tbuckley/cabot-search huggingface dataset:
Role of platelet-activating factor in Chinese hamster ovary cell responses to cholera toxin.
Authors: N M Thielman, M Marcinkiewicz, J Sarosiek, G D Fang, R L Guerrant
Journal: Journal of Clinical Investigation (1997)

Cholera toxin (CT)-induced intestinal secretion and Chinese hamster ovary cell (CHO) elongation involves cyclic adenosine monophosphate and protein synthesis-dependent prostaglandin formation. We previously reported inhibition of CT-induced intestinal secretion and CHO elongation by platelet-activating factor (PAF) receptor antagonists and secretion of PAF by human intestinal epithelial cells exposed to CT. Herein, we show that PAF is involved after cAMP and that PAF, like CT, mediates prostaglandin E2 synthesis in CHO cells. CT-induced CHO elongation was blocked by specific PAF receptor antagonists, BN52021 and SR27417. SR27417 blocked dibutyryl cAMP-induced CHO elongation, but did not alter CHO elongation caused by PGE2. Neither CT-stimulated cAMP accumulation nor PGE2 production was inhibited by SR27417. Both PGE2 and PAF caused significant CHO elongation, but the latter did not stimulate significant cAMP production. In addition, PAF, like CT and dibutyryl cAMP, stimulated significant PGE2 production. Finally, the protein synthesis inhibitor cycloheximide, which completely blocks the effect of CT on prostaglandin synthesis, also blocked that of PAF, suggesting that PAF also mediates protein synthesis-dependent prostaglandin formation. We conclude that PAF is involved in CHO cytoskeletal responses to CT after the accumulation of cAMP and, like CT, PAF stimulates protein synthesis-dependent prostaglandin accumulation.
Post-partum Mental Disorders
Authors: B. H. Burne
Journal: BMJ (1965)

we can at least cope with our N.H.S. patients under the present scheme, but the thought of some of our private insurance patients, having paid their annual fee and out to get their pound of flesh, is terrifying.None of us can feel completely satisfied with Dr. Jones's insistence that there should be no reconsideration even of some minor form of item-of-service charge.Insurance companies will have the last word, of course, but they are not usually so inflexible as to be unable to provide some compromise to overcome what appears to be a major defect in the scheme.The ludicrous part of the Meeting came, however, when, having got away without much difficulty from this " item-of-service " issue, the conference fell overboard in insist- ing on .theinclusion of it in the Charter.As a convinced " item-of-service " general practi- tioner, I was amazed to see, the chance
Beneficence, Clinical Urgency, and the Return of Individual Research Results to Relatives
Authors: Stephanie M. Fullerton, Susan Brown Trinidad, Gail P. Jarvik, Wylie Burke
Journal: The American Journal of Bioethics (2012)

"Beneficence, Clinical Urgency, and the Return of Individual Research Results to Relatives." The American Journal of Bioethics, 12(10), pp. 9–10
Naturally occurring chronic gastritis and C pylori infection in the rhesus monkey: a potential model for gastritis in man.
Authors: A Baskerville, D G Newell
Journal: Gut (1988)

Histological examination of the stomachs of Rhesus monkeys at autopsy showed chronic gastritis in a high proportion of all ages. Lesions consisted of mild to heavy infiltration of the lamina propria by lymphocytes, plasma cells, and histiocytes. The antrum was most consistently affected, but lesions were also present in the fundus and pylorus. Gastric Campylobacter-like organisms (GCLO) apparently identical to human C pylori were cultured and/or detected immunohistologically in several animals. Electron microscopy showed the spiral bacteria on the epithelial surface and in gastric pits. They did not penetrate the cells but were intimately attached to the apical plasma membrane and caused loss of microvilli. Antibodies to C pylori were detected in serum of the monkeys by ELISA. The immunospecificity of this antibody response was confirmed by Western blotting techniques. A small number of cynomolgus monkeys examined had gastritis, which may also be associated with the presence of C pylori. Baboons did not have gastritis, nor was C pylori cultured from their stomachs. The study indicates that the Rhesus monkey has a naturally occurring gastritis associated with C pylori infection and may therefore be a suitable experimental animal for the human disease.
Developmental Epigenetic Modification Regulates Stochastic Expression of Clustered Protocadherin Genes, Generating Single Neuron Diversity
Authors: Shunsuke Toyoda, Masahumi Kawaguchi, Toshihiro Kobayashi, Etsuko Tarusawa, Tomoko Toyama, Masaki Okano, Masaaki Oda, Hiromitsu Nakauchi, Yumiko Yoshimura, Makoto Sanbo, Masumi Hirabayashi, Teruyoshi Hirayama, Takahiro Hirabayashi, Takeshi Yagi
Journal: Neuron (2014)
The Elevated GC Content at Exonic Third Sites Is Not Evidence Against Neutralist Models of Isochore Evolution
Authors: Laurent Duret, Laurence D. Hurst
Journal: Molecular Biology and Evolution (2001)

The human genome is divided into isochores, large stretches (>>300 kb) of genomic DNA with more or less consistent GC content. Mutational/neutralist and selectionist models have been put forward to explain their existence. A major criticism of the mutational models is that they cannot account for the higher GC content at fourfold-redundant silent sites within exons (GC4) than in flanking introns (GCi). Indeed, it has been asserted that it is hard to envisage a mutational bias explanation, as it is difficult to see how repair enzymes might act differently in exons and their flanking introns. However, this rejection, we note, ignores the effects of transposable elements (TEs), which are a major component of introns and tend to cause them to have a GC content different from (usually lower than) that dictated by point mutational processes alone. As TEs tend not to insert at the extremities of introns, this model predicts that GC content at the extremities of introns should be more like that at GC4 than are the intronic interiors. This we show to be true. The model also correctly predicts that small introns should have a composition more like that at GC4 than large introns. We conclude that the logic of the previous rejection of neutralist models is unsafe.
Immunocompetent cells from the lower respiratory tract of normal human lungs.
Authors: R P Daniele, M D Altose, D T Rowlands
Journal: Journal of Clinical Investigation (1975)

Subpopulations of lymphocytes in the broncho-alveolar air spaces of normal human lungs were compared with those in peripheral blood. Bone marrow-derived (bursal-equivalent) cells (B cells) were identified by complement receptors (EAC rosettes) and by surface immunoglobulin. Thymus-derived lymphocytes (T cells) were identified by their proliferative response to mitogens and the E rosette technique. Cells in lung air spaces were recovered from eight healthy nonsmoking volunteers by segmental lavage with the flexible bronchofiberscope. On the average, macrophages constituted 78% and lymphocytes 17% of the cells in the aspirates. B cells detected by surface immunoglobulin and complement receptors equaled 22% and 15% of lung lymphocytes, respectively. The distribution of lung B cells into heavy chain immunoglobulin classes revealed IgM and IgG to be the predominant classes, with mean values of 14.5% and 9.3%, respectively; the corresponding value for IgA was 5%. A comparable order of frequency (IgM greater than IgG greater than IgA) was observed for purified peripheral blood lymphocytes in the same and other control subjects. T cells comprised the majority (47%) of identifiable lung lymphocytes by the E rosette method. The presence of lung T cells was also corroborated by their proliferative response to mitogens (phytohemagglutinin and concanavallin A), but the response was less than that of equal numbers of peripheral blood lymphocytes from the same subjects. The B/T cell ratio for lung lymphocytes was comparable to results with peripheral blood lymphocytes in the same subjects, but a higher proportion of lung lymphocytes could not be identified as either T or B cells. It is postulated that lung lymphocytes participate in the local immune defenses of the lung.
Nerve Replacement Strategies for Cavernous Nerves
Authors: F. May, M. Vroemen, K. Matiasek, J. Henke, T. Brill, A. Lehmer, M. Apprich, W. Erhardt, S. Schoeler, R. Paul, A. Blesch, R. Hartung, B. Gansbacher, N. Weidner
Journal: European Urology (2005)
Standardization of Hepatitis C Virus RNA Quantification
Authors: Jean-Michel Pawlotsky, Magali Bouvier-Alias, Christophe Hezode, Francoise Darthuy, Jocelyne Remire, Daniel Dhumeaux
Journal: Hepatology (2000)

It was recently recommended that hepatitis C virus (HCV) RNA quantification be used to tailor the duration of combined interferon alfa (IFN-alpha)/ribavirin therapy in patients infected by HCV genotypes 1, 4, and 5. This recommendation has been difficult to implement in the absence of standardized quantitative units for HCV RNA. The aim of this work was to define clinically relevant HCV RNA loads in standardized international units (IU), for use in routine clinical and research applications based on standardized quantitative assays. Two hepatitis C virus RNA quantitative assays were used: (1) the Superquant assay (National Genetics Institute, Los Angeles, CA), for which possibly relevant thresholds were established; and (2) the semi-automated Cobas Amplicor HCV Monitor assay version 2.0 (Cobas v2.0, Roche Molecular Systems, Pleasanton, CA) that measures HCV RNA loads in IU/mL. Quantification in the Cobas v2.0 assay was linear over the entire range of values tested, including viral loads higher than 850,000 IU/mL after 100-fold dilution. The accuracy and precision of the measures in IU/mL were satisfactory with Cobas v2.0. The results obtained with Superquant and Cobas v2.0 correlated (r =.932; P <.0001). A value of 2,000,000 copies/mL (6.3 log(10) copies/mL) with Superquant was converted to nearly 800,000 IU/mL (5.9 log(10) IU/mL). In conclusion, all HCV RNA quantitative assays should give HCV RNA loads in international units and be validated with appropriate calibrated panels; 800,000 IU/mL in any of these assays should be used as the decision threshold to tailor the IFN-alpha/ribavirin treatment duration in patients infected by HCV genotypes 1, 4, and 5.
CLK2 Is an Oncogenic Kinase and Splicing Regulator in Breast Cancer
Authors: Taku Yoshida, Jee Hyun Kim, Kristopher Carver, Ying Su, Stanislawa Weremowicz, Laura Mulvey, Shoji Yamamoto, Cameron Brennan, Shenglin Mei, Henry Long, Jun Yao, Kornelia Polyak
Journal: Cancer Research (2015)

Abstract Genetically activated kinases have been attractive therapeutic targets in cancer due to the relative ease of developing tumor-specific treatment strategies for them. To discover novel putative oncogenic kinases, we identified 26 genes commonly amplified and overexpressed in breast cancer and subjected them to a lentiviral shRNA cell viability screen in a panel of breast cancer cell lines. Here, we report that CLK2, a kinase that phosphorylates SR proteins involved in splicing, acts as an oncogene in breast cancer. Deregulated alternative splicing patterns are commonly observed in human cancers but the underlying mechanisms and functional relevance are still largely unknown. CLK2 is amplified and overexpressed in a significant fraction of breast tumors. Downregulation of CLK2 inhibits breast cancer growth in cell culture and in xenograft models and it enhances cell migration and invasion. Loss of CLK2 in luminal breast cancer cells leads to the upregulation of epithelial-to-mesenchymal transition (EMT)-related genes and a switch to mesenchymal splice variants of several genes, including ENAH (MENA). These results imply that therapeutic targeting of CLK2 may be used to modulate EMT splicing patterns and to inhibit breast tumor growth. Cancer Res; 75(7); 1516–26. ©2015 AACR.
Author's reply to Sharpe
Authors: P. A. Coventry
Journal: BMJ (2015)

I thank Professor Sharpe for his comments on the COINCIDE trial report and related editorial.1 2 3

I agree that we should not conclude that all collaborative care approaches are equivalent and that the COINCIDE results are the best that can be achieved for patients with complex mixes of mental and physical health problems. The point I would emphasise, and that we drew out in our discussion, is that the kind of collaborative care we tested was modelled on a more …
Nursing in the Crossfire
Authors: Robert Steinbrook
Journal: New England Journal of Medicine (2002)

What is exceptional in nursing is the nature of the work: the continuous and intimate association with pain and not infrequent contact with death. . . . Not every man or woman would feel themselves able to undertake the duties of a nurse.Brian Abel-Smith, A History of the Nursing Profession, 1960.1 Nursing is an embattled profession. Many nurses who work in hospitals feel that they are overworked and often unable to provide good patient care. The young people who traditionally have embarked on careers in nursing are increasingly choosing other fields, such as medicine or business, in which the . . .
Syntometrine as a possible cause of neonatal jaundice.
Authors: J M Gate
Journal: BMJ (1978)

49including at least three sets of identical twins.3The pattern of aggregation in these families has suggested an inherited basis for a pro- portion of patients with vesicoureteric reflux, but no uniform pattern of inheritance has been apparent.In Christchurch we have investigated the immediate family of 42 patients with reflux nephropathy and in 12 of these families there were one or more affected members.4To assess whether there may be an easily delineated genetic marker for reflux nephropathy we have looked at the tissue typing of all patients presenting recently to our departments with chronic renal failure due to reflux nephropathy and compared this with the tissue types of patients with renal failure due to other causes.The results are showni in the accompanying table and indicate that HLA- B12 is occurring with significantly greater frequency in patients with reflux nephropathy.Presence of HLA-B12 in patients according to aetiology of renal failure Cause of renal No of No with failure patients HLA-B12 Reflux nephropathy 19 9 All other causes 46 8X2 test with Yatesis correction: Z2=4.9; 0-02 <P <0-05.In larger centres it may be possible to confirm whether this is a valid observation and therefore possibly a genetic marker for a disease that not infrequently results in end-stage renal failure.
Apical Ballooning Syndrome (Takotsubo Cardiomyopathy) Presenting With Typical Left Ventricular Morphology at Initial Presentation and Mid-Ventricular Variant During a Recurrence
Authors: Aaron M. From, Gurpreet S. Sandhu, Vuyisile T. Nkomo, Abhiram Prasad
Journal: Journal of the American College of Cardiology (2011)
Variability over 1 Week in the Urinary Concentrations of Metabolites of Diethyl Phthalate and Di(2-Ethylhexyl) Phthalate among Eight Adults: An Observational Study
Authors: James L. Preau, Lee-Yang Wong, Manori J. Silva, Larry L. Needham, Antonia M. Calafat
Journal: Environmental Health Perspectives (2010)

Phthalates are metabolized and eliminated in urine within hours after exposure. Several reports suggest that concentrations of phthalate metabolites in a spot urine sample can provide a reliable estimation of exposure to phthalates for up to several months.We examined inter- and intraperson and inter- and intraday variability in the concentrations of monoethyl phthalate (MEP), the major metabolite of diethyl phthalate, commonly used in personal care products, and mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), a metabolite of di(2-ethylhexyl) phthalate (DEHP), a polyvinyl chloride plasticizer of which diet is the principal exposure source, among eight adults who collected all urine voids (average, 7.6 samples/person/day) for 1 week.We analyzed the urine samples using online solid-phase extraction coupled to isotope dilution-high-performance liquid chromatography-tandem mass spectrometry.Regardless of the type of void (spot, first morning, 24-hr collection), for MEP, interperson variability in concentrations accounted for > 75% of the total variance. By contrast, for MEHHP, within-person variability was the main contributor (69-83%) of the total variance. Furthermore, we observed considerable intraday variability in the concentrations of spot samples for MEHHP (51%) and MEP (21%).MEP and MEHHP urinary concentrations varied considerably during 1 week, but the main contributors to the total variance differed (interday variability, MEHHP; interperson variability, MEP) regardless of the sampling strategy (spot, first morning, 24-hr collection). The nature of the exposure (diet vs. other lifestyle factors) and timing of urine sampling to evaluate exposure to phthalates should be considered. For DEHP and phthalates to which people are mostly exposed through diet, collecting 24-hr voids for only 1 day may not be advantageous compared with multiple spot collections. When collecting multiple spot urine samples, changing the time of collection may provide the most complete approach to assess exposure to diverse phthalates.
Book Review Handbook of Bipolar Disorder: Diagnosis and Therapeutic Approaches (Medical Psychiatry. 32.) Edited by Siegfried Kasper and Robert M.A. Hirschfeld. 454 pp. Boca Raton, Fla., Taylor &amp; Francis, 2005. $199.95. 0-8247-2935-8
Authors: Henry A. Nasrallah
Journal: New England Journal of Medicine (2006)
Clinical Significance of Tumour Regression Grade in Locally-Advanced Rectal Cancer Treated with Preoperative Chemoradiotherapy
Authors: Hernandez Alba, Polo Eduardo, Ponce Jose Miguel, Hörndler Carlos, Monzon Andres, Sarria Luis, Hernando Jorge, Anton Antonio, S. Rosero-Cuesta David, Alonso-Orduña Vicente
Journal: Annals of Oncology (2014)
Influence of age and hemodynamics on myocardial blood flow and flow reserve.
Authors: J Czernin, P Müller, S Chan, R C Brunken, G Porenta, J Krivokapich, K Chen, A Chan, M E Phelps, H R Schelbert
Journal: Circulation (1993)

BACKGROUND Aging is associated with changes of the systolic blood pressure that may increase cardiac work and myocardial blood flow at rest and reduce the myocardial flow reserve. This might be misinterpreted as age-related impairment of the coronary vasodilator capacity. METHODS AND RESULTS Myocardial blood flow was quantified at rest and after administration of intravenous dipyridamole in 40 healthy volunteers (12 women and 28 men) with 13N-ammonia and positron emission tomography. Eighteen of the normal subjects were less than and 22 were older than 50 years (31 +/- 9 versus 64 +/- 9 years). The resting rate-pressure product was lower in the younger than in the older subjects (6895 +/- 1070 versus 8634 +/- 1890; P &lt; 0.01). Myocardial blood flow at rest averaged 0.76 +/- 0.17 mL.min-1.g-1 in the younger volunteers and 0.92 +/- 0.25 mL.min-1.g-1 in the older volunteers (P &lt; 0.05). Hyperemic blood flows did not differ between younger and older subjects (3.0 +/- 0.8 versus 2.7 +/- 0.6 mL.min-1.g-1; P = NS); however, minimal coronary resistance was higher in the older subjects. Corrected for indexes of coronary driving pressure, hyperemic flow was lower in older than in younger normal subjects. The higher resting blood flows combined with similar hyperemic flows resulted in a lower myocardial flow reserve in the older than in the younger normal subjects (4.1 +/- 0.9 versus 3.0 +/- 0.70; P &lt; 0.0001). The flow reserve was more closely correlated with resting than with hyperemic blood flows. CONCLUSIONS Aging does not alter significantly dipyridamole-induced hyperemic flows; although coronary vascular resistance after dipyridamole was somewhat increased in older subjects. The gradual decline of the myocardial blood flow reserve correlates with an age-related increase of baseline myocardial work and blood flow. These findings suggest that the reduced flow reserve with age is primarily due to increased cardiac work and blood flow at rest rather than to an abnormal vasodilator capacity.
Nuclear Weapons Testing Fallout and Thyroid Disease
Authors: Howard J. Dworkin
Journal: JAMA (1994)

To the Editor.  —In a recent article by Kerber et al 1 an attempt was made to study thyroid disease in relation to fallout from nuclear weapons testing. While such information would definitely be of interest, the reported study had little hope from the start of succeeding or achieving the authors' goals. The shortcomings of their methods cannot be made light of. Dietary histories obtained 22 years after the fact would cause one to scoff at the likelihood of an accurate depiction of radioiodine intake. The authors report a method for determining dose to the thyroid from iodine 131 ( 131 I) based on a largely untested modeling approach. The actual radiation dose to the thyroid in human beings has not been carefully examined in a group of subjects whose dietary history was collected as reported. The background radiation to the thyroid for the nonradioactive iodine—exposed population in Arizona leads to
Angioscopic Evaluation of Rotational Atherectomy Followed by Additional Balloon Angioplasty Versus Balloon Angioplasty Alone in Coronary Artery Disease: A Prospective, Randomized Study
Authors: Hélène Eltchaninoff, Alain Cribier, René Koning, Charles Chan, Valérie Sicard, Arthur Tan, Brice Letac
Journal: Journal of the American College of Cardiology (1997)
Glutaraldehyde and contact dermatitis.
Authors: K. V. Sanderson, E. Cronin
Journal: BMJ (1968)

Finally, there may be an association between sexual promiscuity and the preva- lence of M. hominis in the genital tract, but the social status of the mothers whose babies had sticky eyes is only worthy of note if it is different from the status of the 242 or so mothers whose babies were not affected.Unfortunately, one is left to conjecture that this was so.-We are, etc.,
The autoimmune background in lichen planus
Authors: D. SHUTTLEWORTH, R.A.C. GRAHAM-BROWN, A.C. CAMPBELL
Journal: British Journal of Dermatology (1986)

Fifty-four patients with lichen planus (LP) and 54 age- and sex-matched controls were studied. No increase in the incidence of autoimmune disease was found in the patients with LP or their relatives. There was no increase in the frequency of autoantibodies in the LP group and serum immunoglobulin levels were not altered significantly. In the majority of cases, LP is not part of a generalized autoimmune disturbance.
Echocardiography in mechanical alternans. With a note on the findings in discordant alternans within the left ventricle.
Authors: I D'Cruz, H C Cohen, R Prabhu, G Glick
Journal: Circulation (1976)

We described the echocardiographic manifestations of mechanical alternation of left ventricular (LV) contraction during regular sinus rhythm. Chronic LV dilatation and failure existed in all our four cases. Alternation was observed with respect to the following echocardiographic variables: amplitude and rate of increase of amplitude of systolic excursions of the LV posterior wall and ventricular septum (VS); reciprocal changes in the duration of LV ejection and pre-ejection periods (on the aortic valve echo) such that the total duration of LV electromechanical systole remained constant; reciprocal changes in the duration of RV ejection and pre-ejection periods (on the pulmonic valve echo) such that the total duration of RV electromechanical systole remained constant; systolic anterior excursion of the aortic root as a whole; steepness of the mitral EF slope; septal and LV posterior wall diastolic position; and end-systolic LV diameter. In two patients, discordant alternans of the motion of the LV posterior wall and the VS was observed.