tbuckley/cabot-search huggingface dataset:
Echocardiographic detection of mitral valve prolapse. Exclusion of false positive diagnosis and determination of inheritance.
Authors: A N Weiss, J W Mimbs, P A Ludbrook, B E Sobel
Journal: Circulation (1975)

An important potential source of error in the echocardiographic diagnosis of mitral valve prolapse has been identified -- namely a systolic hammock-like pattern of the anterior and/or posterior mitral leaflet echoes, similar to that associated with true mitral valve prolapse, produced artifactually when the ultrasonic transducer is angulated inferiorly. Utilizing a modified, more specific technique we characterized the mode of inheritance and familial prevalence of this disorder. Among 74 subjects, composed of 57 first-degree relatives and 17 propositi with mitral valve prolapse, mitral valve prolapse was detected in 27 of 57 (47%) of the first-degree relatives. Fifty-three percent of female and 36% of male progeny of propositi were affected. Furthermore, familial transmission occurred from propositi to both sexes. Results of this study indicate that mitral valve prolapse is transmitted in an autosomal dominant mode with reduced male expressivity and a familial prevalence of 47% and that appropriate echocardiographic techniques must be employed to avoid a high incidence of false positive diagnosis.
Tousled-like Kinases Modulate Reactivation of Gammaherpesviruses from Latency
Authors: Patrick J. Dillon, Sean M. Gregory, Kristen Tamburro, Marcia K. Sanders, Gary L. Johnson, Nancy Raab-Traub, Dirk P. Dittmer, Blossom Damania
Journal: Cell Host & Microbe (2013)

Kaposi's sarcoma-associated herpesvirus (KSHV) is linked to human malignancies. The majority of tumor cells harbor latent virus, and a small percentage undergo spontaneous lytic replication. Both latency and lytic replication are important for viral pathogenesis and spread, but the cellular players involved in the switch between the two viral life-cycle phases are not clearly understood. We conducted a small interfering RNA (siRNA) screen targeting the cellular kinome and identified Tousled-like kinases (TLKs) as cellular kinases that control KSHV reactivation from latency. Upon treatment of latent KSHV-infected cells with siRNAs targeting TLKs, we saw robust viral reactivation. Knockdown of TLKs in latent KSHV-infected cells induced expression of viral lytic proteins and production of infectious virus. TLKs were also found to play a role in regulating reactivation from latency of another related oncogenic gammaherpesvirus, Epstein-Barr virus. Our results establish the TLKs as cellular repressors of gammaherpesvirus reactivation.
Erratum: Corrigendum: Mutations in RDH12 encoding a photoreceptor cell retinol dehydrogenase cause severe childhood-onset retinal dystrophy
Authors: A R Janecke, D A Thompson, G Utermann, C Becker, C A Hübner, E Schmid, C L McHenry, A R Nair, F Rüschendorf, J Heckenlively, B Wissinger, P Nürnberg, A Gal
Journal: Nature Genetics (2004)
Disseminated Tuberculosis Masquerading as Metastatic Breast Carcinoma on PET-CT
Authors: Chandan Jyoti Das, Rakesh Kumar, Vijay Babu Balakrishnan, Madhavi Chawla, Arun Malhotra
Journal: Clinical Nuclear Medicine (2008)

PET has an established role in the management of breast cancer. However, F-18 FDG uptake sometimes has been associated with benign disease leading to false positive results. We present a case of a 37-year-old woman who presented with a 3-month history of a left breast lump and palpable left axillary lymph nodes. Whole-body PET-CT scan demonstrated multiple focal areas of intense FDG uptake in the left breast and multiple axillary, cervical, and mediastinal lymph nodes. PET-CT findings mimicked metastatic breast cancer, which was subsequently confirmed as disseminated tuberculosis by mammotome-guided biopsy of the breast lesion and fine needle aspiration biopsy of lymph nodes.
The augmentation of intracellular delivery of peptide therapeutics by artificial protein transduction domains
Authors: Tomoaki Yoshikawa, Toshiki Sugita, Yohei Mukai, Yasuhiro Abe, Shinsaku Nakagawa, Haruhiko Kamada, Shin-ichi Tsunoda, Yasuo Tsutsumi
Journal: Biomaterials (2009)
Haemoptysis after breath-hold diving
Authors: A Boussuges, C Pinet, P Thomas, E Bergmann, JM Sainty, D Vervloet
Journal: European Respiratory Journal (1999)

Pulmonary oedema has been described in swimmers and self-contained underwater breathing apparatus (Scuba) divers. This study reports three cases of haemoptysis secondary to alveolar haemorrhage in breath-hold divers. Contributory factors, such as haemodynamic modifications secondary to immersion, cold exposure, exercise and exposure to an increase in ambient pressure, could explain this type of accident. Furthermore, these divers had taken aspirin, which may have aggravated the bleeding.
The Relative and Combined Ability of High-Sensitivity Cardiac Troponin T and N-Terminal Pro-B-Type Natriuretic Peptide to Predict Cardiovascular Events and Death in Patients With Type 2 Diabetes
Authors: Graham S. Hillis, Paul Welsh, John Chalmers, Vlado Perkovic, Clara K. Chow, Qiang Li, Min Jun, Bruce Neal, Sophia Zoungas, Neil Poulter, Giuseppe Mancia, Bryan Williams, Naveed Sattar, Mark Woodward
Journal: Diabetes Care (2013)

OBJECTIVE Current methods of risk stratification in patients with type 2 diabetes are suboptimal. The current study assesses the ability of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) to improve the prediction of cardiovascular events and death in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS A nested case-cohort study was performed in 3,862 patients who participated in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. RESULTS Seven hundred nine (18%) patients experienced a major cardiovascular event (composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) and 706 (18%) died during a median of 5 years of follow-up. In Cox regression models, adjusting for all established risk predictors, the hazard ratio for cardiovascular events for NT-proBNP was 1.95 per 1 SD increase (95% CI 1.72, 2.20) and the hazard ratio for hs-cTnT was 1.50 per 1 SD increase (95% CI 1.36, 1.65). The hazard ratios for death were 1.97 (95% CI 1.73, 2.24) and 1.52 (95% CI 1.37, 1.67), respectively. The addition of either marker improved 5-year risk classification for cardiovascular events (net reclassification index in continuous model, 39% for NT-proBNP and 46% for hs-cTnT). Likewise, both markers greatly improved the accuracy with which the 5-year risk of death was predicted. The combination of both markers provided optimal risk discrimination. CONCLUSIONS NT-proBNP and hs-cTnT appear to greatly improve the accuracy with which the risk of cardiovascular events or death can be estimated in patients with type 2 diabetes.
Beneficial effects of MDL 74,405, a cardioselective water soluble tocopherol analogue, on the recovery of function of stunned myocardium in intact dogs
Authors: M. E Zughaib, X.-L. Tang, M. Schleman, M. O Jeroudi, R. Bolli
Journal: Cardiovascular Research (1994)

Objective: Postischaemic myocardial dysfunction (“stunning”) is caused in part by the generation of reactive oxygen species resulting in oxidant stress. The aim of this study was to test the hypothesis that the systemic administration of MDL 74,405, a hydrophilic cardioselective a tocopherol analogue, is beneficial in attenuating myocardial stunning. Methods: Open chest dogs undergoing a 15 min coronary artery occlusion and 4 h of reperfusion received an intravenous infusion of either saline (controls, n = 9) or MDL 74,405 (n = 8) at a dose of 0.3 mg·kg−1·h−1 starting 30 min before coronary occlusion and ending 60 min after reflow. Results: Regional myocardial function (assessed as systolic wall thickening) was similar in control and treated groups at baseline and during ischaemia. Following reperfusion, however, the dogs treated with MDL 74,405 had significant improvement in the recovery of function, which was evident 2 h after restoration of flow and was sustained throughout the rest of the reperfusion phase. Analysis of covariance showed that the differences in wall thickening after reperfusion between the two groups were independent of collateral flow during occlusion. Furthermore, the enhanced recovery effected by MDL 74,405 could not be attributed to non-specific factors such as coronary flow after reperfusion, arterial pressure, heart rate, or other haemodynamic variables. Measurements of MDL 74,405 showed that the myocardial content of the antioxidant at 4 h of reperfusion was approximately 30 times greater than the plasma concentration at 1 h of reperfusion, suggesting preferential cardiac accumulation of this drug. Conclusions: This study shows (1) that systemic administration of the a tocopherol analogue MDL 74,405 in the setting of myocardial ischaemia and reperfusion does not result in adverse cardiovascular effects, at least in the first few hours after injection; (2) that the drug accumulates in myocardial tissue at concentrations much higher than in the plasma; (3) that intravenous infusion of MDL 74,405 produces an attenuation of myocardial stunning comparable to that previously observed with intracoronary administration of other antioxidants; and (4) that this beneficial effect is independent of non-specific actions on haemodynamic variables or coronary flow. The results suggest that the systemic administration of hydrophilic, cardioselective a tocopherol analogues represents an effective therapeutic approach to the alleviation of postischaemic dysfunction. Cardiovascular Research 1994;28:235-241
Association between Lower Level Lead Concentrations and Hyperactivity in Children
Authors: Oliver J. David
Journal: Environmental Health Perspectives (1974)

Hyperactive children were compared with a nonhyperactive control group on two measures that reflect the presence of body lead and on a lead exposure questionnaire. The overall hypothesis that was tested was that a relationship exists between hyperactivity in children and a concommitant condition of increased body lead stores. Operationally, the hypothesis was reduced to a comparison of the hyperactive group and control group on the following measures: (1) blood lead levels; (2) post-penicillamine urine lead levels; (3) scores on a lead exposure questionnaire. The designation hyperactive or nonhyperactive was arrived at by using three different measurements: a doctor's diagnosis; a teacher's rating scale; a parent questionnaire. Hyperactive children had significantly higher values on all three measures than did the controls. More than half the hyperactive children had blood lead levels in the range considered to be raised but not toxic, and 60% of post-penicillamine urine levels were in the “toxic” range. It is concluded that there is an association between hyperactivity and raised lead levels, that a large body-lead burden may exact consequencies that have hitherto been unrealized; that the definition of what is a toxic level for blood lead needs reevaluation and that physicians should look for raised lead levels in children with hyperactivity.
EFFECTS OF BACTERIAL ENDOTOXIN ON RABBIT PLATELETS
Authors: Herbert I. Horowitz, Roger M. Des Prez, Edward W. Hook
Journal: The Journal of Experimental Medicine (1962)

Incubation of rabbit platelet-rich plasma with bacterial endotoxin results in activation of platelet factor 3, a precursor of blood thromboplastin. This platelet-endotoxin interaction is dose- and temperature-dependent, and is similar to the effects of antigen-antibody union in the presence of platelets. Injection of endotoxin intravenously is associated with a transient increase in platelet factor 3. Since platelet factor 3 can be demonstrated in platelet-poor plasma as well as platelet-rich plasma after endotoxin injection, it seems likely that an actual transfer of factor 3 from platelets to plasma occurs and that this activity is then rapidly inactivated or cleared from the blood stream.
ST ELEVATION MYOCARDIAL INFARCTION DUE TO LEFT MAIN CULPRIT LESIONS: PERCUTANEOUS CORONARY INTERVENTION OUTCOMES
Authors: Gilbert J. Zoghbi, Vijay K. Misra, Brigitta C. Brott, Silvio E. Papapietro, David Dai, Fang-Shu Ou, Tracy Y. Wang, Lloyd W. Klein, John C. Messenger, William B. Hillegass
Journal: Journal of the American College of Cardiology (2010)
Following Her Path, Oncologist Highlights Issue of Cancer in Native Americans
Authors: R. Twombly
Journal: JNCI Journal of the National Cancer Institute (2008)

W hen Judith Salmon Kaur , M.D., wants to get a little laugh from an audience of oncologists, she talks about her maiden Choctaw Cherokee surname. “I tell them it’s very appropriate to be a salmon and going into cancer re search and cancer prevention because you’re always swimming upstream.” But that’s not so true nowadays, given the recent recognition of Kaur’s research. After decades of studying and treating cancer in American Indians, Kaur is now coauthor of a federal report showing that the progress the country has been making as a whole in reducing cancer is not being generally refl ected in American Indian populations. And solving the problem will not be simple because several cancers occur at much higher rates in some tribes than in others. This information, from the Annual Report to the Nation on the Status of Cancer, 1975 – 2004, released last October, was the fi rst nationwide assessment of cancer rates in American Indians. And its results were markedly different from those that were presented to Kaur in 1984, when she fi rst started treating Northern Plain Indians. Cancer isn’t much of a problem in the 4 million Americans who are Indians, she was told, so reducing the alcoholism believed to be so rampant in Indians was the major focus of research and treatment. But Kaur and James Hampton, M.D., a 76-year-old oncologist in private practice in Oklahoma City — the only two oncologists in the nation who are members of an Indian tribe — helped to accurately portray the disease. They were the fi rst to detail growing rates of cancer in Indians and the fi rst to call for the creation of an American Indian cancer control plan. Kaur pioneered a cancer outreach program to American Indians that has since become a national model. “She has done a remarkable job in both educating Native Americans about cancer in their communities as well as highlighting the issue for the public,” Hampton said. “She is not only an excellent scientist but brings her own Native American perspective to cancer control. She has compassion, is very dedicated, and knows how to speak to the issue.” Kaur believes that her work on the American Indian cancer section of the report refl ects the notion that she was meant to do this work. “Indian philosophy says that there’s a path that you’re supposed to take, and if you stay on that, good things will happen.”
Agency tells surgeons not to use a type of hip implant cup liner because of high revision rates
Authors: D. Cohen
Journal: BMJ (2012)

Surgeons should stop using a particular type of cup liner that is used in some metal-on-metal hip operations because the revision rate is higher than it should be, the Medicines and Healthcare Products Regulatory Agency (MHRA) has said.

The R3 metal cup liner—part of the implant that fits into the cup—is used with the R3 Acetabular System total hip replacement prostheses made by UK company Smith and Nephew.

“Post-market surveillance data has shown a high revision rate of …
Conflicting Views on Chemical Carcinogenesis Arising from the Design and Evaluation of Rodent Carcinogenicity Studies
Authors: Ronald L. Melnick, Kristina A. Thayer, John R. Bucher
Journal: Environmental Health Perspectives (2007)

Conflicting views have been expressed frequently on assessments of human cancer risk of environmental agents based on animal carcinogenicity data; this is primarily because of uncertainties associated with extrapolations of toxicologic findings from studies in experimental animals to human circumstances. Underlying these uncertainties are issues related to how experiments are designed, how rigorously hypotheses are tested, and to what extent assertions extend beyond actual findings. National and international health agencies regard carcinogenicity findings in well-conducted experimental animal studies as evidence of potential carcinogenic risk to humans. Controversies arise when both positive and negative carcinogenicity data exist for a specific agent or when incomplete mechanistic data suggest a possible species difference in response. Issues of experimental design and evaluation that might contribute to disparate results are addressed in this article. To serve as reliable sources of data for the evaluation of the carcinogenic potential of environmental agents, experimental studies must include a) animal models that are sensitive to the end points under investigation; b) detailed characterization of the agent and the administered doses; c) challenging doses and durations of exposure (at least 2 years for rats and mice); d) sufficient numbers of animals per dose group to be capable of detecting a true effect; e) multiple dose groups to allow characterization of dose-response relationships, f) complete and peer-reviewed histopathologic evaluations; and g) pairwise comparisons and analyses of trends based on survival-adjusted tumor incidence. Pharmacokinetic models and mechanistic hypotheses may provide insights into the biological behavior of the agent; however, they must be adequately tested before being used to evaluate human cancer risk.
Hereditary Osteolysis With Hypertension and Nephropathy
Authors: David B. Shurtleff, Robert S. Sparkes, D. Kay Clawson, Warren G. Guntheroth, N. Karle Mottet
Journal: JAMA (1964)

A dominant form of "arthritis" was studied intensively in three members of a sibship with 11 involved members. The "arthritis" is manifested by clinical symptoms of heat, tenderness, and swelling of the joints in childhood, followed by a period of progressive collapse and osteolysis of the carpal and tarsal bones, and finally terminating with extrusion of the involved bones through the volar surfaces of the involved joints. Numerous biochemical studies have been reported with a failure to define the suspected single metabolic error. Biopsy and other laboratory tests indicate an absence of an inflammatory process. Arteriolar thickening was found in all tissues biopsied. Hypertension and abnormal cellular elements found in a high percentage of the involved patients suggest a systemic disorder being manifested primarily by vascular involvement.
Abstract 1916: Divergent trends for gastric cancer incidence by anatomic subsite in U.S. adults
Authors: M. Constanza Camargo, William F. Anderson, Jessica B. King, Pelayo Correa, Cheryll C. Thomas, Philip S. Rosenberg, Christie R. Eheman, Charles S. Rabkin
Journal: Cancer Research (2011)

Abstract Background and aims: Age-specific analyses for noncardia gastric cancer reveal divergent trends among United States (U.S.) whites: rates are declining in older adults (over age 40) but rising in younger persons. To further investigate this heterogeneity, we evaluated incidence trends by anatomic subsite, age, and race/ethnicity. Methods: Gastric cancer incidence data for 1976-2007 were obtained from the U.S. National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program and the Centers for Disease Control and Prevention's National Program of Cancer Registries (NPCR). Incidence rates and estimated annual percentage change (EAPC) were obtained by gastric subsite, age group (25-39, 40-59, and 60-84 years), and race/ethnicity. Results: Based on data from the nine oldest SEER registries (covering about 10% of the U.S. population), long term age-specific incidence rates for corpus cancer increased between 1976 and 2007 with EAPCs of 1.0%/yr (95% CI, 0.1-1.9) for whites and 3.5%/yr (95% CI, 1.8-5.2) for blacks. All other subsite-specific rates decreased in whites and blacks, whereas all noncardia subsites including corpus cancer declined among other races. In the shorter term, age-specific analyses using combined data from NPCR and SEER registries (covering 89.4% of the U.S. population), corpus cancer significantly increased among younger and middle-aged whites from 1999 to 2007; in ethnic-specific analyses, the increase was significant among non-Hispanic whites aged 40-59 years. Age-specific rates for all subsites declined or were stable in this period among blacks and other races. Conclusions: Long- and short-term incidence trends for noncardia gastric cancers indicate a shifting distribution by anatomic subsite, age and race/ethnicity, consistent with changing risk factor exposures and warranting further investigation. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention and the National Cancer Institute. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1916. doi:10.1158/1538-7445.AM2011-1916
Enumeration of IgA producing cells by the enzyme linked immunospot (ELISPOT) technique to evaluate sulphasalazine effects in inflammatory arthritides.
Authors: N Feltelius, S Gudmundsson, L Wennersten, O Sjoberg, R Hallgren, L Klareskog
Journal: Annals of the Rheumatic Diseases (1991)

Numbers of IgA producing cells in peripheral blood were determined by the enzyme linked immunospot (ELISPOT) technique in 15 patients with inflammatory arthritides receiving sulphasalazine treatment. The numbers of IgA producing cells decreased significantly after the first three weeks of treatment. In 11 of the patients this decrease persisted, whereas a subsequent increase was seen in the four others; in two of these latter patients this increase coincided with a temporary withdrawal of the sulphasalazine treatment. A reduction of serum concentrations of IgA and haptoglobin was seen after three months9 treatment. Eleven of the patients had a subjective improvement in their joint disease during the first three months of treatment. Analysis of circulating cells committed for IgA secretion may constitute one way of assessing gut associated immunity indirectly, and the present data suggest that sulphasalazine has a rapid effect on lymphocytes possibly originating from the gut and that such an effect precedes improvement in laboratory parameters and clinical symptoms in arthritic diseases.
Excess corticotropin releasing hormone-binding protein in the hypothalamic-pituitary-adrenal axis in transgenic mice.
Authors: H L Burrows, M Nakajima, J S Lesh, K A Goosens, L C Samuelson, A Inui, S A Camper, A F Seasholtz
Journal: Journal of Clinical Investigation (1998)

Corticotropin-releasing hormone (CRH) is the primary hypothalamic releasing factor that mediates the mammalian stress response. The CRH-binding protein (CRH-BP) is secreted from corticotropes, the pituitary CRH target cells, suggesting that the CRH-BP may modulate hypothalamic-pituitary-adrenal (HPA) axis activity by preventing CRH receptor stimulation. Transgenic mice were generated that constitutively express elevated levels of CRH-BP in the anterior pituitary gland. RNA and protein analyses confirmed the elevation of pituitary CRH-BP. Basal plasma concentrations of corticosterone and adrenocorticotropin hormone (ACTH) are unchanged, and a normal pattern of increased corticosterone and ACTH was observed after restraint stress. However, CRH and vasopressin (AVP) mRNA levels in the transgenic mice are increased by 82 and 35%, respectively, to compensate for the excess CRH-BP, consistent with the idea that CRH-BP levels are important for homeostasis. The transgenic mice exhibit increased activity in standard behavioral tests, and an altered circadian pattern of food intake which may be due to transgene expression in the brain. Alterations in CRH and AVP in response to elevated pituitary CRH-BP clearly demonstrate that regulation of CRH-BP is important in the function of the HPA axis.