tbuckley/cabot-search huggingface dataset:
Formation, mineralization, and resorption of bone in vitamin D—deficient rats
Authors: D. Baylink, M. Stauffer, J. Wergedal, C. Rich
Journal: Journal of Clinical Investigation (1970)

Quantitative histologic methods have been devised to measure several processes dealing with formation and mineralization of matrix and bone resorption. In vitamin D-deficient rats, the total osteoblastic matrix formation rate was 20% less and the total osteoclastic bone resorption rate was 80% more than in pair-fed control rats. These changes were found to be primarily because of changes in the rates of matrix formation and of bone resorption per unit area of forming or resorbing surfaces rather than to changes in the areas of these surfaces. The rate of maturation of osteoid and the rate of initial mineralization both were reduced to half of normal in the vitamin D-deficient rats. These variables related to matrix formation and mineralization were significantly correlated with the concentration of calcium but not with the concentration of phosphate in serum. The occurrence of hypocalcemia is interpreted as the consequence, both of reduced calcium absorption and of inadequate resorptive response of bone cells to homeostatic stimuli, such that, although bone resorption was greater than normal, it did not adequately compensate for the reduced intestinal absorption.
Monitoring Platelet Function in Glycoprotein IIb/IIIa Inhibitor Therapy
Authors: Kenneth K. Wu, James T. Willerson
Journal: Circulation (2001)

latelet aggregation is a key step in thrombus formation on the ruptured atherosclerotic plaque and after percutaneous coronary intervention (PCI).It is induced and amplified by several potent agonists, such as collagen, ADP, thromboxane A 2 , and thrombin.Each agonist binds to a specific platelet membrane receptor and signals the conformational change of glycoprotein IIb/IIIa (GP IIb/IIIa), which becomes an active receptor for fibrinogen.The binding of fibrinogen to GP IIb/IIIa mediates platelet aggregation. 1At high shear stress, von Willebrand factor also binds to GP IIb/IIIa and contributes to platelet aggregation. 2Thus, platelet surface GP IIb/IIIa plays a critical role in coronary arterial thrombosis and is a target for antithrombotic therapy.
A Novel Retinoic Acid Receptor β Isoform and Retinoid Resistance in Lung Carcinogenesis
Authors: W. Jeffrey Petty, Na Li, Adrian Biddle, Rebecca Bounds, Christopher Nitkin, Yan Ma, Konstantin H. Dragnev, Sarah J. Freemantle, Ethan Dmitrovsky
Journal: JNCI Journal of the National Cancer Institute (2005)

We previously reported that all-trans-retinoic acid (RA) treatment can prevent in vitro transformation of immortalized human bronchial epithelial (HBE) cells.To determine whether methylation inhibits RARbeta expression in HBE cells, we used sodium bisulfite sequencing to compare RARbeta P2 promoter methylation patterns in RA-sensitive (BEAS-2B) and RA-resistant (BEAS-2B-R1) HBE cells. Immunoblotting was used to assess induction of the RARbeta, placental transforming growth factor beta (PTGF-beta), Fos-related antigen 1 (Fra-1), and transglutaminase II (TGase II) proteins by RA following treatment with azacitidine, a DNA demethylating agent. The expression, transcriptional activity, and growth suppressive activity of RARbeta1', a novel RAR isoform, were evaluated in lung cancer cells transfected with RARbeta1', and expression was also studied in paired normal lung tissues and lung tumors. All statistical tests were two-sided.Hypermethylation was observed in the 3' region of the RARbeta P2 promoter of BEAS-2B-R1 but not BEAS-2B cells. Azacitidine treatment of BEAS-2B-R1 cells restored RA-inducible RARbeta2 and PTGF-beta expression but not that of RARbeta1', Fra-1, or TGase II. RARbeta1' expression was repressed in RA-resistant BEAS-2B-R1 cells and in lung cancers, compared with adjacent normal lung tissues. BEAS-2B-R1 cells transiently transfected with RARbeta1' had increased RA-dependent activation of a retinoic acid receptor element (RARE)-containing reporter plasmid compared with vector control (mean = 3.2, 95% confidence interval [CI] = 3.1 to 3.3 versus mean = 1.4, 95% CI = 1.3 to 1.5; P<.001). In H358 lung cancer cells transiently transfected with RARbeta1', RA treatment restored target gene expression compared with that in vector-transfected cells and suppressed cell growth compared with that in untreated cells (4 microM; treated mean = 0.49 versus untreated mean = 1.0, difference = 0.51, 95% CI = 0.35 to 0.67, P = .003; 8 microM: treated mean = 0.50 versus untreated mean = 1.0, difference = 0.50, 95% CI = 0.26 to 0.74, P = .015).Restoration of RARbeta1' expression may overcome retinoid resistance in lung carcinogenesis.
Effect of Darkness on Acoustic Startle in Vietnam Veterans With PTSD
Authors: Christian Grillon, Charles A. Morgan, Michael Davis, Steve M. Southwick
Journal: American Journal of Psychiatry (1998)

Exaggerated startle is a symptom of posttraumatic stress disorder (PTSD), but empirical studies have not consistently documented elevated baseline startle in PTSD. The authors proposed in a previous study that Vietnam veterans with PTSD exhibit exaggerated startle only under stressful conditions. They reported that darkness facilitated startle in humans, suggesting that the startle reflex is sensitive to the aversive nature of darkness. In the present study they tested the hypothesis that the magnitude of facilitation of startle by darkness would be greater in Vietnam veterans with PTSD than in comparison groups of subjects without PTSD. Prepulse inhibition was also investigated.The magnitude of startle and prepulse inhibition were assessed in alternating periods of darkness and light in 19 nonmedicated Vietnam veterans with PTSD, 13 Vietnam veterans without PTSD, and 20 civilians without PTSD.The overall startle level was higher in the veterans with PTSD than in either of the two groups of subjects without PTSD. Startle was facilitated by darkness, and the magnitude of this facilitation was greater in the veterans with PTSD than in the civilians without PTSD, but it was not greater in the veterans without PTSD. Prepulse inhibition was not affected by darkness and did not significantly differ among groups.Contrary to the hypothesis, elevated sensitivity to darkness was specific to individuals with combat experience, not to individuals with PTSD, perhaps because veterans had become aversively conditioned to darkness during their combat experiences. The more general increase in startle reactivity in the veterans with PTSD is consistent with clinical observations and descriptions of symptoms in DSM-IV.
Prognosis in Clostridium difficile infection complicating inflammatory bowel disease
Authors: C. D Stone
Journal: Gut (2008)

Since the earliest descriptions of Clostridium difficile as a cause of pseudomembranous colitis,1 clinicians have been familiar with the typical clinical setting in which infection can arise. It is well recognised that, classically, infection follows exposure to antibiotics targeting gut anaerobes and that transmission occurs nosocomially from one host to another.2 Yet, it has also been appreciated that the role that this Gram-positive bacillus plays in the colonic flora is complex and the circumstances that promote infection are variable. Early on, for instance, the term C difficile -associated disease (CDAD) came into use as it became apparent that positive stool testing failed to distinguish between an asymptomatic carrier state and true infection. Adoption of this term is an example of how physicians have had to adjust to the knowledge that has accumulated about this opportunistic organism. Over time, our understanding of C difficile has continued to expand and it is now known that infection can occur under a variety of conditions, in disparate settings, with a wide spectrum of severity and can recur despite treatment.3

In the past several years, some disturbing reports about C difficile have compelled the health care community to revisit its epidemiological and clinical importance. For one, several studies indicate a dramatic increase in the incidence of CDAD. Incidence has doubled in 10 years or less, and this has been demonstrated within various different patient populations and health care settings.4 5 Emergence of an epidemic strain of C difficile , characterised by greater virulence and conferring higher morbidity, explains part of this trend.6 7 Furthermore, clinicians increasingly recognise that CDAD may occur without prior antibiotic exposure. Controversy persists as to whom to treat and how best to treat, particularly given the development of increasing resistance to metronidazole.8–10 Even …
Combination therapy with vitamin D analogues
Authors: S. Lamba, M. Lebwohl
Journal: British Journal of Dermatology (2001)

Monotherapy with vitamin D analogues has been shown to be effective in the treatment of psoriasis. Vitamin D analogues have also been used in combination with other topical therapies, systemic therapies and phototherapy. In many instances, the efficacy of these other treatments can be maximized and adverse effects minimized when combined with vitamin D analogues. The combination of a topical corticosteroid with a vitamin D analogue can work synergistically to improve efficacy and reduce the side-effects from both treatments. However, caution must be used when mixing the two agents, as some topical corticosteroids will result in the degradation of the vitamin D analogue. Benefit from phototherapy is also increased when using vitamin D analogues, so that greater improvement occurs with fewer treatments. Effects on minimal erythema dose must be considered and the potential for ultraviolet blocking by vitamin D analogues may affect treatment. Some vitamin D analogues may also be susceptible to degradation by certain wavelengths of ultraviolet light. Combining vitamin D analogues with systemic agents exerts a dose-sparing effect, thus reducing the possibility of side-effects, but such combinations require further study. As long as treatments are used correctly, the benefits of combination therapy with vitamin D analogues usually outweigh the few drawbacks.
Why intraspecific trait variation matters in community ecology
Authors: Daniel I. Bolnick, Priyanga Amarasekare, Márcio S. Araújo, Reinhard Bürger, Jonathan M. Levine, Mark Novak, Volker H.W. Rudolf, Sebastian J. Schreiber, Mark C. Urban, David A. Vasseur
Journal: Trends in Ecology & Evolution (2011)
Caveolin-1 limits the contribution of BK(Ca) channel to EDHF-mediated arteriolar dilation: implications in diet-induced obesity
Authors: A. Feher, I. Rutkai, T. Beleznai, Z. Ungvari, A. Csiszar, I. Edes, Z. Bagi
Journal: Cardiovascular Research (2010)

Caveolin-1 (Cav-1) interacts with large conductance Ca2+-activated potassium channels (BKCa) and likely exerts a negative regulatory effect on the channel activity. We investigated the role of Cav-1 in modulating BK(Ca) channel-mediated, endothelium-derived hyperpolarizing factor (EDHF)-dependent arteriolar dilation in normal condition and in an experimental model of obesity. In isolated, pressurized (80 mmHg) gracilis muscle arterioles (∼100 µm) of Cav-1 knockout mice, acetylcholine (ACh)-induced, EDHF-mediated dilations were enhanced and were significantly reduced by the BK(Ca) channel inhibitor, iberiotoxin (IBTX), whereas IBTX had no effect on EDHF-mediated dilations in the wild-type mice. Dilations to the selective BK(Ca) channel opener, NS-1619 were augmented in the Cav-1 knockout mice. In high-fat diet-treated, obese rats ACh-induced coronary arteriolar dilations were preserved, whereas IBTX-sensitive, ACh-induced and also NS-1619-evoked vasodilations were augmented when compared with lean animals. In coronary arterioles of obese rats a reduced protein expression of Cav-1 was detected by western immunoblotting and immunohistochemistry. Moreover, in coronary arterioles of lean rats, disruption of caveolae with methyl-β-cyclodextrin augmented IBTX-sensitive, ACh-induced, and also NS-1619-evoked dilations. Thus, under normal conditions, Cav-1 limits the contribution of the BK(Ca) channel to EDHF-mediated arteriolar dilation. In obesity, a reduced expression of Cav-1 leads to greater contribution of the BK(Ca) channel to EDHF-mediated response, which seems essential for maintained coronary dilation.
C. E. KLAFS and D. D. ARNHEIM "Modern Principles of Athletic Training"
Authors: P. N. Sperryn
Journal: British Journal of Sports Medicine (1983)

This is an interesting volume assembled by two physical educationists in four main sections.Part 1, "The Field of Athletic Training" generally reviews the background to physical education and training, the role of the trainer and his responsibilities and relevant facilities.While much of the detail is relevant mainly to American practice, this is generally the best section of the book with clear definitions of job skills and the basic preparation of the sportsman in training.There are dear guidelines for a code of ethics, based on the American National Athletic Trainers Association's code which defines the limits of competence and responsibility of the trainer and could well act as the model for such work.The lavish facilities indicated in the relevant section would embarrass many British hospitals and can add a certain perspective to our professional ambitionsl
Concerted Evolution of Sea Anemone Neurotoxin Genes Is Revealed through Analysis of the Nematostella vectensis Genome
Authors: Yehu Moran, Hagar Weinberger, James C. Sullivan, Adam M. Reitzel, John R. Finnerty, Michael Gurevitz
Journal: Molecular Biology and Evolution (2008)

Gene families, which encode toxins, are found in many poisonous animals, yet there is limited understanding of their evolution at the nucleotide level. The release of the genome draft sequence for the sea anemone Nematostella vectensis enabled a comprehensive study of a gene family whose neurotoxin products affect voltage-gated sodium channels. All gene family members are clustered in a highly repetitive ∼30-kb genomic region and encode a single toxin, Nv1. These genes exhibit extreme conservation at the nucleotide level which cannot be explained by purifying selection. This conservation greatly differs from the toxin gene families of other animals (e.g., snakes, scorpions, and cone snails), whose evolution was driven by diversifying selection, thereby generating a high degree of genetic diversity. The low nucleotide diversity at the Nv1 genes is reminiscent of that reported for DNA encoding ribosomal RNA (rDNA) and 2 hsp70 genes from Drosophila, which have evolved via concerted evolution. This evolutionary pattern was experimentally demonstrated in yeast rDNA and was shown to involve unequal crossing-over. Through sequence analysis of toxin genes from multiple N. vectensis populations and 2 other anemone species, Anemonia viridis and Actinia equina, we observed that the toxin genes for each sea anemone species are more similar to one another than to those of other species, suggesting they evolved by manner of concerted evolution. Furthermore, in 2 of the species (A. viridis and A. equina) we found genes that evolved under diversifying selection, suggesting that concerted evolution and accelerated evolution may occur simultaneously.
Words in the brain are not just labelled concepts
Authors: Manfred Bierwisch
Journal: Behavioral and Brain Sciences (1999)

Pulverm&amp;uuml;ller assumes that words are represented as associations of two cell assemblies formed according to Hebb's coincidence rule. This seems to correspond to the linguistic notion that words consist of lexemes connected to lemmas. Standard examples from theoretical linguistics, however, show that lemmas and lexemes have properties that go beyond coincidence-based assemblies. In particular, they are inherently disposed toward combinatorial operations; push-down storage, modelled by decreasing reverberation in cell assemblies, cannot capture this. Hence, even if the language capacity has an associationist characterization at some level, it cannot just be co-occurrence-based assembly formation.
Matched-pair analysis of female and male breast cancer: a comprehensive cohort study.
Authors: R Foerster, FG Foerster, V Wulff, B Schubotz, R Lange, J Habeck, D Baaske, C Rudlowski
Journal: Cancer Research (2009)

Abstract Abstract #4129 Introduction:&amp;#x2028; Male breast cancer (MBC) is a rare disease accounting for approximately 1% of all breast carcinomas. Due to the low incidence treatment guidelines based on prospective studies are lacking. Presently treatment recommendations are derived from the standards for female breast cancer. However, those approaches might be inadequate because of distinct gender specific differences in tumor biology of breast cancer. This study was planned in order to elucidate potential differences between female and male breast cancer in both tumor biological behavior and clinical practice.&amp;#x2028; Patients and Methods:&amp;#x2028; MBC diagnosed 1995-2007 (region Chemnitz/Zwickau, Saxony, Germany) was retrospectively analyzed. Tumor characteristics, treatment and follow-up of the patients were documented. In order to highlight potential differences matched-pairs of female and male breast cancer patients were created. Each MBC was matched with a female counterpart (FBC) that showed accordance in at least 5-7 tumor characteristics (age, TNM, grade, hormone receptors, HER2 stage).&amp;#x2028; Results:&amp;#x2028; FBC and MBC (n=113 patients each) were evaluable for this analysis. For MBC the following tumor characteristics were documented: &amp;gt;60% advanced stages (T2-4), only 6% well differentiated, 42.5% nodal-positive, 86% hormone-sensitive (ER-positive 79.2%, PR-positive 76.9%), 6.2% HER2 positive.&amp;#x2028; 83.2% of MBC had a mastectomy/axillary dissection (FBC 49.0%), 55% adjuvant radiotherapy (FBC 66.7%), 64% adjuvant systemic therapy (FBC 80.6%), 32.7% chemotherapy (FBC 49.5%) and 47.8% endocrine treatment (FBC 60.1%). 31% of MBC had a relapse (FBC 25.9%), 68.1% overall survival (OS) (FBC 70.4%), 98 months (FBC 76 months) median survival time. In univariate analyses reduced OS of MBC was significant associated with advanced tumor stages (p&amp;lt;.005), poor histological grade (p&amp;lt;.05), receptor negative (p&amp;lt;.05) and nodal-positive tumors (p&amp;lt;.05). Furthermore adjuvant radiotherapy showed survival benefit. However, in multivariate analysis only tumor stage showed statistical significance (p&amp;lt;.01). Regarding these tumor characteristics no OS differences could be observed between FBC and MBC. However, MBC showed a trend to a shortened survival for receptor negative tumors in comparison to FBC (p=.055).&amp;#x2028; Discussion:&amp;#x2028; 1. Delayed diagnosis of MBC; 2. Our study showed more advanced and undifferentiated tumors with a high percentage of nodal positivity; 3. In our analysis these unfavorable tumor characteristics were not related to a poor OS; 4. We found no significant differences regarding disease outcome between FBC and MBC; despite of a more aggressive adjuvant treatment for FBC. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4129.
Aberrant extrathymic T cell receptor gene rearrangement in the small intestinal mucosa: a risk factor for coeliac disease?
Authors: A Bas, G Forsberg, V Sjoberg, S Hammarstrom, O Hernell, M-L Hammarstrom
Journal: Gut (2008)

<h3>Background:</h3> Coeliac disease is a small intestine enteropathy caused by permanent intolerance to wheat gluten. Gluten intake by patients with coeliac disease provokes a strong reaction by intestinal intraepithelial lymphocytes (IELs), which normalises on a gluten-free diet. <h3>Aim:</h3> To investigate whether impaired extrathymic T cell maturation and/or secondary T cell receptor (TCR) gene recombination in IELs are features of coeliac disease which could contribute to the failure of establishing tolerance to gluten. <h3>Methods:</h3> Expression levels of the four splice-forms of recombination activating gene-1 (RAG1) mRNA and preT α-chain (preTα) mRNA were determined in IEL-subsets of children with coeliac disease and controls. Frequencies of RAG1 expressing IELs were determined by immunomorphometry. <h3>Results:</h3> In controls, the RAG1-1A/2 splice-form selectively expressed outside the thymus, was dominant and expressed in both mature (TCR<sup>+</sup>) and immature (CD2<sup>+</sup>CD7<sup>+</sup>TCR<sup>−</sup>) IELs (∼8 mRNA copies/18S rRNA U). PreTα was expressed almost exclusively in CD2<sup>+</sup>CD7<sup>+</sup>TCR<sup>−</sup> IELs (∼40 mRNA copies/18S rRNA U). By contrast, RAG1 and preTα mRNA levels were low in patients with coeliac disease compared to controls, both with active disease and with inactive, symptom-free disease on a gluten-free diet (p values &lt;0.01 for mature and &lt;0.05 for immature IELs). Similarly, the frequencies of RAG1+ IELs were significantly lower in patients with coeliac disease compared to controls (p&lt;0.001). <h3>Conclusions:</h3> Patients with coeliac disease appear to have an impaired capacity for extrathymic TCR gene rearrangement. This is an inherent feature, which probably plays a pivotal role in the failure to efficiently downregulate the T cell response to gluten.
The role of matrix metalloproteinases in heart disease
Authors: J. P.M. Cleutjens
Journal: Cardiovascular Research (1996)

The heart can be subdivided into cellular and extracellular compartments. Approximately one third of cells from this cellular compartment are cardiomyocytes whereas two thirds of the cells are non-cardiomyocytes. Because of their dimensions, cardiomyocytes occupy two thirds of the total myocardial volume. Non-myocytes, predominantly fibroblasts, endothelial cells and to a 1esSer extent mast cells, macrophages and smooth muscle cells in the media of the myocardial vasculature, together with the extracellular matrix and tissue fluid, fill the remaining one third of cardiac tissue. The extracellular matrix compartment consists of a structural network of interstitial type I and III fibrillar collagens, which have a high rigidity and are extremely resistant to proteolytic digestion [ 11. Besides the fibrillar collagen network, the extracellular compartment consists of basement membranes, which in the heart surround individual cardiomyocytes and smooth muscle cells, and separate endothelial cells, even in capillaries, from the media or surrounding connective tissue. Basement membranes contain a structural backbone of type IV collagen to which other components like laminins, fibronectin, heparan sulphate proteoglycan, and other extracellular matrix components can attach 121. Type V collagen has been localized in basement membranes and interspersed in the interstitium [3]. Type VI collagen was found predominantly between cardiomyo-cytes linking basement membranes of the individual myocytes to the surrounding extracellular matrix and interstitial cells. The cardiac extracellu-