tbuckley/cabot-search huggingface dataset:
Trps1 Functions Downstream of Bmp7 in Kidney Development
Authors: Zhibo Gai, Gengyin Zhou, Shunji Itoh, Yoshifumi Morimoto, Hiroyuki Tanishima, Ikuji Hatamura, Kohsaku Uetani, Masataka Ito, Yasuteru Muragaki
Journal: Journal of the American Society of Nephrology (2009)

During embryonic development, the mesenchyme of the lungs, gut, kidneys, and other tissues expresses Trps1, an atypical member of the GATA-type family of transcription factors. Our previous work suggested the possibility that Trps1 acts downstream of bone morphogenic protein 7 (Bmp7), which is essential for normal renal development. To examine the role of Trps1 during early renal development, we generated Trps1-deficient mice and examined their renal histology. Compared with wild-type mice, Trps1-deficient newborn mice had fewer tubules and glomeruli, an expanded renal interstitium, and numerous uninduced metanephric mesenchymal cells, which resulted in fewer nephrons. In wild-type kidneys, Trps1 expression was present in ureteric buds, cap mesenchyme, and renal vesicles, whereas Trps1 was virtually absent in Bmp7-deficient kidneys. Furthermore, Trps1-deficient kidneys had low levels of Pax2 and Wt1, which are markers of condensed mesenchymal cells, suggesting that a lack of Trps1 affects the differentiation of cap mesenchyme to renal vesicles. In cultured metanephric mesenchymal cells, Bmp7 induced Trps1 and E-cadherin and downregulated vimentin. Knockdown of Trps1 with small interference RNA inhibited this Bmp7-induced mesenchymal-to-epithelial transition. Last, whole-mount in situ hybridization of Wnt9b and Wnt4 demonstrated prolonged branching of ureteric buds and sparse cap mesenchyme in the kidneys of Trps1-deficient mice. Taken together, these findings suggest that normal formation of nephrons requires Trps1, which mediates mesenchymal-to-epithelial transition and ureteric bud branching during early renal development.
NKT cells depend on SAP
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2005)

An intracellular adaptor protein is indispensable for the development of natural killer T (NKT) cells, according to Pasquier et al. (page 695). The loss of these cells might contribute to the genesis of a lethal immunodeficiency syndrome.

The adaptor protein in question—SAP (SLAM-associated protein)—is expressed in T, NK, and NKT cells and responds to SLAM family receptors by recruiting and activating the downstream tyrosine kinase Fyn. Fyn was known to be required for NKT cell development in the thymus, but the upstream cell surface signals remained unknown.

Pasquier and colleagues now implicate the SLAM family of receptors in NKT cell development by showing that the loss of SAP results in a complete absence of NKT cells in both mice and humans. SAP-transmitted signaling events were uniquely required for the development of NKT cells, as conventional T cells and NK cells developed normally in the absence of SAP.

The need for SAP-mediated signals may reflect the unique requirements for positive selection of NKT cells in the thymus. Whereas conventional T cells interact with thymic epithelial cells for selection, NKT cells must interact with CD1d-expressing thymocytes via their invariant T cell receptors. This unique interaction might also provide the required SLAM-mediated signals.

In an intriguing twist, mutations in SAP cause a fatal disease called X-linked lymphoproliferative syndrome (XLP), which is characterized by uncontrolled Epstein-Barr virus (EBV) infections and B cell lymphomas. The loss of SAP impacts the function of multiple cell types including NK cells and T cells, but based on the current study, NKT cells may also contribute to XLP. Studying NKT cell activation during human EBV infection may give clues about why the lack of SAP, which results in so many immune cell defects, would preferentially increase susceptibility to only one type of virus.
Efficacy and tolerability of MK-0974 (telcagepant), a new oral antagonist of calcitonin gene-related peptide receptor, compared with zolmitriptan for acute migraine: a randomised, placebo-controlled, parallel-treatment trial
Authors: Tony W Ho, Michel D Ferrari, David W Dodick, Vince Galet, James Kost, Xiaoyin Fan, Heather Leibensperger, Samar Froman, Christopher Assaid, Christopher Lines, Hille Koppen, Paul K Winner
Journal: The Lancet (2008)
Heterosubtypic neutralizing antibodies are produced by individuals immunized with a seasonal influenza vaccine
Authors: Davide Corti, Amorsolo L. Suguitan, Debora Pinna, Chiara Silacci, Blanca M. Fernandez-Rodriguez, Fabrizia Vanzetta, Celia Santos, Catherine J. Luke, Fernando J. Torres-Velez, Nigel J. Temperton, Robin A. Weiss, Federica Sallusto, Kanta Subbarao, Antonio Lanzavecchia
Journal: Journal of Clinical Investigation (2010)

The target of neutralizing antibodies that protect against influenza virus infection is the viral protein HA. Genetic and antigenic variation in HA has been used to classify influenza viruses into subtypes (H1-H16). The neutralizing antibody response to influenza virus is thought to be specific for a few antigenically related isolates within a given subtype. However, while heterosubtypic antibodies capable of neutralizing multiple influenza virus subtypes have been recently isolated from phage display libraries, it is not known whether such antibodies are produced in the course of an immune response to influenza virus infection or vaccine. Here we report that, following vaccination with seasonal influenza vaccine containing H1 and H3 influenza virus subtypes, some individuals produce antibodies that cross-react with H5 HA. By immortalizing IgG-expressing B cells from 4 individuals, we isolated 20 heterosubtypic mAbs that bound and neutralized viruses belonging to several HA subtypes (H1, H2, H5, H6, and H9), including the pandemic A/California/07/09 H1N1 isolate. The mAbs used different VH genes and carried a high frequency of somatic mutations. With the exception of a mAb that bound to the HA globular head, all heterosubtypic mAbs bound to acid-sensitive epitopes in the HA stem region. Four mAbs were evaluated in vivo and protected mice from challenge with influenza viruses representative of different subtypes. These findings reveal that seasonal influenza vaccination can induce polyclonal heterosubtypic neutralizing antibodies that cross-react with the swine-origin pandemic H1N1 influenza virus and with the highly pathogenic H5N1 virus.
Caution this drug may cause serious harm! Why we must report adverse effects of physical activity promotion
Authors: Evert Verhagen, Caroline Bolling, Caroline F Finch
Journal: British Journal of Sports Medicine (2014)

The impact of (in)sufficient levels of physical activity (PA) have been well described and without argument, the promotion of PA—defined as moderate to vigorous physical activities, including sports and exercise—is now a cornerstone of contemporary public health.1 In our global effort to decrease the individual and public burden of chronic and lifestyle-related diseases, PA is being promoted as a medicine or drug , with the implication that it is a treatment and a preventive measure. Although the pharmacological benefits of PA have been well described,2 the analogy between PA as medicine is not drawn in full, because any substance that is capable of producing a therapeutic effect can also produce unwanted or adverse effects.3 The potential for adverse effects of PA, and the need to mitigate them, are mostly ignored in PA research and PA interventions alike.

An adverse drug reaction is defined by the WHO as “a response to a drug that is noxious and unintended and occurs at doses normally used in man for the prophylaxis, diagnosis or therapy of disease, or for modification of physiological function.”3 An injury resulting from the recommended daily dose of 30 min of moderate to vigorous PA certainly fits this definition. However, truth be …
Does This Patient Have Generalized Anxiety or Panic Disorder?
Authors: Nathaniel R. Herr, John W. Williams, Sophiya Benjamin, Jennifer McDuffie
Journal: JAMA (2014)

In primary care settings, generalized anxiety disorder (GAD) and panic disorder are common but underrecognized illnesses. Identifying accurate and feasible screening instruments for GAD and panic disorder has the potential to improve detection and facilitate treatment.To systematically review the accuracy of self-report screening instruments in diagnosing GAD and panic disorder in adults.We searched MEDLINE, PsycINFO, and the Cochrane Library for relevant articles published from 1980 through April 2014.Prospective studies of diagnostic accuracy that compared a self-report screening instrument for GAD or panic disorder with the diagnosis made by a trained clinician using Diagnostic and Statistical Manual of Mental Disorders or International Classification of Diseases criteria.We screened 3605 titles, excluded 3529, and performed a more detailed review of 76 articles. We identified 9 screening instruments based on 13 articles from 10 unique studies for the detection of GAD and panic disorder in primary care patients Across all studies, diagnostic interviews determined that 257 of 2785 patients assessed had a diagnosis of GAD while 224 of 2637 patients assessed had a diagnosis of panic disorder. The best-performing test for GAD was the Generalized Anxiety Disorder Scale 7 Item (GAD-7), with a positive likelihood ratio of 5.1 (95% CI, 4.3-6.0) and a negative likelihood ratio of 0.13 (95% CI, 0.07-0.25). The best-performing test for panic disorder was the Patient Health Questionnaire, with a positive likelihood ratio of 78 (95% CI, 29-210) and a negative likelihood ratio of 0.20 (95% CI, 0.11-0.37).Two screening instruments, the GAD-7 for GAD and the Patient Health Questionnaire for panic disorder, have good performance characteristics and are feasible for use in primary care. However, further validation of these instruments is needed because neither instrument was replicated in more than 1 primary care population.
Use of a Local Indicator Dilution Technique for the Measurement of Oscillatory Flow
Authors: R. D. LOWE
Journal: Circulation Research (1968)

An indicator dilution method for measuring oscillatory flow in a vessel is analyzed in terms of a mixing chamber with a constant volume. For the correct measurement of mean flow, the time constant of detection of the indicator should be very much shorter than the shortest time constant of the mixing volume. The performance of such a system was examined with a thermal indicator. Although the apparent mixing volume was found not to be constant but to vary with flow, the method showed no significant error in the measurement of mean flow. There was no significant "distance distortion error" when the indicator was detected at two different points downstream from the site of infusion; this was attributed to the pattern of mixing, with detection within or close to the limits of the mixing volume. It is concluded that a properly designed indicator dilution system can measure mean blood flow without significant error, even when there is an socillatory component.
Non-invasive determination of transpulmonary gradient and pulmonary vascular resistance in potential heart transplant candidates: Can right heart catheterization be avoided?
Authors: James H. Stein, Alex Neumann, Lynn M. Preston, Jeffrey S. Sobie, Susan M. Quinn, Maria R. Costanzo, Joseph E. Parrillo, Maryl R. Johnson, Richard H. Marcus
Journal: Journal of the American College of Cardiology (1996)
Multiple crm- mutations in familial hypercholesterolemia. Evidence for 13 alleles, including four deletions.
Authors: H H Hobbs, E Leitersdorf, J L Goldstein, M S Brown, D W Russell
Journal: Journal of Clinical Investigation (1988)

The low density lipoprotein (LDL) receptors in fibroblasts from 132 subjects with the clinical syndrome of homozygous familial hypercholesterolemia were analyzed by immunoprecipitation with an anti-LDL receptor monoclonal antibody. 16 of the 132 cell strains (12%) synthesized no immunodetectable LDL receptor protein, indicating the presence of two mutant genes that failed to produce cross-reacting material (crm- mutations). DNA and mRNA from 15 of the 16 crm- patients, representing 30 crm- genes, were available for further study. Haplotype analysis based on 10 restriction fragment length polymorphisms (RFLPs) suggested that the 30 crm- genes represent 13 mutant alleles. Four of the alleles produced no mRNA. Three of these four mRNA- alleles had large deletions ranging from 6 to 20 kb that eliminated the promoter region of the gene. The fourth mRNA- allele did not contain any deletion or alteration in the promoter sequence; the reason for the mRNA- phenotype was not apparent. Nine alleles were positive for mRNAs, of which three encoded mRNAs of abnormal size. One of the abnormal mRNAs was produced by a gene harboring a deletion, and another was produced by a gene with a complex rearrangement. The third abnormal-sized mRNA (3.1 kb larger than normal) was produced by an allele that had no detectable alterations as judged by Southern blotting. The other six mRNA+ alleles appeared normal by Southern blotting and produced normal-sized mRNA but no receptor protein. The current studies demonstrate that mRNA analysis coupled with haplotype determination by Southern blot analysis can be used to classify crm- mutations at a genetic locus where multiple alleles exist.
Pulmonary arterial aneurysm
Authors: E. Trell
Journal: Thorax (1973)

<b>Trell, E. (1973).</b><i>Thorax</i>, <b>28</b>, 644-649. <b>Pulmonary arterial aneurysm.</b> This is the case report of the clinical, radiographic, and physiological progress of a patient with increasing aneurysmal dilatation of the main pulmonary arteries, followed over a period of 10 years.
Vascular endothelial dysfunction resulting from l-arginine deficiency in a patient with lysinuric protein intolerance
Authors: Yoshihiro Kamada, Hiroyuki Nagaretani, Shinji Tamura, Tohru Ohama, Takao Maruyama, Hisatoyo Hiraoka, Shizuya Yamashita, Akira Yamada, Shinichi Kiso, Yoshiaki Inui, Nobuyuki Ito, Yoshiro Kayanoki, Sumio Kawata, Yuji Matsuzawa
Journal: Journal of Clinical Investigation (2001)

Although L-arginine is the only substrate for nitric oxide (NO) production, no studies have yet been reported on the effect of an L-arginine deficiency on vascular function in humans. Lysinuric protein intolerance (LPI) is a rare autosomal recessive defect of dibasic amino acid transport caused by mutations in the SLC7A7 gene, resulting in an L-arginine deficiency. Vascular endothelial function was examined in an LPI patient who was shown to be a compound heterozygote for two mutations in the gene (5.3-kbp Alu-mediated deletion, IVS3+1G→Α). The lumen diameter of the brachial artery was measured in this patient and in healthy controls at rest, during reactive hyperemia (endothelium-dependent vasodilation [EDV]), and after sublingual nitroglycerin administration (endothelium-independent vasodilation [EIV]) using ultrasonography. Both EDV and NOx concentrations were markedly reduced in the patient compared with those for the controls. They became normal after an L-arginine infusion. EIV was not significantly different between the patient and controls. Positron emission tomography of the heart and a treadmill test revealed ischemic changes in the patient, which were improved by the L-arginine infusion. Thus, in the LPI patient, L-arginine deficiency caused vascular endothelial dysfunction via a decrease in NO production.
Dietary Fat Intake Predicts 1-Year Change in Body Fat in Adolescent Girls With Type 1 Diabetes
Authors: Stefan Särnblad, Ulf Ekelund, Jan Åman
Journal: Diabetes Care (2006)

OBJECTIVE—The purpose of this study was to determine whether objectively measured physical activity and dietary macronutrient intake differentially predict body fat in adolescent girls with type 1 diabetes and control girls. RESEARCH DESIGN AND METHODS—This study comprised 23 girls (12–19 years) with type 1 diabetes and 19 age-matched healthy control girls. At baseline, physical activity and energy intake were assessed for 7 consecutive days by accelerometry and a structured food diary, respectively. Body composition was measured by dual-energy X-ray absorptiometry at baseline and after 1 year. RESULTS—Fat intake was positively related to a 1-year change in percentage body fat (P = 0.006), after adjustment for total energy intake. No significant interaction was observed (case-control group × main exposure), indicating that the association between fat intake and gain in body fat was similar in both groups. Physical activity did not predict gain in body fat; however, total physical activity was positively associated with a gain in lean body mass (P &amp;lt; 0.01). Girls treated with six daily dosages of insulin increased their percentage of body fat significantly more than those treated with four daily injections (P &amp;lt; 0.05). CONCLUSIONS—In this prospective case-control study, we found that fat intake predicted gain in percentage of body fat in both adolescent girls with type 1 diabetes and healthy control girls. The number of daily insulin injections seems to influence the accumulation of body fat in girls with type 1 diabetes.
Lenalidomide plus R-CHOP21 in elderly patients with untreated diffuse large B-cell lymphoma: results of the REAL07 open-label, multicentre, phase 2 trial
Authors: Umberto Vitolo, Annalisa Chiappella, Silvia Franceschetti, Angelo Michele Carella, Ileana Baldi, Giorgio Inghirami, Michele Spina, Vincenzo Pavone, Marco Ladetto, Anna Marina Liberati, Anna Lia Molinari, Pierluigi Zinzani, Flavia Salvi, Pier Paolo Fattori, Alfonso Zaccaria, Martin Dreyling, Barbara Botto, Alessia Castellino, Angela Congiu, Marcello Gaudiano, Manuela Zanni, Giovannino Ciccone, Gianluca Gaidano, Giuseppe Rossi
Journal: The Lancet Oncology (2014)
Effect of narrowband ultraviolet B phototherapy on melanocytic naevi
Authors: C.Y. Lin, A. Oakley, M. Rademaker, S. Hill, A. Yung
Journal: British Journal of Dermatology (2013)

Melanocytic naevi have been observed to undergo morphological changes following exposure to narrowband ultraviolet (NB-UV)B radiation.To analyse changes in naevi exposed to NB-UVB in a large cohort of patients.Subjects referred for phototherapy had macroscopic and dermoscopic images taken of prominent melanocytic naevi at the following time points: immediately prior to NB-UVB treatment, after 10 exposures, after 30 exposures or at the end of treatment if earlier, and 3 months after discontinuing treatment. Four dermatologists, by consensus, examined each naevus for specific clinical and dermoscopic features at each time point. The size (area) of each naevus was determined by plenimetry.Complete sets of images were taken for 36 out of 51 patients. The most common global dermoscopic patterns in the 440 naevi examined were reticular (50%) and globular (32%). Following NB-UVB exposure, blurring or merging of lines was observed in 45% of reticular naevi. An increase in colour intensity and in the number of dots or globules was observed in 63% of globular naevi, and 167 naevi (40%) underwent a change in size. Of these, 91/167 (54%) decreased in size, with a median area reduction of 8% (0·9-42%); while 76/167 (46%) increased in size, with a median area increase of 9% (1-76%).Around half of naevi exposed to a course of NB-UVB treatment undergo size or morphological changes. Naevi that enlarged tended to revert to pretreatment size 3 months after discontinuation of phototherapy.
Probability, Predictors, and Prognosis of Posttransplantation Glomerulonephritis
Authors: Worawon Chailimpamontree, Svetlana Dmitrienko, Guiyun Li, Robert Balshaw, Alexander Magil, R. Jean Shapiro, David Landsberg, John Gill, Paul A. Keown
Journal: Journal of the American Society of Nephrology (2009)

Glomerulonephritis (GN) is the leading cause of chronic kidney disease among recipients of renal transplants. Because modern immunosuppressive regimens have reduced the incidence of rejection-related graft loss, the probability and clinical significance of posttransplantation GN (PTGN) requires reevaluation. In this Canadian epidemiologic study, we monitored 2026 sequential renal transplant recipients whose original renal disease resulted from biopsy-proven GN (36%), from presumed GN (7.8%), or from disorders other than GN (56%) for 15 yr without loss to follow-up. Kaplan-Meier estimates of PTGN in the whole population were 5.5% at 5 yr, 10.1% at 10 yr, and 15.7% at 15 yr. PTGN was diagnosed in 24.3% of patients whose original renal disease resulted from biopsy-proven GN, compared with 11.8% of those with presumed GN and 10.5% of those with disorders other than GN. Biopsy-proven GN in the native kidney, male gender, younger age, and nonwhite ethnicity predicted PTGN. Current immunosuppressive regimens did not associate with a reduced frequency of PTGN. Patients who developed PTGN had significantly reduced graft survival (10.2 versus 69.7%; P < 0.0001). In summary, in the Canadian population, PTGN is a common and serious complication that causes accelerated graft failure, despite the use of modern immunosuppressive regimens.
Lack of replication of thirteen single-nucleotide polymorphisms implicated in Parkinson's disease: a large-scale international study
Authors: Alexis Elbaz, Lorene M Nelson, Haydeh Payami, John PA Ioannidis, Brian K Fiske, Grazia Annesi, Andrea Carmine Belin, Stewart A Factor, Carlo Ferrarese, Georgios M Hadjigeorgiou, Donald S Higgins, Hideshi Kawakami, Rejko Krüger, Karen S Marder, Richard P Mayeux, George D Mellick, John G Nutt, Beate Ritz, Ali Samii, Caroline M Tanner, Christine Van Broeckhoven, Stephen K Van Den Eeden, Karin Wirdefeldt, Cyrus P Zabetian, Marie Dehem, Jennifer S Montimurro, Audrey Southwick, Richard M Myers, Thomas A Trikalinos
Journal: The Lancet Neurology (2006)
Acute effects of antiglomerular basement membrane antibody on the process of glomerular filtration in the rat.
Authors: R C Blantz, C B Wilson
Journal: Journal of Clinical Investigation (1976)

Nehron filtration rate (sngfr) and the factors controlling filtration were examined before and with 60 min of the intravenous infusion of 225-450 mug of antiglomerular basement membrane antibody (AGBM Ab) (greater than 50% antigenic saturation) in plasma-expanded (2.5% body wt) Munich-Wistar rats. Pressures in glomerular capillaries (PG) and bowman's space (Pt) were measured with a servo-nulling device, systemic (piA) and efferent arteriolar oncotic pressures (piE) were measured by microprotein methods, and nephron plasma flow (rpf) and sngfr were measured by micropuncture techniques in both control and post-AGBM Ab conditions in each rat. The sngfr fell from 52.7+/-2.9 to 24.1+/-1.9 nl/min per g kidney wt (n = 7, P less than 0.001). Both afferent and efferent arteriolar resistances increased and rpf fell from 221+/-25 to 90+/-9 nl/min per g kidney wt (P less than 0.001) but the hydrostatic pressure gradient across the glomerular membrane deltaP = PG - Pt) increased from 37+/- 1 to 50+/-2 mm Hg (P less than 0.001). The increase in deltaP and a numerical decrease in piA both acted to maintain sngfr after AGBM Ab and effectively nullified the influence of decreased rpf upon sngfr. The mean effective filtration pressure (EFP = deltaP - pi) increased from 14+/-2 to 30+/-3 mm Hg (P less than 0.001) while sngfr decreased. The major and critical reason for this reduction in sngfr was a decrease in the glomerular permeability coefficient from 0.077+/-0.017 to 0.014+/-0.001 nl/s per g kidney wt per mm Hg P less than 0.001) where sngfr=EFP-LpA.
Father-son incest: underreported psychiatric problem?
Authors: K N Dixon, L E Arnold, K Calestro
Journal: American Journal of Psychiatry (1978)

Six families are described in which 10 sons were involved incestuously with a natural father (N=4) or step-father (N=2). Father-son incest as a part of the spectrum of child abuse appears to be a more frequent clinical entity than was thought previously.