Fibrin regulates neutrophil migration in response to interleukin 8, leukotriene B4, tumor necrosis factor, and formyl-methionyl-leucyl-phenylalanine

We have examined the capacity of four different chemoattractants/cytokines to promote directed migration of polymorphonuclear leukocytes (PMN) through three-dimensional gels composed of extracellular matrix proteins. About 20% of PMN migrated through fibrin gels and plasma clots in response to a gradient of interleukin 8 (IL-8) or leukotriene B4 (LTB4). In contrast, < 0.3% of PMN migrated through fibrin gels in response to a gradient of tumor necrosis factor alpha (TNF) or formyl-methionyl-leucyl-phenylalanine (FMLP). All four chemoattractants stimulated PMN to migrate through gels composed of collagen IV or of basement membrane proteins (Matrigel), or through filters to which fibronectin or fibrinogen had been adsorbed. PMN stimulated with TNF or FMLP adhered and formed zones of close apposition to fibrin, as measured by the exclusion of a 10-kD rhodamine-polyethylene glycol probe from the contact zones between PMN and the underlying fibrin gel. By this measure, IL-8- or LTB4-treated PMN adhered loosely to fibrin, since 10 kD rhodamine-polyethylene glycol permeated into the contact zones between these cells and the underlying fibrin gel. PMN stimulated with FMLP and IL-8, or FMLP and LTB4, exhibited very little migration through fibrin gels, and three times as many of these cells excluded 10 kD rhodamine-polyethylene glycol from their zones of contact with fibrin as PMN stimulated with IL-8 or LTB4 alone. These results show that PMN chemotaxis is regulated by both the nature of the chemoattractant and the composition of the extracellular matrix; they suggest that certain combinations of chemoattractants and matrix proteins may limit leukocyte movements and promote their localization in specific tissues in vivo

Exponential Distribution of Locomotion Activity in Cell Cultures

In vitro velocities of several cell types have been measured using computer controlled video microscopy, which allowed to record the cells' trajectories over several days. On the basis of our large data sets we show that the locomotion activity displays a universal exponential distribution. Thus, motion resulting from complex cellular processes can be well described by an unexpected, but very simple distribution function. A simple phenomenological model based on the interaction of various cellular processes and finite ATP production rate is proposed to explain these experimental results.Comment: 4 pages, 3 figure

Relativistic effects and two-body currents in 2H(e⃗,e′p)n^{2}H(\vec{e},e^{\prime}p)n using out-of-plane detection

Measurements of the ${^2}H(\vec{e},e^{\prime}p)n$ reaction were performed using an 800-MeV polarized electron beam at the MIT-Bates Linear Accelerator and with the out-of-plane magnetic spectrometers (OOPS). The longitudinal-transverse, $f_{LT}$ and $f_{LT}^{\prime}$, and the transverse-transverse, $f_{TT}$, interference responses at a missing momentum of 210 MeV/c were simultaneously extracted in the dip region at Q$^2$=0.15 (GeV/c)$^2$. On comparison to models of deuteron electrodisintegration, the data clearly reveal strong effects of relativity and final-state interactions, and the importance of the two-body meson-exchange currents and isobar configurations. We demonstrate that these effects can be disentangled and studied by extracting the interference response functions using the novel out-of-plane technique.Comment: 4 pages, 4 figures, and submitted to PRL for publicatio

A Measurement of the Interference Structure Function, R_LT, for the 12C(e,e'p) reaction in the Quasielastic Region

The coincidence cross-section and the interference structure function, R_LT, were measured for the 12C(e,e'p) 11B reaction at quasielastic kinematics and central momentum transfer of q=400 MeV/c. The measurement was at an opening angle of theta_pq=11 degrees, covering a range in missing energy of E_m = 0 to 65 MeV. The R_LT structure function is found to be consistent with zero for E_m > 50 MeV, confirming an earlier study which indicated that R_L vanishes in this region. The integrated strengths of the p- and s-shell are compared with a Distorted Wave Impulse Approximation calculation. The s-shell strength and shape are compared with a Hartree Fock-Random Phase Approximation calculation. The DWIA calculation overestimates the cross sections for p- and s-shell proton knockout as expected, but surprisingly agrees with the extracted R_LT value for both shells. The HF-RPA calculation describes the data more consistently, which may be due to the inclusion of 2-body currents in this calculation.Comment: 8 Pages LaTex, 5 postscript figures. Submitted to Phys. Rev.

Multiparametric, Longitudinal Optical Coherence Tomography Imaging Reveals Acute Injury and Chronic Recovery in Experimental Ischemic Stroke

Progress in experimental stroke and translational medicine could be accelerated by high-resolution in vivo imaging of disease progression in the mouse cortex. Here, we introduce optical microscopic methods that monitor brain injury progression using intrinsic optical scattering properties of cortical tissue. A multi-parametric Optical Coherence Tomography (OCT) platform for longitudinal imaging of ischemic stroke in mice, through thinned-skull, reinforced cranial window surgical preparations, is described. In the acute stages, the spatiotemporal interplay between hemodynamics and cell viability, a key determinant of pathogenesis, was imaged. In acute stroke, microscopic biomarkers for eventual infarction, including capillary non-perfusion, cerebral blood flow deficiency, altered cellular scattering, and impaired autoregulation of cerebral blood flow, were quantified and correlated with histology. Additionally, longitudinal microscopy revealed remodeling and flow recovery after one week of chronic stroke. Intrinsic scattering properties serve as reporters of acute cellular and vascular injury and recovery in experimental stroke. Multi-parametric OCT represents a robust in vivo imaging platform to comprehensively investigate these properties

Brachytherapy for rhabdomyosarcoma: Survey of international clinical practice and development of guidelines.

BACKGROUND AND PURPOSE: The purpose of this study was to address the lack of published data on the use of brachytherapy in pediatric rhabdomyosarcoma by describing current practice as starting point to develop consensus guidelines. MATERIALS AND METHODS: An international expert panel on the treatment of pediatric rhabdomyosarcoma comprising 24 (pediatric) radiation oncologists, brachytherapists and pediatric surgeons met for a Brachytherapy Workshop hosted by the European paediatric Soft tissue Sarcoma Study Group (EpSSG). The panel's clinical experience, the results of a previously distributed questionnaire, and a review of the literature were presented. RESULTS: The survey indicated the most common use of brachytherapy to be in combination with tumor resection, followed by brachytherapy as sole local therapy modality. HDR was increasingly deployed in pediatric practice, especially for genitourinary sites. Brachytherapy planning was mostly by 3D imaging based on CT. Recommendations for patient selection, treatment requirements, implant technique, delineation, dose prescription, dose reporting and clinical management were defined. CONCLUSIONS: Consensus guidelines for the use of brachytherapy in pediatric rhabdomyosarcoma have been developed through multicenter collaboration establishing the basis for future work. These have been adopted for the open EpSSG overarching study for children and adults with Frontline and Relapsed RhabdoMyoSarcoma (FaR-RMS)