via the lectin pathway, and act as soluble pattern recognition molecules in the innate immune system. Although numerous reports have revealed the importance of MBL in infectious diseases and autoimmune disorders, the role of ficolin is still unclear. To define the specific role of ficolin in vivo, we generated model mice deficient in ficolins. The ficolin A (FcnA)-deficient (Fcna(-/-)) and FcnA/ficolin B double-deficient (Fcna(-/-)b(-/-)) mice lacked FcnA-mediated complement activation in the sera, because of the absence of complexes comprising FcnA and MBL-associated serine proteases. When the host defense was evaluated by transnasal infection with a Streptococcus pneumoniae strain, which was recognized by ficolins, but not by MBLs, the survival rate was significantly reduced in all three ficolin-deficient (Fcna(-/-), Fcnb(-/-), and Fcna(-/-)b(-/-)) mice compared with wild-type mice. Reconstitution of the FcnA-mediated lectin pathway in vivo improved survival rate in Fcna(-/-) but not in Fcna(-/-)b(-/-) mice, suggesting that both FcnA and ficolin B are essential in defense against S. pneumoniae. These results suggest that ficolins play a crucial role in innate immunity against pneumococcal infection through the lectin complement pathway.

Mouse ficolin B has an ability to form complexes with mannose-binding lectin-associated serine proteases and activate complement through the lectin pathway.

Ficolins are thought to be pathogen-associated-molecular-pattern-(PAMP-) recognition molecules that function to support innate immunity. Like mannose-binding lectins (MBLs), most mammalian ficolins form complexes with MBL-associated serine proteases (MASPs), leading to complement activation via the lectin pathway. However, the ability of murine ficolin B, a homologue of human M-ficolin, to perform this function is still controversial. The results of the present study show that ficolin B in mouse bone marrow is an oligomeric protein. Ficolin B, pulled down using GlcNAc-agarose, contained very low, but detectable, amounts of MASP-2 and small MBL-associated protein (sMAP) and showed detectable C4-deposition activity on immobilized N-acetylglucosamine. These biochemical features of ficolin B were confirmed using recombinant mouse ficolin B produced in CHO cells. Taken together, these results suggest that like other mammalian homologues, murine ficolin B has an ability to exert its function via the lectin pathway.