Prognostic factors in seminomas with special respect to HCG: results of a prospective multicenter study. Seminoma Study Group.

Objective: In a prospective multicenter trial, it was our intention to elucidate clinical prognostic factors of seminomas with special reference to the importance of human chorionic gonadotropin (HCG) elevations in histologically pure seminomas.

Methods: Together with 96 participating urological departments in Germany, Austria, and Switzerland, we recruited 803 seminoma patients between 1986 and 1991. Out of 726 evaluable cases, 378 had elevated, while 348 had normal HCG values in the cubital vein.

Comparison of extracorporeal shock wave lithotripsy and ureteroscopy in the treatment of ureteral calculi: a prospective study.

146 patients whose ureteral stones did not pass spontaneously participated in a prospective study on optimal management. Patients were offered two treatment options: extracorporeal shock wave lithotripsy (ESWL) and ureteroscopy (URS). The stone was treated with the technique preferred by the patient.

The human tumor necrosis factor (TNF) receptor-associated factor 1 gene (TRAF1) is up-regulated by cytokines of the TNF ligand family and modulates TNF-induced activation of NF-kappaB and c-Jun N-terminal kinase.

To understand how the TNF receptor-associated factor 1 (TRAF1) is transcriptionally regulated, in vitro DNA binding assays, promoter-reporter gene assays, and RNase protection assays were performed with the human TRAF1 gene. Binding of NF-kappaB to three of five putative binding sites within the human TRAF1 promoter was found in electrophoretic mobility shift assay studies, and analysis of TRAF1 gene promoter luciferase constructs confirmed the functional importance of these elements. Moreover, triggering of TNF-R1, CD40, and the interleukin-1 receptor resulted in transcription of the TRAF1 gene, whereas receptors that are not activators or only poor activators of NF-kappaB in HeLa cells failed to show a significant TRAF1 induction.

TWEAK can induce cell death via endogenous TNF and TNF receptor 1.

TWEAK is a recently cloned novel member of the TNF ligand family. Here we show that soluble TWEAK is sufficient to induce apoptosis in Kym-1 cells within 18 h. TWEAK-induced apoptosis is indirect and is mediated by the interaction of endogenous TNF and TNF receptor (TNFR)1, as each TNFR1-Fc, neutralizing TNF-specific antibodies and TNFR1-specific Fab fragments efficiently antagonize cell death induction.

TRAIL/Apo2L activates c-Jun NH2-terminal kinase (JNK) via caspase-dependent and caspase-independent pathways.

In this study we show that TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), also called Apo2L, activates the c-Jun N-terminal kinase (JNK). Interestingly, TRAIL-induced JNK activation occurs in a cell type-specific manner. In HeLa cells, TRAIL-induced JNK activation can be completely blocked with the cysteine protease inhibitor zVAD-fmk, whereas the same inhibitor has no, or even a stimulatory, effect on JNK activation in Kym-1 cells.

Design and retrospective analysis of the Los Angeles Prehospital Stroke Screen (LAPSS).

Objectives: The therapeutic window for intervention in acute cerebral ischemia is brief. Prehospital identification of acute stroke patients and paramedic administration of neuroprotective agents may soon become critical components of successful acute stroke treatment. This preliminary study sought to demonstrate that a new prehospital screening instrument, the Los Angeles Prehospital Stroke Screen (LAPSS), sensitively identifies acute stroke patients.

Induced magnetic fields as evidence for subsurface oceans in Europa and Callisto.

The Galileo spacecraft has been orbiting Jupiter since 7 December 1995, and encounters one of the four galilean satellites-Io, Europa, Ganymede and Callisto-on each orbit. Initial results from the spacecraft's magnetometer have indicated that neither Europa nor Callisto have an appreciable internal magnetic field, in contrast to Ganymede and possibly Io. Here we report perturbations of the external magnetic fields (associated with Jupiter's inner magnetosphere) in the vicinity of both Europa and Callisto.

Europa's differentiated internal structure: inferences from four Galileo encounters.

Radio Doppler data from four encounters of the Galileo spacecraft with the jovian moon Europa have been used to refine models of Europa's interior. Europa is most likely differentiated into a metallic core surrounded by a rock mantle and a water ice-liquid outer shell, but the data cannot eliminate the possibility of a uniform mixture of dense silicate and metal beneath the water ice-liquid shell. The size of a metallic core is uncertain because of its unknown composition, but it could be as large as about 50 percent of Europa's radius.

Pharmacodynamic profile of a novel inhibitor of the hepatic glucose-6-phosphatase system.

The glucose-6-phosphatase (G-6-Pase) system catalyzes the terminal enzymatic step of gluconeogenesis and glycogenolysis. Inhibition of the G-6-Pase system in the liver is expected to result in a reduction of hepatic glucose production irrespective of the relative contribution of gluconeogenesis or glycogenolysis to hepatic glucose output. In isolated perfused rat liver, S-3483, a derivative of chlorogenic acid, produced concentration-dependent inhibition of gluconeogenesis and glycogenolysis in a similar concentration range.

High-temperature silicate volcanism on Jupiter's moon Io.

Infrared wavelength observations of Io by the Galileo spacecraft show that at least 12 different vents are erupting lavas that are probably hotter than the highest temperature basaltic eruptions on Earth today. In at least one case, the eruption near Pillan Patera, two independent instruments on Galileo show that the lava temperature must have exceeded 1700 kelvin and may have reached 2000 kelvin. The most likely explanation is that these lavas are ultramafic (magnesium-rich) silicates, and this idea is supported by the tentative identification of magnesium-rich orthopyroxene in lava flows associated with these high-temperature hot spots.

Distribution of rock, metals, and ices in Callisto.

Radio Doppler data from a single encounter (C3) of the Galileo spacecraft with Callisto, the outermost Galilean moon of Jupiter, indicated that Callisto was probably undifferentiated. Now, similar data from a second encounter (C9) corroborate this conclusion, but more accurate data from a third encounter (C10) indicate that the rock and ice within Callisto have partially, but not completely, separated. Callisto may be differentiated into a rock-metal core less than 25 percent of Callisto's radius, an outer layer of clean ice less than 350 km thick, and a middle layer of mixed rock and ice.

Chlorogenic acid analogue S 3483: a potent competitive inhibitor of the hepatic and renal glucose-6-phosphatase systems.

S 3483, a synthetic derivative of chlorogenic acid (CHL), was found to be a reversible, linear competitive inhibitor of the glucose-6-phosphatase (Glc-6-Pase) system in rat renal microsomes and rat and human liver microsomes. The Ki for S 3483 in rat liver microsomes (129 nM) is three orders of magnitude smaller than the Ki for CHL. S 3483 up to 100 microM had no effect on the Glc-6-Pase enzyme activity or on the system inorganic pyrophosphatase activity (i.

Direct evidence for the involvement of two glucose 6-phosphate-binding sites in the glucose-6-phosphatase activity of intact liver microsomes. Characterization of T1, the microsomal glucose 6-phosphate transport protein by a direct binding assay.

S 5627 is a synthetic analogue of chlorogenic acid. S 5627 is a potent linear competitive inhibitor of glucose 6-phosphate (Glc-6-P) hydrolysis by intact microsomes (Ki = 41 nM) but is without effect on the enzyme in detergent- or NH4OH-disrupted microsomes. 3H-S 5627 was synthesized and used as a ligand in binding studies directed at characterizing T1, the Glc-6-P transporter.

Dominant-negative FADD inhibits TNFR60-, Fas/Apo1- and TRAIL-R/Apo2-mediated cell death but not gene induction.

Fas/Apo1 and other cytotoxic receptors of the tumor necrosis factor receptor (TNFR) family contain a cytoplasmic death domain (DD) [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] that activates the apoptotic process by interacting with the DD-containing adaptor proteins TNFR-associated DD protein (TRADD) [12] [13] and Fas-associated DD protein (FADD/MORT1) [14] [15], leading to the activation of cysteine proteases of the caspase family [16]. Stimulation of Fas/Apo1 leads to the formation of a receptor-bound death-inducing signaling complex (DISC), consisting of FADD and two different forms of caspase-8 [17] [18] [19]. Transient expression of a dominant-negative mutant of FADD impairs TNFR60-mediated and Fas/Apo1-mediated apoptosis [13] [20], but has no effect on TNF-related apoptosis-inducing ligand (TRAIL/Apo2L)-induced cell death [7] [8] [9] [10] [21].

Three-dimensional simulations of plume-lithosphere interaction at the hawaiian swell.

Rapid lithospheric thinning by mantle plumes has not been achieved in numerical experiments performed to date. Efficient thinning depends on small-scale instabilities that convectively remove lithospheric material. These instabilities are favored by hotter plumes or stronger temperature dependence of viscosity, and a simple scaling independent of rheology controls their onset.

Geological evidence for solid-state convection in Europa's ice shell.

The ice-rich surface of the jovian satellite Europa is sparsely cratered, suggesting that this moon might be geologically active today. Moreover, models of the satellite's interior indicate that tidal interactions with Jupiter might produce enough heat to maintain a subsurface liquid water layer. But the mechanisms of interior heat loss and resurfacing are currently unclear, as is the question of whether Europa has (or had at one time) a liquid water ocean.

Evidence for a subsurface ocean on Europa.

Ground-based spectroscopy of Jupiter's moon Europa, combined with gravity data, suggests that the satellite has an icy crust roughly 150 km thick and a rocky interior. In addition, images obtained by the Voyager spacecraft revealed that Europa's surface is crossed by numerous intersecting ridges and dark bands (called lineae) and is sparsely cratered, indicating that the terrain is probably significantly younger than that of Ganymede and Callisto. It has been suggested that Europa's thin outer ice shell might be separated from the moon's silicate interior by a liquid water layer, delayed or prevented from freezing by tidal heating; in this model, the lineae could be explained by repetitive tidal deformation of the outer ice shell.

Europa's differentiated internal structure: inferences from two Galileo encounters.

Doppler data generated with the Galileo spacecraft's radio carrier wave during two Europa encounters on 19 December 1996 (E4) and 20 February 1997 (E6) were used to measure Europa's external gravitational field. The measurements indicate that Europa has a predominantly water ice-liquid outer shell about 100 to 200 kilometers thick and a deep interior with a density in excess of about 4000 kilograms per cubic meter. The deep interior could be a mixture of metal and rock or it could consist of a metal core with a radius about 40 percent of Europa's radius surrounded by a rock mantle with a density of 3000 to 3500 kilograms per cubic meter.

Gravitational evidence for an undifferentiated Callisto.

Before the arrival of the Galileo spacecraft at Jupiter, models for the interior structure of the four galilean satellites--Io, Europa, Ganymede and Callisto-ranged from uniform mixtures of rock and ice (that is, undifferentiated objects) or rocky cores surrounded by a mantle of water ice. Now it appears that Io has a large metallic core and that Ganymede is strongly differentiated, most probably into a three-layer structure consisting of a metallic core, a silicate mantle and a deep outer layer of ice. Direct information on the interior structure of Callisto determined from previous spacecraft fly-bys was essentially limited to an estimate of the mean density being intermediate between pure ice and pure rock.

Thermal Structure of Jupiter's Upper Atmosphere Derived from the Galileo Probe.

Temperatures in Jupiter's atmosphere derived from Galileo Probe deceleration data increase from 109 kelvin at the 175-millibar level to 900 ± 40 kelvin at 1 nanobar, consistent with Voyager remote sensing data. Wavelike oscillations are present at all levels. Vertical wavelengths are 10 to 25 kilometers in the deep isothermal layer, which extends from 12 to 0.

Chlorogenic acid and hydroxynitrobenzaldehyde: new inhibitors of hepatic glucose 6-phosphatase.

We have studied the interactions of chlorogenic acid (CHL) and 2-hydroxy-5-nitrobenzaldehyde (HNB) with the components of the rat hepatic glucose 6-phosphatase (Glc-6-Pase) system. CHL and HNB are competitive inhibitors of glucose 6-phosphate (Glc-6-P) hydrolysis in intact microsomes with Ki values of 0.26 and 0.

Chlorogenic acid and synthetic chlorogenic acid derivatives: novel inhibitors of hepatic glucose-6-phosphate translocase.

The enzyme system glucose-6-phosphatase (EC 3.1.3.

[Snow white small intestinal villi in hypobetalipoproteinemia].

In contrast to the severe clinical picture of abetalipoproteinemia patients with hypobetalipoproteinemia are often asymptomatic. We demonstrate a 52-years-old female patient with a white mucosa of the small intestine casually observed by endoscopy. The white appearance of the mucosa was limited to the villi.

Penetrative Convection and Zonal Flow on Jupiter.

Measurements by the Galileo probe support the possibility that the zonal winds in Jupiter's atmosphere originate from convection that takes place in the deep hydrogen-helium interior. However, according to models based on recent opacity data and the probe's temperature measurements, there may be radiative and nonconvective layers in the outer part of the jovian interior, raising the question of how deep convection could extend to the surface. A theoretical model is presented to demonstrate that, because of predominant rotational effects and spherical geometry, thermal convection in the deep jovian interior can penetrate into any outer nonconvective layer.

A transient role of the kidney in the maintenance of hypertension.

Using the Prague hypertensive rat (PHR), a model derived from the Wistar rat, in which a normotensive parallel, the Prague normotensive rat (PNR), was bred from the same parent pair (so that transplantation of organs between both these parallel rat model lines results in no distinct signs of rejection), we were able to show that hypertension travels with the kidney. Transplantation of a kidney from PHR to a bilaterally nephrectomized (BNX) PNR led to an increase in systolic blood pressure (SBP) in the recipient for 10 weeks after grafting. Similarly, a decrease in SBP was seen in BNX PHR for the same period of time after grafting a kidney from PNR.