Inflammation markers in young post-myocardial patients exhibiting various expressions of classic coronary risk factors

OBJECTIVE: We investigated inflammation markers in young post-myocardial infarction patients exhibiting various expressions of classical risk factors. METHODS: Forty-one male patients with high (n=20) and low (n=21) expression of classical risk factors (risk of coronary events calculated by the prospective cardiovascular Munster study program high or low, respectively), on average 44 years old, who were in the stable phase after myocardial infarction (on average 20.5 months after myocardial infarction) were included in the study. The control group consisted of 25 healthy, age-matched men. The following inflammation markers were measured: leukocyte count, high-sensitive C-reactive protein, interleukin-6, tumor necrosis factor-alpha, intracellular adhesion molecule-1, vascular cellular adhesion molecule-1, selectin-P and selectin-E. RESULTS: No differences in the levels of leukocytes, high-sensitive C-reactive protein, tumor necrosis factor-alpha, intracellular adhesion molecule-1, vascular cellular adhesion molecule-1, selectin-P and selectin-E were found between the group of patients and the controls. In contrast, interleukin-6 was significantly (P<0.01) elevated in the group of patients with high [2.5 (1.9-5.3) ng/ml] and low [3.2 (1.5-8.4) ng/ml] expression of risk factors compared with the controls [1.4 (0.9-2.3) ng/ml]. Significantly, there was no difference in interleukin-6 between the two groups of patients. CONCLUSIONS: We did not find differences in inflammation markers between young post-myocardial infarction patients with or without classical risk factors. Thus, it seems that the presence of (treated) risk factors or their absence does not affect the levels of inflammation markers in the stable period after myocardial infarction. Importantly, we found similarly elevated interleukin-6 in both groups of patients, most probably indicating slight local vascular inflammation. Interleukin-6 appears to be the most suitable marker of vascular inflammation in post-myocardial infarction patients who are aggressively treated pharmacologically.     

Probing the genetic basis for thyrotropin receptor antibodies and hyperthyroidism in immunized CXB recombinant inbred mice

Immunization with adenovirus encoding the TSH receptor (TSHR) or its A-subunit induces Graves' hyperthyroidism in BALB/c and BALB/c x C57BL/6 offspring but not C57BL/6 mice. High-resolution genetic maps are available for 13 recombinant inbred CXB strains generated from BALB/c x C57BL/6 progeny by repeated brother x sister matings to establish fully inbred lines. CXB strains were studied before and after A-subunit adenovirus immunization for TSHR antibodies (TBI, inhibition of TSH binding), serum T4, and thyroid histology. All strains developed TBI activity (at variable levels), six strains became hyperthyroid, and one was overtly thyrotoxic. No low TBI responders became hyperthyroid, but high TBI did not predict hyperthyroidism. Preimmunization T4 levels varied in different CXB strains and was unrelated to subsequent T4 elevation. Linkage analysis indicated that different chromosomes were involved in generating TSHR antibodies and serum T4 before and after immunization. TBI activity was linked in part with major histocompatibility (MHC) genes on chromosome 17 (Chr 17) but induced Graves' disease involved non-MHC genes (Chr 19 and 10). The Chr 10 locus is close to the Trhde gene that encodes TSH-releasing hormone degrading enzyme. Expression of Trhde is controlled by thyroid hormones and linkage with a thyroid function-related gene is intriguing. Our data, the first genome scan in murine Graves' disease, provides insight into the role of MHC and non-MHC genes in human and murine Graves' disease. Finally, our study demonstrates the potential of recombinant inbred mice for discriminating between immune-response genes and thyroid function susceptibility genes in Graves' disease.     

A left-sided asymptomatic supraclavicular cystic mass in a 14-year-old girl

A 14-year-old girl was referred to our department with a 3-month history of an asymptomatic swelling in the left cervical triangle. The girl, an active ski jumper, was used to carrying her skis on the left shoulder. There was a history of many minor falls and contusions of her body. The left posterior cervical triangle was enlarged by an elastic, partially fluctuating and clearly delineated swelling with 4–6 cm in diameter. The trapezius was elevated and the overlaying skin was intact. It was clear that the mass was spreading infraclavicularly. Nevertheless, the distal boundaries of the mass were not quite clear (Fig. 1). The infraclavicular spreading was confirmed with an ultrasound examination which revealed a hypoechogenic echo-free mass of the size of 7–10 × 3.6 cm. The mass was sonocompressible, clearly outlined and there were no signs of any infiltrating growth. No internal perfusion was found by colour-coded Doppler investigation. The blood count or biochemical tests did not reveal any pathological findings.     

Molecular noise of capping protein binding induces macroscopic instability in filopodial dynamics

Capping proteins are among the most important regulatory proteins involved in controlling complicated stochastic dynamics of filopodia, which are dynamic finger-like protrusions used by eukaryotic motile cells to probe their environment and help guide cell motility. They attach to the barbed end of a filament and prevent polymerization, leading to effective filament retraction due to retrograde flow. When we simulated filopodial growth in the presence of capping proteins, qualitatively different dynamics emerged, compared with actin-only system. We discovered that molecular noise due to capping protein binding and unbinding leads to macroscopic filopodial length fluctuations, compared with minuscule fluctuations in the actin-only system. Thus, our work shows that molecular noise of signaling proteins may induce micrometer-scale growth–retraction cycles in filopodia. When capped, some filaments eventually retract all the way down to the filopodial base and disappear. This process endows filopodium with a finite lifetime. Additionally, the filopodia transiently grow several times longer than in actin-only system, since less actin transport is required because of bundle thinning. We have also developed an accurate mean-field model that provides qualitative explanations of our numerical simulation results. Our results are broadly consistent with experiments, in terms of predicting filopodial growth retraction cycles and the average filopodial lifetimes.     

Validity of primary motor area localization with fMRI versus electric cortical stimulation: A comparative study

Background  

Functional magnetic resonance imaging (fMRI) is a widely used method for research and visualization of the brain function. However, its clinical use is still limited. Our objective was to study fMRI reliability in localizing the primary hand motor cortex (M1) under pathological conditions caused by the proximity of a brain tumour. The results were then compared with standard technique of cortical function mapping—electric cortical stimulation (ECS).     

Reconstruction of elbow flexion in arthrogryposis multiplex congenita type I. Part I: surgical anatomy and vascular and nerve supply of the pectoralis major muscle as a basis for muscle transfer

Purpose  The anatomy and neurovascular supply of the pectoralis major muscle was studied in order to establish the safe and functional muscle transfer for the reconstruction of elbow flexion in patients with arthrogryposis multiplex congenita (AMC). Methods  Twenty pectoralis major muscles were dissected in 11 adult cadavers. The distribution of the motor end plates was studied in five pectoralis major muscles in foetuses by the detection of esterases. Results  The pectoralis major muscle consists of clavicular, manubrial, sternocostal, costal and abdominal parts. Each part has a distinct vascular and nerve supply. The motor nerves arise from the medial and lateral pectoral nerves. The motor end plates are localised in one zone in the clavicular and manubrial parts and in two oblique zones in the distal parts of the muscle. In 15 cases, each of the muscle parts were supplied by one nerve branch. In four cases, six nerves were distinguished and the clavicular part was supplied by two nerves. In one case, four nerves were found, with the clavicular and manubrial parts supplied by one common nerve. Three branches (13 cases) or two arterial branches (seven cases) supplied the muscle, arising from thoracoacromial and lateral thoracic arteries, respectively. The superior branch supplied the clavicular and manubrial parts, whereas the dominant pectoral branch supplied the manubrial, sternocostal and costal parts of the muscle. The inferior branch of the lateral thoracic artery supplied the abdominal part in 13 cases. In seven cases, the inferior branch failed and the abdominal part was supplied from the dominant branch. Conclusion  This study presents guidelines for the transfer of the distal parts of the pectoralis major muscle for the reconstruction of elbow flexion. The sternocostal, costal and abdominal parts of the muscle can be released as a unit from the chest wall after dissection between the second and third rib and be transferred to the brachium. They are sufficiently supplied from the dominant pectoral branch of the thoracoacromial artery in all cases and inconstantly from the inferior branch of the lateral thoracic artery and from three motor nerves.     

Deletion of a conserved noncoding sequence in Plzf intron leads to Plzf down‐regulation in limb bud and polydactyly in the rat

Lx mutation in SHR.Lx rat manifests in homozygotes as hindlimb preaxial polydactyly. It was previously mapped to a chromosome 8 segment containing the Plzf gene. Plzf (promyelocytic leukemia zinc finger protein) influences limb development as a direct repressor of posterior HoxD genes. However, the Plzf coding sequence is intact in the Lx mutants. Using linkage mapping in F2 hybrids, we downsized the segment containing Lx to 155 kb and sequenced conserved noncoding elements (CNEs) inside. A 2,964‐bp deletion in Plzf intron 2, never detected in control animals, is the only candidate for Lx. The deletion removes the most deeply conserved CNE in the 155‐kb segment, suggesting a regulatory influence on Plzf expression. Correspondingly, using in situ hybridization and quantitative real‐time polymerase chain reaction, we found a decrease of Plzf expression in Lx/Lx limb buds with concomitant anterior expansion of expression domains of its targets, Hoxd10–13 genes, in the absence of ectopic Sonic hedgehog expression. Upstream regulation of Plzf in limb buds is currently unknown. We present here the first candidate Plzf cis‐regulatory sequence. Developmental Dynamics 238:673–684, 2009. © 2009 Wiley‐Liss, Inc.     

Intra-abdominal drainage following pancreatic resection: A systematic review

AIM: To study all the aspects of drain management in pancreatic surgery.METHODS: We conducted a systematic review according to the PRISMA guidelines. We searched the Cochrane Central Registry of Controlled Trials, EMBASE, Web of Science, and PubMed (MEDLINE) for relevant articles on drain management in pancreatic surgery. The reference lists of relevant studies were screened to retrieve any further studies. We included all articles that reported clinical studies on human subjects with elective pancreatic resection and that compared various strategies of intra-abdominal drain management, such as drain vs no drain, selective drain use, early vs late drain extraction, and the use of different types of drains.RESULTS: A total of 19 studies concerned with drain management in pancreatic surgery involving 4194 patients were selected for this systematic review. We included studies analyzing the outcomes of pancreatic resection with and without intra-abdominal drains, studies comparing early vs late drain removal and studies analyzing different types of drains. The majority of the studies reporting equal or superior results for pancreatic resection without drains were retrospective and observational with significant selection bias. One recent randomized trial reported higher postoperative morbidity and mortality with routine omission of intra-abdominal drains. With respect to the timing of drain removal, all of the included studies reported superior results with early drain removal. Regarding the various types of drains, there is insufficient evidence to determine which type of drain is more suitable following pancreatic resection.CONCLUSION: The prophylactic use of drains remains controversial. When drains are used, early removal is recommended. Further trials comparing types of drains are ongoing.     

Identification of Hepatitis C Virus Inhibitors Targeting Different Aspects of Infection Using a Cell-Based Assay

With 2 to 3% of the worldwide population chronically infected, hepatitis C virus (HCV) infection continues to be a major health care burden. Unfortunately, current interferon-based treatment options are not effective in all patients and are associated with significant side effects. Consequently, there is an ongoing need to identify and develop new anti-HCV therapies. Toward this goal, we previously developed a cell-based HCV infection assay for antiviral compound screening based on a low-multiplicity-of-infection approach that uniquely allows for the identification of antiviral compounds that target cell culture-derived HCV (HCVcc) at any step of the viral infection cycle. Using this assay, here we report the screening of the NCI Diversity Set II library, containing 1,974 synthesized chemical compounds, and the identification of compounds with specific anti-HCV activity. In combination with toxicity counterscreening, we identified 30 hits from the compound library, 13 of which showed reproducible and dose-dependent inhibition of HCV with mean therapeutic indices (50% cytotoxic concentration [CC₅₀]/50% effective concentration [EC₅₀]) of greater than 6. Using HCV pseudotype and replicon systems of multiple HCV genotypes, as well as infectious HCVcc-based assembly and secretion analysis, we determined that different compounds within this group of candidate inhibitors target different steps of viral infection. The compounds identified not only will serve as biological probes to study and further dissect the biology of viral infection but also should facilitate the development of new anti-HCV therapeutic treatments.