The prevalence of alexithymia in fifty-five motor vehicle accident survivors who had chronic pain complaints and met DSM-III-R criteria for somatoform pain disorder was 53%. Alexithymic and ...non-alexithymic patients did not differ on self-reports of current pain severity or in the number of pain locations. Alexithymic patients were found to use significantly more words to describe their pain, suggesting they may have a more diffuse style in communicating their pain experience.
We sought to assess the relation between plasma lipoprotein(a) Lp(a) levels, clinical variables and angiographic coronary artery disease (CAD) in patients with chronic stable angina.
The relation ...between plasma Lp(a) levels and the severity and extent of angiographic CAD has not been studied in well characterized patients with stable angina pectoris.
We investigated clinical variables, lipid variables and angiographic scores in 129 consecutive white patients (43 women) undergoing coronary angiography for chronic stable angina.
Plasma Lp(a) levels were significantly higher in patients with than in those without significant angiographic stenoses (> or =70%) (372 mg/liter interquartile range 87 to 884 vs. 105 mg/liter interquartile range 56 to 366, respectively, p=0.002). This difference remained significant when patients with mild or severe angiographic disease were compared with those with completely normal coronary arteries (312 mg/liter interquartile range 64 to 864 vs. 116 mg/liter interquartile range 63 to 366, respectively, p=0.02). However, subset analysis indicated that this difference achieved statistical significance only in women. Multiple logistic regression analysis indicated that Lp(a) concentration was independently predictive of significant angiographic stenoses (adjusted odds ratio OR 9.1, 95% confidence interval CI 2.0 to 42.1, p=0.006) and remained true even after exclusion of patients receiving lipid-lowering treatment (n=27) (OR 10.4, 95% CI 1.1 to 102.9, p=0.05). Lp(a) also had independent predictive value in a similar analysis using mild or severe angiographic disease as the outcome variable (OR 11.8, 95% CI 1.5 to 90.8, p=0.02).
Our results indicate that elevated plasma Lp(a) is an independent risk factor for angiographic CAD in chronic stable angina and may have particular significance in women.
Rat parvalbumin (PV), an EF-hand type Ca(2+)-binding protein, was expressed in Escherichia coli and mutated by replacing a
Phe at position 102 with a unique Trp in order to introduce a distinct ...fluorescent label into the protein. Mass spectroscopy
and NMR data indicate that the recombinant wild-type (PVWT) and F102W mutant (PVF102W) proteins have the expected molecular
weight and retain the native structure. Both proteins contain two non-cooperative Ca2+/Mg(2+)-binding sites with intrinsic
affinity constants, KCa and KMg, of 2.4 +/- 0.9 x 10(7) M-1 and of 2.9 +/- 0.2 x 10(4) M-1, respectively, for PVWT, and KCa
and KMg, of 2.7 +/- 1.1 x 10(7) M-1 and of 4.4 +/- 0.3 x 10(4) M-1, respectively, for PVF102W. Based on the highly similar
metal binding properties of PVWT and PVF102W the latter protein was used to study cation-dependent conformational changes.
Trp fluorescence emission and UV difference spectra of PVF102W indicated that the Trp residue at position 102 is confined
to a hydrophobic core and conformationally strongly restricted. Upon Ca2+ or Mg2+ binding the structural organization of the
region around the Trp is hardly affected, but there are significant changes in its electrostatic environment. The conformational
change upon binding of Ca2+ and Mg2+, as monitored by UV difference spectrophotometry, increases linearly from 0 to 2 cations
bound, indicating that the binding of both ions contributes equally to the structural organization in this protein.
Editorial: A Global Lab against Influenza Layne, Scott P.; Beugelsdijk, Tony J.; C. Kumar N. Patel ...
Science (American Association for the Advancement of Science),
09/2001, Letnik:
293, Številka:
5536
Journal Article
Recenzirano
Layne et al discuss the World Health Organization's Influenza Program and its limitations. Current time-consuming and labor-intensive lab methods and analyzation techniques greatly hinder efforts to ...contain and control influenza.
The discovery of expression quantitative trait loci ("eQTLs") can help to unravel genetic contributions to complex traits. We identified genetic determinants of human liver gene expression variation ...using two independent collections of primary tissue profiled with Agilent (n = 206) and Illumina (n = 60) expression arrays and Illumina SNP genotyping (550K), and we also incorporated data from a published study (n = 266). We found that ∼30% of SNP-expression correlations in one study failed to replicate in either of the others, even at thresholds yielding high reproducibility in simulations, and we quantified numerous factors affecting reproducibility. Our data suggest that drug exposure, clinical descriptors, and unknown factors associated with tissue ascertainment and analysis have substantial effects on gene expression and that controlling for hidden confounding variables significantly increases replication rate. Furthermore, we found that reproducible eQTL SNPs were heavily enriched near gene starts and ends, and subsequently resequenced the promoters and 3'UTRs for 14 genes and tested the identified haplotypes using luciferase assays. For three genes, significant haplotype-specific in vitro functional differences correlated directly with expression levels, suggesting that many bona fide eQTLs result from functional variants that can be mechanistically isolated in a high-throughput fashion. Finally, given our study design, we were able to discover and validate hundreds of liver eQTLs. Many of these relate directly to complex traits for which liver-specific analyses are likely to be relevant, and we identified dozens of potential connections with disease-associated loci. These included previously characterized eQTL contributors to diabetes, drug response, and lipid levels, and they suggest novel candidates such as a role for NOD2 expression in leprosy risk and C2orf43 in prostate cancer. In general, the work presented here will be valuable for future efforts to precisely identify and functionally characterize genetic contributions to a variety of complex traits.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objectives. We sought to assess the relation between plasma lipoprotein(a) Lp(a) levels, clinical variables and angiographic coronary artery disease (CAD) in patients with chronic stable angina.
...Background. The relation between plasma Lp(a) levels and the severity and extent of angiographic CAD has not been studied in well characterized patients with stable angina pectoris.
Methods. We investigated clinical variables, lipid variables and angiographic scores in 129 consecutive white patients (43 women) undergoing coronary angiography for chronic stable angina.
Results. Plasma Lp(a) levels were significantly higher in patients with than in those without significant angiographic stenoses (≥70%) (372 mg/liter interquartile range 87 to 884 vs. 105 mg/liter interquartile range 56 to 366, respectively, p = 0.002). This difference remained significant when patients with mild or severe angiographic disease were compared with those with completely normal coronary arteries (312 mg/liter interquartile range 64 to 864 vs. 116 mg/liter interquartile range 63 to 366, respectively, p = 0.02). However, subset analysis indicated that this difference achieved statistical significance only in women. Multiple logistic regression analysis indicated that Lp(a) concentration was independently predictive of significant angiographic stenoses (adjusted odds ratio OR 9.1, 95% confidence interval CI 2.0 to 42.1, p = 0.006) and remained true even after exclusion of patients receiving lipid-lowering treatment (n = 27) (OR 10.4, 95% CI 1.1 to 102.9, p = 0.05). Lp(a) also had independent predictive value in a similar analysis using mild or severe angiographic disease as the outcome variable (OR 11.8, 95% CI 1.5 to 90.8, p = 0.02).
Conclusions. Our results indicate that elevated plasma Lp(a) is an independent risk factor for angiographic CAD in chronic stable angina and may have particular significance in women.
Neurogranin (Ng), a post-synaptic protein involved in memory formation, has been investigated as a biomarker in the cerebrospinal fluid (CSF) in Alzheimer's disease (AD) and ageing. CSF Ng levels are ...elevated in AD relative to healthy controls and correlate with cognition; however, few studies have focused on Ng abundance in the brain. Synapse loss in the brain correlates closely with cognitive decline in AD making synaptic biomarkers potentially important for tracking disease progression, but the links between synaptic protein changes in CSF and brain remain incompletely understood. In the current study, Ng abundance was examined in post-mortem human brain tissue across AD, healthy ageing (HA), and mid-life (ML) cohorts. Ng levels were quantified in three brain regions associated with cognitive change found during ageing and neurodegenerative diseases, namely the middle temporal gyrus, primary visual cortex and the posterior hippocampus using immunohistochemistry. To support immunohistochemical analysis, total homogenate and biochemically enriched synaptic fractions from available temporal gyrus tissues were examined by immunoblot. Finally, we examined whether Ng is associated with lifetime cognitive ageing. Ng levels were significantly reduced in AD relative to HA and ML cases across all regions. Additionally Ng was significantly reduced in HA in comparison to ML in the primary visual cortex. Immunoblotting confirms reduced Ng levels in AD cases supporting immunohistochemical results. Interestingly, there was also a significant reduction of synapse-associated Ng in our group who had lifetime cognitive decline in comparison to the group with lifetime cognitive resilience indicating loss of neurogranin in remaining synapses during ageing is associated with cognitive decline. Our findings indicate that increases in CSF Ng reflect loss of brain neurogranin and support the use of CSF Ng as a biomarker of AD and potentially of cognitive decline in healthy ageing.
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•Neurogranin levels decrease in Alzheimer's disease brain tissue.•Synaptic fractionation of brain reveals neurogranin is decreased in Alzheimer's synapses.•The loss of neurogranin from Alzheimer's synapses potentially explains previously observed increases in CSF.
Morphologists have historically had to rely on destructive procedures to visualize the three‐dimensional (3‐D) anatomy of animals. More recently, however, non‐destructive techniques have come to the ...forefront. These include X‐ray computed tomography (CT), which has been used most commonly to examine the mineralized, hard‐tissue anatomy of living and fossil metazoans. One relatively new and potentially transformative aspect of current CT‐based research is the use of chemical agents to render visible, and differentiate between, soft‐tissue structures in X‐ray images. Specifically, iodine has emerged as one of the most widely used of these contrast agents among animal morphologists due to its ease of handling, cost effectiveness, and differential affinities for major types of soft tissues. The rapid adoption of iodine‐based contrast agents has resulted in a proliferation of distinct specimen preparations and scanning parameter choices, as well as an increasing variety of imaging hardware and software preferences. Here we provide a critical review of the recent contributions to iodine‐based, contrast‐enhanced CT research to enable researchers just beginning to employ contrast enhancement to make sense of this complex new landscape of methodologies. We provide a detailed summary of recent case studies, assess factors that govern success at each step of the specimen storage, preparation, and imaging processes, and make recommendations for standardizing both techniques and reporting practices. Finally, we discuss potential cutting‐edge applications of diffusible iodine‐based contrast‐enhanced computed tomography (diceCT) and the issues that must still be overcome to facilitate the broader adoption of diceCT going forward.
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