tbuckley/cabot-search huggingface dataset:
Of Men and Mitochondria — Intracellular and Subcellular Acid-Base Relations
Authors: Eugene D. Robin
Journal: New England Journal of Medicine (1961)

THIS paper deals with one small aspect of the general problem that concerns the relation between organisms and their environment. Current concepts concerning this interrelation spring from the work of 3 men — an Englishman, a Frenchman and an American.The Englishman was, of course, the great British biologist, Charles Darwin, who developed the thesis that the external environment, in the last analysis, determines the nature of the organism. Specifically, he demonstrated that the external forms of organisms seem to be best explained as adaptations subserving the function of permitting survival in the face of vicissitudes and changes occurring in . . .
Authors' reply to Crilly, and Willoughby and Graham
Authors: M. A. Mugglestone, P. Eunson, M. S. Murphy
Journal: BMJ (2012)

Opinions differ on the place of selective dorsal rhizotomy in managing spasticity in children. In a recent debate in the House of Commons it was strongly advocated, as being “more robust than any other treatment for cerebral palsy.”1

We as guideline developers knew about the lack of high quality clinical evidence for the procedure, particularly in relation to important functional benefits and long term outcomes. We considered the three randomised controlled trials in the meta-analysis cited by Crilly. …
Various mechanisms cause RET-mediated signaling defects in Hirschsprung's disease.
Authors: A Pelet, O Geneste, P Edery, A Pasini, S Chappuis, T Atti, A Munnich, G Lenoir, S Lyonnet, M Billaud
Journal: Journal of Clinical Investigation (1998)

Hirschsprung's disease (HSCR) is a common congenital malformation characterized by the absence of intramural ganglion cells of the hindgut. Recently, mutations of the RET tyrosine kinase receptor have been identified in 50 and 15-20% of familial and sporadic HSCR, respectively. These mutations include deletion, insertion, frameshift, nonsense, and missense mutations dispersed throughout the RET coding sequence. To investigate their effects on RET function, seven HSCR missense mutations were introduced into either a 1114-amino acid wild-type RET isoform (RET51) or a constitutively activated form of RET51 (RET-MEN 2A). Here, we report that one mutation affecting the extracytoplasmic cadherin domain (R231H) and two mutations located in the tyrosine kinase domain (K907E, E921K) impaired the biological activity of RET-MEN 2A when tested in Rat1 fibroblasts and pheochromocytoma PC12 cells. However, the mechanisms resulting in RET inactivation differed since the receptor bearing R231H extracellular mutation resulted in an absent RET protein at the cell surface while the E921K mutation located within the catalytic domain abolished its enzymatic activity. In contrast, three mutations mapping into the intracytoplasmic domain neither modified the transforming capacity of RET-MEN 2A nor stimulated the catalytic activity of RET in our ligand-independent system (S767R, P1039L, M1064T). Finally, the C609W HSCR mutation exerts a dual effect on RET since it leads to a decrease of the receptor at the cell surface and converted RET51 into a constitutively activated kinase due to the formation of disulfide-linked homodimers. Taken together, our data show that allelic heterogeneity at the RET locus in HSCR is associated with various molecular mechanisms responsible for RET dysfunction.
Monarticular Bacterial Arthritis of the Sternoclavicular Joint
Authors: Ronald L. Linscheid
Journal: JAMA (1961)

MONARTICULAR bacterial arthritis of the sternoclavicular joint appears to be rare. Arlet and Ficat<sup>1</sup>reported one proved and one probable case of staphylococcal infection of this joint. Members of our group<sup>2</sup>reported this joint involved once in 84 joints affected by bacterial arthritis. Waring<sup>3</sup>states that bacterial arthritis of either the acromioclavicular or the sternoclavicular joint is rare except in polyarticular bacterial arthritis. We wish to report 2 additional cases recently encountered. <h3>Report of Cases</h3><h3>Case 1.—</h3> A 59-year-old male had stiffness and soreness of his left shoulder that came on quickly in October, 1959, and he had 1<sup>°</sup>of fever. He was admitted to his local hospital with a diagnosis of pneumonia and received antibiotic therapy for 12 days. On dismissal from the hospital he was told that possibly he had a tumor in the apex of his left lung. He came to the
ADENOSINE AND SODIUM NITROPRUSSIDE VERSUS CONTROL FOR THE ATTENUATION OF INFARCT SIZE AND MICROVASCULAR OBSTRUCTION: THE REFLO-STEMI TRIAL
Authors: Sheraz Ahmed Nazir, Jamal Khan, Islam Z. Mahmoud, John Greenwood, Daniel Blackman, Vijayalakshmi Kunadian, Martin Been, Keith R. Abrams, Lorraine Shipley, Robert Wilcox, Jennifer Adgey, Gerry McCann, Anthony Gershlick
Journal: Journal of the American College of Cardiology (2015)
The Language of Fractures
Authors: Reginald R. Cooper
Journal: JAMA (1991)

The second edition of this textbook, with a limited but well-defined scope, is organized in a manner parallel to the first edition. Some additional excellent illustrations have been added to depict critical points made in the text. The author accomplishes his stated purpose of allowing physicians to communicate with each other about fractures by using a more precise vocabulary. The monograph is devoted nearly entirely to fracture nomenclature and classification. Some sections have a cursory overview of anatomy and fracture healing, but most of the book consists of a detailed, systematic description of fractures so that the reader should have an excellent knowledge of how to describe fractures in general and in specific anatomic locations. The first section gives the foundation for a vocabulary to be used in describing the various types of fractures, their locations, their appearances, and the types of displacement seen. The second section deals specifically with
Major Dietary Protein Sources and Risk of Coronary Heart Disease in Women
Authors: Adam M. Bernstein, Qi Sun, Frank B. Hu, Meir J. Stampfer, JoAnn E. Manson, Walter C. Willett
Journal: Circulation (2010)

Background— With the exception of fish, few major dietary protein sources have been studied in relation to the development of coronary heart disease (CHD). Our objective was to examine the relation between foods that are major dietary protein sources and incident CHD. Methods and Results— We prospectively followed 84 136 women aged 30 to 55 years in the Nurses’ Health Study with no known cancer, diabetes mellitus, angina, myocardial infarction, stroke, or other cardiovascular disease. Diet was assessed by a standardized and validated questionnaire and updated every 4 years. During 26 years of follow-up, we documented 2210 incident nonfatal infarctions and 952 deaths from CHD. In multivariable analyses including age, smoking, and other risk factors, higher intakes of red meat, red meat excluding processed meat, and high-fat dairy were significantly associated with elevated risk of CHD. Higher intakes of poultry, fish, and nuts were significantly associated with lower risk. In a model controlling statistically for energy intake, 1 serving per day of nuts was associated with a 30% (95% confidence interval, 17% to 42%) lower risk of CHD compared with 1 serving per day of red meat. Similarly, compared with 1 serving per day of red meat, a lower risk was associated with 1 serving per day of low-fat dairy (13%; 95% confidence interval, 6% to 19%), poultry (19%; 95% confidence interval, 3% to 33%), and fish (24%; 95% confidence interval, 6% to 39%). Conclusions— These data suggest that high red meat intake increases risk of CHD and that CHD risk may be reduced importantly by shifting sources of protein in the US diet.
Abstract 4806: <i>Claudin</i> downregulation in head and neck squamous cell carcinoma (HNSCC) may be caused by aberrant promoter methylation
Authors: Aline A. Nagado, Ana Carolina de Carvalho, Roberta C. Lessa, Silvia V. Lourenço, Claudia M. Coutinho-Camillo, Marcilei E.C. Buim, Fernando A. Soares, André L. Carvalho, André Luiz Vettore de Oliveira
Journal: Cancer Research (2011)

Abstract Claudins are a family of transmembrane proteins that compose the tight junctions, playing an essential role in cell-to-cell adhesion, maintenance of cell polarity and recruiting signaling proteins. The expression of these proteins has been found to be altered in several human cancers, suggesting that this family of proteins might represent potential molecular markers for cancer detection, diagnosis and therapy. We analyzed the expression profile of a claudin member gene in Head and Neck Squamous Cell Carcinomas (HNSCC) cases using Real-Time PCR, and found low expression in 78% of the evaluated cases. The expression of this gene was restored in an HNSCC cell line after treatment with the demethylating agent 5-Aza-2′-Deoxycytidine. After that, we designed primers for methylation analysis (MSP) and examined the expression and methylation status of this gene in several cell lines. A positive correlation between the expression level and methylation pattern was found. Besides, preliminary analyses of aberrant methylation status in HNSCC and normal samples showed 100% of specificity and 24% of sensitivity. This result suggests that aberrant methylation of claudin members could play a major role in the expression control of this gene. 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 4806. doi:10.1158/1538-7445.AM2011-4806
Outing the Foley catheter
Authors: M. E. Black
Journal: BMJ (2010)

I attended Serbia’s second gay pride event on a lovely autumn Sunday on 10 October, along with 1000 other marchers, 5000 police, a zillion members of the press, and an orchestrated mob of disaffected youth in search of distraction and destruction. Walking through a masked gang of teenagers carrying large steel pins and rocks, I thought most of them looked a bit lost. I asked one which street we were on, and he was quite helpful; then he ran off to wave a stick randomly and shout at the police.

The official access …
AN UNUSUAL REACTION TO THE BITE OF THE DOVE LOUSE FLY, STILBOMETOPA PODOPOSTYLA SPEISER
Authors: D. E. Howell
Journal: JAMA (1941)

Entomologic and medical literature contain but few references to hippoboscid flies biting human beings, and we have found no instances of severe reactions following the bites of these insects. Brumpt<sup>1</sup>stated that the injury is scarcely felt and that one must notice the engorgement of the fly's abdomen with blood to be sure of the bite. Moutier<sup>2</sup>recorded the case of a servant girl who had been bitten by several louse flies, Crataerina pallida (Lat.) but mentioned only the lesions resulting from scratching. Hippobosca equina (Linn.), the forest fly, is known to feed on man in the absence of its normal host, but no records of severe reactions are available. Hippobosca camelina (Savigny) has a relatively painless bite but does leave a slightly itching pimple at the site of the bite. Brumpt fed Lipoptena cervi (Linn.) on himself but scarcely noticed the bite. The location of the bite
Abstract 3525: Targeting Group VIA phospholipase A2 using small molecules for ovarian cancer treatment
Authors: Yan Xu, Hui Li, Zhenwen Zhao, Caryl Antalis, Robert Emerson, Sheng Zhang, Zhongyin Zhang, Zhanzhong Zhao, Wei Gang, Libo Yan, Qingchun Cai
Journal: Cancer Research (2011)

Abstract Epithelial ovarian cancer (EOC) causes estimated 13,850 deaths in 2010 in the United State. More effective treatment regimens are urgently required for this deadly disease. We and others have obtained ample evidence indicating that lysophosphatidic acid (LPA) plays an important role in EOC development. We have recently shown that the levels of LPA and several other bioactive lipids in the tumor environment of EOC are regulated by Group VIA calcium-independent phospholipase A2 beta (iPLA2β) expressed in tumor microenvironment, suggesting that targeting iPLA2β in both host and tumor cells will likely to be beneficial. To test this idea, we used bromoenol lactone (BEL), a selective inhibitor of iPLA2β in vivo, and found that BEL significantly inhibited EOC tumorigenesis and metastasis in mouse xenograft models using human SKOV3 and HEY ovarian cancer cells. Moreover, the combination of BEL with paclitaxel (PTX), one of the mostly commonly used therapeutics in EOC, almost completely blocked tumor development in the xenograft mouse model. BEL showed very low or no detectable cytotoxic effects in mice. Another iPLA2 inhibitor, FKGK11, also inhibited tumor development in the xenograft mouse model, supporting that the major target of action was iPLA2. The combinational effects of BEL and PTX in vivo likely stem from their distinct cellular effects. BEL and FKGK11 reduced adhesion, migration, and invasion of EOC cells in vitro; the reduced ability appears to increase the vulnerability of tumor cells to PTX. In summary, this is the first attempt to target iPLA2 using a small inhibitor molecule for cancer treatment in vivo. In addition, the work is also rather unique by targeting activity of the same molecule (iPLA2) in both host and tumor cells. These results provide an important basis for development of new treatment modalities for EOC. 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 3525. doi:10.1158/1538-7445.AM2011-3525
A new approach to noninvasive evaluation of aortic regurgitant fraction by two-dimensional Doppler echocardiography.
Authors: A Kitabatake, H Ito, M Inoue, J Tanouchi, K Ishihara, T Morita, K Fujii, Y Yoshida, T Masuyama, H Yoshima
Journal: Circulation (1985)

The aortic regurgitant fraction was estimated noninvasively in 20 patients with aortic regurgitation from systolic aortic and pulmonary volume flow determined by duplex Doppler echocardiography. By assuming that an excess of the aortic volume flow (AF) compared with the pulmonary volume flow (PF) is due to aortic regurgitant flow, the aortic regurgitant fraction (RF) was calculated as follows: RF(%) = (AF - PF)/AF X 100. The aortic and pulmonary volume flows were determined as products of systolic integrals of ejection flow velocities and cross-sectional areas of the left and right ventricular outflow tracts, respectively. The Doppler estimate of the regurgitant fraction was compared by semiquantitative grading (1+ to 4+) by cineaortography and with the measurement of regurgitant fraction by catheter technique. The mean Doppler-determined aortic regurgitant fraction was 2.4% for normal subjects, 28.0% for the patients with 1+, 32.6% for the patients with 2+, 53.3% for the patients with 3+, and 62.4% for the patients with 4+. A fair correlation was found between Doppler estimates of regurgitant fraction and semiquantitative cineaortographic grades (r = .80, p less than .01). In the patients without associated mitral regurgitation, a close correlation was observed between Doppler and catheter estimates of regurgitant fraction (r = .96, p less than .01; y = 1.0x - 0.08). In the patients with associated mild mitral regurgitation, however, Doppler estimates of regurgitant fraction substantially underestimated those determined by the conventional catheter technique, which cannot separately quantitate the aortic regurgitant fraction in the presence of mitral regurgitation. These observations indicate that the proposed Doppler technique provides a useful method to evaluate the aortic regurgitant fraction specifically regardless of the presence of associated mitral lesions.
Interferon-α Treatment of Six Patients with the Idiopathic Hypereosinophilic Syndrome
Authors: Joseph H. Butterfield
Journal: Annals of Internal Medicine (1994)

Objective: To examine the response to interferon-α 2B therapy in six patients with the idiopathic hypereosinophilic syndrome. Design: Prospective cohort study. Setting: Tertiary referral center, university hospital inpatient and outpatient clinics, and offices of private practice physicians. Patients: Six patients satisfying the criteria for the hypereosinophilic syndrome, five of whom were resistant to or intolerant of conventional treatment. Intervention: Individualized dosages of interferon-α based on clinical response and side effects. Measurements: Measurements of eosinophilia (peripheral and bone marrow counts), levels of serum eosinophil major basic protein, doses of glucocorticoid and cytotoxic medications, and transfusion requirements. Results: Various dosages of interferon-α from 1.5 MU/d to 8 MU/d decreased the total eosinophil count to less than 1000/mm3 in five of six patients. All patients were able to taper and discontinue prednisone and hydroxyurea. Both patients with incapacitating mucosal ulcers had resolution and no recurrence of these previously resistant lesions. Interferon-α was generally well tolerated except for dose-limiting side effects, including thrombocytopenia in one patient and in a second patient, temporary worsening of mucosal lesions and constitutional symptoms. Conclusions: Interferon-α is a valuable agent for patients with the hypereosinophilic syndrome who are resistant to or intolerant of conventional therapy and for patients with this syndrome who have incapacitating mucosal ulcers.
Diabetes in British Nursing and Residential Homes
Authors: Terence J. Aspray, Karen Nesbit, Timothy P. Cassidy, Emma Farrow, Gillian Hawthorne
Journal: Diabetes Care (2006)

In the U.K., 8–10% of those >65 years of age have diabetes (1), and more than a quarter of care-home residents may have the condition (2). Diabetes is often undiagnosed (2), and screening is recommended (3). However, the use of fasting glucose measurements alone has not been validated in the elderly population, and concerns have been expressed that results using this method are inconsistent in older people when compared with the oral glucose tolerance test (OGTT) (4). The aim of this study was to estimate the prevalence of diabetes and impaired fasting glucose (IFG) in a range of care-home types and to decide which tests were best for diagnostic screening: fasting capillary glucose, 2-h postprandial capillary glucose (PPG), or both.

Newcastle upon Tyne has a population of ∼260,000, of whom 3.5% have diabetes. There are 68 care homes in the city, comprising residential care homes offering 24-h social support and nursing homes offering additional nursing care. Residential and nursing homes for the elderly mentally infirm (EMI) provide specialist care for older adults with dementia. We recruited residents from all four types of care home.

After consent/assent was obtained, all volunteers gave 200 μl of capillary whole blood, for glucose estimation, using a glucose analyzer (glucose dehydrogenase method; …
'Fundamentally Sound' FDA Advisory Committee System Expects to Use Most Improvement Ideas
Authors: Charles Marwick
Journal: JAMA (1993)

FOOD AND DRUG Administration (FDA) officials say that, while they could use more advice from the Institute of Medicine to help manage what they view as a conflict-of-interest problem, they are pleased with a new Institute of Medicine report ( JAMA . 1992;268:3417) now that they have studied it in detail.   report, which deals with the FDA's advisory committee system, was commissioned 2 years ago. Apart from conflict-of-interest issues raised by FDA Commissioner David A. Kessler, MD, JD, it covers the evolution of the advisory committee system and how it is used by the agency.  Carol Scheman, the FDA's deputy commissioner for external affairs, says: The report sums up the advisory committee process in a manner that would be really helpful to those appointed to advisory committees, enabling them to understand the system and so give the agency the scientific impartial advice it needs.  There are 42 recommendations and we have
Trials of AIDS vaccine to start in India
Authors: S. Kumar
Journal: BMJ (2003)

India is getting ready for the first trials of an AIDS vaccine. Phase I trials will begin later this year or early next year at the National AIDS Research Institute in Pune, Maharashtra.

The International AIDS Vaccine Initiative has been working closely with the Indian Council of Medical Research and the National AIDS Control Organisation since December 2000 to develop and evaluate AIDS vaccines in India.

To reduce fears that Indians will be used as guinea pigs for the trial of an AIDS vaccine that will be used only in the Western …
GPs' prescribing is irrational, says Audit Commission
Authors: A Tonks
Journal: BMJ (1994)

Irrational and inconsistent prescribing by British general practitioners costs the NHS over £ 400m a year, says a report by the Audit Commission published this week. There are, it says, few limits to what and how much a general practitioner may prescribe, and although family health services authorities are supposed to keep general practice spending on drugs within preset limits, last year all English family health services authorities failed to meet spending targets.

The commission criticises the least cost conscious general practitioners for relying too heavily on drug treatment for minor complaints just to keep patients happy, for prescribing drugs that do not work, for prescribing expensive formulations that have no advantage over cheaper alternatives, and for being too quick to use new expensive drugs when older, cheaper ones are as effective.

Drugs being handed out to patients unnecessarily include antibiotics, drugs that heal ulcers, laxatives, tranquillisers, anti-inflammatory drugs, and drugs …
Cytokines Cause Functional and Structural Damage to Isolated Islets of Langerhans
Authors: T. Mandrup‐Poulsen, K. Bendtzen, J. Høiriis Nielsen, G. Bendixen, J. Nerup
Journal: Allergy (1985)

Cytokines are soluble, antigen non‐specific, non‐immunoglobulin mediators produced and secreted by blood mononuclear cells interacting in the cellular immune‐response. To test the possibility that cytokines participate in the autoimmune destruction of the pancreatic beta‐cells leading to insulin‐dependent diabetes mellitus, isolated human or rat islets of Langerhans were incubated for 7 days with cytokine‐rich, cell‐free supernatants of blood mononuclear cells from healthy human donors stimulated with or without purified protein derivative of tuberculin or phytohaemagglutinin. Glucose stimulated insulin‐release, and contents of insulin and glucagon in islets incubated with cytokine‐rich supernatants were markedly reduced. This impairment of islet function was due to a cytotoxic effect of cytokine‐rich supernatants as judged by disintegration of normal light‐microscopic morphology.