Reproductive and hormonal patterns in the African green monkey (Cercopithecus aethiops).

The results of breeding Cercopithecus aethiops under time-mated laboratory conditions and analysis of total estrogen, progesterone, and LH concentrations in plasma during the menstrual cycle and plasma estrogen and progesterone concentrations during pregnancy indicate that this species is a suitable alternative for the rhesus monkey as a model for investigations of reproductive function in man.     

Preventing Staphylococcus aureus sepsis through the inhibition of its agglutination in blood

Staphylococcus aureus infection is a frequent cause of sepsis in humans, a disease associated with high mortality and without specific intervention. When suspended in human or animal plasma, staphylococci are known to agglutinate, however the bacterial factors responsible for agglutination and their possible contribution to disease pathogenesis have not yet been revealed. Using a mouse model for S. aureus sepsis, we report here that staphylococcal agglutination in blood was associated with a lethal outcome of this disease. Three secreted products of staphylococci--coagulase (Coa), von Willebrand factor binding protein (vWbp) and clumping factor (ClfA)--were required for agglutination. Coa and vWbp activate prothrombin to cleave fibrinogen, whereas ClfA allowed staphylococci to associate with the resulting fibrin cables. All three virulence genes promoted the formation of thromboembolic lesions in heart tissues. S. aureus agglutination could be disrupted and the lethal outcome of sepsis could be prevented by combining dabigatran-etexilate treatment, which blocked Coa and vWbp activity, with antibodies specific for ClfA. Together these results suggest that the combined administration of direct thrombin inhibitors and ClfA-antibodies that block S. aureus agglutination with fibrin may be useful for the prevention of staphylococcal sepsis in humans.     

Steroid radiommuoassay: contribution of standards to blank values

The sensitivity of the radioimmunoassay of steroids is considerably reduced by high blank values which may be derived in part from co-chromatographed standards. Blank levels approach the detection limit of the radioimmunoassay of aldosterone, testosterone and androstenedione when 10,000 dpm (30–35 pg) labeled steroids are used as reference standard. When 20 μg aldosterone, testosterone, or androstenedione is used as standard, blank levels of up to 12,800 pg were measured in the radioimmunoassay. Application of the standards on a separate strip does not improve the results. From our experiments it seems clear that contamination is transported by the solvent.     

On the Definition of Signal-To-Noise Ratio and Contrast-To-Noise Ratio for fMRI Data

Signal-to-noise ratio, the ratio between signal and noise, is a quantity that has been well established for MRI data but is still subject of ongoing debate and confusion when it comes to fMRI data. fMRI data are characterised by small activation fluctuations in a background of noise. Depending on how the signal of interest and the noise are identified, signal-to-noise ratio for fMRI data is reported by using many different definitions. Since each definition comes with a different scale, interpreting and comparing signal-to-noise ratio values for fMRI data can be a very challenging job. In this paper, we provide an overview of existing definitions. Further, the relationship with activation detection power is investigated. Reference tables and conversion formulae are provided to facilitate comparability between fMRI studies.     

CD98 marks a subpopulation of head and neck squamous cell carcinoma cells with stem cell properties

Patients with advanced head and neck squamous cell carcinomas (HNSCCs) are often treated with concomitant chemotherapy and radiotherapy, but only 50% is cured. A possible explanation for treatment failure is therapy resistance of the cancer stem cells (CSCs). The application of compounds specifically targeting these CSCs, in addition to routinely used therapeutics, would likely improve clinical outcome. We demonstrate that the previously described monoclonal antibody K984 recognizes the CD98 cell surface protein, which is specifically expressed by cells forming the squamous basal cell layer, the region where the squamous stem cells reside. Moreover, CD98 is highly resistant to the proteolytic enzymes required for CSC enrichment procedures. We show that CD98^high cells, in contrast to CD98^low cells, are able to generate tumors in immunodeficient mice, indicating that CD98^high cells have stem cell characteristics. Furthermore, the CD98^high subpopulation expresses high levels of cell cycle control and DNA repair genes, while the CD98^low fraction shows expression patterns that represent the more differentiated cells forming the bulk of the tumor. CD98 is a promising CSC enrichment marker in HNSCC. Our data support the CSC concept in head and neck cancer and the potential relevance of these cells for treatment outcome.     

Pregnant Mothers with Resolved Anxiety Disorders and Their Offspring Have Reduced Heart Rate Variability: Implications for the Health of Children

Objective

Active anxiety disorders have lasting detrimental effects on pregnant mothers and their offspring but it is unknown if historical, non-active, maternal anxiety disorders have similar effects. Anxiety-related conditions, such as reduced autonomic cardiac control, indicated by reduced heart rate variability (HRV) could persist despite disorder resolution, with long-term health implications for mothers and children. The objective in this study is to test the hypotheses that pregnant mothers with a history of, but not current anxiety and their children have low HRV, predicting anxiety-like offspring temperaments.

Methods

The participants in this case-control study consist of 56 women during their first trimester and their offspring (15 male, 29 female). Women had a history of an anxiety disorder (n=22) or no psychopathology (n=34) determined using the Mini-International Neuropsychiatric Interview. The main outcome measures were indices of autonomic cardiac control including root mean square of successive differences (RMSSD) and high frequency (HF) variability. Children’s fearfulness was also assessed using the Laboratory Temperament Assessment Battery (Lab-TAB)-Locomotor Version.

Results

HRV was lower in women and children in the past anxiety group compared to controls. HRV measures for mothers and children were positively correlated in the anxiety group only. In all children, low HRV measures at 2-4 months were associated with a higher chance of fearful behavior at 9-10 months.

Conclusions

Pregnant women with previous but not current anxiety and their children have low HRV. Children with low HRV tend to show more fearfulness. These findings have implications for identifying children at risk of anxiety disorders and point to possible underlying mechanisms of child psychopathology.     

Regulation of secretory activity in the albumen gland of the pulmonate snail Lymnaea stagnalis (L.)

The secretory activity of the albumen gland of the freshwater snail Lymnaea stagnalis was studied morphometrically (both at the light- and at the electron-microscope level) and biochemically under the following experimental conditions: (1) glandular tissue was implanted into acceptor snails and the glandular activity of the implants was compared to that of the glands of the donors and acceptors; (2) glandular activity was measured at various periods after oviposition; and (3) the activity was measured during a 24 h cycle (diurnal activity). The results indicate that cellular release of secretion material is regulated by a nervous mechanism, whereas synthetic activity is under hormonal control.     

The antitumor activity of hydrophobin SC3, a fungal protein

The use of mushroom extracts has been common practice in traditional medicine for centuries, including the treatment of cancer. Proteins called hydrophobins are very abundant in mushrooms. Here, it was examined whether they have antitumor activity. Hydrophobin SC3 of Schizophyllum commune was injected daily intraperitoneally starting 1 day after tumor induction in two tumor mouse models (sarcoma and melanoma). SC3 reduced the size and weight of the melanoma significantly, but the sarcoma seemed not affected. However, microscopic analysis of the tumors 12 days after induction revealed a strong antitumor effect of SC3 on both tumors. The mitotic activity of the tumor decreased 1.6- (melanoma) to 2.3-fold (sarcoma), while the vital mass decreased 2.3- (melanoma) to 4.3-fold (sarcoma) compared to the control. Treatment did not cause any signs of toxicity. Behavior, animal growth, and weight of organs were similar to animals injected with vehicle, and no histological abnormalities were found in the organs. In vitro cell culture studies revealed no direct cytotoxic effect of SC3 towards sarcoma cells, while cytotoxic activity was observed towards melanoma cells at a high SC3 concentration. Daily treatment with SC3 did not result in detectable levels of anti-SC3 antibodies in the plasma. Instead, a cellular immune response was observed. Incubation of spleen cells with SC3 resulted in a 1.5- to 2.5-fold increase in interleukin-10 and TNF-α mRNA levels. In conclusion, the nontoxic fungal hydrophobin SC3 showed tumor-suppressive activity possibly via immunomodulation and may be of benefit as adjuvant in combination with chemotherapy and radiation.