tbuckley/cabot-search huggingface dataset:
Functional Characteristics of the Diluting Segment of the Dog Nephron and the Effect of Extracellular Volume Expansion on its Reabsorptive Capacity*
Authors: Garabed Eknoyan, Wadi N. Suki, Floyd C. Rector, Donald W. Seldin
Journal: Journal of Clinical Investigation (1967)

The functional characteristics of the ascending limb of Henle's loop were examined during hypotonic saline infusion by measuring solutefree water clearance (C(H2O)) at varying rates of solute delivery. The influence of expansion of extracellular volume was studied by comparing C(H2O) during hypotonic saline diuresis in normal dogs with dogs whose extracellular volume had been expanded acutely by saline infusions or chronically by the administration of deoxycorticosterone acetate and salt. In normal animals hypotonic saline infusions greatly increased urine flow (V) and C(H2O) without appreciably augmenting osmolar clearance (C(osm)). C(H2O) was, therefore, analyzed as a function of V, rather than C(osm), since V was the best estimate of delivery of filtrate to the diluting segment. C(H2O) increased as a linear function of V without any evidence of saturation.The validity of interpreting increases in C(H2O) and V as indications of increased sodium reabsorption and delivery was reinforced by tissue studies that disclosed a rise in papillary osmolality with rising urine flows. The observed increase in C(H2O) and V could not, therefore, be due to a decrease in back diffusion of solute-free water as a result of a diminished osmotic driving force, but probably represented increased formation consequent to augmented delivery as a result of decreased fractional reabsorption in the proximal tubule. In animals whose extracellular volume was acutely or chronically overexpanded before the infusion of hypotonic saline, sodium excretion was greater, and C(H2O) less, at any given V. Although the curve relating C(H2O) to V was flatter than in the control group, no tubular maximum was observed. The diminished C(H2O) in this group was interpreted to mean that massive expansion of extracellular volume inhibits sodium reabsorption in the ascending limb of Henle's loop.
Monocyte Subsets Responsible for Immunoglobulin G-Dependent Effector Functions In Vivo
Authors: Markus Biburger, Susanne Aschermann, Inessa Schwab, Anja Lux, Heike Albert, Heike Danzer, Melissa Woigk, Diana Dudziak, Falk Nimmerjahn
Journal: Immunity (2011)
Interaction Between Dietary Antioxidants and Passive Smoking On The Risk Of Asthma Modified By GSTP1(rs1695) Polymorphism
Authors: Young-Hwa Song, Hye Lim Shin, Seo Ah Hong, Sung-Ok Kwon, Young Ho Jung, Eun Lee, Song I. Yang, Ji-Won Kwon, Hyung Young Kim, Ju-Hee Seo, Byoung-Ju Kim, Hyo-Bin Kim, Se-Young Oh, Soo-Jong Hong, Bong-Seong Kim
Journal: Journal of Allergy and Clinical Immunology (2014)
Chronic granulocytic leukemia: Correlation of elastic transformation type with karyotypic evolution
Authors: F. M. O'Malley, O. Margaret Garson
Journal: American Journal of Hematology (1985)

Abstract Over a 3‐year period, 26 patients with Philadelphia chromosome‐positive chronic granulocytic leukemia were studied cytogenetically in both the chronic and blastic transformation phases of the disease; a further three patients were studied only after blastic transformation. Sixteen were considered to have adequate evidence of the type of transformation and form the basis of this report, where chromosome changes have been correlated with the morphological type of blastic transformation. Seven patients developed a myeloblastic transformation, seven a lymphoblastic transformation, and two an erythroblastic transformation. All patients in the myeloid group acquired one or more of the nonrandom changes associated with CGL blastic transformation, viz. +8,i(17q), + 19,+22q‐. Patients in the lymphoblastic group acquired structural abnormalities, apparently random in nature and usually in a small percentage of cells. The two patients with erythroblastic transformation developed markedly hyperdiploid cells (&gt; 50 chromosomes) with both numerical and structural abnormalities. Patients in the lymphoblastic group appeared to have a slightly better prognosis than the myeloid group, whilst the patients with erythroblastic transformation had a very poor prognosis.
Molecular Evolution across the Asteraceae: Micro- and Macroevolutionary Processes
Authors: N. C. Kane, M. S. Barker, S. H. Zhan, L. H. Rieseberg
Journal: Molecular Biology and Evolution (2011)

The Asteraceae (Compositae) is a large family of over 20,000 wild, weedy, and domesticated species that comprise approximately 10% of all angiosperms, including annual and perennial herbs, shrubs and trees, and species on every continent except Antarctica. As a result, the Asteraceae provide a unique opportunity to understand the evolutionary genomics of lineage radiation and diversification at numerous phylogenetic scales. Using publicly available expressed sequence tags from 22 species representing four of the major Asteraceae lineages, we assessed neutral and nonneutral evolutionary processes across this diverse plant family. We used bioinformatic tools to identify candidate genes under selection in each species. Evolution at silent and coding sites were assessed for different Gene Ontology functional categories to compare rates of evolution over both short and long evolutionary timescales. Our results indicate that patterns of molecular change across the family are surprisingly consistent on a macroevolutionary timescale and much more so more than would be predicted from the analysis of one (or many) examples of microevolution. These analyses also point to particular classes of genes that may be crucial in shaping the radiation of this diverse plant family. Similar analyses of nuclear and chloroplast genes in six other plant families confirm that many of these patterns are common features of the plant kingdom.
Rebound eosinophilia after treatment of hypereosinophilic syndrome and eosinophilic gastroenteritis with monoclonal anti–IL-5 antibody SCH55700
Authors: Yae-Jean Kim, Calman Prussin, Brian Martin, Melissa A. Law, Thomas P. Haverty, Thomas B. Nutman, Amy D. Klion
Journal: Journal of Allergy and Clinical Immunology (2004)
CapR: revealing structural specificities of RNA-binding protein target recognition using CLIP-seq data
Authors: Tsukasa Fukunaga, Haruka Ozaki, Goro Terai, Kiyoshi Asai, Wataru Iwasaki, Hisanori Kiryu
Journal: Genome biology (2014)

Abstract RNA-binding proteins (RBPs) bind to their target RNA molecules by recognizing specific RNA sequences and structural contexts. The development of CLIP-seq and related protocols has made it possible to exhaustively identify RNA fragments that bind to RBPs. However, no efficient bioinformatics method exists to reveal the structural specificities of RBP–RNA interactions using these data. We present CapR, an efficient algorithm that calculates the probability that each RNA base position is located within each secondary structural context. Using CapR, we demonstrate that several RBPs bind to their target RNA molecules under specific structural contexts. CapR is available at https://sites.google.com/site/fukunagatsu/software/capr .
Effects of Developmental Activation of the AhR on CD4 <sup>+</sup> T-Cell Responses to Influenza Virus Infection in Adult Mice
Authors: Lisbeth A. Boule, Bethany Winans, B. Paige Lawrence
Journal: Environmental Health Perspectives (2014)

Epidemiological and animal studies indicate that maternal exposure to pollutants that bind the aryl hydrocarbon receptor (AhR) correlates with poorer ability to combat respiratory infection and lower antibody levels in the offspring. These observations point to an impact on CD4+ T cells. Yet, the consequence of developmental exposure to AhR ligands on the activation and differentiation of CD4+ T cells has not been directly examined.Our goal was to determine whether maternal exposure to an AhR ligand directly alters CD4+ T cell differentiation and function later in life.C57BL/6 mice were exposed to a prototypical AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), in utero and via suckling. We then measured CD4+ T-cell activation and differentiation into distinct effector populations in adult offspring that were infected with influenza A virus (IAV). Reciprocal adoptive transfers were used to define whether modifications in CD4+ T-cell responses resulted from direct effects of developmental TCDD exposure on CD4+ T cells.Developmental exposure skewed CD4+ T-cell responses to IAV infection. We observed fewer virus-specific, activated CD4+ T cells and a reduced frequency of conventional CD4+ effector-cell subsets. However, there was an increase in regulatory CD4+ T cells. Direct effects of AhR activation on CD4+ T cells resulted in impaired differentiation into conventional effector subsets; this defect was transferred to mice that had not been developmentally exposed to TCDD.Maternal exposure to TCDD resulted in durable changes in the responsive capacity and differentiation of CD4+ T cells in adult C57BL/6 mice.
Rejection triggers liver transplant tolerance: Involvement of mesenchyme‐mediated immune control mechanisms in mice
Authors: Miwa Morita, Daniel Joyce, Charles Miller, John J. Fung, Lina Lu, Shiguang Qian
Journal: Hepatology (2015)

Liver tolerance was initially recognized by the spontaneous acceptance of liver allografts in many species. The underlying mechanisms are not completely understood. However, liver transplant (LT) tolerance absolutely requires interferon (IFN)-γ, a rejection-associated inflammatory cytokine. In this study, we investigated the rejection of liver allografts deficient in the IFN-γ receptor and reveal that the liver graft is equipped with machineries capable of counterattacking the host immune response through a mesenchyme-mediated immune control (MMIC) mechanism. MMIC is triggered by T effector (Tef) cell-derived IFN-γ that drives expression of B7-H1 on graft mesenchymal cells leading to Tef cell apoptosis. We describe the negative feedback loop between graft mesenchymal and Tef cells that ultimately results in LT tolerance. Comparable elevations of T-regulatory cells and myeloid-derived suppressor cells were observed in both rejection and tolerance groups and were not dependent on IFN-γ stimulation, suggesting a critical role of Tef cell elimination in tolerance induction. We identify potent MMIC activity in hepatic stellate cells and liver sinusoidal endothelial cells. MMIC is unlikely exclusive to the liver, given that spontaneous acceptance of kidney allografts has been reported, although less commonly, probably reflecting variance in MMIC activity.MMIC may represent an important homeostatic mechanism that supports peripheral tolerance and could be a target for the prevention and treatment of transplant rejection. This study highlights that the graft is an active participant in the equipoise between tolerance and rejection and warrants more attention in the search for tolerance biomarkers.
Environmental Noise Pollution in the United States: Developing an Effective Public Health Response
Authors: Monica S. Hammer, Tracy K. Swinburn, Richard L. Neitzel
Journal: Environmental Health Perspectives (2013)

Tens of millions of Americans suffer from a range of adverse health outcomes due to noise exposure, including heart disease and hearing loss. Reducing environmental noise pollution is achievable and consistent with national prevention goals, yet there is no national plan to reduce environmental noise pollution.
Collagen-induced arthritis in T cell receptor V beta congenic B10.Q mice.
Authors: G H Nabozny, M J Bull, J Hanson, M M Griffiths, H S Luthra, C S David
Journal: The Journal of Experimental Medicine (1994)

B10.Q (H-2q) mice congenic for the truncated T cell receptor (TCR) V beta a and V beta c haplotypes were derived to examine the influence of TCR V beta genomic deletions in murine collagen-induced arthritis (CIA). Previous studies using gene complementation and segregation analyses suggested that in SWR (H-2q) mice, possession of the V beta a gene deletion results in CIA resistance. However, other studies have suggested alternative hypotheses. Thus, analysis of TCR V beta congenic mice allows for direct examination of V beta genotypes in CIA control. After immunization with bovine type II collagen, B10.Q-V beta a mice showed no difference in arthritis susceptibility, onset, or severity when compared with prototype B10.Q mice. In contrast, B10.Q-V beta c mice, which lack the V beta 6, 15, 17, and 19 families in addition to the V beta a deletion, were highly resistant to CIA. In vivo depletion of V beta 6+ T cells in B10.Q-V beta a mice significantly delayed arthritis onset suggesting that, among those V beta genes present in V beta a but absent in V beta c, V beta 6+ T cells contribute to arthritogenesis. Our findings show that, in B10.Q-V beta congenic mice, while the V beta a genotype does not prevent CIA, the highly truncated V beta c genotype renders B10.Q mice resistant to CIA. Thus, deletions within the V beta TCR genome can indeed influence CIA and suggests that the TCR repertoire displays only marginal flexibility in response to arthritogenic stimuli.
Biomarkers to identify sputum eosinophilia in different adult asthma phenotypes
Authors: Guus A. Westerhof, Daniël A. Korevaar, Marijke Amelink, Selma B. de Nijs, Jantina C. de Groot, Junfeng Wang, Els J. Weersink, Anneke ten Brinke, Patrick M. Bossuyt, Elisabeth H. Bel
Journal: European Respiratory Journal (2015)

Several biomarkers have been used to assess sputum eosinophilia in asthma. It has been suggested that the diagnostic accuracy of these biomarkers might differ between asthma phenotypes. We investigated the accuracy of biomarkers in detecting sputum eosinophilia (≥3%) in different adult asthma phenotypes. Levels of eosinophils in blood and sputum, exhaled nitric oxide fraction ( F eNO ) and total immunoglobulin (Ig)E from 336 adult patients, enrolled in three prospective observational clinical trials and recruited at five pulmonology outpatient departments, were analysed. Areas under the receiver operating characteristics curves (AUC) for detecting sputum eosinophilia were calculated and compared between severe and mild, obese and nonobese, atopic and nonatopic and (ex-)smoking and never-smoking asthma patients. Sputum eosinophilia was present in 116 patients (35%). In the total group the AUC was 0.83 (95% CI 0.78–0.87) for blood eosinophils, 0.82 (0.77–0.87) for F eNO and 0.69 (0.63–0.75) for total IgE. AUCs were similar for blood eosinophils and F eNO between different phenotypes. Total IgE was less accurate in detecting sputum eosinophilia in atopic and obese patients than in nonatopic and nonobese patients. Blood eosinophils and F eNO had comparable diagnostic accuracy (superior to total IgE) in identifying sputum eosinophilia in adult asthma patients, irrespective of asthma phenotype such as severe, nonatopic, obese and smoking-related asthma.
Adiponectin Reduces Atherosclerosis in Apolipoprotein E-Deficient Mice
Authors: Yoshihisa Okamoto, Shinji Kihara, Noriyuki Ouchi, Makoto Nishida, Yukio Arita, Masahiro Kumada, Koji Ohashi, Naohiko Sakai, Iichiro Shimomura, Hideki Kobayashi, Naoki Terasaka, Toshimori Inaba, Tohru Funahashi, Yuji Matsuzawa
Journal: Circulation (2002)

Dysregulation of adipocyte-derived bioactive molecules plays an important role in the development of atherosclerosis. We previously reported that adiponectin, an adipocyte-specific plasma protein, accumulated in the injured artery from the plasma and suppressed endothelial inflammatory response and vascular smooth muscle cell proliferation, as well as macrophage-to-foam cell transformation in vitro. The current study investigated whether the increased plasma adiponectin could actually reduce atherosclerosis in vivo.Apolipoprotein E-deficient mice were treated with recombinant adenovirus expressing human adiponectin (Ad-APN) or beta-galactosidase (Ad-betagal). The plasma adiponectin levels in Ad-APN-treated mice increased 48 times as much as those in Ad-betagal treated mice. On the 14th day after injection, the lesion formation in aortic sinus was inhibited in Ad-APN-treated mice by 30% compared with Ad-betagal-treated mice (P<0.05). In the lesions of Ad-APN-treated mice, the lipid droplets became smaller compared with Ad-betagal-treated mice (P<0.01). Immunohistochemical analyses demonstrated that the adenovirus-mediated adiponectin migrate to foam cells in the fatty streak lesions. The real-time quantitative polymerase chain reaction revealed that Ad-APN treatment significantly suppressed the mRNA levels of vascular cell adhesion molecule-1 by 29% and class A scavenger receptor by 34%, and tended to reduce levels of tumor necrosis factor-alpha without affecting those of CD36 in the aortic tissue.These findings documented for the first time that elevated plasma adiponectin suppresses the development of atherosclerosis in vivo.
A Comprehensive Study of Polymorphic Sites along the HLA-G Gene: Implication for Gene Regulation and Evolution
Authors: E. C. Castelli, C. T. Mendes-Junior, L. C. Veiga-Castelli, M. Roger, P. Moreau, E. A. Donadi
Journal: Molecular Biology and Evolution (2011)

HLA-G molecule plays an important role on immune response regulation and has been implicated on the inhibition of T and natural killer cell cytolytic function and inhibition of allogeneic T-cell proliferation. Due to its immune-modulator properties, the HLA-G gene expression has been associated with the outcome of allograft and of autoimmune, infectious, and malignant disorders. Several lines of evidence indicate that HLA-G polymorphisms at the 5'-upstream regulatory region (5' URR) and 3'-untranslated region (3' UTR) may influence the HLA-G expression levels. Because Brazilians represent one of the most heterogeneous populations in the world with the widest HLA-G coding region variability already detected among the studied populations, a high level of variability and haplotype diversity would be expected in Brazilians. On this basis, the 5' URR, coding, and 3' UTR variability were evaluated in a Brazilian series consisting of 100 healthy bone marrow donors, as well as the linkage disequilibrium pattern along the gene and the extended haplotypes encompassing several gene segment variations. The HLA-G locus seems to present six different HLA-G lineages showing functional variations mainly in nucleotides of the regulatory regions. Differences were observed at the 5' URR in positions that either coincide with or are close to transcription factor-binding sites and at the 3' UTR mainly in positions that have already been reported to influence HLA-G mRNA availability. We report several lines of evidence for balancing selection acting on the regulatory regions, which may indicate that these HLA-G lineages may be related to the differential HLA-G expression profiles.
Altered Brain Activation Patterns Under Different Working Memory Loads in Patients With Type 2 Diabetes
Authors: Yaojing Chen, Zhen Liu, Junying Zhang, Kai Xu, Sisi Zhang, Dongfeng Wei, Zhanjun Zhang
Journal: Diabetes Care (2014)

OBJECTIVE Type 2 diabetes mellitus (T2DM) has important effects on cognition and the risk for Alzheimer disease (AD). Working memory (WM) is a susceptible cognitive domain of mild cognitive impairment and AD. Thus, the identification of brain activation patterns under different WM loads can potentially enhance our understanding of the mechanisms underlying cognitive dysfunction in T2DM. RESEARCH DESIGN AND METHODS The current study assessed the effects of T2DM on cognitive performance and explored the related neuronal damage through a visual n-back task and functional magnetic resonance imaging. RESULTS We found that patients with T2DM exhibited worse executive and memory abilities than control subjects. Furthermore, the patterns of brain activation changed under different WM loads in the T2DM patients, who exhibited reduced activation in the left inferior frontal gyrus under low loads and reduced activation in the left middle frontal gyrus and superior frontal gyrus (SFG) under high loads. Thus, more regions of diminished activation were seen in the frontal cortex with increasing task difficulty. Furthermore, we found that lower SFG activation was associated with worse cognitive function. CONCLUSIONS The findings demonstrate deficient WM in patients with T2DM and the relation between cognitive function and degree of neuronal activity and their relevance to AD risk. Further longitudinal studies are needed to replicate these results and to evaluate the clinical value of brain imaging methods in the prediction of disease progress in these patients.
Vitiligo. What is it? Is it important?
Authors: A. B. Lerner
Journal: JAMA (1978)

IF WE were to rank disorders according to the discrepancy between the interest to the patient vs the interest to the physician, vitiligo would probably be at the top of the list. The patient with moderate to severe anxiety will seek help for a disfiguring loss of pigment. The physician will say, "You have vitiligo. There is no cure and we do not know the cause. Your health in general is fine, so please try to adjust to the presence of white spots on your skin and try not be vain. Use makeup if you wish." The patient does not respond. The physician, satisfied that the patient understands, believes that it was proper to be direct, to be straightforward. The patient departs quietly but with inner turmoil and anger. The physician has tried to shame the patient into believing that no real problem exists. The patient wishes that the physician
Effects of a Telephone-Delivered Multiple Health Behavior Change Intervention (CanChange) on Health and Behavioral Outcomes in Survivors of Colorectal Cancer: A Randomized Controlled Trial
Authors: Anna L. Hawkes, Suzanne K. Chambers, Kenneth I. Pakenham, Tania A. Patrao, Peter D. Baade, Brigid M. Lynch, Joanne F. Aitken, Xingqiong Meng, Kerry S. Courneya
Journal: Journal of Clinical Oncology (2013)

Purpose Colorectal cancer survivors are at risk for poor health outcomes because of unhealthy lifestyles, but few studies have developed translatable health behavior change interventions. This study aimed to determine the effects of a telephone-delivered multiple health behavior change intervention (CanChange) on health and behavioral outcomes among colorectal cancer survivors. Methods In this two-group randomized controlled trial, 410 colorectal cancer survivors were randomly assigned to the health coaching intervention (11 theory-based telephone-delivered health coaching sessions delivered over 6 months focusing on physical activity, weight management, dietary habits, alcohol, and smoking) or usual care. Assessment of primary (ie, physical activity [Godin Leisure Time Index], health-related quality of life [HRQoL; Short Form–36], and cancer-related fatigue [Functional Assessment of Chronic Illness Therapy Fatigue Scale]) and secondary outcomes (ie, body mass index [kg/m 2 ], diet and alcohol intake [Food Frequency Questionnaire], and smoking) were conducted at baseline and 6 and 12 months. Results At 12 months, significant intervention effects were observed for moderate physical activity (28.5 minutes; P = .003), body mass index (−0.9 kg/m 2 ; P = .001), energy from total fat (−7.0%; P = .006), and energy from saturated fat (−2.8%; P = .016). A significant intervention effect was reported for vegetable intake (0.4 servings per day; P = .001) at 6 months. No significant group differences were found at 6 or 12 months for HRQoL, cancer-related fatigue, fruit, fiber, or alcohol intake, or smoking. Conclusion The CanChange intervention was effective for improving physical activity, dietary habits, and body mass index in colorectal cancer survivors. The intervention is translatable through existing telephone cancer support and information services in Australia and other countries.