High-quality Far Ultraviolet Spectroscopic Explorer (FUSE) observations at 20 km s super(-1) resolution of interstellar and intergalactic absorption from 910 to 1187 AA are presented for the ...X-ray-bright BL Lac object Mrk 421. These observations are supplemented with FUSE data for the distant halo stars BD +38 degree 2182 and HD 93521 near the Mrk 421 line of sight, in order to obtain information about the distance to absorbing structures in the Milky Way toward Mrk 421. The FUSE ISM observations provide measures of absorption by O VI and many other species commonly found in warm neutral and warm ionized gas, including H I, C II, C III, O I, N I, N II, Fe II, and Fe III. In this study we consider the O VI absorption between -140 and 165 km s super(-1) and its relationship to the lower ionization absorption and strong absorption produced by O VII and O VIII at X-ray wavelengths. The O VI absorption extending from -140 to 60 km s super(-1) is associated with strong low-ionization gas absorption and originates in the Galactic thick disk/halo. This O VI appears to be produced by a combination of processes, including conductive interfaces between warm and hot gas and possibly cooling Galactic fountain gas and hot halo gas bubbles. The O VI absorption extending from 60 to 165 km s super(-1) has unusual ionization properties in that there is very little associated low-ionization absorption, with the exception of C III. This absorption is not observed toward the two halo stars, implying that it occurs in gas more distant than 3.5 kpc from the Galactic disk. Over the 60-165 km s super(-1) velocity range, O VI and C III absorption have the same kinematic behavior. The ratio N(O super(VI))/N(C super(III)) = 10 plus or minus 3 over the 60-120 km s super(-1) velocity range. Given the association of O VI with C III, it is unlikely that the high-velocity O VI coexists with the hotter gas responsible for the O VII and O VIII absorption. The O VI positive velocity absorption wing might be tracing cooler gas entrained in a hot Galactic fountain outflow. The O VII and O VIII absorption observed by Chandra and XMM-Newton may trace the hot gas in a highly extended ( similar to 100 kpc) Galactic corona or hot gas in the Local Group. The low resolution of the current X-ray observations ( similar to 750-900 km s super(-1)) and the kinematical complexity of the O VI absorption along typical lines of sight through the Milky Way halo make it difficult to clearly associate the O VI absorption with that produced by O VII and O VIII. A search for metal lines associated with the Ly alpha absorber at z = 0.01, which is situated in a galactic void, was unsuccessful.
Current understanding of blood oxygenation level dependent (BOLD) fMRI physiology predicts a close relationship between BOLD signal and blood hematocrit level. However, neither this relationship nor ...its effect on BOLD percent activation (BPA) has been empirically examined in man. To that end, BPA in primary visual cortex in response to photic stimulation was determined in a group of 24 normal subjects. A positive linear relationship between BPA and hematocrit was seen, particularly in men. To evaluate the effect of change in hematocrit on BPA, 9 men were studied before and following isotonic saline hemodilution, resulting in an average 6% reduction in hematocrit and an 8–31% reduction in BPA. No significant change in the number of activated pixels was seen. A model of predicted BPA as a function of hematocrit and vessel size was developed, and results from this model closely mirrored the empiric data. These results suggest that hematocrit significantly influences the magnitude of BPA and that such baseline factors should be accounted for when comparing BOLD data across groups of subjects, particularly in the many instances in which hematocrit may vary systematically. Such instances include several disease states as well as studies involving sex differences, drug administration, stress and other factors. Finally, the robust agreement between predicted and empiric data serves to validate a semiquantitative approach to the analysis of BOLD fMRI data.
To further investigate neural effects on leptin and uncoupling proteins (UCPs), we studied in vivo perturbations intended to block adrenergic input to peripheral tissues. We examined plasma leptin, ...leptin mRNA, and adipose and muscle UCP subtype mRNA in rats treated with alpha-methyl-p-tyrosine methyl ester (AMPT-ME), which inhibits catecholamine synthesis and 6-hydroxydopamine (6HDA), which is toxic to catecholinergic nerve terminals but, unlike AMPT-ME, does not enter the central nervous system. Intraperitoneal AMPT-ME, 250 mg/kg, was administered at 1800 and 0700 the following day, and rats were killed at 1200-1400. All rats were fasted with free access to water during this time. Intraperitoneal AMPT-ME increased plasma leptin by 15-fold, increased interscapular brown adipose tissue (IBAT) and epididymal fat leptin mRNA by 2- to 2.5-fold, and also increased plasma insulin and glucose concentrations. Intraperitoneal AMPT-ME decreased IBAT UCP-3 mRNA to 40% of control, while it increased epididymal adipose UCP-3 mRNA approximately twofold. Intravenous AMPT-ME, 250 mg/kg, administered to conscious rats for 5 h decreased lumbar sympathetic nerve activity, increased plasma leptin (5.89 +/- 1.43 compared with 2.75 +/- 0.31 ng/ml in vehicle-treated rats, n = 7, P < 0.05), and decreased cardiac rate with no sustained change in blood pressure. Intraperitoneal 6HDA, 100 mg/kg, as a single dose at 1800, increased plasma leptin approximately twofold after 18-20 h, increased IBAT (but not epididymal fat) leptin mRNA by two- to threefold, and decreased IBAT UCP-3 mRNA to 30-40% of control. Neither AMPT-ME nor 6HDA significantly altered mRNA encoding gastrocnemius muscle UCP-3, IBAT UCP-1, or IBAT and epididymal UCP-2. In summary, AMPT-ME and 6HDA increased plasma leptin and upregulated leptin mRNA expression. AMPT-ME also resulted in complex tissue and subtype-specific modulation of adipose UCP mRNA. These data are consistent with interaction between leptin and sympathetic nerve activity (SNA) in regulation of fat cell energy utilization. However, the in vivo modulation of leptin and UCPs appears complex and, beyond a causal effect of SNA per se, may depend on concurrent changes in plasma insulin, glucose, and circulatory hemodynamics.
The recently commissioned Recoil Mass Spectrometer (RMS) at the Holifield Radioactive Ion Beam Facility (HRIBF) is described. Consisting of a momentum separator followed by an E-D-E Rochester-type ...mass spectrometer, the RMS is the centerpiece of the nuclear structure endstation at the HRIBF. Designed to transport ions with rigidities near
K=100, the RMS has acceptances of ±10% in energy and ±4.9% in mass-to-charge ratio. Recent experimental results are used to illustrate the detection capabilities of the RMS, which is compatible with many detectors and devices.
After surgical resection or repair of a torn meniscus, the healed area may have areas of abnormal signal intensity on MR images. Consequently, routine MR imaging is not reliable for detecting ...recurrent meniscal tears. As a result, we studied the efficacy of MR imaging with intraarticular contrast material (MR arthrography) for detecting recurrent tears of the meniscus.
Thirty-seven patients who previously had a meniscal tear treated by either meniscal resection or repair had conventional MR imaging and MR arthrography with 40-50 ml of a 1:100 solution of gadopentetate dimeglumine in saline. All patients had arthroscopy shortly after the MR studies. Follow-up arthroscopic surgery was performed within an average of 6.6 weeks after the MR arthrograms. The routine MR images and MR arthrograms were reviewed separately and randomly, and these results were compared with the arthroscopic findings. Meniscal morphology, signal intensity, and the presence of joint fluid tracking into recurrent tears were evaluated.
The overall accuracy in diagnosing recurrent meniscal tears in the post-operative meniscus was 66% when conventional MR imaging was used and 88% when MR arthrography was used. In patients who had only minimal meniscal resection, both methods had an accuracy of 89%. In patients who had more extensive meniscal resection, accuracy was 65% with conventional MR imaging and 87% with MR arthrography. In four patients who had only a small meniscal remnant, the accuracy was 50% with routine MR imaging and 100% with MR arthrography. On conventional MR images, the presence of an effusion tracking into a meniscal tear had a sensitivity and positive predictive value of 90% for detection of recurrent meniscal tears; however, the sensitivity was only 41%.
Our results show that the sensitivity of MR imaging in detecting meniscal tears after surgery varies with the extent of the resection. Sensitivity was considerably improved when intraarticular contrast material was used. MR arthrography should be considered as an alternative to arthroscopy in patients who have had resection or repair of the meniscus.
The secretory products of some of the cell types which respond directly to actions of progesterone in the female rat brain and pituitary were determined by combining immunocytochemistry with ...autoradiography following systemic administration of the synthetic progestin ligand 3H-R5020. Four major findings are reported: (1) Approximately 90% of the tyrosine hydroxylase (TH)-immunoreactive neurons in the hypothalamic arcuate nucleus have progesterone receptors, while TH-immunoreactive neurons in other portions of the hypothalamus (e.g. the periventricular region and the zona incerta) do not. (2) Approximately 30% of the beta-endorphin neurons in the hypothalamus have progesterone receptors. (3) None of the luteinizing hormone-releasing hormone neurons examined have progesterone receptors. (4) Approximately 98% of the cells in the anterior pituitary that have progesterone receptors contain luteinizing hormone. Lactotrophs do not contain progesterone receptors. Many progestin targets in the brain remain to be characterized chemically. The implications for progesterone-inducible genes and neuroendocrine control systems are discussed.
Background Patients with non-Q-wave acute coronary syndromes (ACS) have substantial rates of recurrent ischemic events, but prognostic studies have been small or preceded the routine use of ...aggressive combination antithrombotic therapy. We sought to identify predictors of these events after antithrombotic treatment of non-Q-wave ACS. Methods We assessed 30-day rates of a composite triple end point (death, infarction, or refractory angina) and double end point (death or infarction) among 3171 patients with non-ST-segment elevation ACS randomly assigned to enoxaparin or heparin, plus aspirin, for 2 to 8 days. We created multivariable regression models to predict these end points from baseline factors. Results Overall, 682 patients (21%) reached the triple end point and 220 (6.8%) reached the double end point. Independent predictors of the triple end point were admission with myocardial necrosis, ST-segment depression, prior angina severity, symptom duration, and allocation to enoxaparin treatment in patients with ST-segment depression (significant interaction). Independent predictors of the double end point were admission with myocardial necrosis, ST-segment depression, enrollment region, age >75 years, prior angina severity, and rales. By deciles, the average predicted risk for the double end point ranged from 2% to 20%: a patient aged <75 years with no risk factors had a 3.5% risk, whereas a patient aged >75 years with 2 additional high-risk features (myonecrosis and ST depression) had a risk of death or reinfarction of 26%. Conclusions Patients with non-ST-segment elevation ACS exhibit a broad range of risk of adverse recurrent ischemic events. The predictive power of the model for the triple end point, using baseline variables, was modest. However, a subgroup at very low risk of the double end point (average 2%) can be identified with baseline variables. (Am Heart J 2000;139:962-70.)
To test the hypothesis that pulmonary vasodilator responses of ketamine are dependent on activation of L-type calcium channels, independent of synthesis of nitric oxide from L-arginine, activation of ...adenosine triphosphate-sensitive potassium channels, and the release of cyclooxygenase products.
Prospective study.
Research laboratory.
Isolated lobar lung preparation, mongrel cats.
In separate experiments, the effects of nicardipine; N omega-I-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase; glibenclamide, an adenosine triphosphate-sensitive potassium channel antagonist; and meclofenamate, a cyclooxygenase blocker, were investigated in the pulmonary vascular bed of the cat. The effects of these agents were evaluated on the pulmonary arterial responses of ketamine, acetylcholine, and isoproterenol during elevated tone conditions induced by the thromboxane A2 mimic, U46619 (Upjohn, Kalamazoo, MI).
Lobar arterial perfusion pressure, systemic pressure, and left atrial pressure were continuously monitored, electronically averaged, and permanently recorded.
Under elevated tone conditions in the isolated left lower lobe vascular bed of the cat, N omega-I-nitro-L-arginine methyl ester, glibenclamide, and meclofenamate had no significant effect on the vasodilator responses to ketamine. Nicardipine, in a dose that reduced significantly vasopressor effects to BAY K 8644, a calcium-channel opener, attenuated significantly vasodilator responses to ketamine, whereas the L-type calcium-channel blocker had no significant effects on responses to acetylcholine and to isoproterenol.
These data show that ketamine has significant vasodilator activity in the pulmonary vascular bed of the cat. The present data also suggest that responses to ketamine during elevated tone conditions may in part be mediated by the activation of L-type calcium channels.
Cancer research would greatly benefit from technologies that allow simultaneous screening of several unknown gene mutations. Lack of such methods currently hampers the large-scale detection of ...genetic alterations in complex DNA samples. We present a novel mismatch-capture methodology for the highly efficient isolation and amplification of mutation-containing DNA from diverse nucleic acid fragments of unknown sequence. To demonstrate the potential of this method, heteroduplexes with a single A/G mismatch are formed via cross-hybridization of mutant (T-->G) and wild-type DNA-fragment populations. Aldehydes are uniquely introduced at the position of mismatched adenines via the Escherichia coli glycosylase, MutY. Subsequent treatment with a biotinylated hydroxylamine results in highly specific and covalent biotinylation of the site of mismatch. For PCR amplification, synthetic linkers are then ligated to the DNA fragments. Biotinylated DNA is then isolated and PCR amplified. Mutation-containing DNA fragments can subsequently be sequenced to identify type and position of mutation. This method correctly detects a single T-->G transversion introduced into a 7-kb plasmid containing full-length cDNA from the p53 gene. In the presence of a high excess wild-type DNA (1:1000 mutant:normal plasmids) or in the presence of diverse DNA fragment sizes, the DNA fragments containing the mutation are readily detectable and can be isolated and amplified. The present Aldehyde-Linker-Based Ultrasensitive Mismatch Scanning has a current limit of detection of one base substitution in 7 Mb of DNA and increases the limit for unknown mutation scanning by two to three orders of magnitude. Homozygous and heterozygous p53 regions (G-->T, exon 4) from genomic DNA are also examined, and correct identification of mutations is demonstrated. This method should allow large-scale detection of genetic alterations in cancer samples without any assumption as to the genes of interest.
