ALBERT

Description: We have investigated the direct effect of dimethyl prostaglandin A1 (dmPGA1) on the replication of herpes simplex virus (HSV) and human immunodeficiency virus type 1 (HIV-1). dmPGA1 significantly inhibited viral replication in both HSV and HIV infection systems at concentrations of dmPGA1 that did not adversely alter cellular DNA synthesis. The 50% inhibitory concentration (ID50) for several HSV type 1 (HSV-1) strains ranged from 3.8 to 5.6 micrograms/ml for Vero cells and from 4.6 to 7.3 micrograms/ml for human foreskin fibroblasts. The ID50s for two HSV-2 strains varied from 3.8 to 4.5 micrograms/ml for Vero cells; the ID50 was 5.7 micrograms/ml for human foreskin fibroblasts. We found that closely related prostaglandins did not have the same effect on the replication of HSV; dmPGE2 and dmPGA2 caused up to a 60% increase in HSV replication compared with that in untreated virus-infected cells. HIV-1 replication in acutely infected T cells (VB line) and chronically infected macrophages was assessed by quantitative decreases in p24 concentration. The effective ID50s were 2.5 micrograms/ml for VB cells acutely infected with HIV-1 and 5.2 micrograms/m for chronically infected macrophages. dmPGA1 has an unusual broad-spectrum antiviral activity against both HSV and HIV-1 in vitro and offers a new class of potential therapeutic agents for in vivo use.

Description: Studies from space flights over the past two decades have demonstrated that there are basic physiological changes in humans during space flight. These changes include cephalad fluid shifts, loss of fluid and electrolytes, loss of muscle mass, space motion sickness, anemia, reduced immune response, and loss of calcium and mineralized bone. The cause of most of these manifestations is not known but the general approach has been to investigate systemic and hormonal changes. However, data from the 1973-1974 Skylabs, Spacelab 3 (SL-3), Spacelab D-I (SL-DI), and now the new SLS-1 missions support a more basic biological response to microgravity that may occur at the tissue, cellular, and molecular level. This report summarizes ground-based and SLS-1 experiments that examined the mechanism of loss of red blood cell mass in humans, the loss of bone mass and lowered osteoblast growth under space flight conditions, and loss of immune function in microgravity.

Description: X-ray testing of the AXAF outer mirror pairs, in the VETA-1 configuration, reveals a point spread function (PSF) with unexpectedly large wings at low energies. Although the angular dependence in the wings of the PSF is close to that expected for diffractive scattering from surface roughness, the energy dependence differs substantially. Analyses of the observed X-ray PSF, images near ring focus, and single-quadrant images at conjugate focus suggest that the excess scattering observed at low X-ray energies results from diffractive scattering by relatively small grains (as small as a few tenths micrometer in radius). We develop a simple model for the contribution of scattering by particulates to the PSF. Merging this model with that for scattering by surface roughness, we fit the combined model to the observed energy-dependent PSF, in order to estimate parameters and associated uncertainties characterizing the grain-size distribution and the surface-roughness power spectral density. In particular, we find that the fractional coverage of the mirrors by particulates is approximately 1 x 10 exp -4 (for grain radii between 0.1 and 10 microns), and that the rms surface-roughness is approximately 0.7 nm (for spatial frequencies between 1/mm and 1000/mm).

Description: Initial core scan data of the VETA-1 X-ray mirror proved disappointing, showing considerable unpredicted image structure and poor measured FWHM. 2-D core scans were performed, providing important insight into the nature of the distortion. Image deconvolutions using a raytraced model PSF was performed successfully to reinforce our conclusion regarding the origin of the astigmatism. A mechanical correction was made to the optical structure, and the minor was tested successfully (FWHM 0.22 arcsec) as a result.

Description: We found that the cytoplasmic concentration of calcium (Cai) of MC3T3-E1 osteoblasts was influenced by the type of pH buffer we used in the perfusing medium, suggesting that intracellular pH (pHi) might influence Cai. To study this effect, the Cai and pHi were monitored as we applied various experimental conditions known to change pHi. Exposure to NH4Cl caused a transient increase in both pHi and Cai without a change in extracellular pH (pHo). Decreasing pHo and pHi by lowering the bicarbonate concentration of the medium decreased Cai, and increasing pHi by the removal of 5% CO2 increased Cai. Clamping pHi to known values with 10 microM nigericin, a potassium proton ionophore, also influenced Cai: acid pHi lowered Cai, whereas alkaline pHi increased it. The rise in Cai appears to be very sensitive to the extracellular concentration of calcium, suggesting the existence of a pH-sensitive calcium influx mechanism. We conclude that physiologic changes in pH could modulate Cai by controlling the influx of calcium ions and could change the time course of the Cai transient associated with hormonal activation.

Description: Our previous studies have implied that prostaglandins inhibit cell growth independent of cAMP. Recent reports, however, have suggested that prostaglandin arrest of the cell cycle may be mediated through protein kinase A. In this report, in order to eliminate the role of c-AMP in prostaglandin mediated cell cycle arrest, we use the -49 lymphoma variant (cyc-) cells that lack adenylate cyclase activity. We demonstrate that dimethyl prostaglandin A1 (dmPGA1) inhibits DNA synthesis and cell growth in cyc- cells. DNA synthesis is inhibited 42% by dmPGA1 (50 microM) despite the fact that this cell line lacks cellular components needed for cAMP generation. The ability to decrease DNA synthesis depends upon the specific prostaglandin structure with the most effective form possessing the alpha, beta unsaturated ketone ring. Dimethyl PGA1 is most effective in inhibiting DNA synthesis in cyc- cells, with prostaglandins PGE1 and PGB1 being less potent inhibitors of DNA synthesis. DmPGE2 caused a significant stimulation of DNA synthesis. S-49 cyc- variant cells exposed to (30-50 microns) dmPGA1, arrested in the G1 phase of the cell cycle within 24 h. This growth arrest was reversed when the prostaglandin was removed from the cultured cells; growth resumed within hours showing that this treatment is not toxic. The S-49 cyc- cells were chosen not only for their lack of adenylate cyclase activity, but also because their cell cycle has been extensively studied and time requirements for G1, S, G2, and M phases are known. Within hours after prostaglandin removal the cells resume active DNA synthesis, and cell number doubles within 15 h suggesting rapid entry into S-phase DNA synthesis from the G1 cell cycle block.(ABSTRACT TRUNCATED AT 250 WORDS).

Description: The VETA-I mirror was calibrated with the use of a collimated soft X-ray source produced by electron bombardment of various anode materials. The FWHM, effective area and encircled energy were measured with the use of proportional counters that were scanned with a set of circular apertures. The pulsers from the proportional counters were sent through a multichannel analyzer that produced a pulse height spectrum. In order to characterize the properties of the mirror at different discrete photon energies one desires to extract from the pulse height distribution only those photons that originated from the characteristic line emission of the X-ray target source. We have developed a code that fits a modeled spectrum to the observed X-ray data, extracts the counts that originated from the line emission, and estimates the error in these counts. The function that is fitted to the X-ray spectra includes a Prescott function for the resolution of the detector a second Prescott function for a pileup peak and a X-ray continuum function. The continuum component is determined by calculating the absorption of the target Bremsstrahlung through various filters correcting for the reflectivity of the mirror and convolving with the detector response.

Description: We employ the X-ray measurements of the VETA-I taken at the X-Ray Calibration Facility (XRCF) of the Marshall Space Flight Center (MSFC) to extract information about the surface finish quality of the outermost pair of AXAF mirrors. The particular measurements we consider are one dimensional scans of the core of the point response function (PRF) (full width half maximum (FWHM) scans), the encircled energy as a function of radius, and one dimensional scans of the wings of the PRF. We discuss briefly our ray trace model which incorporates the numerous effects present in the VETA-I test, such as the finite source distance, the size and shape of the X-ray source, the residual gravitational distortions of the optic, the despace of the VETA-I, and particulate contamination. We show how the data constrain the amplitude of mirror surface deviations for spatial frequencies greater than about 0.1 mm(exp -1). Constraints on the average amplitude of circumferential slope errors are derived as well.

Description: The x-ray reflectivity of the VETA-I optic, the outermost shell of the AXAF x-ray telescope, with a bare Zerodur surface, is measured and compared with theoretical predictions. Measurements made at energies of 0.28, 0.9, 1.5, 2.1, and 2.3 keV are compared with predictions based on ray trace calculations. The data were obtained at the x-ray calibrations facility at Marshall Space Flight Center with an electron impact x-ray source located 528 m from the grazing incidence mirror. The source used photoelectric absorption filters to eliminate bremsstrahlung continuum. The mirror has a diameter of 1.2 m and a focal length of 10 m. The incident and reflected x-ray flux are detected using two proportional counters, one located in the incident beam of x-rays at the entrance aperture of the VETA-I, and the other in the focal plane behind an aperture of variable size. Results on the variation of the reflectivity with energy as well as the absolute value of the reflectivity are presented. We also present a synchrotron reflectivity measurement with high energy resolution over the range 0.26 to 1.8 keV on a flat Zerodur sample, done at NSLS. We present evidence for contamination of the flat by a thin layer of carbon on the surface, and the possibility of alteration of the surface composition of the VETA-I mirror perhaps by the polishing technique. The overall agreement between the measured and calculated effective area of VETA-I is between 2.6 percent and 10 percent, depending on which model for the surface composition is adopted. Measurements at individual energies deviate from the best-fitting calculation to 0.3 to 0.8 percent, averaging 0.6 percent at energies below the high energy cutoff of the mirror reflectivity, and are as high as 20.7 percent at the cutoff. We also discuss the approach to the final preflight calibration of the full AXAF flight mirror.

Description: The AXAF VETA-I mirror encircled energy was measured with a series of apertures and two flow gas proportional counters at five X-ray energies ranging from 0.28 to 2.3 keV. The proportional counter has a thin plastic window with an opaque wire mesh supporting grid. Depending on the counter position, this mesh can cause the X-ray transmission to vary as much as +/-9 percent, which directly translates into an error in the encircled energy. In order to correct this wire mesh effect, window scan measurements were made, in which the counter was scanned in both horizontal (Y) and vertical (Z) directions with the aperture fixed. Post VETA measurement of the VXDS setup were made to determine the exact geometry and position of the mesh grid. Computer models of the window mesh were developed to simulate the X-ray transmission based on this measurement. The window scan data were fitted to such mesh models and corrections were made. After this study, the mesh effect was well understood and the final results of the encircled energy were obtained with an uncertainty of less than 0.8 percent.