The authors describe the use of pulsed field gel electrophoresis for chromosomal mapping of the ubiquitin gene family. Saccharomyces cerevisiae chromosomes were resolved on alternating ...contour-clamped homogeneous electric field (CHEF) gel electrophoresis. Following electrophoresis, the gel was stained with ethidium bromide and then denatured, neutralized, dried and hybridized with oligonucleotide probes directly in the dried gel wafer as previously described. Synthetic oligonucleotide probes were made to the four ubiquitin genes and to the genes SUC2, TRP3 , and PPR1 which have been mapped to chromosomes 9, 11, and 12 respectively.
A series of thienothiazines was synthesized and tested for their ability to inhibit P‐glycoprotein, which is responsible for multidrug resistance in tumor cells. Highest activity was found for ...compounds with a homoveratryl side chain, which is also present in other modulators of multidrug resistance, such as verapamil. Although for several classes of MDR‐modulators lipophilicity was shown to be a major determinant for high activity, no satisfactory correlation was obtained for the set of thienothiazines (r = 0.35). However, the use of molar refractivity as descriptor yields a good correlation with biological activity. This gives renewed evidence for the importance of molar refractivity and indicates that, in addition to lipophilicity, polar interactions also play an important role in ligand/receptor interaction.
In order to study 1) the mechanisms responsible for generating free ubiquitin monomer and 2) the function of ubiquitin carboxyl extension proteins in eukaryotes, we have developed a system for ...expression of human ubiquitin carboxyl extension proteins in prokaryotic and eukaryotic hosts. When expressed in Saccharomyces cerevisiae, the intact ubiquitin carboxyl extension proteins were rapidly processed to free ubiquitin monomer and extension protein. Furthermore, expression in this host conferred a slow growth phenotype mediated by the extension protein. Expression in Escherichia coli did not result in processing of the fusion proteins. However, when the expressed fusion proteins were purified from E. coli and incubated with a rabbit reticulocyte extract, the proteins were rapidly processed to free ubiquitin monomer and extension protein. These results show that human ubiquitin carboxyl extension proteins are processed to ubiquitin and extension protein when expressed in eukaryotic but not prokaryotic cells and that pre- and co-translational events are not necessary for their processing. Establishment of this system will allow for large scale purification of these proteins which will aid future studies on the function and structure of ubiquitin carboxyl extension proteins, as well as the mechanisms responsible for their processing.
In 30 adolescent patients with 36 structural curves undergoing posterior spinal arthrodesis using Cotrel-Dubousset (CD) instrumentation, computer tomography (CT) was performed to evaluate the change ...in rotation and in the sagittal plane. The average preoperative Cobb angle was 51.7 degrees, and improved to 18.7 degrees postoperatively, or 64.9%. The angle of rotation of the apical vertebra relative to the anterior midline of the body (RAML) improved from 27.9 degrees preoperatively to 21.5 degrees postoperatively (23.9%). The angle of rotation relative to the sagittal plane (RAsag) improved from 15.2 degrees preoperatively to 13.4 degrees postoperatively (14.3%). The kyphotic angle increased an average of 10.6 degrees in the 14 patients whose preoperative angle was less than 25 degrees. As measured by CT, CD instrumentation improves both the rotational and sagittal plane deformities better than that reported for other systems.
Objective. To evaluate and quantify the prediction of multiple neonatal outcomes by sonographically estimated fetal weight across a broad range of gestational ages. Methods. A retrospective cohort ...analysis was conducted among women with certain gestational age (n = 1376) seen at the University of California San Francisco from 1994 through 1997. The relative risks for small size at birth, small (low birth weight) for gestational age, and adverse neonatal outcomes were compared between small and average‐sized fetuses. Results. Fetuses with an estimated fetal weight in the 5th percentile or less for gestational age were at increased risk of a birth weight less than 2000 g (relative risk, 6.5), a birth weight in less than the 3rd percentile for gestational age (relative risk, 10.1), preterm birth (relative risk, 2.2), extreme preterm birth (relative risk, 5.7), prolonged neonatal hospital stay (relative risk, 2.7), neonatal intensive care unit admission (relative risk, 3.2), and stillbirth or neonatal death (relative risk, 7.7) compared with average‐sized fetuses (all P < .0001). With intrauterine growth restriction defined as an estimated fetal weight in the 5th percentile or less for gestational age, up to 29% of fetuses with adverse neonatal outcomes were detected, for false‐positive rates of only 4% to 5%. After adjusting for confounding variables, low estimated fetal weight remained a significant predictor of neonatal morbidity and mortality. Conclusions. Morbidity and mortality are significantly increased among fetuses with an estimated fetal weight in the 5th percentile or less for gestational age.
Proposed as satellite-based weapons during the 1980s, X-ray lasing was for a long time only achieved with enormous amounts of pump energy in either nuclear explosions or at kilojoule-class laser ...installations. During the last few years a tremendous development was achieved, most visible in the realisation of the FEL lasers at DESY and SLAC. As important for a wider applicability is the enormous reduction in pump energy for laser pumped plasma X-ray lasers, which now brings such devices into the range of applications for diagnostics and spectroscopy even in smaller laboratories. Main developments were the transient excitation scheme and the optimized pumping concepts. This paper concentrates on developments at the GSI Helmholtzcenter at Darmstadt aiming towards reliable X-ray laser sources in the range from 50 to several 100 eV. The main driving forces for the laser development at GSI are the possible application for the spectroscopy of Li-like ions in the storage ring ESR and the future storage ring NESR at FAIR, and the interest in novel plasma diagnostics.
Bone defects in the tibial plateau present technical problems in primary knee replacement surgery. A variety of techniques is available to solve these problems. Of 59 patients treated with a cement ...fill and followed an average of 7.1 years (range, five to 11 years), there was only one failure requiring revision. Overall, knee scores averaged 78 points and roentgenogram scores averaged 85 points. Radiolucent lines were noted in 43 of the 59 patients, but none were progressive except in the one failure. There was no clinical correlation between the presence of radiolucent lines and clinical symptoms. Good long-term results might be expected from the cement fill when the bone defects are smaller than 20 mm and affect less than 50% of either plateau.
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