Connexins regulate calcium signaling by controlling ATP release

Forced expression of gap junction proteins, connexins, enables gap junction-deficient cell lines to propagate intercellular calcium waves. Here, we show that ATP secretion from the poorly coupled cell lines, C6 glioma, HeLa, and U373 glioblastoma, is potentiated 5- to 15-fold by connexin expression. ATP release required purinergic receptor-activated intracellular Ca²⁺ mobilization and was inhibited by Cl⁻ channel blockers. Calcium wave propagation also was reduced by purinergic receptor antagonists and by Cl⁻ channel blockers but insensitive to gap junction inhibitors. These observations suggest that cell-to-cell signaling associated with connexin expression results from enhanced ATP release and not, as previously believed, from an increase in intercellular coupling.     

Incidence,Prevalence, Etiology,and Prognosis of First-Time Chronic Pancreatitis in Young Patients: A Nationwide Cohort Study

Background/Aims  

Publications on etiology of chronic pancreatitis (CP) are infrequent. Etiologies today encompass genetic disorders. We wanted to describe etiologies of today and identify patients with genetic disorders like hereditary pancreatitis (HP), mutations in Serine Protease Inhibitor Kazal type1 (SPINK1), and the Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR) among patients formerly considered to have idiopathic CP.     

The prognostic value of polycomb group protein B‐cell‐specific moloney murine leukemia virus insertion site 1 in stage II colon cancer patients

The aim of this study was to investigate the prognostic value of B‐cell‐specific moloney murine leukemia virus insertion site 1 (BMI1) protein expression in primary tumors of stage II colon cancer patients. BMI1 protein expression was assessed by immunohistochemistry in a retrospective patient cohort consisting of 144 stage II colon cancer patients. BMI1 expression at the invasive front of the primary tumors correlated with mismatch repair status of the tumors. Furthermore, BMI1 expression at the luminal surface correlated with T‐stage, tumor location, and the histological subtypes of the tumors. In a univariate Cox proportional hazard analysis, no statistical significant association between risk of relapse and BMI1 protein expression at the invasive front (HR: 1.12; 95% CI 0.78–1.60; p = 0.53) or at the luminal surface of the tumor (HR: 1.06; 95% CI 0.75–1.48; p = 0.70) was found. Likewise, there was no association between 5‐year overall survival and BMI1 expression at the invasive front (HR: 1.12; 95% CI 0.80–1.56; p = 0.46) or at the luminal surface of the tumor (HR: 1.16; 95% CI 0.86–1.60; p = 0.33). In conclusion, BMI1 expression in primary tumors of stage II colon cancer patients could not predict relapse or overall survival of the patients, thus having a limited prognostic value in stage II colon cancer patients.     

New avian influenza A virus subtype combination H5N7 identified in Danish mallard ducks

During the past years increasing incidences of influenza A zoonosis have made it of uppermost importance to possess methods for rapid and precise identification and characterisation of influenza A viruses. We present here a convenient one-step RT-PCR method that will amplify full-length haemagglutinin (HA) and neuraminidase (NA) directly from clinical samples and from all known subtypes of influenza A. We applied the method on samples collected in September 2003 from a Danish flock of mallards with general health problems and by this a previously undescribed influenza A subtype combination, H5N7, was identified. The HA gene showed great sequence similarity to the highly pathogenic avian influenza A virus (HPAIV) A/Chicken/Italy/312/97 (H5N2); however, the cleavage site sequence between HA1 and HA2 had a motif typical for low pathogenic avian influenza viruses (LPAIV). The full-length NA sequence was most closely related to the HPAIV A/Chicken/Netherlands/01/03 (H7N7) that infected chickens and humans in the Netherlands in 2003. Ten persons with direct or indirect contact with the Danish mallard ducks showed signs of influenza-like illness 2-3 days following the killing of the ducks, but no evidence of influence infections was detected. To our knowledge this is the first report of an H5N7 influenza A virus.     

Preoperative Systemic Bone Quality Does Not Affect Tibial Component Migration in Knee Arthroplasty: A 2-Year Radiostereometric Analysis of a Hundred Consecutive Patients

BackgroundBone quality and other preoperative predictive factors may affect implant migration and the survival of knee arthroplasty.MethodsIn a prospective cohort of 100 consecutive patients (65 women) at a mean age of 67.7 years (range 39-87 years), we investigated preoperative predictors of postoperative tibial component migration in cemented and cementless total knee arthroplasties or cemented unicompartmental knee arthroplasty. Predictors consisted of Knee Injury and Osteoarthritis Outcome Score (KOOS) and Oxford Knee Score, questionnaires, bone turnover markers of CTX and P1NP, systemic bone mineral density (BMD), and knee osteoarthritis (OA) grade. Tibial component migration was measured with radiostereometry postoperative, at 1 and 2 years of follow-up.ResultsBetween 1 and 2 years, 19 tibial components migrated continuously (maximum total point motion [MTPM] > 0.2 mm). In general, there was no difference in age, body mass index, BMD, KOOSs, or OA grade between patients with continuous tibial migration compared to patients without continuous migration (P > .11). However, cementless tibial components with continuous migration had a lower KOOS pain score (more pain), lower vitamin D, and a higher bone turnover (CTX) value than patients without continuous migration. There was no association between the BMD and MTPM at 1-year follow-up regardless of prothesis type (P > .17). Patients with osteoporosis and normal BMD had similar mean tibial component MTPM at 2 years (3 prostheses combined; P = .34).ConclusionMigration of tibial components inserted with or without bone cement was not affected by the preoperative bone quality in terms of systemic BMD, bone turnover markers, and OA grade in the knee.     

Bone Mineral Density Measurements Around Osseointegrated Implants: A Precision Study and Validation of Scan Protocol for Transfemoral Amputees

Visual evaluation of bone changes around an osseointegration (OI) implant in femoral amputees examined on plain radiographs shows that periprosthetic bone resorption takes place during the first years after OI surgery, but the bone mineral density (BMD) change has not been previously quantified by dual-energy X-ray absorptiometry (DXA). Precision is vital when monitoring BMD changes around implants, and thus the aim of this study was to evaluate the precision and feasibility of a scan protocol for BMD measurements in proximity of OI implants. The proximal part of 2 human cadaveric femoral bones (specimens A and B) with OI implants were mounted in a positioning jig and DXA scans were repeated 5 times in increments of 5° from neutral (0°) to 20° flexion and rotation. BMD changes as a result of change in leg position were evaluated. Repeated patient examinations (n?=?20) were conducted in a clinical setting and the precision error was calculated for each of 7 periprosthetic custom-made regions of interest (ROIs). The precision of cadaveric BMD measurements in neutral position was <3.3%. Even 5° flexion or rotation in femur position caused significant changes in average BMD (p?<0.04). Depending on ROI, the percentage of coefficient of variation (%CV) and average BMD was?<6% at 10° flexion and rotation. At 20° flexion, %CV increased up to 12.7% and average BMD increased up to 9.9%. The clinical short-term precision root mean square standard deviation ranged from 0.031?g/cm² to 0.047?g/cm² and %CV ranged from 3.12% to 6.57% depending on ROI. Simulated hip flexion or rotation of the femur affected periprosthetic BMD measurements around OI implants in cadaveric femoral bones, which stresses the importance of a reproducible set-up during DXA scans to reduce measurement errors caused by variation in leg position. Adherence to the scan protocol with a relaxed position of the residual limb resulted in an acceptable short-term precision below 6.6%.     

Reconstructing the anterolateral ligament does not decrease rotational knee laxity in ACL-reconstructed knees

Purpose

Little is known about the anterolateral ligament’s (ALL) influence on knee laxity. The purpose of this study was to investigate rotational knee laxity against a pure axial rotational stress using radiostereometric analysis (RSA) after cutting and reconstructing both the anterior cruciate ligament (ACL) and the ALL.

Methods

Eight human donor legs were positioned and stereoradiographically recorded at 0°, 30° and 60° of knee flexion using a motorised fixture, while an internally rotating force of 4 Nm was applied to the foot. Anterior–posterior and rotational laxity were investigated for knees with intact ligaments and compared with those observed after successive ACL and ALL resection and reconstruction.

Results

After cutting the ALL in ACL-deficient knees, the internal rotation was increased in all three knee flexion angles, 0° (p?=?0.04), 30° (p?=?0.03) and 60° (p?<?0.01) by 1.0°, 1.6° and 2.5°, respectively. However, no decrease in laxity was found after reconstructing the ALL in ACL-reconstructed knees.

Conclusions

The ALL was confirmed as a stabiliser of internal rotation in ACL-deficient knees. However, reconstructing the ALL using a gracilis autograft tendon did not decrease the internal rotation laxity in the ACL-reconstructed knee. Based on the results of this study, we do not recommend reconstructing the ALL in ACL-reconstructed knees to decrease internal knee laxity.