Inhibition of CXCR4-CXCL12 chemotaxis in melanoma by AMD11070.

BACKGROUND: Despite intensive research and novel adjuvant therapies, there is currently no cure for metastatic melanoma. The chemokine receptor CXCR4 controls metastasis to sites such as the liver; however, the therapeutic blockade with the existing agents has proven difficult. METHODS: AMD11070, a novel orally bioavailable inhibitor of CXCR4, was tested for its ability to inhibit the migration of melanoma cells compared with the commonly described antagonist AMD3100. RESULTS: AMD11070 abrogated melanoma cell migration and was significantly more effective than AMD3100. Importantly for the clinical context, the expression of B-RAF-V600E did not the affect the sensitivity of AMD11070. CONCLUSION: Liver-resident myofibroblasts excrete CXCL12, which is able to promote the migration of CXCR4-expressing tumour cells from the blood into the liver. Blockade of this axis by AMD11070 thus represents a novel therapeutic strategy for both B-RAF wild-type and mutated melanomas.

Multicrystal designs for efficient third-harmonic generation.

Efficient frequency tripling of high-fluence, narrow-band laser pulses is routinely accomplished with a doubling crystal and a sum-frequency mixer. The addition of a second mixer can dramatically improve conversion efficiencies for the large bandwidths of interest for inertial confinement fusion. Designs that involve two doublers similarly offer a higher dynamic range of conversion efficiency versus intensity than the usual two-crystal design.

Performance of a prototype for a large-aperture multipass Nd:glass laser for inertial confinement fusion.

The Beamlet is a single-beam prototype of future multibeam megajoule-class Nd:glass laser drivers for inertial confinement fusion. It uses a multipass main amplifier, adaptive optics, and efficient, high-fluence frequency conversion to the third harmonic. The Beamlet amplifier contains Brewster-angle glass slabs with a clear aperture of 39 cm x 39 cm and a full-aperture plasma-electrode Pockels cell switch. It has been successfully tested over a range of pulse lengths from 1-10 ns up to energies at 1.053 mum of 5.8 kJ at 1 ns and 17.3 kJ at 10 ns. A 39-actuator deformable mirror corrects the beam quality to a Strehl ratio of as much as 0.4. The 1.053-mum output has been converted to the third harmonic at efficiencies as high as 80% and fluences as high as 8.7 J/cm(2) for 3-ns pulses.

A study of human respiratory tract chlamydial infections in Cambridgeshire 1986-88.

Human respiratory tract chlamydial infections have been studied in Cambridgeshire for many years, but until recently we have been unable to distinguish between infection with Chlamydia psittaci or Chlamydia pneumoniae (TWAR). In this study, we have employed the micro-immunofluorescence (micro-IF) test for this purpose and to look for the relative incidence of C. psittaci and C. pneumoniae infections in Cambridgeshire. Among 50 patients with community-acquired respiratory tract symptoms whose serum samples had Chlamydia complement fixation test titres greater than or equal to 64, 25 had evidence of recent C. psittaci or C. pneumoniae infection. Nineteen (76%) of the 25 patients had evidence of recent C. psittaci infection and of these 16 (84%) had recently had contact with birds. Six patients (24%) had evidence of recent C. pneumoniae infection, and of these, only two (33%) had recently had contact with birds. While C. psittaci was grown from several of the birds associated with human C. psittaci infection, it was not cultured from any of the birds in contact with the two human C. pneumoniae cases.

Evaluation of Serodia Myco II particle agglutination test for detecting Mycoplasma pneumoniae antibody: comparison with mu-capture ELISA and indirect immunofluorescence.

The Serodia Myco II particle agglutination test, which the manufacturers claim exclusively detects IgM antibody, was compared with two IgM-specific tests, a mu-capture ELISA, and indirect immunofluorescence for their ability to detect recent Mycoplasma pneumoniae infection. In general there was good agreement among the three tests, all three having similar sensitivity. One hundred and nine (78%) of serum samples gave concordant results in all three assays. Several sera gave positive particle agglutination titres, however, while being negative by the two other assays, and the Serodia Myco II test may not be as specific for detecting M pneumoniae IgM as the other two tests. While the Serodia Myco II test may be a good screening assay, it is unlikely to be a definitive test for M pneumoniae IgM, but may be better than the complement fixation test, particularly in younger patients in whom M pneumoniae IgM is found more frequently.

Rise-fall ambiguities and their removal from frequency-domain nonlinear-optical techniques.

Most frequency-domain nonlinear-optical techniques measure only the magnitude of the Fourier transform of a temporal response and, hence, do not uniquely determine the response. We show that, for the commonly used response, h(t) = A exp(-t/tau(f)) + B exp(-t/tau(s)),where A identical with alpha/tau(f) and B identical with (1 - alpha)/tau(s), the spectral line shape can always be fitted by two different values of alpha. A measurement of the optical Kerr transient of carbon disulfide illustrates this ambiguitv. We also demonstrate a single-scan method that is free from such ambiguities. It involves adding coherent background with a nonzero quadrature-phase wavelength.