Growth-promoting effect of carbon material upon bacterial cells propagating through a distance

Carbon material such as graphite and activated charcoal, but not diamond, causes the promotion of growth of certain bacteria under ordinarily non-permissive stress conditions over a distance of several centimeters. Bacillus carboniphilus under the stress of a high KCl concentration and high temperature responded to this remote effect of carbon material with enhanced growth, and thermophile bacterium Bacillus stearothermophilus responded similarly yet moderately under the stress of low temperature. The remote effect of carbon was caused by its activation with external energy, probably of electromagnetic nature, as this effect was markedly decreased by sheltering the experimental system with an iron or aluminum barrier. Carbon material probably transforms the external oscillatory pulses or radiation into a signal exerting, far-reaching, growth-promoting effect upon cells. The most plausible candidate of signals emitted from carbon was considered to be (ultra)sonic.     

A new radioimmunoassay for human chorionic gonadotropin using monoclonal antibody

A new radioimmunoassay (RIA) for human Chorionic Gonadotropin (hCG) was developed using murine monoclonal antibody to the beta-subunit of hCG (beta-hCG). The IgG fraction of the monoclonal antibody which did not react with 125I-beta-hCG was purified from hybridoma ascites, and covalently coupled to Sepharose 4B. This solid-phase antibody was incubated with standard hCG or serum sampled for 48 hours. The reaction medium was then removed by centrifugation and 125I-beta-hCG and anti-beta-hCG rabbit polyclonal antibody were added to the precipitate. The alcohol precipitation method was used for separating "bound" and "free" forms in the second reaction. The sensitivity for hCG in this assay system was 0.5 mIU/ml serum and the cross-reactivity with human Luteinizing Hormone (hLH) was 0.4%. This assay system was shown to be clinically applicable. Serial serum samples from two patients with trophoblastic disease were assayed and minute amounts of hCG, which could not be determined by conventional assay methods, could be assayed by this new RIA.     

Different responses in skin and muscle sympathetic nerve activity to static muscle contraction

We microneurographically recorded the traffic of sympathetic nerves leading to foot volar skin activity (SSA) and leg skeletal muscle activity (MSA) during isometric handgrip and simultaneously determined sweat rate by the ventilated capsule method and skin blood flow by laser-Doppler flowmetry in the innervating area of SSA. SSA increased abruptly and was almost constant during handgrip, accompanied by an increase in sweat rate, whereas skin blood flow showed no significant change during the handgrip. MSA showed a time-dependent increase during the course of handgrip. During arterial occlusion of the working forearm after handgrip, SSA decayed to the precontraction control level, whereas MSA remained at a higher level than during control. During involuntary biceps muscle contraction induced by electrical stimulation, both SSA and MSA increased. The results suggest that the SSA response during voluntary handgrip, which was demonstrated to contain mainly sudomotor activity, might be influenced by central command and input from peripheral mechanoreceptors but be influenced little by input from muscle chemoreceptors.     

The Dual RAF/MEK Inhibitor CH5126766/RO5126766 May Be a Potential Therapy for RAS-Mutated Tumor Cells

Although melanoma is the most aggressive skin cancer, recent advances in BRAF and/or MEK inhibitors against BRAF-mutated melanoma have improved survival rates. Despite these advances, a treatment strategy targeting NRAS-mutated melanoma has not yet been elucidated. We discovered CH5126766/RO5126766 as a potent and selective dual RAF/MEK inhibitor currently under early clinical trials. We examined the activity of CH5126766/RO5126766 in a panel of malignant tumor cell lines including melanoma with a BRAF or NRAS mutation. Eight cell lines including melanoma were assessed for their sensitivity to the BRAF, MEK, or RAF/MEK inhibitor using in vitro growth assays. CH5126766/RO5126766 induced G1 cell cycle arrest in two melanoma cell lines with the BRAF V600E or NRAS mutation. In these cells, the G1 cell cycle arrest was accompanied by up-regulation of the cyclin-dependent kinase inhibitor p27 and down-regulation of cyclinD1. CH5126766/RO5126766 was more effective at reducing colony formation than a MEK inhibitor in NRAS- or KRAS-mutated cells. In the RAS-mutated cells, CH5126766/RO5126766 suppressed the MEK reactivation caused by a MEK inhibitor. In addition, CH5126766/RO5126766 suppressed the tumor growth in SK-MEL-2 xenograft model. The present study indicates that CH5126766/RO5126766 is an attractive RAF/MEK inhibitor in RAS-mutated malignant tumor cells including melanoma.