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Biomedical subjects

A Pines

Publications and source records attributed to A Pines.

At least 19 recordsLinked to original sources
PubMed2002

The impact of hormonal therapy for infertility on the age at menopause.

OBJECTIVES: To look for possible association between past history of ovulation induction and age at menopause. DESIGN: Women attending our postmenopausal outpatient clinic were asked to fill questionnaires with demographic data, obstetrical history (including treatment for infertility), and medical details related to menopause. PATIENTS: The study group (n=31) consisted of women with a history of ovulation induction, and a control group (n=200) included women who did not experience such intervention. RESULTS: The age at the final menstrual bleeding was 46.4+/-5 in the study group, and 50+/-4 for the control group (P<0.001). This difference was most prominent for women who had induction of ovulation prior to age 35 years: they entered menopause at age 43.8+/-5 years. Smoking had a weak effect on the age at menopause (48.5+/-4 for current, vs. 49.9+/-4 for non- or past-smokers; P<0.03). CONCLUSIONS: This retrospective and preliminary study raises the question whether hormonal manipulations and ovarian over-stimulation during fertility treatments could be a risk factor for premature menopause.

Adult↗
PubMed2002

Two-dimensional NMR correlations of liquid crystals using switched angle spinning.

We present the first application of switched angle spinning (SAS) to correlate the first-order dipolar spectrum of a liquid crystalline sample with the isotropic magic angle spinning (MAS) spectrum in a two-dimensional experiment. In this experiment we are able to select the degree of dipolar couplings introduced via mechanical manipulations of the liquid crystal director in a single oriented sample. The (19)F SAS-COSY correlation of iodotrifluoroethylene, an AMX spin system, dissolved in the nematic liquid crystal 4-octylphenyl-2-chloro-4-(4-heptylbenzoyloxy)-benzoate provides assignment of both the J and dipolar couplings in a single experiment. This work demonstrates the use of oriented samples and sample spinning to resolve homonuclear dipolar couplings using isotropic chemical shifts.

Journal Article↗
PubMed2002

APE/Ref-1 is controlled by both redox and cAMP-dependent mechanisms in rat thyroid cells.

APE/Ref-1 is a multifunctional protein possessing both redox and DNA repair functions. Through its redox activity, APE/Ref-1 controls the DNA-binding function of several transcriptional regulators (AP1, NF-kappaB, p53, Pax proteins). We have previously shown that APE/Ref-1 upregulates the transcriptional activity of the thyroid-specific transcription factor Pax8. In thyroid cells, APE/Ref-1 can be detected both in the nuclear and cytoplasmatic compartments. In this study regulatory mechanisms acting on APE/Ref-1 were revealed using the FRTL-5 cell line. TSH induces both cytoplasm-to-nucleus translocation and neosynthesis of APE/Ref-1 protein. Interestingly, only neosynthesis is dependent on cAMP signalling. In contrast, the cytoplasm-to-nucleus translocation is dependent on redox-mediated mechanisms. Based upon the data shown in this study and in others, a bimodal control of APE/Ref-1 by TSH can be delineated.

Animals↗
PubMed2001

An experimental and theoretical investigation of the chemical shielding tensors of (13)C(alpha) of alanine, valine, and leucine residues in solid peptides and in proteins in solution.

We have carried out a solid-state magic-angle sample-spinning (MAS) nuclear magnetic resonance (NMR) spectroscopic investigation of the (13)C(alpha) chemical shielding tensors of alanine, valine, and leucine residues in a series of crystalline peptides of known structure. For alanine and leucine, which are not branched at the beta-carbon, the experimental chemical shift anisotropy (CSA) spans (Omega) are large, about 30 ppm, independent of whether the residues adopt helical or sheet geometries, and are in generally good accord with Omega values calculated by using ab initio Hartree-Fock quantum chemical methods. The experimental Omegas for valine C(alpha) in two peptides (in sheet geometries) are also large and in good agreement with theoretical predictions. In contrast, the "CSAs" (Deltasigma) obtained from solution NMR data for alanine, valine, and leucine residues in proteins show major differences, with helical residues having Deltasigma values of approximately 6 ppm while sheet residues have Deltasigma approximately 27 ppm. The origins of these differences are shown to be due to the different definitions of the CSA. When defined in terms of the solution NMR CSA, the solid-state results also show small helical but large sheet CSA values. These results are of interest since they lead to the idea that only the beta-branched amino acids threonine, valine, and isoleucine can have small (static) tensor spans, Omega (in helical geometries), and that the small helical "CSAs" seen in solution NMR are overwhelmingly dominated by changes in tensor orientation, from sheet to helix. These results have important implications for solid-state NMR structural studies which utilize the CSA span, Omega, to differentiate between helical and sheet residues. Specifically, there will be only a small degree of spectral editing possible in solid proteins since the spans, Omega, for the dominant nonbranched amino acids are quite similar. Editing on the basis of Omega will, however, be very effective for many Thr, Val, and Ileu residues, which frequently have small ( approximately 15-20 ppm) helical CSA (Omega) spans.

Alanine↗
PubMed2001

Solid-state NMR studies of the secondary structure of a mutant prion protein fragment of 55 residues that induces neurodegeneration.

The secondary structure of a 55-residue fragment of the mouse prion protein, MoPrP(89-143), was studied in randomly aggregated (dried from water) and fibrillar (precipitated from water/acetonitrile) forms by (13)C solid-state NMR. Recent studies have shown that the fibrillar form of the P101L mutant of MoPrP(89-143) is capable of inducing prion disease in transgenic mice, whereas unaggregated or randomly aggregated samples do not provoke disease. Through analysis of (13)C chemical shifts, we have determined that both wild-type and mutant sequence MoPrP(89-143) form a mixture of beta-sheet and alpha-helical conformations in the randomly aggregated state although the beta-sheet content in MoPrP(89-143, P101L) is significantly higher than in the wild-type peptide. In a fibrillar state, MoPrP(89-143, P101L) is completely converted into beta-sheet, suggesting that the formation of a specific beta-sheet structure may be required for the peptide to induce disease. Studies of an analogous peptide from Syrian hamster PrP verify that sequence alterations in residues 101-117 affect the conformation of aggregated forms of the peptides.

Amino Acid Sequence↗
PubMed2001

Functionalized xenon as a biosensor.

The detection of biological molecules and their interactions is a significant component of modern biomedical research. In current biosensor technologies, simultaneous detection is limited to a small number of analytes by the spectral overlap of their signals. We have developed an NMR-based xenon biosensor that capitalizes on the enhanced signal-to-noise, spectral simplicity, and chemical-shift sensitivity of laser-polarized xenon to detect specific biomolecules at the level of tens of nanomoles. We present results using xenon "functionalized" by a biotin-modified supramolecular cage to detect biotin-avidin binding. This biosensor methodology can be extended to a multiplexing assay for multiple analytes.

Avidin↗
PubMed2001

Approach to high-resolution ex situ NMR spectroscopy.

Nuclear magnetic resonance (NMR) experiments are typically performed with samples immersed in a magnet shimmed to high homogeneity. However, there are many circumstances in which it is impractical or undesirable to insert objects or subjects into the bore of a high-field magnet. Here we present a methodology based on an adaptation of nutation echoes that provides resolved spectra in the presence of matched inhomogeneous static and radiofrequency fields, thereby opening the way to high-resolution ex situ NMR. The observation of chemical shifts is regained through the use of multiple-pulse sequences of correlated, composite z-rotation pulses, producing resolved NMR spectra of liquid samples.

Magnetic Resonance Spectroscopy↗
PubMed2001

Mitochondrial localization of APE/Ref-1 in thyroid cells.

Mutations of mitochondrial DNA (mtDNA) are associated with different human diseases, including cancer and aging. Reactive oxygen species produced during oxidative phosphorylation are a major source of mtDNA damage. It is not clear, however, whether DNA repair mechanisms, able to abolish effects due to oxidative damage, are present in mitochondria. APE/Ref-1 is a nuclear protein possessing both redox activity (by which activates, "in vitro", the DNA-binding functions of several transcription factors) and DNA repair activity over apurinic/apyrimidinic sites. Immunohistochemical evidences indicate that in follicular thyroid cells, APE/Ref-1 is located in both nucleus and cytoplasm. Electronmicroscopy immunocytochemistry performed in the rat thyroid FRTL-5 cell line, indicates that part of the cytoplasmatic APE/Ref-1 is located in mitochondria. The presence of APE/Ref-1 inside mitochondria is further demonstrated by western blot analysis after cell fractionation. In the Kimol cell line (which is derived from FRTL-5, transformed by the Ki-ras oncogene) the amount of mitochondrial APE/Ref-1 is reduced by three to fourfold with respect to the normal FRTL-5 cells. These results suggest that: (i) a machinery capable of repairing DNA damaged by oxidative stress is present in mitochondria and (ii) mtDNA repair mechanisms may be impaired during cell transformation.

Animals↗
PubMed2001

Characterization of the effects of nonspecific xenon-protein interactions on (129)Xe chemical shifts in aqueous solution: further development of xenon as a biomolecular probe.

The sensitivity of (129)Xe chemical shifts to weak nonspecific xenon-protein interactions has suggested the use of xenon to probe biomolecular structure and interactions. The realization of this potential necessitates a further understanding of how different macromolecular properties influence the (129)Xe chemical shift in aqueous solution. Toward this goal, we have acquired (129)Xe NMR spectra of xenon dissolved in amino acid, peptide, and protein solutions under both native and denaturing conditions. In general, these cosolutes induce (129)Xe chemical shifts that are downfield relative to the shift in water, as they deshield the xenon nucleus through weak, diffusion-mediated interactions. Correlations between the extent of deshielding and molecular properties including chemical identity, structure, and charge are reported. Xenon deshielding was found to depend linearly on protein size under denaturing solution conditions; the denaturant itself has a characteristic effect on the (129)Xe chemical shift that likely results from a change in the xenon solvation shell structure. In native protein solutions, contributions to the overall (129)Xe chemical shift arise from the presence of weak xenon binding either in cavities or at the protein surface. Potential applications of xenon as a probe of biological systems including the detection of conformational changes and the possible quantification of buried surface area at protein-protein interfaces are discussed.

Amino Acids↗
PubMed2001

Retrograde embolism and atherosclerosis development in the human thoracic aorta: are the fluid dynamics explanations valid?

The mechanisms of atherosclerosis development in the thoracic aorta is miscellaneous and still only partially understood. The marked variability of the sites of deposition of atherosclerotic plaques in the aorta could not be clarified based solely on the risk-factors theory of atherosclerosis. The sites of deposition of atherosclerotic plaques are considered to be affected by blood-flow patterns that cause areas of altered shear stress on the aortic wall. Close relations between protruding aortic plaques (PAP), stroke and peripheral emboli were established. The analysis of PAP distribution and motion to characterize atherogenesis in the human thoracic aorta and the pathogeneses of embolic events was performed. We concluded that protruding aortic plaques and markers of relative aortic flow instability (occurrences of vortices) are predominantly noticed in the human arch and in the descending aorta, whereas the ascending aorta showed lesser prevalence of atheromatosis. Reversal and rotational blood-flow in the thoracic aorta most likely exist in all patients with systemic emboli and mobile protruding aortic atheromas. Therefore, retrograde cerebral embolism from distal aortic plaques is conceivable.

Adolescent↗
PubMed2001

Hypertension in menopausal women--a special case, for special treatment?

After the menopause the consequences of hypertension in women change. Their risks of myocardial infarction and stroke rise steeply, a rise that has been blamed in part on the loss of estrogen and the onset of menopausal metabolic syndrome, with endothelial dysfunction, hyperlipidemia, insulin resistance and derangement in coagulation. Hypertensive menopausal women have not had optimum treatment. They have poorer prognoses than men of the same age. Their antihypertensive management therefore merits special attention. Hormone replacement, aspirin prophylaxis and lipid-lowering drugs have their place. The antihypertensive drug chosen should not worsen the metabolic syndrome: angiotensin-II converting enzyme (ACE) inhibitors are therefore among the first-line drugs. Few drugs have been specifically aimed at menopausal hypertension and these are reviewed here.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

The combined cough frequency/severity scoring: a new approach to cough evaluation in clinical settings.

Cough assessment is an important component in the clinical evaluation of patients with respiratory and cardiovascular disorders (asthma, chronic obstructive lung disease, congestive heart failure, etc.). A dry bothersome cough is the most common adverse class effect of all angiotensin-converting enzyme inhibitors (ACE-I). The present study was aimed to determine the feasibility of a new combined frequency/severity cough scoring method in patients with ACE-I induced cough before and after their modification with aspirin addition. The study was designed to compare two different regimens of active treatment: intermediate (500 mg) versus low (100 mg) dose aspirin in ACE-I cough suppression (self-matched control data) and comprised 21 patients (14 men, 7 women; mean age 62 +/- 11 years) on ACE-I treatment. ACE-I treatment was discontinued and the dry cough completely disappeared, but returned in all patients within one week (rechallenge period) after ACE-I reintroducing. Severity of cough was defined as follows: 0--no cough at all; 1--occasional hems; 2--mild, isolated cough, without additional symptoms; 3--moderate, paroxysmal cough, without additional symptoms; 4--severe, strenuous cough, accompanied by chest discomfort. In addition to cough severity score, cough frequency score (0-10) was obtained using a visual analog scale: 0 = I never cough; 10 = I cough all day. Low doses of aspirin were ineffective to suppress ACE-I induced cough. In contrast, intermediate doses completely abolished cough in 14 patients and reduced coughing in all but one patient. Cough severity and cough frequency scores decreased, respectively, from 2.6 +/- 1.1 to 0.7 +/- 1.0 (p<0.001) and from 6.9 +/- 2.2 to 2.1 +/- 2.4 (p<0.0001). Overall, the cough frequency score method alone could identify a beneficial modification of cough in 17 (81%) patients and cough severity score method alone in 17 (76%). Using the combined cough frequency/severity scoring, a beneficial modification of cough could be identified in 20 (95%) of patients. The new combined cough frequency/severity scoring is suitable for clinical practice and can improve the identification of dynamic cough modifications during treatment period as compared with the conventional frequency score method. It may have important implications in the evaluation of patients with respiratory and cardiovascular disorders.

Aged↗
PubMed2000

The effect of oophorectomy and estrogen replacement therapy on Doppler derived parameters of aortic flow.

OBJECTIVES: The immediate consequences of surgical castration and estrogen replacement therapy (ERT) on left ventricular systolic performance as assessed by Doppler-derived parameters of aortic flow were examined. METHODS: A follow up study comprising two groups: eight premenopausal women who underwent hysterectomy and bilateral oophorectomy and started ERT 1 week after surgery - the study group, and a control group consisted of eight premenopausal women who did not start ERT following hysterectomy. Doppler echocardiography was performed before surgery, 1 week and 1 month post surgery. RESULTS: In both groups significant increase in heart rate was observed after 1 week, remaining high after 1 month in the control group only. The early post-operative period in all women was characterized by an increase in aortic flow velocity, but was statistically significant in the study group only. After initiation of ERT a significant decrease in peak flow velocity (PFV) and mean acceleration (MA) was recorded. CONCLUSIONS: Changes in estradiol level may be associated with alterations in left ventricular function. The initial and acute effect of estrogen on the heart muscle after surgical castration is towards a decrease in Doppler-derived parameters of aortic flow. Whether these effects represent a depression of left ventricular function, or alternatively, reflect peripheral vasculature reactivity, requires further evaluation.

Adult↗