Expression of mRNAs related to connective tissue metabolism in rat hepatic stellate cells and myofibroblasts

Hepatic stellate cells (HSC) and liver myofibroblasts (MFB) are two cell populations most likely responsible for the synthesis of most connective tissue components in fibrotic liver. They differ in their origin and location, and possibly in patterns of gene expression. Normal and carbon tetrachloride-cirrhotic livers from rats were used to isolate HSC. Liver was perfused with pronase and collagenase solutions, followed by centrifugation of the cell suspension on a density gradient. HSC were quiescent 2 days after plating on plastic but they became activated after another 5 days in culture. When the culture was passaged 5 times, its character changed profoundly as HSC were replaced by MFB. Microarray analysis was used to determine gene expression in quiescent HSC, activated HSC and MFB. The expression of 49 genes coding for connective tissue proteins, proteoglycans, metalloproteinases and their inhibitors, growth factors and cellular markers was determined. The pattern of gene expression changed during HSC activation and there were distinct differences between HSC and MFB. Little difference between normal cells and cells isolated from cirrhotic liver was found.     

Analysis of LMNB1 Duplications in Autosomal Dominant Leukodystrophy Provides Insights into Duplication Mechanisms and Allele‐Specific Expression

Autosomal dominant leukodystrophy (ADLD) is an adult onset demyelinating disorder that is caused by duplications of the lamin B1 (LMNB1) gene. However, as only a few cases have been analyzed in detail, the mechanisms underlying LMNB1 duplications are unclear. We report the detailed molecular analysis of the largest collection of ADLD families studied, to date. We have identified the minimal duplicated region necessary for the disease, defined all the duplication junctions at the nucleotide level and identified the first inverted LMNB1 duplication. We have demonstrated that the duplications are not recurrent; patients with identical duplications share the same haplotype, likely inherited from a common founder and that the duplications originated from intrachromosomal events. The duplication junction sequences indicated that nonhomologous end joining or replication‐based mechanisms such fork stalling and template switching or microhomology‐mediated break induced repair are likely to be involved. LMNB1 expression was increased in patients’ fibroblasts both at mRNA and protein levels and the three LMNB1 alleles in ADLD patients show equal expression, suggesting that regulatory regions are maintained within the rearranged segment. These results have allowed us to elucidate duplication mechanisms and provide insights into allele‐specific LMNB1 expression levels.     

Microanalysis of Worn Surfaces of Selected Rotating Parts of an Internal Combustion Engine

The present paper analyzes the damage of surfaces at spots of frictional contact, namely, the friction nodes on a camshaft and the connecting rod pins of a crankshaft. The resulting wear of the monitored friction nodes reduces the technical life of the machines, which can lead to the decommissioning of the machine. Wear was assessed by measuring roughness and microhardness and by observing the microstructures of the materials. The results of the experiments show that the rotating parts displayed visible wear on the cams, as well as on the connecting rod pins. The experiments revealed that wear was caused by the heating of the material to a high temperature during the operation of the machine and that there was a gradual cooling and tempering of the material, which led to a reduction in the microhardness of the monitored object. Lower microhardness values can be a cause of greater wear of the monitored objects. When comparing the microhardness of the used and the new camshaft, the hardened layer of the new camshaft from secondary production has a significantly smaller thickness compared to worn cams, which leads to the finding of a different material quality compared to the original parts from primary production. This fact indicates that the wear of a new camshaft as a spare part can contribute to the shortening of the technical life of friction nodes.     

S-POEM in treatment of achalasia and esophageal epiphrenic diverticula – single center experience

Abstract

Background: Standard treatment for esophageal epiphrenic diverticula associated with achalasia includes surgical diverticulectomy, myotomy and anterior fundoplication. However, several case reports published recently suggest that endoscopic approach using per oral endoscopic myotomy is a safe and effective alternative.

Methods: This is a retrospective review of a single center case series of patients with achalasia and epiphrenic diverticula. During the treatment, the POEM guided on the opposite site of the diverticular neck without diverticulotomy was performed. Symptomatic outcome was evaluated 3 months after procedure and afterwards with the median follow-up time of 24 months. High resolution manometry was performed 3 months after the procedure.

Results: Seven patients with esophageal epiphrenic diverticula were included. POEM was successfully performed in all patients, with no complications in the periprocedural period. We observed a significant reduction of Eckardt score and the relaxation pressure of the lower esophageal sphincter (31.8 vs. 8.8?mmHg, p < .0001).

Conclusions: POEM is a promising approach in the management of achalasia and esophageal epiphrenic diverticula. We demonstrated its safety, efficiency and ability to provide symptom reduction and decrease of the LES relaxation pressure even without diverticulotomy. Multicentric studies on larger cohorts of patients and with longer follow-up time are required to confirm these results.     

Treatment outcome and survival in participants of phase I oncology trials carried out from 2003 to 2006 at Institut Gustave Roussy.

BACKGROUND: The oncology community usually perceives phase I oncology trials as associated with poor or limited benefits and substantial risks. There is scarce data concerning outcome and survival of patients enrolled in current phase I oncology trials. PATIENTS AND METHODS: We reviewed all phase I oncology trials conducted by investigators from the Adult Phase I Unit at Institut Gustave Roussy from 2003 to 2006. We report data concerning patient demographics, treatment outcome, toxicity, survival and type of care after trial exit. RESULTS: We analyzed 10 trials involving 180 participants. The overall response rate was 7.2%. Disease control (objective response plus stable disease) was achieved in 48.2% of patients. The rate of toxic death was 0.5%. In all, 38% of patients had at least one episode of grade 3 or 4 toxic events. The median progression-free survival and the median overall survival (OS) were 2.3 and 8.7 months, respectively. On multivariate analysis, a time between diagnosis of disease and inclusion in the phase I trial > or =24 months and evidence of disease control were statistically significant predictors of improved OS. CONCLUSION: Current phase I oncology trials are safe and are associated with clinical benefit in a substantial proportion of patients.     

Human leukocyte and fibroblast interferon in a combination therapy of dendritic keratitis

Summary Thirty-eight patients with virologically proven dendritic keratitis were treated using either debridement plus human leukocyte interferon (HLI) or debridement plus human fibroblast interferon (HFI) in a randomized, doubleblind study. We administered one drop of HLI or HFI (1×10⁶ reference units/ml) daily and found no significant difference in the action of either type of interferon.

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Zusammenfassung 38 Patienten mit virologisch verifizierter Keratitis dendritica wurden in einer randomisierten Doppelblindstudie entweder mit Abrasio plus Humanleukozyteninterferon (HLI) oder Abrasio plus Humanfibroblasteninterferon (HFI) behandelt. Nur ein Tropfen Interferon (1×10⁶ Einheiten/ml) wurde täglich gegeben. Es fand sich kein signifikanter Unterschied zwischen der Wirkung beider Interferone.

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With support from the Deutsche Forschungsgemeinschaft