Recent studies showed that a brief interruption of dopamine (DA) action markedly increased the thyrotropin-releasing hormone (TRH)-stimulated prolactin (PRL) release. It is thus of interest to ...delineate whether the estrogen-induced afternoon PRL surge involves the same mechanism. Long-term ovariectomized rats pretreated with polyestradiol phosphate (PEP, 0.1 mg/rat s.c.) for 6 days were used in this study. They also received either p-chlorophenylalanine (PCPA, 250 mg/kg i.p.) or ketanserin (Ket, 10 mg/kg i.p.), two serotonergic drugs known to inhibit the estrogen-induced afternoon PRL surge. Then the animals were either treated with a DA antagonist, domperidone (Domp, 0.01 mg/rat i.v.), or vehicle at 16.00 h on the sampling day. Ten minutes later, the ones receiving Domp were injected with a DA agonist, 2-bromo-alpha-ergocryptine (CB154, 0.5 mg/rat i.v.), followed 50 min later by the administration of TRH (1 microgram/rat i.v.). Plasma samples taken through indwelling intraatrial catheters were assayed for PRL by radioimmunoassay. The estrogen-induced afternoon PRL surges were completely blocked in both PCPA- and Ket-treated animals. A significant PRL surge with similar amplitude, however, was induced by either Domp or TRH, although pretreatment with Domp did not cause any potentiating effect on the action of TRH. On the other hand, Domp induced only a small rise of PRL secretion and TRH was totally ineffective in rats untreated with PEP. It is concluded that both DA antagonism and TRH stimulation can induce significant PRL release in the afternoon of estrogen-treated, serotonin-blocked rats.
Twenty-five patients, each of whom had peripheral intrathoracic lesions that were smaller than 5.0 X 5.0 cm in size and not diagnosed by conventional methods, underwent real-time sonography and ...ultrasonically guided aspiration biopsy. The lesions included 18 nodules, two infiltrates, and five cavitary lesions. Sonography showed homogeneous hypoechoic or isoechoic density with well-defined margins in 16 of the nodules, and heterogeneous echogenicity with irregular margins in infiltrates. The cavitary lesions showed a hyperechoic ring with a central sonolucent area. Biopsy specimens were successfully obtained by percutaneous aspiration under ultrasound guidance in 24 (96%) of the patients, and a positive diagnosis was established in 21 (84%) by cytology and/or histology. All 17 malignant lesions were diagnosed by aspiration biopsy, while only four of seven benign lesions were diagnosed by this method. Two patients (8%) experienced minimal pneumothorax after aspiration biopsy. We conclude that real-time sonography, including ultrasonically guided aspiration biopsy, is a useful and safe method for examination of peripheral intrathoracic lesions and has a high diagnostic yield.
The relationship between atherogenic lipoproteins and subclinical coronary atherosclerosis has not been thoroughly evaluated in low-risk adults.
The purpose of this study was to assess the ...association of low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (HDL-C), and apolipoprotein B (apoB) with coronary atherosclerosis in adults without traditional risk factors.
We assessed atherosclerosis on coronary computed tomography angiography among asymptomatic adults in the Miami Heart Study not taking lipid-lowering therapy and without hypertension, diabetes, or active tobacco use. Prevalence of atherosclerosis was evaluated based on serum LDL-C, non-HDL-C, and apoB, and multivariable logistic regression with forward selection was used to assess variables associated with coronary plaque.
Among 1,033 adults 40 to 65 years of age, 55.0% were women and 86.3% had estimated 10-year atherosclerotic cardiovascular disease risk <5%. Coronary atherosclerosis prevalence was 35.9% (50.6% in men; 23.8% in women) and 3.4% had ≥1 high-risk plaque feature. Atherosclerosis prevalence increased with LDL-C, ranging from 13.2% in adults with LDL-C <70 mg/dL up to 48.2% with ≥160 mg/dL. Higher LDL-C (adjusted OR aOR: 1.13 95% CI: 1.08-1.18 per 10 mg/dL), age (aOR: 1.43 95% CI: 1.28-1.60 per 5 years), male sex (aOR: 3.81 95% CI: 2.86-5.10), and elevated lipoprotein(a) (aOR: 1.46 95% CI: 1.01-2.09) were associated with atherosclerosis. Higher serum non-HDL-C and apoB were similarly associated with atherosclerosis. In adults with optimal risk factors, 21.2% had atherosclerosis with greater prevalence at higher lipoprotein levels.
Among asymptomatic middle-aged adults without traditional risk factors, coronary atherosclerosis is common and increasingly prevalent at higher levels of atherogenic lipoproteins. These findings emphasize the importance of lipid-lowering strategies to prevent development and progression of atherosclerosis regardless of risk factors.
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Mitral regurgitation (MR) was evaluated by Doppler echocardiography in 59 patients with mitral stenosis before, immediately after and 1 year after balloon mitral valvuloplasty (BMV). The severity of ...MR was graded on a scale from 1+ to 4+. Echocardiographic and hemodynamic variables were analyzed to study the potential factor(s) that might predict the long-term persistence of MR. Echocardiographic variables were mitral valve thickness and motion, subvalvular change, left atrial dimension, commissural calcification and effective balloon/mitral anular diameters. Hemodynamic variables were mitral pressure gradient, pulmonary arterial pressure, ejection fraction, mitral valve area index, age, gender and cardiac rhythm. Mitral valve area index increased from 0.9 +/- 0.5 to 1.5 +/- 0.8 cm2/m2 immediately after BMW, and to 1.4 +/- 0.3 cm2/m2 at 1 year follow-up (p less than 0.01). Immediately after BMV, MR grading did not change in 30 patients (51%), increased by 1+ in 23 patients (39%), by 2+ in 2 patients (3.3%) and by 3+ in 2 patients (3.3%), and decreased by 1+ in 2 others. At 1-year follow-up, only 1 patient with severe MR required valve replacement. Fifty-one patients (88%) had no change in the extent of MR (less than or equal to 1+) and 6 patients (10%) had a 1-grade decrease in their MR; only 1 patient had a 1-grade increase in MR. No clinical or hemodynamic variables or morphologic characteristics of the mitral valve could predict the development of significant MR after BMV. It is concluded that an increment in MR severity less than or equal to 2+ is frequently seen after BMV.
The experiment Androic, D.; Armstrong, D. S.; Asaturyan, A. ...
Hyperfine interactions,
3/2013, Letnik:
214, Številka:
1-3
Journal Article
Recenzirano
In May 2012, the
collaboration completed a two year measurement program to determine the weak charge of the proton
at the Thomas Jefferson National Accelerator Facility (TJNAF). The experiment was ...designed to produce a 4.0 % measurement of the weak charge, via a 2.5 % measurement of the parity violating asymmetry in the number of elastically scattered 1.165 GeV electrons from protons, at forward angles. At the proposed precision, the experiment would produce a 0.3 % measurement of the weak mixing angle at a momentum transfer of
Q
2
= 0.026 GeV
2
, making it the most precise stand alone measurement of the weak mixing angle at low momentum transfer. In combination with other parity measurements,
will also provide a high precision determination of the weak charges of the up and down quarks. At the proposed precision, a significant deviation from the Standard Model prediction could be a signal of new physics at mass scales up to ≃ 6 TeV, whereas agreement would place new and significant constraints on possible Standard Model extensions at mass scales up to ≃ 2 TeV. This paper provides an overview of the physics and the experiment, as well as a brief look at some preliminary diagnostic and analysis data.
Kinetic results in this paper show that, contrary to earlier reports, pig pancreatic prophospholipase A2 (proPLA2) does not hydrolyze monodisperse short chain phosphatidylcholine below the critical ...micelle concentration. ProPLA2 is active on an anionic interface, but at a rate that is decreased by more than 100-fold compared to that of PLA2, the active form. Solution studies show that both proPLA2 and PLA2 bind to an anionic interface and also bind a tetrahedral intermediate mimic at the active site. The 1.5 Å resolution crystal structure of the anion-assisted dimer of proPLA2 reported in this paper is compared with the corresponding structure for PLA2 Pan, Y. H., et al. (2001) Biochemistry 40, 609−617. As a mimic for the forms bound to the anionic interface, these structures provide insights into the possible structural basis for the impaired chemical step of the zymogen. The proPLA2 dimer contained within one crystallographic asymmetric unit has one molecule of the inhibitor 1-hexadecyl-3-(trifluoroethyl)-sn-glycero-2-phosphomethanol and is bridged by four coplanar sulfate anions. Relative to the structure of PLA2, the subunit contact surface in proPLA2 displays a tilted orientation, an altered mode of inhibitor binding, displacement of a mechanistically significant loop that includes Tyr69, and a critical active site water seen in PLA2 that is not seen in proPLA2. These differences are interpreted to suggest possible origins of the functional differences between the pro and active enzyme at an anionic interface. A structural origin of this difference is discussed in terms of the calcium-coordinated activated water mechanism of the esterolysis reaction. Together, a comparison of the structures of the anion-assisted dimers of PLA2 and proPLA2 not only offers an explanation of why the zymogen form is k* cat-impaired and binds poorly even to the anionic interface but also supports a mechanism for the activated enzyme that includes a critical second-sphere assisting water bridging His48 and the calcium-coordinated catalytic water.
An introduction to a symposium on e-governance, "Challenges & Opportunities for Democracy, Administration, & Law," notes that the papers were originally presented at the July 2004 Twenty-sixth ...International Congress of Administrative Sciences in Seoul, Korea. New phenomena that have resulted from the increasing importance of information & communication technologies (ICT) are pointed out. Four sub-themes of the Congress are explored: 1) the effect of e-governance on civil society, transparency, & democracy; 2) ways in which e-governance has changed administrative structures/processes; 3) challenges of e-governance for countries in transition & development; & 4) e-governance & the evolution of law. It is suggested that the future may include "u-governance" that involves a ubiquitous network-free, device-free paradigm capable of providing services anywhere, anytime. Emphasis is placed on the need to define a clear vision for future government that stresses cooperation & coordination; has the capacity to respond to such potential ICT hazards as security breaches; & recognizes that technology is "only an enabler, never a panacea." A synopsis of the four articles is included. 42 References. J. Lindroth
Background and purpose: To further assess the clinical potential of the blockade of metabotropic glutamate receptors (mGluR1) for the treatment of pain. Experimental approach: We characterized the ...effects of A-841720, a novel, potent and non-competitive mGluR1 antagonist in models of pain and of motor and cognitive function. Key results: At recombinant human and native ra GluR1 receptors, A-841720 inhibited agonist-induced calcium mobilization, with IC sub(S0) values of 10.7 plus or minus 3.9 and 1.0 plus or minus 0.2nM, respectively, while showing selectivity over other mGluR receptors, in addition to other neurotransmitter receptors, ion channels, and transporters. Intraperitoneal injection of A-841720 potently reduced complete Freund's adjuvant-induced inflammatory pain (ED sub(50) = 23 mu molkg super(-1)) and monoiodoacetate-induced joint pain (ED sub(S0) = 4 mu 3molkg super(-1)). A-841720 also decreased mechanical allodynia observed in both the sciatic nerve chronic constriction injury and L5-L6 spinal nerve ligation (SNL) models of neuropathic pain (ED sub(50) = 28 and 27 mu t1molkg super(-1), respectively). Electrophysiological studies demonstrated that systemic administration of A-841720 in SNL animals significantly reduced evoked firing in spinal wide dynamic range neurons. Significant motor side effects were observed at analgesic doses and A-841720 also impaired cognitive function in the Y-maze and the Water aze tests. Conclusions and implications. The analgesic effects of a selective mGluR1 receptor antagonist are associated with motor and cognitive side effects. The lack of separation between efficacy and side effects in pre-clinical models indicates that mGluR1 antagonism may not provide an adequate therapeutic window for the development of such antagonists as novel analgesic agents in humans.
Eleven patients with Pancoast tumor, who failed to yield diagnostic materials by conventional sputum cytology and fiberoptic bronchoscopy, were studied by real-time linear-array and sector ...ultrasonography. The sector scanner through the supraclavicular approach adequately visualized the external profile and the internal texture of the lesions in all 11 patients, which is a significant improvement (p<0.05) over what can be accomplished with linear-array scanner through the intercostal approach. All patients received percutaneous transthoracic aspiration under ultrasound guidance. Positive cytologic diagnosis was established in ten of the 11 patients (91 percent). Additional biopsies performed in seven patients under similar ultrasonic guidance also provided concordant results. No complications were observed in this series. This study has clearly shown that ultrasound-guided aspiration biopsy can be a safe and useful means for obtaining materials for pathologic confirmation of Pancoast tumor. It may also assist in defining the tumor extension to pleura and adjacent structures.
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