The Rap-B-Raf signalling pathway is activated by glucose and glucagon-like peptide-1 in human islet cells.

AIMS/HYPOTHESIS: Glucose and glucagon-like peptide-1 have been shown to activate extracellular signal-regulated kinase (ERK) and phosphoinositide 3-kinase in beta cells. We examined the contributions of the small GTPases Rap and Ras and the serine-threonine kinases B-Raf and Raf-1 to the activation of these kinases in human islet cells. METHODS: The expression of Rap, Ras, B-Raf and Raf-1 in human islets was examined by immunohistochemistry and immunoblotting. Human islets were incubated in glucose at concentrations of 2.5 and 15 mmol/l and were stimulated with 10 nmol/l glucagon-like peptide-1. The activation of ERK and Raf kinases was examined by phosphorylation-specific antibodies and immuno-complexed kinase assays. The activation of Rap and Ras was determined by pull-down assays. Stimulation of phosphoinositide 3-kinase was detected by immuno-complexed lipid kinase assays. RESULTS: Extracellular-regulated kinase and protein kinase B (a downstream target of phosphoinositide 3-kinase) were activated in islets stimulated with glucose and glucagon-like peptide-1. In these islets, the Rap-B-Raf signalling pathway was activated preferentially compared with Ras and Raf-1, and activated Rap and B-Raf mediated ERK stimulation in kinase assays in vitro. In addition, Rap rather than Ras mediated activation of phosphoinositide 3-kinase in islets stimulated with glucose and glucagon-like peptide-1. CONCLUSIONS/INTERPRETATION: In human islet cells, glucose and glucagon-like peptide-1 activate the Rap and B-Raf signalling module, which mediates ERK activation in assays in vitro. Rap also activates phosphoinositide 3-kinase, delineating central roles for Rap and B-Raf as therapeutic targets for beta cell growth in diabetes mellitus.

The Compact Central Object in Cassiopeia A: A Neutron Star with Hot Polar Caps or a Black Hole?

The central pointlike X-ray source of the Cassiopeia A supernova remnant was discovered in the Chandra first light observation and found later in the archival ROSAT and Einstein images. The analysis of these data does not show statistically significant variability of the source. Because of the small number of photons detected, different spectral models can fit the observed spectrum. The power-law fit yields the photon index gamma=2.6-4.1, and luminosity L(0.1-5.0 keV&parr0;=&parl0;2-60&parr0;x1034 ergs s-1 for d=3.4 kpc. The power-law index is higher, and the luminosity lower, than those observed from very young pulsars. One can fit the spectrum equally well with a blackbody model with T=6-8 MK, R=0.2-0.5 km, and Lbol=&parl0;1.4-1.9&parr0;x1033 ergs s-1. The inferred radii are too small, and the temperatures too high, for the radiation to be interpreted as emitted from the whole surface of a uniformly heated neutron star. Fits with the neutron star atmosphere models increase the radius and reduce the temperature, but these parameters are still substantially different from those expected for a young neutron star. One cannot exclude, however, the possibility that the observed emission originates from hot spots on a cooler neutron star surface. An upper limit on the (gravitationally redshifted) surface temperature is Tinfinitys<1.9-2.3 MK, depending on the chemical composition of the surface and the star's radius. Among several possible interpretations, we favor a model of a strongly magnetized neutron star with magnetically confined hydrogen or helium polar caps (Tinfinitypc approximately 2.8 MK, Rpc approximately 1 km) on a cooler iron surface (Tinfinitys approximately 1.7 MK). Such temperatures are consistent with the standard models of neutron star cooling. Alternatively, the observed radiation may be interpreted as emitted by a compact object (more likely, a black hole) accreting from a residual disk or from a late-type dwarf in a close binary.

A Lunar Occultation of the Dust-Scattering Halo Around GX 5-1 Observed with ROSAT.

The x-ray source GX 5-1 in the galactic bulge has been observed with the position-sensitive proportional counter onboard the Röntgen satellite (ROSAT) during and after a lunar occultation. Extended emission around the source was unambiguously discovered while the central source was behind the lunar rim. This emission is interpreted as a dust-scattering halo around GX 5-1 that has a fractional intensity of 28 percent, implying a grain column density between GX 5-1 and Earth of approximately 3 x 10(10) per square centimeter. The halo derived from imaging during the ROSAT all-sky survey is identical to that obtained from the lunar occultation, thus demonstrating that the ROSAT x-ray mirror scattering has not changed as compared with the mirror properties as measured in preflight calibrations.

Influence of pH adjustment agents on the biologic behavior of osmium-191 impurity in iridium-191m generator eluates.

The influence of four pH adjustment agents on the biologic behavior of osmium-191 (191Os) impurity in 191Os/191mIr generator eluates was studied. Extended body clearance and biodistribution studies were performed in mice. The solutions to be injected were obtained by eluting generators with a 0.9% NaCl solution at pH 1. The pH of these eluates was adjusted to 5-9 with succinate, phosphate, lysine or NaOH solution. Our results demonstrate that the biologic behavior of these generator eluates is significantly dependent on the agent used for pH adjustment. Buffering with lysine leads to the best results: (a) the mice show no adverse reaction after injection of 150 human doses and the body clearance is very rapid and (b) more than 75% I.D. at 24 hr postinjection. Preliminary calculations based on these results suggest a significant decrease in the estimated patient radiation dose when lysine buffered 191Os/191mIr generator eluates are used for radionuclide angiography.

Osmium-191/iridium-191m generator based on silica gel impregnated with tridodecylmethylammonium chloride.

A new separation system for an 191Os/191mIr generator is described. The system is composed of two columns in a series: a main column, packed with silica gel impregnated with tridodecylmethylammonium chloride (loaded with high activity 191Os as an osmyl chloride); and a scavenger column, packed with activated charcoal. Iridium-191m is eluted from the generator by pH 1 saline. For clinical use the eluate is buffered by succinate solution before injection. This new system is characterized by high performance (approximately 25% 191mIr recovery with 5 X 10(-4)% 191Os breakthrough) and long shelf-life (3 wk). The buffered eluate is sterile, pyrogen-free, and nontoxic, and contains no 192Ir. It is suitable for first-pass radionuclide angiocardiography with a very low radiation dose to the patient.

Evaluation of ventricular function with first-pass iridium-191m radionuclide angiocardiography.

Iridium-191m would appear to be a highly useful agent for first-pass radionuclide angiocardiography (FPNA), with its very short half-life (4.96 sec), dual photopeaks (65 and 129 keV), and high injectable activity levels (greater than 100 mc). In order to compare 191mIr FPNA to current methods used to define cardiac function, 20 patients referred for cardiac catheterization were studied. Count rate data, right ventricular (RV), and left ventricular ejection fraction (LVEF), LV and diastolic volume (EDV), and end diastolic long axis (AXIS) were evaluated. Count rate data using 191mIr FPNA was consistently better than similar data obtained by 99mTc FPNA. There were acceptable correlations between 191mIr and 99mTc FPNA RVEF (r = 0.848), 191mIr FPNA and contrast angiography LVEF (r = 0.944), LVEDV (r = 0.917), and LV AXIS (r = 0.866). The data thus suggests that 191mIr FPNA has great potential in the evaluation of cardiac function.

[Statistical analysis of a neonatal service opened within a 2-year period]. / Análisis estadístico de un servicio abierto de patología neonatal en un período de dos años.

We present a statistical study of unit 2 for newborns in Children's Hospital R. Gutiérrez, of the Buenos Aires municipality. An investigation was made which covered newborns who left the hospital from August 1976 to July 1978; during that period, 381 newborns finished their treatment. Summarizing the data assigned to death rate (22%) we could see a greater number during the first week; this tells us about the severe illness of the newborns that come into our service; we could also observe a significant mortality in newborns of high weight for their gestational age. The newborns with malformations have presented increased degree of illness and higher percentage of deaths (36%). From this review we had the idea of making a prospective study of our medical work, introducing, for a more correct evaluation, the degree of severeness when they come into the hospital and the classification of levels of high risk of the newborns.

Fabrication of transmission gratings for use in cosmic x-ray and XUV astronomy.

The manufacturing process of open transmission gratings with high efficiency and high line density is described. This process is developed by Dr. Johannes Heidenhain GmbH in cooperation with the Max- Planck-Institut and involves two steps, the mechanical ruling of the original master and the photochemical replication of the individual grating facets. The freestanding transmission grating is added by a regular support structure obstructing about one-third of the grating area. For application in space astronomy, gratings have been subjected to vibration and acoustic-noise tests.

Tc-99m pyridoxylidene glutamate in jaundiced patients.

Ninety patients, 85 of them jaundiced, were examined after the injection of Tc-99m pyridoxylidene glutamate, a substance rapidly concentrated by normal hepatocytes and excreted into the biliary tract. It appears in the gallbladder after 10-15 min, and in the gastrointestinal tract at 30 min. On the basis of the time of appearance in the intestine, four groups of patients were recognized: 1. Seventeen patients with a normal pattern, with visualization of the gut at 30 min. 2. Nineteen patients with a slight delay in passage, with appearance in the gut between 30-180 min. 3. Twenty-nine patients showing very slow excretion visualized only at 24 hr; 21 of these had parenchymatous disease of the liver, three choledocholithiasis and five had malignant disease causing partial obstruction. 4. Twenty-five patients with no visualization of the intestine; eight of them proved to be cases of medical jaundice, and 17 were surgical cases. Groups 3 and 4 comprise 54 patients where the question of medical or surgical jaundice was critical. If lack of intestinal activity is considered an indicating surgical jaundice, the accuracy of this study was only 72.4%.

Aberrations of a facet-type transmission grating for cosmic x-ray and XUV spectroscopy.

The aberrations of various types of curved constant-period transmission gratings are discussed, using Fermat's principle. We show that optimal performance is achieved with a grating assembled from individual facets which form a nonclosed surface. For this geometry, primary coma and astigmatism are proportional to the facet size and, hence, may be adapted to the angular resolution of a Wolter-type telescope.