Distant metastases of a squamous cell carcinoma of the tongue in peripheral skeletal muscles and adjacent soft tissues

A 66-year-old female patient was admitted to our department with a large tumor of the tongue measuring 10 cm in diameter. The tumor occupied nearly the entire oral cavity and showed exophytic and ulcerative areas. Histological analysis revealed a low grade squamous cell carcinoma (SCC) of the tongue. Bilateral enlarged cervical lymphatic masses were also present. The extent of the tumor infiltration was assessed by fluoro-2-deoxy-glucose-positron emission tomography (PET) scans showing an elevated activity of the tracer corresponding to the assumed cervical metastases. Additionally, pulmonary metastases were identified. Contrast enhanced computed tomography (CT) scans showed metastases in the soft tissues of the abdomen, legs and arms. Foci of distant metastases were found in the left upper anterior thoracal wall, near the intraabdominal portion of the aorta, near the right iliac crest and in both the right vastus medialis- and adductor magnus muscles. The final diagnosis was a T4N3M1(G3)(C3) SCC of the tongue with multiple distant thoracal, abdominal and intramuscular metastases. The survival expectancy was five weeks, and the patient finally deceased by cardiopulmonary complications

Altered expression of the TCR signaling related genes CD3 and FcεRIγ in patients with aplastic anemia

<p>Abstract</p> <p>Background</p> <p>Aplastic anemia (AA) is characterized by pancytopenia and bone marrow hypoplasia, which results from immune-mediated hematopoiesis suppression. Understanding the pathophysiology of the immune system, particularly T cells immunity, has led to improved AA treatment over the past decades. However, primary and secondary failure after immunosuppressive therapy is frequent. Thus, knowledge of the immune mechanisms leading to AA is crucial to fundamentally understand the disease.</p> <p>Findings</p> <p>To elucidate the T cell receptor (TCR) signal transduction features in AA, the expression levels of CD3γ, δ, ε and ζ chain and FcεRIγ genes, which are involved in TCR signal transduction, and the negative correlation of the expression levels between the CD3ζ and FcεRIγ genes in T cells from peripheral blood mononuclear cells (PBMCs) were analyzed. Real-time RT-PCR using the SYBR Green method was used to detect the expression level of these genes in PBMCs from 18 patients with AA and 14 healthy individuals. The β2microglobulin gene (β2M) was used as an endogenous reference. The expression levels of the CD3γ, CD3δ, CD3ε and CD3ζ genes in patients with AA were significantly increased compared to a healthy control group, whereas the FcεRIγ gene expression level was significantly decreased in patients with AA in comparison with the healthy control group. Moreover, the negative correlation of the expression levels between the CD3ζ and FcεRIγ genes was lost.</p> <p>Conclusions</p> <p>To our knowledge, this is the first report of the CD3γ, CD3δ, CD3ε, CD3ζ and FcεRIγ gene expression in patients with AA. The abnormally expressed TCR signaling related genes may relate to T cells dysfunction in AA.</p

1H, 13C, 15N backbone resonance assignments of the apo and holo forms of the ABC transporter solute binding protein PiuA from Streptococcus pneumoniae

Streptococcus pneumoniae is a Gram-positive human pathogen that causes millions of infections worldwide with an increasing occurrence of antibiotic resistance. Iron acquisition is essential for its survival and virulence, especially under host-imposed nutritional immunity. S. pneumoniae expresses several ATP-binding cassette (ABC) transporters to facilitate acquisition under iron limitation, including PitABCD, PiaABCD, and PiuBCDA. The substrate specificity of PiuBCDA is not fully established. Herein, we report the backbone 1H, 13C and 15N resonance assignments of the 31 kDa soluble, extracellular domain of the substrate binding protein PiuA in the apo form and in complex with Ga(III) and the catechol siderophore-mimic 4-LICAM. These studies provide valuable information for further functional studies of interactions with other proteins, metals, and small molecules

Association of depressive disorders, depression characteristics and antidepressant medication with inflammation

Growing evidence suggests that immune dysregulation may be involved in depressive disorders, but the exact nature of this association is still unknown and may be restricted to specific subgroups. This study examines the association between depressive disorders, depression characteristics and antidepressant medication with inflammation in a large cohort of controls and depressed persons, taking possible sex differences and important confounding factors into account. Persons (18–65 years) with a current (N=1132) or remitted (N=789) depressive disorder according to DSM-IV criteria and healthy controls (N=494) were selected from the Netherlands Study of Depression and Anxiety. Assessments included clinical characteristics (severity, duration and age of onset), use of antidepressant medication and inflammatory markers (C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α)). After adjustment for sociodemographics, currently depressed men, but not women, had higher levels of CRP (1.33 versus 0.92 mg l−1, P<0.001, Cohen's d=0.32) and IL-6 (0.88 versus 0.72 pg ml−1, P=0.01, Cohen's d=0.23) than non-depressed peers. Associations reduced after considering lifestyle and disease indicators — especially body mass index — but remained significant for CRP. After full adjustment, highest inflammation levels were found in depressed men with an older age of depression onset (CRP, TNF-α). Furthermore, inflammation was increased in men using serotonin–norepinephrine reuptake inhibitors (CRP, IL-6) and in men and women using tri- or tetracyclic antidepressants (CRP), but decreased among men using selective serotonin reuptake inhibitors (IL-6). In conclusion, elevated inflammation was confirmed in depressed men, especially those with a late-onset depression. Specific antidepressants may differ in their effects on inflammation

Financial Incentive Increases CPAP Acceptance in Patients from Low Socioeconomic Background

OBJECTIVE: We explored whether financial incentives have a role in patients' decisions to accept (purchase) a continuous positive airway pressure (CPAP) device in a healthcare system that requires cost sharing. DESIGN: Longitudinal interventional study. PATIENTS: The group receiving financial incentive (n = 137, 50.8±10.6 years, apnea/hypopnea index (AHI) 38.7±19.9 events/hr) and the control group (n = 121, 50.9±10.3 years, AHI 39.9±22) underwent attendant titration and a two-week adaptation to CPAP. Patients in the control group had a co-payment of $330-660; the financial incentive group paid a subsidized price of$55. RESULTS: CPAP acceptance was 43% greater (p = 0.02) in the financial incentive group. CPAP acceptance among the low socioeconomic strata (n = 113) (adjusting for age, gender, BMI, tobacco smoking) was enhanced by financial incentive (OR, 95% CI) (3.43, 1.09-10.85), age (1.1, 1.03-1.17), AHI (>30 vs. <30) (4.87, 1.56-15.2), and by family/friends who had positive experience with CPAP (4.29, 1.05-17.51). Among average/high-income patients (n = 145) CPAP acceptance was affected by AHI (>30 vs. <30) (3.16, 1.14-8.75), living with a partner (8.82, 1.03-75.8) but not by the financial incentive. At one-year follow-up CPAP adherence was similar in the financial incentive and control groups, 35% and 39%, respectively (p = 0.82). Adherence rate was sensitive to education (+yr) (1.28, 1.06-1.55) and AHI (>30 vs. <30) (5.25, 1.34-18.5). CONCLUSIONS: Minimizing cost sharing reduces a barrier for CPAP acceptance among low socioeconomic status patients. Thus, financial incentive should be applied as a policy to encourage CPAP treatment, especially among low socioeconomic strata patients

Neuronal nitric oxide synthase contributes to the regulation of hematopoiesis

Nitric oxide (NO) signaling is important for the regulation of hematopoiesis. However, the role of individual NO synthase (NOS) isoforms is unclear. Our results indicate that the neuronal NOS isoform (nNOS) regulates hematopolesis in vitro and in vivo. nNOS is expressed in adult bone marrow and fetal liver and is enriched in stromal cells. There is a strong correlation between expression of nNOS in a panel of stromal cell lines established from bone marrow and fetal liver and the ability of these cell lines to support hematopoietic stem cells; furthermore, NO donor can further increase this ability. The number of colonies generated in vitro from the bone marrow and spleen of nNOS-null mutants is increased relative to wild-type or inducible- or endothelial NOS knockout mice. These results describe a new role for nNOS beyond its action in the brain and muscle and suggest a model where nNOS, expressed in stromal cells, produces NO which acts as a paracrine regulator of hematopoietic stem cells

Weak temperature dependence of P (+) H A (-) recombination in mutant Rhodobacter sphaeroides reaction centers

International audienceIn contrast with findings on the wild-type Rhodobacter sphaeroides reaction center, biexponential P (+) H A (-) → PH A charge recombination is shown to be weakly dependent on temperature between 78 and 298 K in three variants with single amino acids exchanged in the vicinity of primary electron acceptors. These mutated reaction centers have diverse overall kinetics of charge recombination, spanning an average lifetime from ~2 to ~20 ns. Despite these differences a protein relaxation model applied previously to wild-type reaction centers was successfully used to relate the observed kinetics to the temporal evolution of the free energy level of the state P (+) H A (-) relative to P (+) B A (-) . We conclude that the observed variety in the kinetics of charge recombination, together with their weak temperature dependence, is caused by a combination of factors that are each affected to a different extent by the point mutations in a particular mutant complex. These are as follows: (1) the initial free energy gap between the states P (+) B A (-) and P (+) H A (-) , (2) the intrinsic rate of P (+) B A (-) → PB A charge recombination, and (3) the rate of protein relaxation in response to the appearance of the charge separated states. In the case of a mutant which displays rapid P (+) H A (-) recombination (ELL), most of this recombination occurs in an unrelaxed protein in which P (+) B A (-) and P (+) H A (-) are almost isoenergetic. In contrast, in a mutant in which P (+) H A (-) recombination is relatively slow (GML), most of the recombination occurs in a relaxed protein in which P (+) H A (-) is much lower in energy than P (+) H A (-) . The weak temperature dependence in the ELL reaction center and a YLH mutant was modeled in two ways: (1) by assuming that the initial P (+) B A (-) and P (+) H A (-) states in an unrelaxed protein are isoenergetic, whereas the final free energy gap between these states following the protein relaxation is large (~250 meV or more), independent of temperature and (2) by assuming that the initial and final free energy gaps between P (+) B A (-) and P (+) H A (-) are moderate and temperature dependent. In the case of the GML mutant, it was concluded that the free energy gap between P (+) B A (-) and P (+) H A (-) is large at all times