tbuckley/cabot-search huggingface dataset:
O-Linked Glycosylation Determines the Nephritogenic Potential of IgA Rheumatoid Factor
Authors: Masao Kihara, Kiyoaki Ito, Junichiro Nakata, Masako Otani, Ngoc Lan Tran, Naoki Morito, Satoru Takahashi, Yoshinao Wada, Shozo Izui
Journal: Journal of the American Society of Nephrology (2014)

Deficient glycosylation of O-linked glycans in the IgA1 hinge region is associated with IgA nephropathy in humans, but the pathogenic contribution of the underlying structural aberrations remains incompletely understood. We previously showed that mice implanted with cells secreting the class-switch variant 6-19 IgA anti-IgG2a rheumatoid factor, but not 46-42 IgA anti-IgG2a rheumatoid factor, develop glomerular lesions resembling IgA nephropathy. Because the levels of O-linked glycosylation in the hinge region and the structures of N-linked glycans in the CH1 domain differ in 6-19 IgA and 46-42 IgA, we determined the respective contributions of O- and N-linked glycans to the nephritogenic potential of the 6-19 IgA rheumatoid factor in mice. Wild-type 6-19 IgA secreted by implanted cells induced significant formation of glomerular lesions, whereas poorly O-glycosylated 6-19 IgA glycovariants or a 6-19 IgA hinge mutant lacking O-linked glycans did not. However, we observed no apparent heterogeneity in the structure of N-linked glycans attached to three different sites of the Fc regions of nephritogenic and non-nephritogenic 6-19 IgAs. Collectively, our data suggest a critical role of O-linked glycans attached to the hinge region in the development of IgA nephropathy-like GN induced by 6-19 IgA rheumatoid factor in mice.
Benefits of mammography in women aged 50-69 outweigh risks, says expert panel
Authors: S. Mayor
Journal: BMJ (2015)

The benefits of mammography screening in terms of reduced breast cancer mortality in women aged 50-69 more than outweigh the risks, including false positive results and the effects of radiation exposure, a report has found.1

An expert panel convened by the International Agency for Research on Cancer compiled the report after reviewing the available evidence. The group of 29 independent experts from 16 countries assessed methods of screening for breast cancer in terms of their efficacy in preventing cancer and of their adverse effects. They reviewed all published studies of …
Experimentally induced liver metastases from colorectal cancer can be prevented by mononuclear phagocyte-mediated monoclonal antibody therapy
Authors: Gerben J. van der Bij, Marijn Bögels, Marielle A. Otten, Steven J. Oosterling, Peter J. Kuppen, Sybren Meijer, Robert H.J. Beelen, Marjolein van Egmond
Journal: Journal of Hepatology (2010)
Renal Ca2+ wasting, hyperabsorption, and reduced bone thickness in mice lacking TRPV5
Authors: Joost G.J. Hoenderop, Johannes P.T.M. van Leeuwen, Bram C.J. van der Eerden, Ferry F.J. Kersten, Annemiete W.C.M. van derKemp, Anne-Marie Mérillat, Jan H. Waarsing, Bernard C. Rossier, Volker Vallon, Edith Hummler, René J.M. Bindels
Journal: Journal of Clinical Investigation (2003)

Ca2+ ions play a fundamental role in many cellular processes, and the extracellular concentration of Ca2+ is kept under strict control to allow the proper physiological functions to take place. The kidney, small intestine, and bone determine the Ca2+ flux to the extracellular Ca2+ pool in a concerted fashion. Transient receptor potential (TRP) cation channel subfamily V, members 5 and 6 (TRPV5 and TRPV6) have recently been postulated to be the molecular gatekeepers facilitating Ca2+ influx in these tissues and are members of the TRP family, which mediates diverse biological effects ranging from pain perception to male aggression. Genetic ablation of TRPV5 in the mouse allowed us to investigate the function of this novel Ca2+ channel in maintaining the Ca2+ balance. Here, we demonstrate that mice lacking TRPV5 display diminished active Ca2+ reabsorption despite enhanced vitamin D levels, causing severe hypercalciuria. In vivo micropuncture experiments demonstrated that Ca2+ reabsorption was malfunctioning within the early part of the distal convolution, exactly where TRPV5 is localized. In addition, compensatory hyperabsorption of dietary Ca2+ was measured in TRPV5 knockout mice. Furthermore, the knockout mice exhibited significant disturbances in bone structure, including reduced trabecular and cortical bone thickness. These data demonstrate the key function of TRPV5 in active Ca2+ reabsorption and its essential role in the Ca2+ homeostasis.
EPIDEMIC DIARRHEAL DISEASE OF SUCKLING MICE
Authors: F. Sargent Cheever, J. Howard Mueller
Journal: The Journal of Experimental Medicine (1948)

Four strains of mice—Harvard, Schwentker, CFW (Carworth Farms), and C (National Cancer Institute)—have been kept and bred underidentical conditions over the course of a year in order to determine the effect of strain, of litter, and of season upon the incidence of diarrheal disease among the suckling mice. 1. Significant strain differences were limited to CFW mice. A consistently lower percentage of these mice were weaned in comparison to the others. 2. The effect of litter was definite and consistent: In all four strains first litters fared worse than second and third ones, while fourth and fifth litters showed the highest percentage of mice weaned. 3. The effect of season seemed clear cut only in the case of one strain CFW; the highest percentage of mice weaned were observed during the summer months and the lowest during the autumn and early winter.
Preconditioning with Endoplasmic Reticulum Stress Ameliorates Mesangioproliferative Glomerulonephritis
Authors: Reiko Inagi, Takanori Kumagai, Hiroshi Nishi, Takahisa Kawakami, Toshio Miyata, Toshiro Fujita, Masaomi Nangaku
Journal: Journal of the American Society of Nephrology (2008)

Accumulating evidence suggests a pathophysiologic role of endoplasmic reticulum (ER) stress in kidney disease. This study investigated the potential of therapeutic approaches targeting ER stress in the anti-Thy1 model of mesangioproliferative glomerulonephritis in rats. Immunohistochemistry and Western blotting showed a time-dependent increase in the expression of the ER stress-inducible chaperones glucose-regulated protein 78 (GRP78) and oxygen-related protein 150 in isolated glomeruli, especially in the glomerular epithelial cells and mesangial cells, after induction of anti-Thy1 nephritis. For evaluation of whether preconditioning with ER stress ameliorates the severity of disease, rats were pretreated with a subnephritogenic dose of the ER stress inducer tunicamycin or thapsigargin for 4 d before disease was induced. Although preconditioning with ER stress had no effect on the degree of disease induction, it strongly ameliorated the manifestations of disease, evidenced by marked reductions in microaneurysm formation, mesangial proliferation, and adhesion of Bowman's capsule to the glomerular tuft. This improvement in histologic damage was associated with reduced proteinuria (39.4 +/- 10.5 versus 126.1 +/- 18.1 mg/d; P < 0.01) and with attenuated increases in glucose-regulated protein 78 and oxygen-related protein 150 expression. Of note, pretreatment with tunicamycin or thapsigargin decreased the excessive ER stress-induced intracellular signaling observed in anti-Thy1 nephritis. In conclusion, preconditioning with ER stress ameliorates the severity of disease in rats with anti-Thy1 nephritis. These findings suggest the possibility of therapeutic approaches targeting ER stress in mesangioproliferative glomerulonephritis.
Peach allergy in China: A dominant role for mugwort pollen lipid transfer protein as a primary sensitizer
Authors: Zhong-Shan Gao, Zhao-Wei Yang, Shan-Dong Wu, Hui-Ying Wang, Mei-Ling Liu, Wei-Lin Mao, Jian Wang, Gabriele Gadermaier, Fatima Ferreira, Min Zheng, Ronald van Ree
Journal: Journal of Allergy and Clinical Immunology (2012)
A computational method to predict genetically encoded rare amino acids in proteins.
Authors: Barnali N Chaudhuri, Todd O Yeates
Journal: Genome biology (2005)

Abstract In several natural settings, the standard genetic code is expanded to incorporate two additional amino acids with distinct functionality, selenocysteine and pyrrolysine. These rare amino acids can be overlooked inadvertently, however, as they arise by recoding at certain stop codons. We report a method for such recoding prediction from genomic data, using read-through similarity evaluation. A survey across a set of microbial genomes identifies almost all the known cases as well as a number of novel candidate proteins.
Regional distribution of blood flow during arterial hypertension produced by lesions of the nucleus tractus solitarii in rats.
Authors: D W Snyder, N Doba, D J Reis
Journal: Circulation Research (1978)

Changes in the fractional distribution of cardiac output (FF), organ blood flow, and regional vascular resistance were measured by the isotope dilution technique of Sapirstein using 86Rb as indicator in unanesthetized rats during acute arterial hypertension produced by bilateral lesions of the nucleus tractus solitarii (NTS). After NTS lesions, the FF was significantly reduced in skin, muscle, and colon, increased in ventricular myocardium, spleen, and adrenal glands, and was unchanged elsewhere. Because of a marked reduction in cardiac output (CO) during hypertension, the absolute organ blood flow (FF X CO) was reduced in lesioned rats to 30-40% of control in skin, muscle, and colon and between 60% and 75% of control in most of the remainder of the gastrointestinal tract and renal cortex; it was unchanged in myocardium and endocrine glands. Resistance was substantially increased (4- to 6-fold) in skin, muscle and colon but was only moderately increased (1.5- to 2.5-fold) in the remaining organs. The results indicate that, while NTS lesions will increase resistance in most vascular beds, the response is unequally distributed, influencing skin, muscle, and colon disproportionately to other tissues. Because of an interaction between a reduction in CO and little autoregulation, blood flow is reduced primarily in skin, muscle, and colon. The pattern of redistribution of CO was consistent with the interpretation that NTS hypertension results from interrupting baroreceptor reflexes centrally. The pattern of redistribution of blood flow in rats with NTS lesions differs from that produced by deoxycorticosterone acetate-salt and renal ischemia.
Screen of Drug Use
Authors: Quyen Q. Tiet, Yani E. Leyva, Rudolf H. Moos, Susan M. Frayne, Lars Osterberg, Brandy Smith
Journal: JAMA Internal Medicine (2015)

<h3>Importance</h3> Illicit drug use is prevalent, and primary care provides an ideal setting in which to screen for drug use disorders (DUDs) and negative consequences of drug use (NCDU). Comprehensive reviews have concluded that existing drug use screening instruments are not appropriate for routine use in primary care. <h3>Objective</h3> To develop and validate a screening instrument for drug use. <h3>Design, Setting, and Participants</h3> We revised items drawn from existing screening instruments and conducted signal detection analyses to develop the new instrument. We approached 3173 patients at 2 primary care clinics in a US Department of Veterans Affairs health care system from February 1, 2012, through April 30, 2014. A total of 1300 (41.0%) patients consented to the study, of whom 1283 adults were eligible (mean [SD] age, 62.2 [12.6] years). In the last 12 months, 241 (18.8%) participants reported using illicit drugs or prescription medication for a nonmedical purpose, and 189 (14.7%) reported 1 or more NCDU. A total of 133 (10.4%) patients met<i>DSM-IV</i>criteria for a DUD. The sample was randomly divided first to develop the measure and then to validate it. <h3>Main Outcomes and Measures</h3> The Mini-International Diagnostic Interview was used as the criterion for DUDs, and the Inventory of Drug Use Consequences was used as the criterion for NCDU. <h3>Results</h3> The screening instrument has 2 questions. The first is, “How many days in the past 12 months have you used drugs other than alcohol?” Patients meet that criterion with a response of 7 or more days. The second question asks, “How many days in the past 12 months have you used drugs more than you meant to?” A response of 2 or more days meets that criterion. The screening instrument was 100% sensitive and 93.73% specific for DUDs (643 patients); when replicated in the second half of the sample (640 patients), it was 92.31% sensitive and 92.87% specific. The screening instrument was 93.18% sensitive and 96.03% specific for NCDU (643 patients); when replicated in the second half of the sample (640 patients), it was 83.17% sensitive and 96.85% specific. <h3>Conclusions and Relevance</h3> The 2-item screen of drug use has excellent statistical properties and is a brief screening instrument for DUDs and problems suitable for busy US Department of Veterans Affairs primary care clinics.
Dyspnoea, wheezing and respiratory insufficiency in pregnancy: was it bronchial or cardiac asthma?
Authors: JC Yernault
Journal: European Respiratory Journal (1990)

wheezing and respiratory insufficiency in pregnancy:was it bronchial or cardiac asthma?1989 issue of Chest, 'I'ENHoLDER and the case of a 27 yr old pregnant gestation who presented with ng shortness of breath, cough sputum, and wheezing.When hospi-
Prevalence of oesophageal eosinophils and eosinophilic oesophagitis in adults: the population-based Kalixanda study
Authors: J. Ronkainen, N. J Talley, P. Aro, T. Storskrubb, S.-E. Johansson, T. Lind, E. Bolling-Sternevald, M. Vieth, M. Stolte, M. M Walker, L. Agreus
Journal: Gut (2006)

<b>Background:</b> Eosinophilic oesophagitis may be increasing but the prevalence in the general population remains unknown. Our aim was to assess this and the presence of eosinophils in the distal oesophageal epithelium in the community. <b>Methods:</b> Oesophagogastroduodenoscopy was performed in a random sample (n = 1000) of the adult Swedish population (mean age 54 years, 49% men). Oesophageal biopsy samples were obtained from 2 cm above, and at, the Z-line. Any eosinophil infiltration of the epithelium was defined as "eosinophils present". Definite eosinophilic oesophagitis was defined as ⩾20, probable as 15–19, and possible as 5–14 eosinophils/high-power field (HPF, at magnification ×40) in oesophageal biopsy specimens. <b>Results:</b> Eosinophils were present in 48 subjects (4.8%, 95% CI 3.5 to 6.1%, mean age 54 years, 63% men), in 54% without troublesome reflux symptoms. Definite eosinophilic oesophagitis was present in four subjects (0.4%, 95% CI 0.01 to 0.8%, mean age 51 years, 75% men) and probable eosinophilic oesophagitis in seven subjects (0.7%, 95% CI 0.2 to 1.2%, mean age 58 years, 43% men). Erosive oesophagitis (OR = 2.99, 95% CI 1.58 to 5.66) and absence of dyspepsia (OR = 0.23, 95% CI 0.07 to 0.75) and <i>Helicobacter pylori</i> infection (OR = 0.41, 95% CI 0.19 to 0.92) were independent predictors for "eosinophils present". Definite eosinophilic oesophagitis was associated with dysphagia (2/66 vs 2/926, p = 0.025), and probable eosinophilic oesophagitis with narrowing of the oesophageal lumen (2/15 vs 5/978, p = 0.005). <b>Conclusions:</b> Oesophageal eosinophils were present in nearly 5% of the general population; approximately 1% had definite or probable eosinophilic oesophagitis. Oesophageal eosinophils may be a manifestation of reflux disease in adults, but the condition is as likely to be asymptomatic and go unrecognised.
Detecting BRCA2 Protein Truncation in Tissue Biopsies to Identify Breast Cancers That Arise in <i>BRCA2</i> Gene Mutation Carriers
Authors: Patrice Watson, Rita Lieberman, Carrie Snyder, Vanessa J. Clark, Henry T. Lynch, Jeffrey T. Holt
Journal: Journal of Clinical Oncology (2009)

Mutations in the BRCA2 gene are dominantly inherited but cause cancers when the wild-type allele has loss of heterozygosity (LOH) within the cancer. Because most disease-associated BRCA2 mutations are protein-truncating mutations, a test for truncated BRCA2 proteins should identify most BRCA2 hereditary cancers.We have developed a tissue truncation test to identify truncated BRCA2 proteins in breast cancer tissue biopsies in vivo that does not use amplification or genetic manipulations. N-terminal and C-terminal antibodies are used to visualize protein truncation by demonstrating that the beginning of the protein is present but the end (ie, terminus) is absent.A quantitative C-terminal immunostaining score or a C-terminal to N-terminal truncation ratio correctly classified 20 of 21 breast cancers arising in BRCA2 mutation carriers and 57 of 58 cancers arising outside the context of a multiple-case breast cancer family. This represents a sensitivity of 95% and a specificity of 98%. Because of the presence of C-terminal BRCA2 protein and atypical clinical features of the misclassified cancer in a BRCA2 mutation carrier, we performed polymerase chain reaction and sequence analyses on this cancer. The results showed continued presence of the BRCA2 wild-type allele in the cancer, which indicated that intact BRCA2 protein was present in this cancer.This immunohistochemistry-based test (which takes only 4 hours) appears to identify BRCA2 hereditary cancer with high accuracy. The test also appears to diagnose the biochemical loss of BRCA2 protein in cancers (ie, BRCA2-mutant genotype), which will usually but not always agree with the presence of a germline BRCA2 mutation found by susceptibility testing by DNA sequencing of blood samples.
A Method to Measure Myocardial Calcium Handling in Adult Drosophila
Authors: Na Lin, Nima Badie, Lin Yu, Dennis Abraham, Heping Cheng, Nenad Bursac, Howard A. Rockman, Matthew J. Wolf
Journal: Circulation Research (2011)

Normal cardiac physiology requires highly regulated cytosolic Ca(2+) concentrations and abnormalities in Ca(2+) handling are associated with heart failure. The majority of approaches to identifying the components that regulate intracellular Ca(2+) dynamics rely on cells in culture, mouse models, and human samples. However, a genetically robust system for unbiased screens of mutations that affect Ca(2+) handling remains a challenge.We sought to develop a new method to measure myocardial Ca(2+) cycling in adult Drosophila and determine whether cardiomyopathic fly hearts recapitulate aspects of diseased mammalian myocardium.Using engineered transgenic Drosophila that have cardiac-specific expression of Ca(2+)-sensing fluorescent protein, GCaMP2, we developed methods to measure parameters associated with myocardial Ca(2+) handling. The following key observations were identified: (1) Control w(1118) Drosophila hearts have readily measureable Ca(2+)-dependent fluorescent signals that are dependent on L-type Ca(2+) channels and SR Ca(2+) stores and originate from rostral and caudal pacemakers. (2) A fly mutant, held-up(2) (hdp(2)), that has a point mutation in troponin I and has a dilated cardiomyopathic phenotype demonstrates abnormalities in myocardial Ca(2+) handling that include increases in the duration of the 50% rise in intensity to peak intensity, the half-time of fluorescence decline from peak, the full duration at half-maximal intensity, and decreases in the linear slope of decay from 80% to 20% intensity decay. (3) Hearts from hdp(2) mutants had reductions in caffeine-induced Ca(2+) increases and reductions in ryanodine receptor (RyR) without changes in L-type Ca(2+) channel transcripts in comparison with w(1118).Our results show that the cardiac-specific expression of GCaMP2 provides a means of characterizing propagating Ca(2+) transients in adult fly hearts. Moreover, the adult fruit fly heart recapitulates several aspects of Ca(2+) regulation observed in mammalian myocardium. A mutation in Drosophila that causes an enlarged cardiac chamber and impaired contractile function is associated with abnormalities in the cytosolic Ca(2+) transient as well as changes in transcript levels of proteins associated with Ca(2+) handling. This new methodology has the potential to permit an examination of evolutionarily conserved myocardial Ca(2+)-handing mechanisms by applying the vast resources available in the fly genomics community to conduct genetic screens to identify new genes involved in generated Ca(2+) transients and arrhythmias.
Life must go on
Authors: L. Farrell
Journal: BMJ (1996)

We Celts are notorious for the exuberance of our emotions, and the Farrell clan is no exception. So you cry at weddings? That don't amount to a hill of beans. We cry at baptisms, birthdays, Christmas, Easter, St Paddy's Day, during sad songs, or just randomly—it's usually quite competitive to see who starts blubbering first. And funerals—we yield to none in our unabashed exhibitions of public grief. Distant relatives who haven't seen us for years stand back in amazement as apparently total strangers rend their hair and wail like demented wolverines. If I've had to forcibly restrain one grieving widow from throwing herself into …
Attitudes Toward Information About Genetic Risk for Cognitive Impairment After Cancer Chemotherapy: Breast Cancer Survivors Compared With Healthy Controls
Authors: Michael A. Andrykowski, Jessica L. Burris, Erin Walsh, Brent J. Small, Paul B. Jacobsen
Journal: Journal of Clinical Oncology (2010)

Purpose The trend toward personalized medicine will involve cancer treatment increasingly being tailored to the genetic characteristics of individuals. However, the availability of genetic information does not imply this information is desired or would impact treatment decision making. Methods One hundred sixty breast cancer survivors (BC group) and 205 healthy controls (HC group) were randomly assigned to respond to two different clinical scenarios varying in genetic-related risk of cognitive impairment (CI; little v very likely) and severity of CI (little v moderate problem) after chemotherapy. Ratings of the importance of being told this genetic information (information importance) and the likelihood this information would affect their decision to receive chemotherapy (information impact) were obtained. Results Results indicated the importance ascribed to genetic information was greatest when CI likelihood and severity were both high or low (P &lt; .05). Information impact ratings were not sensitive to differences in CI likelihood or severity; the BC group was less likely to indicate genetic information would affect their decision to receive chemotherapy than the HC group (P &lt; .001). Conclusion Results suggest lessened enthusiasm for genetic information that maintains or increases uncertainty about a specific course of action and highlight the importance of including clinically relevant groups in treatment decision-making research that employs hypothetical scenarios. Although women generally believe it is important to receive genetic information, they might benefit from assistance (eg, decision aid) in the difficult task of integrating information about survival and risk for adverse late effects from cancer treatment.