Mutated Desmoglein‐2 Proteins are Incorporated into Desmosomes and Exhibit Dominant‐Negative Effects in Arrhythmogenic Right Ventricular Cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a hereditary cardiac condition associated with ventricular arrhythmias, heart failure, and sudden death. The most frequent ARVC genes encode desmosomal proteins of which mutations in desmoglein‐2 (DSG2), account for 10%–20% of cases. This study aimed to investigate how DSG2 mutations contribute to the pathogenesis of ARVC. Initial mutation analysis of DSG2 in 71 probands identified the first family reported with recessively inherited ARVC due to a missense mutation. In addition, three recognized DSG2 mutations were identified in 12 families. These results and further mutation analyses of four additional desmosomal genes indicated that ARVC caused by DSG2 mutations is often transmitted by recessive or digenic inheritance. Because desmosomal proteins are also expressed in skin tissue, keratinocytes served as a cell model to investigate DSG2 protein expression by Western blotting, 2D‐PAGE, and liquid chromatography–mass spectrometry. The results showed that heterozygous mutation carriers expressed both mutated and wild‐type DSG2 proteins. These findings were consistent with the results obtained by immunohistochemistry of endomyocardial biopsies and epidermal tissue of mutation carriers, which indicated a normal cellular distribution of DSG2. The results suggested a dominant‐negative effect of the mutated DSG2 proteins because they were incorporated into the desmosomes.     

The effect of acute exercise on collagen turnover in human tendons: influence of prior immobilization period

Mechanical loading of human tendon stimulates collagen synthesis, but the relationship between acute loading responses and training status of the tendon is not clear. We tested the effect of prolonged load deprivation on the acute loading-induced collagen turnover in human tendons, by applying the same absolute load to a relative untrained Achilles tendon (2-week immobilization period prior to acute loading) and a habitually loaded contra-lateral Achilles tendon, respectively, within the same individuals. Eight untrained, healthy males had one lower limb totally immobilized for 2 weeks, whereas the contra-lateral leg was used habitually. Following the procedure both Achilles tendons and calf muscles were loaded with the same absolute load during a 1-h treadmill run. Tissue collagen turnover was measured by microdialysis performed post-immobilization but pre-exercise around both Achilles tendons and compared to values obtained by 72-h post-exercise. Power Doppler was used to monitor alterations in intratendinous blood flow velocity of the Achilles tendon and MRI used to quantitate changes in tendon cross-section area. Acute loading resulted in an increased collagen synthesis 72 h after the run in both Achilles tendons (p < 0.05) with no significant difference. No signs of acute tendon overloading were demonstrated by Power Doppler, and tendon cross-section area did not change as a result of immobilization and reloading. The present study indicates that 2 weeks of tendon load deprivation is not sufficient to affect the normal adaptive response to loading determined as increased collagen synthesis of peritendinous Achilles tendon tissue in humans.     

Analysis of outcome for elderly patients after microvascular flap surgery: a monocentric retrospective cohort study

Objectives

Increasingly, aging societies pose a challenge, particularly in the most developed countries. This trend leads to an increasing group of old and very old patients presenting unique requirements and challenges. One of these challenges consists in reassessment and adaption of established treatment strategies for the elderly patients. There is an ongoing discussion taking place among cranio-maxillo-facial surgeons about the appropriate extent of reconstructive flap surgery for old patients.

Materials and methods

This monocentric retrospective cohort study investigated 281 reconstructions with microvascular flaps by comparing the risk for a negative outcome, which was defined as revision, flap loss, and patient death, between three subgroups of elderly patients and younger patients. The three subgroups of elderly patients were defined as—1: young old (65–74 years), 2: old (75–84 years), and 3: oldest old (≥ 85 years). The group of the younger patients was defined by age between 50 and 64 years. Data were obtained within a defined period of 42 months.

Results

Significant correlations with a negative outcome were found for the variables stay on IMC/ICU, multiple flaps, and radiotherapy prior surgery. Our data showed no significant correlation between age and a higher risk for a negative outcome.

Conclusion

Defect reconstruction with microvascular flaps in old patients is not related with a higher risk for a negative outcome.

Clinical relevance

Independently of age, treatment with microvascular flaps is an option for all operable patients, with an indication for oncologic surgery. For optimal therapy planning, individual patient resources and preferences should be considered instead of chronologic age.

     

Cell Envelope and Shape of Escherichia coli K12

Rod-shaped "ghosts" that are free of murein have been isolated from E. coli. The shape of these "ghosts" is maintained by a unit membrane soluble in sodium dodecyl sulfate. Ghosts consist of about 20-30% phospholipid (almost exclusively phosphatidylethanolamine) and 50-60% protein; a large fraction of the remaining material is lipopolysaccharide. Sodium dodecyl sulfate-gel electrophoresis reveals 4-5 different bands corresponding to molecular weights between 10,000 and 40,000. Treatment of ghosts with Pronase reduces this number to 3, and the rod shape still is not lost. Results of treatment of ghosts with a crude extract from Dictyostelium discoideum have supplied tentative evidence that at least one of these proteins is involved in the maintenance of rod shape. It does not appear too unlikely that these polypeptide chains are the final products of the genetic information specifying cellular shape.