tbuckley/cabot-search huggingface dataset:
<i>NPHP4</i> Variants Are Associated With Pleiotropic Heart Malformations
Authors: Vanessa M. French, Ingrid M.B.H. van de Laar, Marja W. Wessels, Christan Rohe, Jolien W. Roos-Hesselink, Guangliang Wang, Ingrid M.E. Frohn-Mulder, Lies-Anne Severijnen, Bianca M. de Graaf, Rachel Schot, Guido Breedveld, Edwin Mientjes, Marianne van Tienhoven, Elodie Jadot, Zhengxin Jiang, Annemieke Verkerk, Sigrid Swagemakers, Hanka Venselaar, Zohreh Rahimi, Hossein Najmabadi, Hanne Meijers-Heijboer, Esther de Graaff, Wim A. Helbing, Rob Willemsen, Koen Devriendt, John W. Belmont, Ben A. Oostra, Jeffrey D. Amack, Aida M. Bertoli-Avella
Journal: Circulation Research (2012)

Congenital heart malformations are a major cause of morbidity and mortality, especially in young children. Failure to establish normal left-right (L-R) asymmetry often results in cardiovascular malformations and other laterality defects of visceral organs.To identify genetic mutations causing cardiac laterality defects.We performed a genome-wide linkage analysis in patients with cardiac laterality defects from a consanguineous family. The patients had combinations of defects that included dextrocardia, transposition of great arteries, double-outlet right ventricle, atrioventricular septal defects, and caval vein abnormalities. Sequencing of positional candidate genes identified mutations in NPHP4. We performed mutation analysis of NPHP4 in 146 unrelated patients with similar cardiac laterality defects. Forty-one percent of these patients also had laterality defects of the abdominal organs. We identified 8 additional missense variants that were absent or very rare in control subjects. To study the role of nphp4 in establishing L-R asymmetry, we used antisense morpholinos to knockdown nphp4 expression in zebrafish. Depletion of nphp4 disrupted L-R patterning as well as cardiac and gut laterality. Cardiac laterality defects were partially rescued by human NPHP4 mRNA, whereas mutant NPHP4 containing genetic variants found in patients failed to rescue. We show that nphp4 is involved in the formation of motile cilia in Kupffer's vesicle, which generate asymmetrical fluid flow necessary for normal L-R asymmetry.NPHP4 mutations are associated with cardiac laterality defects and heterotaxy. In zebrafish, nphp4 is essential for the development and function of Kupffer's vesicle cilia and is required for global L-R patterning.
Self-dilatation of oesophageal strictures.
Authors: M H Robinson, M W Gear
Journal: Gut (1991)

A new technique for the management of upper and mid-oesophageal benign strictures is reported. A deflated oesophageal balloon catheter coated with steroid paste is passed by the patient through the stricture, the balloon is inflated and then withdrawn. This technique can be used for both strictures caused by tablet or corrosive damage that recur rapidly and where stricturing is the result of a chronic disease not amenable to medical or surgical treatments. Three patients in who this technique has been used with satisfactory patient tolerance and compliance and good relief of symptoms are reported.
Constructing narratives of heroism and villainy: case study of Myriad's BRACAnalysis® compared to Genentech's Herceptin®
Authors: A Baldwin, Robert Cook-Deegan
Journal: Genome Medicine (2013)

The development of Herceptin® is welcomed as a major advance in breast cancer treatment, while Myriad's development of BRACAnalysis® is a widely used diagnostic. However useful and successful this product is, its presence in the public eye is tainted by predominantly negative press about gene patenting and business practices. While retrospection invites a sharp contrast between Genentech's triumphal narrative of scientific achievement and Myriad's public image as a controversial monopolist, a comparative history of these companies' products reveals two striking consistencies: patents and public discontent. Despite these similarities, time has reduced the narrative to that of hero versus villain: Genentech is lauded - at least for the final outcome of the Herceptin® story - as a corporate good citizen, Myriad as a ruthless mercenary. Since patents undergird both products yet the narratives are so different, the stories raise the question: why have patents taken the fall as the scapegoat in current biotechnology policy debate? A widely publicized lawsuit and accompanying bad press have cast Myriad as a villain in the evolving narrative of biotechnology. While the lawsuit suggests that this villainy is attributable to Myriad's intellectual property, we suggest through a comparative case study that, at least in the Myriad case, it is not simply about the patents but also other business strategies the company chose to pursue. Patents were a necessary but not sufficient cause of controversy.
Autoantigens signal through chemokine receptors: uveitis antigens induce CXCR3- and CXCR5-expressing lymphocytes and immature dendritic cells to migrate
Authors: O. M. Zack Howard, Hui Fang Dong, Shao Bo Su, Rachel R. Caspi, Xin Chen, Paul Plotz, Joost J. Oppenheim
Journal: Blood (2005)
Long-Lasting Egg Consumption in Egg Allergic Children Treated with Oral Immunotherapy (OIT): Follow-up from the Consortium of Food Allergy Research (CoFAR) Study
Authors: Stacie M. Jones, A. Wesley Burks, Robert A. Wood, David Mark Fleischer, Scott H. Sicherer, Alice Henning, Robert Lindblad, Peter Dawson, Brian P. Vickery, Corinne Keet, Andrew H. Liu, Amy M. Scurlock, Hugh A. Sampson
Journal: Journal of Allergy and Clinical Immunology (2014)
Process of pulmonary eosinophilia induced by intratracheal administration of Interleukin-33
Authors: Naoko Mato, Masayuki Nakayama, Takakiyo Nakaya, Hideaki Yamasawa, Masashi Bando, Yukihiki Sugiyama
Journal: European Respiratory Journal (2014)

Background and objective: IL-33 is a functional cytokine to enhance the activity of eosinophils and to promote their differentiation. We previously demonstrated that significant increase of IL-33 level in bronchoalveolar lavage fluid (BALF) in the initial phase of acute eosinophilic pneumonia in contrast to chronic eosinophilic pneumonia. From our data, it is speculated that IL-33 plays an important role in the acute induction of eosinophila in lung. Therefore, we investigated the sequential process of eosinophilia by local IL-33 treatment.  Methods: Recombinant IL-33 protein (5μg/mouse) was directly administered into trachea of BALB/c mice. Sequentially, blood and BALF were obtained up to 10 days after the treatment, and examined the cell numbers, the concentration of IL-5 and albumin. Histological change was also evaluated.  Results: Only once IL-33 administration induced prominent pulmonary eosinophilia, and the maximum number of eosinophils in BALF was observed at day 7-10 after the treatment. The concentration of IL-5 of BALF was increased at day 3 and that of albumin attained the peak at day10. Histologically, the accumulation of eosinophis was observed during day 3-10. However, the peripheral blood showed no increase of eosionophils and IL-5.  Conclusion: Local administration of IL-33 induced local eosinophilia in lung, without the increase of eosinophils in peripheral blood. In addition, IL-33 induced local IL-5 production and the albumin leakage due to the increase of permeability. Furthermore, it is speculated that the progenitors of eosinophils in lung are able to respond to IL-33 and IL-5, and local proliferation of eosinophils would participate in eosinophilic lung disease.
Characterization of multiple platelet activation pathways in patients with bleeding as a high-throughput screening option: use of 96-well Optimul assay
Authors: Marie Lordkipanidzé, Gillian C. Lowe, Nicholas S. Kirkby, Melissa V. Chan, Martina H. Lundberg, Neil V. Morgan, Danai Bem, Shaista P. Nisar, Vincenzo C. Leo, Matthew L. Jones, Stuart J. Mundell, Martina E. Daly, Andrew D. Mumford, Timothy D. Warner, Steve P. Watson
Journal: Blood (2014)
Relationship between Moderate to Severe Kidney Disease and Hip Fracture in the United States
Authors: Thomas L. Nickolas, Donald J. McMahon, Elizabeth Shane
Journal: Journal of the American Society of Nephrology (2006)

People with ESRD are at a high risk for hip fracture. However, the effect of moderate to severe chronic kidney disease (CKD) on hip fracture risk has not been well studied. As part of the Third National Health and Nutrition Examination Survey, information on both kidney function and history of hip fracture was obtained. This survey is a complex, multistage, probability sample of the US noninstitutionalized civilian population and was conducted between 1988 and 1994. A history of hip fracture was identified from the response to a questionnaire that was administered to all participants. There were 159 cases of hip fracture. There was a significantly increased likelihood of reporting a hip fracture in participants with estimated GFR <60 ml/min (odds ratio [OR] 2.12; 95% confidence interval [CI] 1.18 to 3.80). In younger participants (aged 50 to 74 yr), the prevalence of CKD was approximately three-fold higher in those with a history of hip fracture versus in those without a history of hip fracture (19.0 versus 6.2%, respectively; P = 0.04). In multivariate logistic regression analysis, only the presence of CKD (OR 2.32; 95% CI 1.13 to 4.74), a reported history of osteoporosis (OR 2.52; 95% CI 1.08 to 5.91), and low physical activity levels (OR 2.10; 95% CI 1.03 to 4.27) were associated with a history of hip fracture. There is a significant association between hip fracture and moderate to severe degrees of CKD, particularly in younger individuals, that is independent of traditional risk factors for hip fracture.
Discussing Prognosis: “How Much Do You Want to Know?” Talking to Patients Who Are Prepared for Explicit Information
Authors: Anthony L. Back, Robert M. Arnold
Journal: Journal of Clinical Oncology (2006)

Mrs D, a 57-year-old woman with metastatic pancreatic cancer, is discussing treatment options with Dr B. How much should I tell her about prognosis? he wonders.She already seems nervous.Do I hand her the death sentence?Or sugarcoat the statistics?Maybe I'll wait to see if she asks.For the first time Mrs D looks up and says, "What should I expect?"Dr B balks, not having decided what to say."Umm, I can't really predict," he mumbles."Every patient is different."Perhaps I am mumbling, thinks Dr B, because I'm not telling her the whole truth.Mrs D nods vaguely without meeting his gaze and picks up her purse to leave.Is she dissatisfied also?Dr B finds himself in a familiar dilemma: how much information should an oncologist give about a bad prognosis?One of his colleagues prides himself on being a realist, "I tell patients the truth because they need to know, whether they want to hear it or not."Another colleague feels he must give hope, "I go into cheerleader mode."Neither alternative seems optimal to Dr B-the nurses tell him that the realist tone is a little brutal, and that the cheerleader is more than a little clueless.Privately, Dr B feels his own practice-avoiding prognosis by emphasizing individual differences-borders on disingenuous.He knows a lot more about what will happen to Mrs D than he is letting on.Realism, optimism, and avoidance are the most common strategies physicians use in discussing prognosis. 1Although these strategies are well intended and commonly used, they also create unintended consequences.In this article, a patient-centered method for disclosing prognosis is proposed and illustrated.The method builds on existing empirical evidence about discussing prognosis 2,3 by drawing on principles of negotiation and patient-centered approaches.This approach enables an oncologist to figure out what kind of prognostic information to disclose with a particular patient at a particular time and how to individualize the discussion.This article describes how the approach works with a patient who is ready for an explicit discussion.
Smoking and dementia in male British doctors: prospective study
Authors: R. Doll
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objective:</b> To assess the possible association between smoking and dementia. <b>Design:</b> Prospective study. <b>Setting:</b> Cohort of British male doctors followed up since 1951. <b>Subjects:</b> 34 439 male British doctors, with 24 133 deaths recorded. <b>Results:</b> For all types of dementia combined the relative risk was 0.96 (95% confidence interval 0.78 to 1.18), based on 473 deaths at a mean age of 81 years. For probable or definite Alzheimer9s disease, the relative risk in continuing smokers was 0.99 (0.78 to 1.25), based on 370 deaths at a mean age of 82 years. In aggregate, however, the other prospective studies indicate a direct, although not clearly significant, association between smoking and the onset of dementia in general and of Alzheimer9s disease in particular. <b>Conclusions:</b> Contrary to previous suggestions persistent smoking does not substantially reduce the age specific onset rate of Alzheimer9s disease or of dementia in general. If anything, it might increase rather than decrease the rate, but any net effect on severe dementia cannot be large in either direction.
Electrical Connections Between Pulmonary Veins
Authors: Atsushi Takahashi, Yoshito Iesaka, Yoshihide Takahashi, Ryoko Takahashi, Kenzaburo Kobayashi, Katsumasa Takagi, Osamu Kuboyama, Takeo Nishimori, Hidenobu Takei, Hiroshi Amemiya, Hideomi Fujiwara, Masayasu Hiraoka
Journal: Circulation (2002)

Background — Electrical disconnection of the myocardial extensions into arrhythmogenic pulmonary veins (PVs) is recognized as a curative technique for paroxysmal atrial fibrillation (AF). However, the presence of electrical connections between the PVs, which may make achievement of PV disconnection difficult, has not been systematically evaluated. Methods and Results — Forty-nine consecutive patients with drug-resistant AF underwent ostial radiofrequency (RF) catheter ablation of arrhythmogenic PVs with foci triggering AF. Pacing from inside the targeted PV was performed after each RF delivery to identify the left atrial exit site of the residual venoatrial conduction. Successful PV disconnection was defined as achieving elimination of the PV potentials during sinus rhythm or left atrial pacing, and the loss of left atrial conduction during intra-PV pacing. A total of 112 arrhythmogenic PVs were identified. PV disconnection was achieved with 10±6.1 minutes of RF delivery to the ostia of 101 targeted PVs. In 7 left superior (LS) PVs from 7 patients (14%), the earliest atrial activity was recorded from the left inferior (LI) PV ostium during intra-LSPV pacing after 11±4.7 minutes of RF delivery to the LSPV ostium. Disconnection of these LSPVs was achieved by LIPV disconnection. In the remaining 4 PVs from 4 patients, PV disconnection could not be achieved. Conclusions — Fourteen percent of the patients had electrical connections between contiguous PVs. In these patients, ostial ablation of an untargeted PV was required for successful targeted PV disconnection.
Analysis of Labeling and Clearance of Lung Surfactant Phospholipids in Rabbit
Authors: Mikko Hallman, Benita L. Epstein, Louis Gluck
Journal: Journal of Clinical Investigation (1981)

Turnover and clearance of lung surfactant phospholipids were studied with particular reference to myoinositol-induced perturbation in the acidic phospholipids. Administration of myoinositol decreased [3H]palmitate and [32P]phosphate incorporation into phosphatidylglycerol by 80-90% in whole lung, and by 94-99% in lamellar bodies and in alveolar lavage. The increased incorporation of radioactive isotopes into phosphatidylinositol following myoinositol, was inverse to the decrease in phosphatidyl-glycerol incorporation. Myoinositol treatment affected neither content nor labeling of phosphatidylcholine or disaturated phosphatidylcholine as studied within 50 h of administration. Phosphatidylglycerol was pulse labeled by intravenous [32P]phosphate and [3H]palmitate, followed by myoinositol. The biological half-lives of phosphatidylglycerol in the microsomal fraction, lamellar bodies, and alveolar lavage were 1.6, 4.6, 5.4 h (with 3H), and 2.8, 6.5, 7.0 h (with 32P), respectively.
Leukostasis in Sézary Syndrome
Authors: Shu-Dean Hsu
Journal: JAMA (1979)

<h3>To the Editor.—</h3> The occurrence of intravascular leukocyte thrombi and aggregates is well documented in both acute and chronic myelogenous leukemia, especially when the total WBC count is more than 50,000/cu mm. Leukostasis is an infrequent complication of lymphocytic leukemias, even with WBC counts of more than 200,000/cu mm.<sup>1</sup>We had a patient with Sézary syndrome in whom leukostasis was believed to be the cause of death. <h3>Report of a Case.—</h3> A 53-year-old man was first seen in July 1974 with a two-year history of diffuse dry, scaling, pruritic skin lesions. The leukocyte count was 30,000/cu mm, with 65% lymphocytes. One half of the lymphocytes were distinctive, large lymphoid cells with convoluted nuclei and PAS-positive cytoplasmic granules, which were resistant to diastase decoloration (typical Sézary cells). Skin and lymph node biopsy specimens showed infiltration by similar cells. The bone marrow was spared. Combination chemotherapy was unsuccessful. The WBC count
Is Exposure Necessary? A Randomized Clinical Trial of Interpersonal Psychotherapy for PTSD
Authors: John C. Markowitz, Eva Petkova, Yuval Neria, Page E. Van Meter, Yihong Zhao, Elizabeth Hembree, Karina Lovell, Tatyana Biyanova, Randall D. Marshall
Journal: American Journal of Psychiatry (2015)

Objective: Exposure to trauma reminders has been considered imperative in psychotherapy for posttraumatic stress disorder (PTSD). The authors tested interpersonal psychotherapy (IPT), which has demonstrated antidepressant efficacy and shown promise in pilot PTSD research as a non-exposure-based non-cognitive-behavioral PTSD treatment. Method: The authors conducted a randomized 14-week trial comparing IPT, prolonged exposure (an exposure-based exemplar), and relaxation therapy (an active control psychotherapy) in 110 unmedicated patients who had chronic PTSD and a score >50 on the Clinician-Administered PTSD Scale (CAPS). Randomization stratified for comorbid major depression. The authors hypothesized that IPT would be no more than minimally inferior (a difference <12.5 points in CAPS score) to prolonged exposure. Results: All therapies had large within-group effect sizes (d values, 1.32–1.88). Rates of response, defined as an improvement of >30% in CAPS score, were 63% for IPT, 47% for prolonged exposure, and 38% for relaxation therapy (not significantly different between groups). CAPS outcomes for IPT and prolonged exposure differed by 5.5 points (not significant), and the null hypothesis of more than minimal IPT inferiority was rejected (p=0.035). Patients with comorbid major depression were nine times more likely than nondepressed patients to drop out of prolonged exposure therapy. IPT and prolonged exposure improved quality of life and social functioning more than relaxation therapy. Conclusions: This study demonstrated noninferiority of individual IPT for PTSD compared with the gold-standard treatment. IPT had (nonsignificantly) lower attrition and higher response rates than prolonged exposure. Contrary to widespread clinical belief, PTSD treatment may not require cognitive-behavioral exposure to trauma reminders. Moreover, patients with comorbid major depression may fare better with IPT than with prolonged exposure.
Patterns and Correlates of Adjuvant Radiotherapy Receipt After Lumpectomy and After Mastectomy for Breast Cancer
Authors: Reshma Jagsi, Paul Abrahamse, Monica Morrow, Sarah T. Hawley, Jennifer J. Griggs, John J. Graff, Ann S. Hamilton, Steven J. Katz
Journal: Journal of Clinical Oncology (2010)

Purpose To use patient self-report to provide more valid estimates of whether radiotherapy (RT) is underutilized than possible with registry data, as well as to evaluate for disparities and the influence of preferences and provider interactions. Methods We considered 2,260 survey respondents who had nonmetastatic breast cancer, were age 20 to 79 years, were diagnosed between July 2005 and February 2007 in Detroit and Los Angeles, and reported to Surveillance, Epidemiology and End Results (SEER) registries (72% response rate). Survey responses were merged with SEER data. We assessed rates and correlates of RT receipt among all patients with invasive cancer receiving breast-conserving surgery (BCS) and among patients undergoing mastectomy with indications for RT (ie, positive lymph nodes or T3-4 tumors). Results Among 904 patients undergoing BCS with strong indications for RT, 95.4% received RT, and 77.6% received RT among the 135 patients undergoing mastectomy with strong indications (P &lt; .001). Among 114 patients undergoing BCS with weaker indications (ie, elderly) for RT, 80.0% received treatment, and 47.5% received RT among the 164 patients undergoing mastectomy with weaker indications (T1N1, T2N1, or T3N0 disease; P &lt; .001). On multivariate analysis, surgery type (P &lt; .001), indication strength (P &lt; .001), age (P = .005), comorbidity (P &lt; .001), income (P = .03), patient desire to avoid RT (P &lt; .001), level of surgeon involvement in decision to have radiation (P &lt; .001), and SEER site (P &lt; .001) were significantly associated with likelihood of RT receipt. Conclusion RT receipt was consistently high across sociodemographic subgroups after BCS but was lower after mastectomy, even among patients with strong indications for treatment, in whom clinical benefit is similar. Surgeon involvement had a strong influence on RT receipt.
Microarray-based genomic surveying of gene polymorphisms in Chlamydia trachomatis.
Authors: Brian W Brunelle, Tracy L Nicholson, Richard S Stephens
Journal: Genome biology (2004)

By comparing two fully sequenced genomes of Chlamydia trachomatis using competitive hybridization on DNA microarrays, a logarithmic correlation was demonstrated between the signal ratio of the arrays and the 75-99% range of nucleotide identities of the genes. Variable genes within 14 uncharacterized strains of C. trachomatis were identified by array analysis and verified by DNA sequencing. These genes may be crucial for understanding chlamydial virulence and pathogenesis.
Genetic Inactivation of ADAMTS15 Metalloprotease in Human Colorectal Cancer
Authors: Cristina G. Viloria, Alvaro J. Obaya, Angela Moncada-Pazos, María Llamazares, Aurora Astudillo, Gabriel Capellá, Santiago Cal, Carlos López-Otín
Journal: Cancer Research (2009)

Matrix metalloproteinases have been traditionally linked to cancer dissemination through their ability to degrade most extracellular matrix components, thus facilitating invasion and metastasis of tumor cells. However, recent functional studies have revealed that some metalloproteases, including several members of the ADAMTS family, also exhibit tumor suppressor properties. In particular, ADAMTS1, ADAMTS9, and ADAMTS18 have been found to be epigenetically silenced in malignant tumors of different sources, suggesting that they may function as tumor suppressor genes. Herein, we show that ADAMTS15 is genetically inactivated in colon cancer. We have performed a mutational analysis of the ADAMTS15 gene in human colorectal carcinomas, with the finding of four mutations in 50 primary tumors and 6 colorectal cancer cell lines. Moreover, functional in vitro and in vivo studies using HCT-116 and SW-620 colorectal cancer cells and severe combined immunodeficient mice have revealed that ADAMTS15 restrains tumor growth and invasion. Furthermore, the presence of ADAMTS15 in human colorectal cancer samples showed a negative correlation with the histopathologic differentiation grade of the corresponding tumors. Collectively, these results provide evidence that extracellular proteases, including ADAMTS15, may be targets of inactivating mutations in human cancer and further validate the concept that secreted metalloproteases may show tumor suppressor properties.