tbuckley/cabot-search huggingface dataset:
The Circulation in Relation to Shock
Authors: R. J. S. McDowall
Journal: BMJ (1940)

14/3/40.Rash appeared 3/3/40.Throat and gums normal; swelling of occipital glands.Pains in joints began 4/3/40 in wr-ists, knees, and ankles.No swelling of joints. ,;>ash disappeared in three days and pains in joints improved,,on disappearance of rash.Temperature 99°on admission; normal since.Miss B., aged 24.-Admitted 8 / 3 / 40; discharged 17 / 3 / 40.Rash appeared 8/3/40, with severe pains in gums.Throat normal; occipital glands enlarged; gums appeared normal.Pains in joints 10/3/40-in wrists and ~.nkles-which kept
Novel Quinazoline-Based Compounds Impair Prostate Tumorigenesis by Targeting Tumor Vascularity
Authors: Jason B. Garrison, Yeng-Jeng Shaw, Ching-Shih Chen, Natasha Kyprianou
Journal: Cancer Research (2007)

Abstract Previous evidence showed the ability of the quinazoline-based α1-adrenoreceptor antagonist doxazosin to suppress prostate tumor growth via apoptosis. In this study, we carried out structural optimization of the chemical nucleus of doxazosin and a subsequent structure-function analysis toward the development of a novel class of apoptosis-inducing and angiogenesis-targeting agents. Our lead compound, DZ-50, was effective at reducing endothelial cell viability via a nonapoptotic mechanism. Treatment with DZ-50 effectively prevented in vitro tube formation and in vivo chorioallantoic membrane vessel development. Confocal microscopy revealed a significantly reduced ability of tumor cells to attach to extracellular matrix and migrate through endothelial cells in the presence of DZ-50. In vivo tumorigenicty studies using two androgen-independent human prostate cancer xenografts, PC-3 and DU-145, showed that DZ-50 treatment leads to significant suppression of tumorigenic growth. Exposure to the drug at the time of tumor cell inoculation led to prevention of prostate cancer initiation. Furthermore, DZ-50 resulted in a reduced formation of prostate-tumor derived metastatic lesions to the lungs in an in vivo spontaneous metastasis assay. Thus, our drug discovery approach led to the development of a class of lead (quinazoline-based) compounds with higher potency than doxazosin in suppressing prostate growth by targeting tissue vascularity. This new class of quinazoline-based compounds provides considerable promise as antitumor drugs for the treatment of advanced prostate cancer. [Cancer Res 2007;67(23):11344–52]
Reasoning, robots, and navigation: Dual roles for deductive and abductive reasoning
Authors: Janet Wiles
Journal: Behavioral and Brain Sciences (2011)

Abstract Mercier &amp; Sperber (M&amp;S) argue for their argumentative theory in terms of communicative abilities. Insights can be gained by extending the discussion beyond human reasoning to rodent and robot navigation. The selection of arguments and conclusions that are mutually reinforcing can be cast as a form of abductive reasoning that I argue underlies the construction of cognitive maps in navigation tasks.
Report of a Meeting; Molecular Basis of Cancer Therapy
Authors: M. M. Gottesman
Journal: JNCI Journal of the National Cancer Institute (1994)

There has been an explosive increase in information relevant to the pathways that determine growth signal transduction, regulation of the cell cycle, mechanism of action of oncogenes and tumor suppressors, and mechanisms of programmed cell death (apoptosis). Additional information is needed to determine the targets for anticancer therapy that are most likely to lead to cancer cell death and/or growth cessation. Current experimental clinical approaches are directed toward killing cells with unique cancer-related phenotypes, such as cell surface antigens or growth factor receptors, or altering the host immune system to attack cancer cells. The following major therapeutic targets were identified during the course of this conference: 1) Reduce activity of gene products associated with stimulation of cell growth and increase activity of gene products that inhibit growth. The major principle here is that genes known to be sufficient for malignant transformation (such as Ras, Raf, and Bcr-Abl) and genes whose expression is necessary, but not sufficient, for malignant transformation (such as some cyclins) both may be important targets for anticancer drugs. The reason genes necessary but not sufficient for cell growth are targets is that progression through the cell cycle is based on a series of "on-off" switches whose activation depends on critical levels of specific kinases and phosphatases. Subtle differences in concentration or activity of these regulators, as may be found in cancer cells, could profoundly influence the position of the switch. There are many ways to affect activity of gene products, including use of anti-sense or ribozyme targeting of mRNAs; manipulation of regulatory controls (i.e., state of phosphorylation of Raf and p53; effect of SOS and GAP on Ras, etc.); alteration of essential covalent modifications (i.e., farnesylation of Ras which is essential for its association with the plasma membrane); and various forms of gene therapy to introduce genes (i.e., addition of wild-type p53) or to reduce activity of genes essential for growth (i.e., dominant negative receptor mutants). 2) Interfere with protein-protein or DNA-protein interactions that are needed for the activity of oncogenes and/or growth factors or the transcription factors essential for cell growth. This approach has been demonstrated to work in vitro to interfere with SH2-tyrosine phosphate interactions (i.e., Grb-2 and EGF receptor) and Ras-Raf interactions using specific peptides (J. Downward), but to be useful therapeutically it must be possible to introduce stable low-molecular-weight drugs into cells to affect these interactions.(ABSTRACT TRUNCATED AT 400 WORDS)
Reply to ‘Skin cancer, photoprotection, and skin of color’
Authors: Henry W. Lim, Oma N. Agbai, Reva Bhushan, Kesha J. Buster, Miguel R. Sanchez, Claudia Hernandez, Roopal V. Kundu, Melvin Chiu, Wendy E. Roberts, Zoe D. Draelos, Susan C. Taylor
Journal: Journal of the American Academy of Dermatology (2014)
Ending Propylthiouracil-Induced Liver Failure in Children
Authors: Scott A. Rivkees, Donald R. Mattison
Journal: New England Journal of Medicine (2009)

To the Editor: Graves' disease is treated with antithyroid drugs, radioactive iodine, or surgery.1,2 Propylthiouracil and methimazole are widely used in children as first-line therapy.1,2 Over the past 60 years of propylthiouracil and methimazole use, reports of propylthiouracil-related liver failure and death have accumulated.3–5 In contrast, this problem has not been reported with methimazole use in children.3,5 Several observations can be made on the basis of the medical literature, adverse event reports from the Food and Drug Administration (FDA), and extensive data presented at a workshop at the Eunice Kennedy Shriver National Institute of Child Health . . .
Retinal vasculitis in rheumatoid arthritis.
Authors: M F Martin, D G Scott, C Gilbert, P A Dieppe, D L Easty
Journal: BMJ (1981)

A woman with exacerbation of severe rheumatoid arthritis developed lesions compatible with retinal vasculitis. Laboratory studies confirmed the diagnosis, and the rapid clinical improvement that accompanied a fall in circulating immune complexes suggested that the vasculitis was a direct consequence of the rheumatoid disease. From these observations retinal vasculitis should probably be sought in any patient with rheumatoid disease and the vasculitis added to the list of ocular complications of rheumatoid arthritis.
Abstract 2562: Efficacy of RG7204 (PLX4032), a selective BRAFV600E inhibitor, in combination with pegylated interferon alpha-2a (Pegasys), paclitaxel, carboplatin, and anti-VEGF MAb B20-4.1 in the LOX-IMVI human melanoma xenograft model
Authors: Brian Higgins, Kenneth Kolinksy, Zenaida Go, Hing Char, Richard Lee, Kathleen Schostack, Gideon Bollag, David Heimbrook, Fei Su, Kathryn E. Packman
Journal: Cancer Research (2011)

Abstract Few drugs are currently approved for the treatment of melanoma, including dacarbazine (chemotherapy) and interferon alpha (immunotherapy). However, only a small fraction of patients with metastatic melanoma respond to dacarbazine and a survival benefit has not been shown with this or any other chemotherapy regimen. Taxanes have demonstrated some activity in melanoma, including modest response rates in combination with carboplatin or bevacizumab. These results contrast with the extraordinary Phase I clinical data reported with the BRAFV600E kinase inhibitor RG7204 (PLX4032), which has demonstrated a remarkable response rate (N Engl J Med 363(9):809-819, 2010). Here we report our preclinical investigation of RG7204 in combination with the biologics interferon alpha-2a (Pegasys) or B20-4.1 (B20) (mouse/ human cross-reactive anti-VEGF MAb), and the chemotherapies paclitaxel and carboplatin in the BRAFV600E mutant LOX-IMVI melanoma model in nude mice.The combination of RG7204 and paclitaxel provided superior survival as compared to either monotherapy. Conversely, the combination of RG7204 plus carboplatin or RG7204 plus B20 did not extend survival as compared to RG7204 monotherapy. When RG7204, paclitaxel, and B20 were given in triplet combination, no improvement in survival was observed over any doublet. Similarly, the triplet combination with RG7204, carboplatin and B20 failed to demonstrate improved survival over any doublets or RG7204 monotherapy. Although complete suppression of tumor growth was readily achieved with either RG7204 or Pegasys monotherapy, the combination provided a remarkable survival benefit with median survival extended by nearly a year as compared to either monotherapy. Taken together, these data support clinical testing of RG7204 with interferon alpha in melanoma patients harboring BRAFV600E mutation in order to extend survival, and may allow for use of lower dose interferon. Clinical investigation of RG7204 and paclitaxel combination may also be warranted. While our data do not support combined therapy with RG7204 plus anti-VEGF therapy, it should be noted that the LOX model was resistant to B20 monotherapy, and therefore these findings might not apply to tumors with intrinsic sensitivity to anti-VEGF therapy. 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 2562. doi:10.1158/1538-7445.AM2011-2562
Paroxysmal nocturnal haemoglobinuria: long-term follow-up and prognostic factors
Authors: Gérard Socié, Jean-Yves Mary, Aimery de Gramont, Bernard Rio, Michel Leporrier, Christian Rose, Phillippe Heudier, Henry Rochant, Jean-Yves Cahn, Eliane Gluckman
Journal: The Lancet (1996)
Value of osteopathy.
Authors: J D Miller
Journal: BMJ (1970)

function to account for reduced antidiuretic hormone production.The cerebral dysfunction in this patient was thought to be due to hypotension at the time of operation.It is interesting that no hypothalamic distur- bance was recognized by Javid et a.1 in their review of neurological complications after open heart surgery.There was no obvious cause for the cere- bral dysfunction in the first case, but it is interesting that polyuria and echolalia began simultaneously and that fluctuations of urine flow coincided with alterations in cerebral function.To have been able to estimate levels of antidiuretic hormone at these times would have been helpful.Polyuria after open heart surgery may be associated with diabetes mellitus, bio- chemical changes, such as hypokalaemia and as an exaggerated response to diuretics, and it can lead to peripheral circulatory failure.It is important to recognize polyuria due to diabetes inspidus as it is so amen- able to Pitressin (vasopressin) therapy.We are, etc., C.
Codon-Substitution Models for Detecting Molecular Adaptation at Individual Sites Along Specific Lineages
Authors: Ziheng Yang, Rasmus Nielsen
Journal: Molecular Biology and Evolution (2002)

The nonsynonymous (amino acid–altering) to synonymous (silent) substitution rate ratio (ω = dN/dS) provides a measure of natural selection at the protein level, with ω = 1, >1, and <1, indicating neutral evolution, purifying selection, and positive selection, respectively. Previous studies that used this measure to detect positive selection have often taken an approach of pairwise comparison, estimating substitution rates by averaging over all sites in the protein. As most amino acids in a functional protein are under structural and functional constraints and adaptive evolution probably affects only a few sites at a few time points, this approach of averaging rates over sites and over time has little power. Previously, we developed codon-based substitution models that allow the ω ratio to vary either among lineages or among sites. In this paper we extend previous models to allow the ω ratio to vary both among sites and among lineages and implement the new models in the likelihood framework. These models may be useful for identifying positive selection along prespecified lineages that affects only a few sites in the protein. We apply those branch-site models as well as previous branch- and site-specific models to three data sets: the lysozyme genes from primates, the tumor suppressor BRCA1 genes from primates, and the phytochrome (PHY) gene family in angiosperms. Positive selection is detected in the lysozyme and BRCA genes by both the new and the old models. However, only the new models detected positive selection acting on lineages after gene duplication in the PHY gene family. Additional tests on several data sets suggest that the new models may be useful in detecting positive selection after gene duplication in gene family evolution.
Ulcerative Colitis and Erythrocyte G6PD Deficiency
Authors: Seymour M. Cohen
Journal: JAMA (1968)

Salicylazosulfapyridine (Azulfidine), a sulfonamide, has been used extensively in the treatment of ulcerative colitis. It has been noted that sulfonamides are the most common drugs which precipitate acute hemolytic episodes in erythrocyte glucose-6-phosphate dehydrogenase (G6PD) deficient subjects. Hemolysis occurred in two erythrocyte G6PD deficient Negroes with ulcerative colitis; we suggest that the anemia complicating ulcerative colitis may in such cases be related to the therapy.
Sex Differences in Factors Associated with Childhood- and Adolescent-Onset Wheeze
Authors: Piush J. Mandhane, Justina M. Greene, Jan O. Cowan, D. Robin Taylor, Malcolm R. Sears
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Factors predicting the development of wheeze may differ between sexes and between childhood and adolescence.A New Zealand birth cohort of 1,037 children was followed to age 26. For this analysis, those reporting recurrent wheezing at two or more assessments were classified as "wheezers." We examined risk factors for development of wheeze before age 10 (childhood) and subsequently (adolescent-onset) for males and for females separately using Cox regression modeling.Males more often developed childhood wheeze (p = 0.002) and females adolescent-onset wheeze (p < 0.001). Maternal atopy (asthma or hay fever) was a risk factor for childhood wheeze in both sexes (hazard ratio [HR], 1.48, p < 0.05 for males; HR, 2.37, p < 0.001 for females). Paternal atopy also influenced childhood wheeze, significantly for males (HR, 1.72; p = 0.01), and similarly but not significantly for females (HR, 1.70; p = 0.08). For adolescent-onset wheeze, neither maternal (HR, 1.41; p = 0.19) nor paternal history (HR, 0.73; p = 0.42) was a risk factor in males, but maternal history (HR, 2.08; p < 0.01) was a significant risk factor for females. When both age ranges were combined, providing greater power for analysis, paternal history was a stronger risk factor for wheeze in females (HR, 1.62; p = 0.02) than in males (HR, 1.35; p = 0.12).The influence of parental atopy on the development for wheeze differs between males and females and between childhood- and adolescent-onset wheeze.
Social Networking Sites
Authors: Mahsa Amir, Blake P. Sampson, Dawnielle Endly, Jennifer M. Tamai, Jill Henley, Ann Chang Brewer, Jeffrey H. Dunn, Cory A. Dunnick, Robert P. Dellavalle
Journal: JAMA Dermatology (2013)

<h3>Importance</h3> The use of social media by dermatology journals and professional and patient-centered dermatology organizations remains largely unknown and, to our knowledge, has yet to be fully evaluated. <h3>Objective</h3> To evaluate and quantify the extent of involvement of dermatology journals, professional dermatology organizations, and dermatology-related patient advocate groups on social networking sites. <h3>Design, Setting, and Participants</h3> We obtained an archived list of 102 current dermatology journals from SCImago on the World Wide Web and used the list to investigate Facebook, Twitter, and individual journal websites for the presence of social media accounts. We identified professional and patient-centered dermatology organization activity on social networks through queries of predetermined search terms on Google, Facebook, Twitter, and LinkedIn. The activity of each entity was documented by recording the following metrics of popularity: the numbers of Facebook "likes," Twitter "followers," and LinkedIn "members." <h3>Main Outcomes and Measures</h3> The numbers of Facebook likes, Twitter followers, and LinkedIn members corresponding to each dermatology journal and each professional and patient-related dermatology organization. <h3>Results</h3> On July 17, 2012, of the 102 dermatology journals ranked by SCImago, 12.7% were present on Facebook and 13.7% on Twitter. We identified popular dermatology journals based on Facebook likes and Twitter followers, led by the<i>Journal of the American Academy of Dermatology</i>and<i>Dermatology Time</i>s, respectively. Popular professional dermatology organizations included dermRounds Dermatology Network (11 251 likes on Facebook and 2900 followers on Twitter). The most popular dermatology patient-centered organizations were the Skin Cancer Foundation (20 119 likes on Facebook), DermaTalk (21 542 followers on Twitter), and the National Psoriasis Foundation (200 members on LinkedIn). <h3>Conclusions and Relevance</h3> Patient-centered and professional dermatology organizations use social networking sites; however, academic journals tend to lag behind significantly. Although some journals are active in social media, most have yet to recognize the potential benefits of fully embracing popular social networks.
Validation of the p21-Activated Kinases as Targets for Inhibition in Neurofibromatosis Type 2
Authors: Chunling Yi, Erik W. Wilker, Michael B. Yaffe, Anat Stemmer-Rachamimov, Joseph L. Kissil
Journal: Cancer Research (2008)

Abstract Neurofibromatosis type 2 (NF2) is a dominantly inherited cancer disorder caused by mutations at the NF2 gene locus. Merlin, the protein product of the NF2 gene, has been shown to negatively regulate Rac1 signaling by inhibiting its downstream effector kinases, the p21-activated kinases (Pak). Given the implication of Paks in tumorigenesis, it is plausible that merlin's tumor suppressive function might be mediated, at least in part, via inhibition of the Paks. We present data indicating this is indeed the case. First, analysis of primary schwannoma samples derived from NF2 patients showed that in a significant fraction of the tumors, the activity of Pak1 was highly elevated. Second, we used shRNAs to knockdown Pak1, 2, and 3 in NIH3T3 cells expressing a dominant-negative form of merlin, NF2BBA (NIH3T3/NF2BBA), and find that simultaneous knockdown of Pak1-3 in these cells significantly reduced their growth rates in vitro and inhibited their ability to form tumors in vivo. Finally, while attempting to silence Pak1 in rat schwannoma cells, we found that these cells were unable to tolerate long-term Pak1 inhibition and rapidly moved to restore Pak1 levels by shutting down Pak1 shRNA expression through a methylation-dependent mechanism. These data suggest that inhibiting Pak could be a beneficial approach for the development of therapeutics toward NF2. In addition, the finding that the shRNA-mediated Pak1 suppression was silenced rapidly by methylation raises questions about the future application of such technologies for the treatment of diseases such as cancer. [Cancer Res 2008;68(19):7932–7]
THE METRIC SYSTEM.
Authors: FRANK G. WHEATLEY
Journal: JAMA (1901)

10.The spread of yellow fever can be most effectually controlled by measures directed to the destruction of mosquitoes and the protection of the sick against the bites of these insects.11.While the mode of propagation of yellow fever has now been definitely determined, the specific cause of this disease remains to be discovered.[For discussion see p. 461.
Use of the pudendo-anal reflex in the treatment of neurogenic faecal incontinence.
Authors: N R Binnie, B M Kawimbe, M Papachrysostomou, A N Smith
Journal: Gut (1990)

An electrical stimulator has been devised to treat neurogenic faecal incontinence caused by pudendal nerve neuropathy and works on the basis of repeated stimulation of the pudendo-anal reflex arc. Although conduction in the pudendo-anal reflex arc may be prolonged, and is so in neurogenic faecal incontinence, it must be shown to be present before the method can be used. This stimulation results in an immediate rise in the pressure in the anal canal and a significant increase in the electromyographic activity of the external anal sphincter. Maintenance of the stimulus over a two month period raised the mean resting pressure significantly in the anal canal and increased the reflex and voluntary responses of the external anal sphincter to coughing and squeezing actions respectively. The length of the sphincter was not affected. There was widening of the mean motor unit potential duration, though this was not significant. The resting electromyogram was enhanced after the course of treatment, indicating greater spontaneous activity in the external sphincter. The changes led to seven of the eight patients studied becoming continent at the end of the treatment.
Peanut allergen in house dust of eating area and bed - a risk factor for peanut sensitization?
Authors: V. Trendelenburg, B. Ahrens, A.-K. Wehrmann, B. Kalb, B. Niggemann, K. Beyer
Journal: Allergy (2013)

It has been hypothesized that high environmental exposure to peanut allergens may be a potent risk factor for cutaneous sensitization. Therefore, we wanted to investigate whether peanut proteins are detectable in house dust of different household areas. Peanut levels of dust samples were measured with ELISA. Overall, peanut was detectable in 19 of 21 households in the eating area and/or in bed. The frequency of peanut consumption correlated with peanut levels. Forty-eight hours after intentional peanut consumption, peanut levels were highly increased. Nevertheless, further research is required to prove whether peanut allergen in house dust can cause sensitization via skin.
Prescribing incentive schemes in two NHS regions: cross sectional survey * Commentary: Prescribing incentive schemes---more evidence is needed of how they work
Authors: M. Ashworth
Journal: BMJ (2002)

The introduction of fundholding in primary care in the United Kingdom contained prescribing costs, although the effect was modest and seemingly not accompanied by parallel improvements in the quality of prescribing. 1 With the advent of primary care groups in 1999 a new incentive scheme was devised to influence prescribing.Financial rewards to general practices could be linked more explicitly to improvements in the quality and appropriateness of prescribing than under fundholding schemes.The money had to be invested in improvements to services available to patients. 2 We surveyed prescribing indicators and financial rewards associated with such schemes in two NHS regions in England.