tbuckley/cabot-search huggingface dataset:
Impact of a High Loading Dose of Atorvastatin on Contrast-Induced Acute Kidney Injury
Authors: Cristina Quintavalle, Danilo Fiore, Francesca De Micco, Gabriella Visconti, Amelia Focaccio, Bruno Golia, Bruno Ricciardelli, Elvira Donnarumma, Antonio Bianco, Maria Assunta Zabatta, Giancarlo Troncone, Antonio Colombo, Carlo Briguori, Gerolama Condorelli
Journal: Circulation (2012)

The role of statins in the prevention of contrast-induced acute kidney injury (CIAKI) is controversial.First, we investigated the in vivo effects of atorvastatin on CIAKI. Patients with chronic kidney disease enrolled in the Novel Approaches for Preventing or Limiting Events (NAPLES) II trial were randomly assigned to (1) the atorvastatin group (80 mg within 24 hours before contrast media [CM] exposure; n=202) or (2) the control group (n=208). All patients received a high dose of N-acetylcysteine and sodium bicarbonate solution. Second, we investigated the in vitro effects of atorvastatin pretreatment on CM-mediated modifications of intracellular pathways leading to apoptosis or survival in renal tubular cells. CIAKI (ie, an increase >10% of serum cystatin C concentration within 24 hours after CM exposure) occurred in 9 of 202 patients in the atorvastatin group (4.5%) and in 37 of 208 patients in the control group (17.8%) (P=0.005; odds ratio=0.22; 95% confidence interval, 0.07-0.69). CIAKI rate was lower in the atorvastatin group in both diabetics and nondiabetics and in patients with moderate chronic kidney disease (estimated glomerular filtration rate, 31-60 mL/min per 1.73 m(2)). In the in vitro model, pretreatment with atorvastatin (1) prevented CM-induced renal cell apoptosis by reducing stress kinases activation and (2) restored the survival signals (mediated by Akt and ERK pathways).A single high loading dose of atorvastatin administered within 24 hours before CM exposure is effective in reducing the rate of CIAKI. This beneficial effect is observed only in patients at low to medium risk.
Follow−up of asthma from childhood to adulthood: Influence of potential childhood risk factors on the outcome of pulmonary function and bronchial responsiveness in adulthood
Authors: Ruurd Jan Roorda, Jorrit Gerritsen, Wim M.C. van Aalderen, Jan P. Schouten, Johanna C. Veltman, Scott T. Weiss, Klaas Knol
Journal: Journal of Allergy and Clinical Immunology (1994)
Magnetic resonance imaging of skeletal muscle involvement in limb restricted vasculitis
Authors: S Gallien
Journal: Annals of the Rheumatic Diseases (2002)

Limb restricted polyarteritis nodosa (PAN) and PAN-type diseases such as isolated vasculitis of skeletal muscle are localised vasculitides affecting the skin, muscles, or peripheral nerves, usually of the lower limbs. These diseases often present with non-specific clinical symptoms and normal laboratory values and electromyograms. The usefulness of magnetic resonance imaging (MRI) of skeletal muscle has been poorly investigated to date.To describe the MRI findings in the legs of three patients with limb restricted vasculitides (two PAN, one isolated vasculitis of the skeletal muscle) with histologically established muscle involvement.MRI was carried out on calf muscles and T(2) weighted images, unenhanced T(1) weighted images, and STIR sequences were obtained.Muscle damage resulted in oedema-like changes on MRI characterised by hyperintense signals in T(2) weighted and slow tau inversion recovery (STIR) sequences and normal unenhanced T(1) weighted sequences of one or several leg muscles.MRI should be considered a useful complementary examination that might facilitate the recognition of limb restricted vasculitides, and possibly indicate the site for muscle biopsy. It could also be useful in monitoring the course of the disease. Future studies should also evaluate MRI for systemic PAN or other systemic vasculitides with muscle involvement.
Consciousness and agency: Explaining what and explaining who
Authors: Richard A. Carlson
Journal: Behavioral and Brain Sciences (1999)

The target article offers an intriguing hypothesis relating the content of phenomenal experience to a qualitative characteristic of information processing. This hypothesis, however, offers only an explanation of the “what” of consciousness, not the “who” – the experiencing agent remains mysterious. Their hypothesis about the unity of consciousness can be linked to an informational account of the agency or subjectivity of consciousness.
Variant diphtheria toxin-interleukin-3 fusion proteins with increased receptor affinity have enhanced cytotoxicity against acute myeloid leukemia progenitors.
Authors: Donna E Hogge, Leman Yalcintepe, Siaw-Hui Wong, Brigitte Gerhard, Arthur E Frankel
Journal: Clinical Cancer Research (2006)

Abstract A fusion protein linking a truncated form of diphtheria toxin (DT(388)) to human interleukin-3 (DT(388)IL3) kills malignant progenitors from some patients with acute myeloid leukemia (AML) while sparing normal progenitors. This study evaluated two variants of DT(388)IL3 with increased affinity for the IL-3 receptor (IL-3R) for their cytotoxicity to AML progenitors and determined the ability of quantitative reverse transcription-PCR assessment of expression of the IL-3R subunits to predict the effectiveness of wild-type DT(388)IL3 and its variants. Both the IL-3 deletion variant (Delta125-133) and the amino acid substitution variant (K116W) showed enhanced toxicity against AML colony-forming cells (AML-CFC; but not normal CFC) compared with wild-type DT(388)IL3 with the K116W variant achieving &amp;gt;90% AML-CFC kill with 17 of 23 patient samples. This variant was also more effective against AML cells engrafting in nonobese diabetic severe combined immunodeficient mice. There was a significant correlation between the expression of the alpha and, particularly, the common beta subunit of the IL-3R on AML blasts detected by quantitative reverse transcription-PCR and AML-CFC kill. Thus, the combined use of IL-3R expression to select patients most likely to respond to DT(388)IL3 and the improved cytotoxicity of the K116W DT(388)IL3 variant against leukemic progenitors may enhance the clinical usefulness of these fusion proteins.
Sarcomeric dysfunction in heart failure
Authors: N. Hamdani, V. Kooij, S. van Dijk, D. Merkus, W. J. Paulus, C. d. Remedios, D. J. Duncker, G. J.M. Stienen, J. van der Velden
Journal: Cardiovascular Research (2007)

Sarcomeric dysfunction plays a central role in reduced cardiac pump function in heart failure. This review focuses on the alterations in sarcomeric proteins in diseased myocardium that range from altered isoform expression to post-translational protein changes such as proteolysis and phosphorylation. Recent studies in animal models of heart failure and human failing myocardium converge and indicate that sarcomeric dysfunction, including altered maximum force development, Ca(2+) sensitivity, and increased passive stiffness, largely originates from altered protein phosphorylation, caused by neurohumoral-induced alterations in the kinase-phosphatase balance inside the cardiomyocytes. Novel therapies, which specifically target phosphorylation sites within sarcomeric proteins or the kinases and phosphatases involved, might improve cardiac function in heart failure.
Complete regression of cutaneous lesions of refractory Ph+ ALL after 4 weeks of treatment with BMS-354825
Authors: Elisabetta Abruzzese, Giovanni Del Poeta, Rosanna Barbato, Stefano Fratoni, Malgorzata M. Trawinska, Daniela Zangrilli, Angela M. Coletta, Ivona M. Patroi, Francesca Francesconi, Giuseppe Santeusanio, Paolo De Fabritiis, Sergio Amadori
Journal: Blood (2006)
GC- and AT-rich chromatin domains differ in conformation and histone modification status and are differentially modulated by Rpd3p
Authors: Job Dekker
Journal: Genome biology (2007)

Base-composition varies throughout the genome and is related to organization of chromosomes in distinct domains (isochores). Isochore domains differ in gene expression levels, replication timing, levels of meiotic recombination and chromatin structure. The molecular basis for these differences is poorly understood. We have compared GC- and AT-rich isochores of yeast with respect to chromatin conformation, histone modification status and transcription. Using 3C analysis we show that, along chromosome III, GC-rich isochores have a chromatin structure that is characterized by lower chromatin interaction frequencies compared to AT-rich isochores, which may point to a more extended chromatin conformation. In addition, we find that throughout the genome, GC-rich and AT-rich genes display distinct levels of histone modifications. Interestingly, elimination of the histone deacetylase Rpd3p differentially affects conformation of GC- and AT-rich domains. Further, deletion of RPD3 activates expression of GC-rich genes more strongly than AT-rich genes. Analyses of effects of the histone deacetylase inhibitor trichostatin A, global patterns of Rpd3p binding and effects of deletion of RPD3 on histone H4 acetylation confirmed that conformation and activity of GC-rich chromatin are more sensitive to Rpd3p-mediated deacetylation than AT-rich chromatin. We find that GC-rich and AT-rich chromatin domains display distinct chromatin conformations and are marked by distinct patterns of histone modifications. We identified the histone deacetylase Rpd3p as an attenuator of these base composition-dependent differences in chromatin status. We propose that GC-rich chromatin domains tend to occur in a more active conformation and that Rpd3p activity represses this propensity throughout the genome.
Different roles for the Fc epsilon RI gamma chain as a function of the receptor context.
Authors: R Paolini, V Renard, E Vivier, K Ochiai, M H Jouvin, B Malissen, J P Kinet
Journal: The Journal of Experimental Medicine (1995)

The high affinity immunoglobulin E receptor (Fc epsilon RI) and the B and T cell antigen receptors (TCR) are multimeric complexes containing subunits with cytoplasmic antigen recognition activation motifs (ARAMs). The presence of multiple motifs may be a way to amplify a single signal or provide independent activation modules. Here we have compared the signaling capacity of the same Fc epsilon RI gamma motif in the context of two different receptors, Fc epsilon RI and TCR/CD3, simultaneously reconstituted on the surface of the same zeta-deficient T cell line. Both reconstituted receptors mediate early (phosphorylation) and late (interleukin [IL]-2 release) signals. Mutation of the two tyrosine residues of ARAM gamma alters early signaling by both receptors, but the set of substrates phosphorylated via ARAM gamma is different for each receptor and is thus dependent on the receptor context. Furthermore, the mutations prevent Fc epsilon RI- but not TCR/CD3-mediated IL-2 release. These data demonstrate that ARAM gamma is necessary for allowing both receptors to phosphorylate the complete set of substrates, and that the CD3 complex, unlike the Fc epsilon RI beta chain, contains activation modules capable of compensating for the absence of a functional ARAM gamma in generating late signals such as IL-2 release.
Angiotensin-Receptor Blockade in Acute Myocardial Infarction — A Matter of Dose
Authors: Douglas L. Mann, Anita Deswal
Journal: New England Journal of Medicine (2003)

Beta-blockers, angiotensin-converting–enzyme (ACE) inhibitors, and aldosterone antagonists have been shown to reduce the overall risk of death as well as the risk of major nonfatal cardiovascular events when they are administered to patients with acute myocardial infarction who also have left ventricular systolic dysfunction, clinical evidence of heart failure, or both.1,2 However, there remains a sizable subgroup of patients in whom clinical heart failure worsens despite optimal medical therapy after acute myocardial infarction. Relevant to this discussion is the observation that ACE inhibitors block only 13 percent of the total production of angiotensin II in the human heart3 because . . .
Prevalence of Alzheimer's disease and vascular dementia: association with education. The Rotterdam study
Authors: A. Ott, M. M B Breteler, F. van Harskamp, J. J Claus, T. J M van der Cammen, D. E Grobbee, A. Hofman
Journal: BMJ (1995)

<h3>Abstract</h3> <b>Objective</b>: To estimate the prevalence of dementia and its subtypes in the general population and examine the relation of the disease to education. <b>Design</b>: Population based cross sectional study. <b>Setting</b>: Ommoord, a suburb of Rotterdam. <b>Subjects</b>: 7528 participants of the Rotterdam study aged 55-106 years. <b>Results</b>: 474 cases of dementia were detected, giving an overall prevalence of 6.3%. Prevalence ranged from 0.4% (5/1181 subjects) at age 55-59 years to 43.2% (19/44) at 95 years and over. Alzheimer9s disease was the main subdiagnosis (339 cases; 72%); it was also the main cause of the pronounced increase in dementia with age. The relative proportion of vascular dementia (76 cases; 16%), Parkinson9s disease dementia (30; 6%), and other dementias (24; 5%) decreased with age. A substantially higher prevalence of dementia was found in subjects with a low level of education. The association with education was not due to confounding by cardiovascular disease. <b>Conclusions</b>: The prevalence of dementia increases exponentially with age. About one third of the population aged 85 and over has dementia. Three quarters of all dementia is due to Alzheimer9s disease. In this study an inverse dose-response relation was found between education and dementia—in particular, Alzheimer9s disease. <h3>Key messages</h3> Key messages Of all cases of dementia, 72% were cases of Alzheimer9s disease The pronounced increase in prevalence of dementia with age was due to a substantial increase in Alzheimer9s disease Alzheimer9s disease was more often diagnosed in less educated people The association between dementia and education could not be explained by cardiovascular disease comorbidity
Fordyce granules and hereditary non-polyposis colorectal cancer syndrome
Authors: C De Felice
Journal: Gut (2005)

<b>Background:</b> Germline mutations in mismatch repair (MMR) genes are found in only about half of clinically diagnosed families with hereditary non-polyposis colorectal cancer syndrome (HNPCC) (or Lynch syndrome). Early identification of gene carriers is essential to reduce cancer incidence and overall mortality. <b>Aims:</b> Recent evidence indicates an increase in size and number of sebaceous glands following activation of the hedgehog pathway, a crucial signalling pathway for animal development that is aberrantly activated in several types of cancer. Here we sought to assess a possible association between Fordyce granules (FGs—that is, ectopic sebaceous glands on the oral mucosa) and HNPCC. <b>Methods:</b> A total of 15 members of five different genetically unrelated HNPCC kindreds (<i>MLH1</i> gene mutation n = 8; undetectable MLH1 protein at immunochemistry n = 4; clinical diagnosis n = 3) and 630 genetically unrelated age and sex matched healthy controls were examined. Following examination of the oral mucosa surface, subjects were categorised as either FGs positive or FGs negative. <b>Results:</b> Evidence of FGs was significantly associated with HNPCC (13/15 (86.7%) affected patients <i>v</i> 6/630 (0.95%) controls; p&lt;0.0001), with a relative risk of 91.0 (95% confidence interval 40.05–206.76). The observed difference remained significant when carriers of germline mutations in MMR genes were considered (8/15 <i>v</i> 6/630; p&lt;0.0001). The most common site for the FGs in HNPCC patients was the lower gingival and vestibular oral mucosa. <b>Conclusions:</b> Our findings suggest that a previously unrecognised activation of the sebaceous glands system occurs in HNPCC. The observation could be of value for attending physicians in identifying affected families and/or increase the accuracy of the currently available molecular genetics screenings.
Endometase/Matrilysin-2 in Human Breast Ductal Carcinoma <b> <i>in Situ</i> </b> and Its Inhibition by Tissue Inhibitors of Metalloproteinases-2 and -4
Authors: Yun-Ge Zhao, Ai-Zhen Xiao, Hyun I. Park, Robert G. Newcomer, Mei Yan, Yan-Gao Man, Sue C. Heffelfinger, Qing-Xiang Amy Sang
Journal: Cancer Research (2004)

Abstract Local disruption of the integrity of both the myoepithelial cell layer and the basement membrane is an indispensable prerequisite for the initiation of invasion and the conversion of human breast ductal carcinoma in situ (DCIS) to infiltrating ductal carcinoma (IDC). We previously reported that human endometase/matrilysin-2/matrix metalloproteinase (MMP) 26-mediated pro-gelatinase B (MMP-9) activation promoted invasion of human prostate carcinoma cells by dissolving basement membrane proteins (Y. G. Zhao et al., J. Biol. Chem., 278: 15056–15064, 2003). Here we report that tissue inhibitor of metalloproteinases (TIMP)-2 and TIMP-4 are potent inhibitors of MMP-26, with apparent Ki values of 1.6 and 0.62 nm, respectively. TIMP-2 and TIMP-4 also inhibited the activation of pro-MMP-9 by MMP-26 in vitro. The expression levels of MMP-26, MMP-9, TIMP-2, and TIMP-4 proteins in DCIS were significantly higher than those in IDC, atypical intraductal hyperplasia, and normal breast epithelia adjacent to DCIS and IDC by immunohistochemistry and integrated morphometry analysis. Double immunofluorescence labeling and confocal laser scanning microscopy revealed that MMP-26 was colocalized with MMP-9, TIMP-2, and TIMP-4 in DCIS cells. Higher levels of MMP-26 mRNA were also detected in DCIS cells by in situ hybridization.
Doctor-patient communication in rheumatology: studies of visual and verbal perception using educational booklets and other graphic material.
Authors: J M Moll
Journal: Annals of the Rheumatic Diseases (1986)

Patients (n = 404) with osteoarthrosis and control subjects (n = 233) were studied to examine the communicational value of five styles of illustration (cartoon (C), matchstick (M), representational (R), symbolic (S), photographic (P) and two levels of text (9easy9, 9hard9), presented as educational booklets about osteoarthrosis. Booklet comprehension was tested with a multiple choice questionnaire (MCQ) scored by two raw score and two, more sensitive, weight-of-evidence methods. Further studies assessed perception of image detail, tone, and colour by ranking, rating, latency, and questionnaire methods. A subgroup was tested psychometrically. The main findings were: pictures in booklets enhance communication; perception of pictorial style depends on its vehicle of presentation, cartoons being most effective in booklets, photographs overall; simplifying text does not significantly enhance communication; certain picture-text 9interactions9 appear to increase comprehension (e.g. 9hard9 text with 9easy9 pictures); several 9endogenous9 factors are associated with increased comprehension: 9psychological9 (e.g., intelligence, memory, reading skill); 9demographic9 (e.g., the young, males, higher social grades, higher educational levels); 9disease9 (e.g., longer disease duration, previous information about the disease).
TICK-TRANSMITTED INFECTIOUS DISEASES IN THE UNITED STATES
Authors: DH Walker
Journal: Annual Review of Public Health (1998)

▪ Abstract The epidemiologic concept of tick-transmitted diseases has increased in importance with the recognition of the emerging infectious diseases, Lyme borreliosis, human monocytotropic and granulocytotropic ehrlichioses, and three different babesioses. Effective public health control of these diseases would depend upon critical knowledge of the vector biology of the ticks that transmit them. Rocky Mountain spotted fever and the human ehrlichioses are life-threatening yet treatable diseases. A major problem remains establishment of the diagnosis when treatment decisions are being made. Clinical manifestations, other than erythema migrans for Lyme borreliosis, do not provide strong diagnostic clues. Ehrlichiae or babesiae are often not detected in peripheral blood smears. Frequently there are no antibodies to these diverse agents at the time of presentation, and isolation does not yield sensitive and timely results. Polymerase chain reaction, still a research tool, promises the greatest sensitivity, specificity, and timeliness. Prevention by vaccines is not yet a reality, although OspA-based vaccines offer hope for the prevention of Lyme disease.
Dynamic Sentinel Lymph Node Biopsy in Patients with Invasive Squamous Cell Carcinoma of the Penis: A Prospective Study of the Long-Term Outcome of 500 Inguinal Basins Assessed at a Single Institution
Authors: Wayne Lam, Hussain M. Alnajjar, Susannah La-Touche, Matthew Perry, Davendra Sharma, Cathy Corbishley, James Pilcher, Sue Heenan, Nick Watkin
Journal: European Urology (2012)
Smoking cessation, decline in pulmonary function and total mortality: a 30 year follow up study among the Finnish cohorts of the Seven Countries Study
Authors: M Pelkonen
Journal: Thorax (2001)

Permanent smoking cessation reduces loss of pulmonary function. Less is known in the long term about individuals who give up smoking temporarily or quitters with lower initial pulmonary function. Little is known also about the relationship between decline in pulmonary function and mortality. We examined these aspects and the association between smoking, decline in pulmonary function, and mortality.Two middle aged male Finnish cohorts of the Seven Countries Study and their re-examinations on five occasions during a 30 year period of follow up were analysed.During the first 15 years (n=1007) adjusted decline in forced expiratory volume in 0.75 seconds (FEV(0.75)) was 46.4 ml/year in never smokers, 49.3 ml/year in past smokers, 55.5 ml/year in permanent quitters, 55.5 ml/year in intermittent quitters, and 66.0 ml/year in continuous smokers (p<0.001 for trend). Quitters across the entire range of baseline FEV(0.75) had a slower decline in FEV(0.75) than continuous smokers. Among both continuing smokers and never smokers, non-survivors had a significantly (p<0.001) more rapid decline in FEV(0.75) than survivors. The adjusted relative hazard for total mortality was 1.73 (95% confidence interval (CI) 1.41 to 2.11) and 1.24 (95% CI 1.02 to 1.52) in the lowest and middle tertiles of decline in FEV(0.75). Never smokers, past smokers, and quitters had significantly lower total mortality than continuous smokers, partly because of their slower decline in FEV(0.75).These results highlight the positive effect of smoking cessation, even intermittent cessation, on decline in pulmonary function. Accelerated decline in pulmonary function was found to be a risk factor for total mortality. The beneficial effect of smoking cessation on mortality may partly be mediated through a reduced decline in pulmonary function.