Keratinocyte-releasable stratifin functions as a potent collagenase-stimulating factor in fibroblasts

Termination of wound healing requires a fine balance between collagen deposition and its hydrolysis. To dissect the underlying control mechanisms for this process, we established a keratinocyte/fibroblast co-culture system and subsequently demonstrated more than a 10-fold increase in collagenase expression in fibroblasts co-cultured with keratinocytes relative to that of control cells. This finding was further confirmed in fibroblasts grown in a keratinocyte/fibroblast collagen-GAG gel. The efficacy of keratinocyte-derived collagenase stimulatory factors on collagenase activity was evaluated, and the results showed that only conditioned medium derived from fibroblasts co-cultured with keratinocytes was able to break down markedly type I collagen to its one-quarter and three-quarter fragments of both alpha (alpha1 and alpha2) and beta (beta1.1 and beta1.2) chains. The results of a dose-response experiment showed that keratinocyte-conditioned medium (KCM) stimulates the expression of collagenase mRNA by dermal fibroblasts in a concentration-dependent fashion. In a similar experiment, the results of a time-response experiment revealed that KCM treatment increases the expression of collagenase mRNA in dermal fibroblasts as early as 6 h and reaches its maximum level within 24-48 h. Considering that this keratinocyte-releasable factor has a potent collagenase stimulatory effect on fibroblasts, which favors the resolution of accumulated type I and type III collagen found in fibrotic tissue, we referred to this protein as a keratinocyte-derived anti-fibrogenic factor (KDAF). In a series of chromatography experiments and a direct trypsin digestion of the proteins and subsequent peptide mapping, a keratinocyte-derived collagenase-stimulating factor turned out to be a releasable form of stratifin, also known as 14-3-3 sigma protein. To validate this finding, stratifin cDNA was cloned into a pGEX-6P-1 expressing vector and more than 50 mg of recombinant stratifin was generated and used to treat fibroblasts with various concentrations for 24 h. The results of northern analysis showed a remarkable dose-response increase in the expression of collagenase mRNA in stratifin-treated fibroblasts relative to that of the control. This finding was consistent with that obtained from collagenase activity assay. In conclusion, we identified a keratinocyte-releasable form of stratifin in KCM that mimics the collagenase stimulatory effect of KCM for dermal fibroblasts. This finding suggests that stratifin is likely to be, at least, one of the KDAFs found in KCM.     

Immediate postoperative arrhythmias follwing pneumonectomy for lung cancer

Immediate postoperative arrhythmias after pneumonectomy for non small cell lung cancer is a serious complication. Frequency is estimated 10 to 28% of all patients. The goal of this study is to evaluate the incidence of this complication in our experience, preoperative risk factors, therapeutic implications and short outcome. 132 consecutive patients underwent pneumonectomy for lung cancer. We retrospectively studied this series of which 29 patients developed arrhythmias postoperatively. Mean age was 58 years (48 to 79), 16 patients were older than 65 years. Seven patients had medical history of either myocardial infarction or hypertension. Arrhythmias appeared post-operatively on days 1 and 2 six times, days 3 ans 4 ten times, days 5 to 6 six times and days 7 to 10 twice. The trouble consisted in atrial fibrillation in 18 patients, atrial associated with ventricular premature beats in 11 patients. Antiarrhythmic medication (amiodarone) was started as soon as the trouble was confirmed by EKG in all cases. Normalization was obtained in 27 patients (95%). One patient remained dysrrhythmic in spite of treatment. One death occurred on day 4 postoperatively. The mean hospitalisation stay was 10 days. CONCLUSION: Cardiac arrhythmia in the immediate postoperative course is not rare. Early diagnosis in patients at risk followed by adequat treatment is necessary to avoid haemodynamic storm in these quite fragile patients. Amiodarone is the treatment of choice.     

Gliosarcoma Metastatic to the Leptomeninges and Dura

We describe a rare case of a patient with left frontotemporal gliosarcoma, which metastasized through the cerebrospinal fluid (CSF) to the leptomeninges and pachymeninges. Pathologically confirmed, magnetic resonance imaging‐visible leptomeningeal spread of gliosarcoma via the CSF has not been previously reported.     

Épilepsie temporale symptomatique d’une méningocèle intracrânienne chez une patiente atteinte de neurofibromatose de type 1

Epilepsy has been rarely reported in patients with neurofibromatosis type 1 (formally known as von Recklinghausen disease), which may occur in 3 to 6% of cases. This condition is generally related to neuronal migration anomalies or cortical malformations. We report a case of temporal epilepsy secondary to temporal meningocele due to sphenoidal dysplasia in a patient who presented with neurofibromatosis type 1 and also discuss this association.     

Morphokinetic parameters using time-lapse technology and day 5 embryo quality: a prospective cohort study

PurposeThe aims of this prospective study were to evaluate whether time-lapse parameters can aid in the prediction of day 5 embryo quality and also to assess their discriminatory capacity.MethodsIn this prospective cohort study, we used time-lapse technology to record specific timings of key events for 380 day 5 blastocysts (originating from 108 patients). Generalized estimating equation regression models were used to evaluate the capacity of these markers to identify a top-quality blastocyst. Multivariable regression models were also constructed, aiming to identify the model with the highest capacity to predict a top-quality blastocyst. The discriminatory capacity of single predictors or composite models was assessed with the use of receiver operating characteristic (ROC) analyses.ResultsEight significant predictive parameters of a top-quality blastocyst were identified: s3, t6, t7, t8, tM, tSB, tB and tEB. A ROC analysis of the identified parameters found s3 (area under the curve—AUC 0.585, 95 % CI 0.534–0.635) to have the best individual discriminatory capacity to predict a top-quality blastocyst prior to embryo compaction. The parameter tEB (AUC 0.727, 95 % CI 0.675–0.775) was the best predictor regardless of embryo stage. A model containing s3, t8 and tEB showed a slightly increased discriminatory capacity for top-quality blastocyst prediction (AUC 0.748, 95 % CI 0.697–0.794).ConclusionsThe identified morphokinetic parameters and their cutoffs, albeit of limited clinical value, add to the increasing knowledge concerning the potential predictive markers of a top-quality blastocyst. Additional evidence is necessary before validated time-lapse parameters can be used for embryo selection in IVF laboratories.     

Lung carcinosarcoma. A case report

Carcinosarcoma of the lung is a rare highly malignant tumor of unknown histogenesis. There is an epithelial carcinomatous component and a malignant mesenchmatous component with heterologous tissue. Survival at two years after surgical resection is not greater than 10%. We report a case observed in a 71-year-old man who developed chest pain. Outcome was fatal at three months. Pathology examination of a transparietal biopsy provided the diagnosis which was confirmed by immunohistochemistry on the surgical resection specimen.