tbuckley/cabot-search huggingface dataset:
Effect of Pap Smear Collection and Carrageenan on Cervicovaginal Human Papillomavirus-16 Infection in a Rhesus Macaque Model
Authors: Jeffrey N. Roberts, Rhonda C. Kines, Hormuzd A. Katki, Douglas R. Lowy, John T. Schiller
Journal: JNCI Journal of the National Cancer Institute (2011)

Human papillomavirus (HPV) infection of the genital mucosa is thought to require trauma to the cervicovaginal epithelium. Therefore, we determined whether a cytology specimen collection procedure (Pap smear), which disrupts the epithelium by design, renders the cervix more susceptible to HPV infection in a primate model.In a series of female rhesus macaques, a speculum examination was performed with (n = 8) or without (n = 4) a cytology specimen collection procedure as it is commonly practiced in a gynecology clinic. An internal digital examination was performed after specimen collection using Surgilube (n = 4) or 1% iota-carrageenan, a previously indentified HPV inhibitor (n = 4) as the lubricant. The cervix was then inoculated with HPV16 pseudovirions expressing red fluorescent protein. After 3 days, the reproductive tracts were excised and the cervix was cryosectioned. Sections were analyzed by fluorescent confocal microscopy for the number of red fluorescent protein-positive keratinocytes.Substantial infection of the ectocervix, the transformation zone, and the endocervix was detected, but only in conjunction with the cytology specimen collection procedure (cytology using Surgilube vs without cytology using Surgilube, mean = 84 infectious events per section vs mean = 0.05 infectious events per section, difference = 84 infectious events per section, 95% confidence interval = 19 to 384 infectious events per section). When the carrageenan gel was substituted for Surgilube for an internal digital examination, the mean number of infectious events decreased (carrageenan gel vs Surgilube, mean = 3.5 events per section vs mean = 84 infectious events per section difference = 81 events per section, 95% confidence interval = 33 to 213 events per section).These findings indicate that cytology screening in women might lead to a transient enhancement of susceptibility to HPV infection and that use of a carrageenan-based gel during the examination might mitigate this enhancement.
Abolition of Hypertension-Induced End-Organ Damage by Androgen Receptor Blockade in Transgenic Rats Harboring the Mouse Ren-2 Gene
Authors: Ovidiu Baltatu, Ce[Combining Acute Accent]cile Cayla, Radu Iliescu, Dmitrii Andreev, Cynthia Jordan, Michael Bader
Journal: Journal of the American Society of Nephrology (2002)

A sexual dimorphism in hypertension has been observed in both human and laboratory animal studies. The mechanisms by which male sex hormones regulate cardiovascular homeostasis are still not yet fully understood and represent the subject of this study. The possible involvement of androgen receptors in the development of hypertension and end-organ damage in transgenic rats harboring the mouse Ren-2 renin gene [TGR(mREN2)27] was studied. Male TGR(mREN2)27 rats were treated with the androgen receptor antagonist Flutamide starting at 4 wk of age. Also, an androgen receptor mutation (testicular feminization mutation [tfm]) was introduced in these rats by crossbreeding male TGR(mREN2)27 rats with tfm rats. The resulting offspring male rats that contain the tfm mutation are insensitive to androgens. Flutamide treatment or tfm mutation produced a significant attenuation of the development of hypertension. Besides a reduction in cardiac hypertrophy, urinary albumin excretion was blunted and no histologic characteristics of end-organ damage were observed in the kidney after Flutamide treatment. Testosterone levels increased 15-fold after Flutamide treatment and 2.7-fold by the tfm mutation. Also, plasma estrogens and luteinizing and follicle-stimulating hormones were significantly increased. Plasma renin concentrations and activity but not plasma angiotensinogen were reduced. Our results indicate that androgens contribute not only to the development of hypertension, but even more importantly to end-organ damage in TGR(mREN2)27 rats.
The ACTH Response to Dexamethasone in PTSD
Authors: Rachel Yehuda, Julia A. Golier, Sarah L. Halligan, Michael Meaney, Linda M. Bierer
Journal: American Journal of Psychiatry (2004)

Enhanced negative feedback and reduced adrenal output are two different models that have been put forth to explain the paradoxical observations of increased release of corticotropin-releasing factor in the face of low cortisol levels in posttraumatic stress disorder (PTSD). To discriminate between these models, the authors measured levels of adrenocorticopic hormone (ACTH) and cortisol at baseline and in response to dexamethasone in medically healthy subjects with and without PTSD. Under conditions of enhanced negative feedback inhibition, ACTH levels would not be altered relative to cortisol levels, but the ACTH response to dexamethasone would be augmented, in concert with the enhanced cortisol response to dexamethasone. In contrast, under conditions of reduced adrenal output, ACTH levels would be expected to be higher at baseline relative to cortisol levels, but the ACTH response to dexamethasone would be unchanged in PTSD relative to healthy comparison subjects.The ACTH and cortisol responses to 0.50 mg of dexamethasone were assessed in 19 subjects (15 men and four women) with PTSD and 19 subjects (14 men and five women) without psychiatric disorder.The ACTH-to-cortisol ratio did not differ between groups before or after dexamethasone, but the subjects with PTSD showed greater suppression of ACTH (as well as cortisol) in response to dexamethasone.The data support the hypothesis of enhanced cortisol negative feedback inhibition of ACTH secretion at the level of the pituitary in PTSD. Pituitary glucocorticoid receptor binding, rather than low adrenal output, is implicated as a likely mechanism for this effect.
Endothelin and vascular reactivity in cirrhosis
Authors: Cornel C. Sieber
Journal: Hepatology (1995)

Background/Aims: Because the vasodilator nitric oxide is overproduced in cirrhosis, this substance may decrease pressor responses to the vasoconstrictor endothelin 1. This study aimed to examine the effects of a NO synthesis inhibitor ( N G -nitro-l-arginine methyl ester; l-NAME) on vascular responsiveness to endothelin 1 in normal and cirrhotic rats. Methods: Pressor dose-response curves to endothelin 1 (0.5, 1, 3, 6, and 10 μg/kg intravenously) were obtained in animals with or without pretreatment with l-NAME. Results: Pressor responses to endothelin 1 alone were significantly lower in cirrhotic than in normal rats. In cirrhotic animals, pressor responses to 3, 6, and 10 μg/kg of endothelin 1 were significantly higher in the presence than in the absence of l-NAME. The responses to the other doses of endothelin 1 were not affected by l-NAME. In normal rats, pressor responses to all doses of endothelin 1 were significantly higher in the presence than in the absence of l-NAME. In animals pretreated with l-NAME, pressor responses to 6 and 10 μg/kg of endothelin 1 did not differ between cirrhotic and normal rats, whereas responses to other doses remained lower in cirrhotic than in normal rats. Conclusions: In rats with cirrhosis, NO seems to contribute to vascular hyporeactivity to high doses but not to low doses of endothelin 1.
Peroxisome Proliferator-Activated Receptor γ Is a Target for Halogenated Analogs of Bisphenol A
Authors: Anne Riu, Marina Grimaldi, Albane le Maire, Gilbert Bey, Kevin Phillips, Abdelhay Boulahtouf, Elisabeth Perdu, Daniel Zalko, William Bourguet, Patrick Balaguer
Journal: Environmental Health Perspectives (2011)

Background: The occurrence of halogenated analogs of the xenoestrogen bisphenol A (BPA) has been recently demonstrated both in environmental and human samples. These analogs include brominated [e.g., tetrabromobisphenol A (TBBPA)] and chlorinated [e.g., tetrachlorobisphenol A (TCBPA)] bisphenols, which are both flame retardants. Because of their structural homology with BPA, such chemicals are candidate endocrine disruptors. However, their possible target(s) within the nuclear hormone receptor superfamily has remained unknown.Objectives: We investigated whether BPA and its halogenated analogs could be ligands of estrogen receptors (ERs) and peroxisome proliferator–activated receptors (PPARs) and act as endocrine-disrupting chemicals.Methods: We studied the activity of compounds using reporter cell lines expressing ERs and PPARs. We measured the binding affinities to PPARγ by competitive binding assays with [3H]-rosiglitazone and investigated the impact of TBBPA and TCBPA on adipocyte differentiation using NIH3T3-L1 cells. Finally, we determined the binding mode of halogenated BPAs to PPARγ by X-ray crystallography.Results: We observed that TBBPA and TCBPA are human, zebrafish, and Xenopus PPARγ ligands and determined the mechanism by which these chemicals bind to and activate PPARγ. We also found evidence that activation of ERα, ERβ, and PPARγ depends on the degree of halogenation in BPA analogs. We observed that the bulkier brominated BPA analogs, the greater their capability to activate PPARγ and the weaker their estrogenic potential.Conclusions: Our results strongly suggest that polyhalogenated bisphenols could function as obesogens by acting as agonists to disrupt physiological functions regulated by human or animal PPARγ.
Osteocyte Mechanobiology and Pericellular Mechanics
Authors: Christopher R. Jacobs, Sara Temiyasathit, Alesha B. Castillo
Journal: Annual Review of Biomedical Engineering (2010)

An impressive range of tissues and cells are regulated by mechanical loading, and this regulation is central to disease processes such as osteoporosis, atherosclerosis, and osteoarthritis. However, other than a small number of specialized excitable cells involved in hearing and touch, cellular mechanosensing mechanisms are generally quite poorly understood. A lack of mechanistic understanding of these processes is one of the primary foci of the nascent field of mechanobiology, which, as a consequence, enjoys enormous potential to make critical new insights into both physiological function and etiology of disease. In this review we outline the process in bone by tracing mechanical effects from the organ level to the cellular and molecular levels and by integrating the biological response from molecule to organ. A case is made that a fundamental roadblock to advances in mechanobiology is the dearth of information in the area of pericellular mechanics.
Early Lung Cancer Detection Using Spiral Computed Tomography and Positron Emission Tomography
Authors: Gorka Bastarrika, María José García-Velloso, Maria Dolores Lozano, Usua Montes, Wenceslao Torre, Natalia Spiteri, Arantza Campo, Luis Seijo, Ana Belén Alcaide, Jesús Pueyo, David Cano, Isabel Vivas, Octavio Cosín, Pablo Domínguez, Patricia Serra, José A. Richter, Luis Montuenga, Javier J. Zulueta
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Rationale: Lung cancer screening using computed tomography (CT) is effective in detecting lung cancer in early stages. Concerns regarding false-positive rates and unnecessary invasive procedures have been raised. Objective: To study the efficiency of a lung cancer protocol using spiral CT and F-18-fluorodeoxyglucose positron emission tomography (FDG-PET). Methods: High-risk individuals underwent screening with annual spiral CTs. Follow-up CTs were done for noncalcified nodules of 5 mm or greater, and FDG-PET was done for nodules 10 mm or larger or smaller (> 7 mm), growing nodules. Results: A total of 911 individuals completed a baseline CT study and 424 had at least one annual follow-up study. Of the former, 14% had noncalcified nodules of 5 mm or larger, and 3.6% had nodules of 10 mm or larger. Eleven non–small cell lung cancers (NSCLC) and one small cell lung cancer (SCLC) were diagnosed in the baseline study (prevalence rate, 1.32%), and two NSCLCs in the annual study (incidence rate, 0.47%). All NSCLCs (92% of prevalence cancers) were diagnosed in stage I (12 stage IA, 1 stage IB). FDG-PET was helpful for the correct diagnosis in 19 of 25 indeterminate nodules. The sensitivity, specificity, positive predictive value, and negative predictive value of FDG-PET for the diagnosis of malignancy were 69, 91, 90, and 71%, respectively. However, the sensitivity and negative predictive value of the screening algorithm, which included a 3-month follow-up CT for nodules with a negative FDG-PET, was 100%. Conclusion: A protocol for early lung cancer detection using spiral CT and FDG-PET is useful and may minimize unnecessary invasive procedures for benign lesions.
Ursodeoxycholic Acid versus Sulfasalazine in Colitis-Related Colon Carcinogenesis in Mice
Authors: Hiroyuki Kohno, Rikako Suzuki, Yumiko Yasui, Shingo Miyamoto, Keiji Wakabayashi, Takuji Tanaka
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Inflammation influences carcinogenesis. In the current study, we investigated whether ursodeoxycholic acid (UDCA) can inhibit colitis-related mouse colon carcinogenesis and compared it with the effects of sulfasalazine. Experimental Design: Male CD-1 mice were given a single i.p. injection of azoxymethane followed by 1-week oral exposure of 1% dextran sodium sulfate in drinking water. They are then maintained on a basal diet mixed with UDCA (0.016%, 0.08%, or 0.4%) or sulfasalazine (0.05%) for 17 weeks. At week 20, the tumor-inhibitory effects of both chemicals were assessed by counting the incidence and multiplicity of colonic neoplasms. The immunohistochemical expression of the proliferating cell nuclear antigen labeling index in colonic epithelial malignancies was also assessed. Finally, at week 5, the mRNA expressions for cyclooxygenase-2, inducible nitric oxide synthase, peroxisome proliferator-activated receptor-γ, and tumor necrosis factor-α were measured in nontumorous mucosa. Results: Feeding the mice with UDCA at all doses significantly inhibited the multiplicity of colonic adenocarcinoma. The treatment also significantly lowered the proliferating cell nuclear antigen labeling index in the colonic malignancies. UDCA feeding reduced the expression of inducible nitric oxide synthase and tumor necrosis factor-α mRNA in the colonic mucosa, while not significantly affecting the expression of cyclooxygenase-2 mRNA and peroxisome proliferator-activated receptor-γ mRNA. Sulfasalazine caused a nonsignificant reduction in the incidence and multiplicity of colonic neoplasia and did not affect these mRNA expression. Conclusions: Our findings suggest that UDCA rather than sulfasalazine could serve as an effective suppressing agent in colitis-related colon cancer development in mice.
Pit patterns in rectal mucosa assessed by magnifying colonoscope are predictive of relapse in patients with quiescent ulcerative colitis
Authors: Y Nishio, T Ando, O Maeda, K Ishiguro, O Watanabe, N Ohmiya, Y Niwa, K Kusugami, H Goto
Journal: Gut (2006)

Relapse of ulcerative colitis is difficult to predict by routine colonoscopy. A high-resolution video-magnifying colonoscope with chromoscopy enables the observation of colorectal mucosal pit patterns.To investigate the association of pit patterns as assessed by magnifying colonoscopy (MCS) with histological inflammation and mucosal chemokine activity in patients with quiescent ulcerative colitis, and to prospectively analyse the prognostic factors that may predict exacerbations.MCS was performed in 113 patients with ulcerative colitis in remission. Pit patterns in the rectal mucosa were classified into four MCS grades on the basis of size, shape and arrangement. Mucosal interleukin (IL) 8 activity was measured in biopsy specimens of rectal mucosa and the specimens were assessed for histological disease activity. The patients were then followed until relapse or for a maximum of 12 months. Multivariate survival analysis was carried out to determine the independent predictors of clinical relapse.A positive correlation was identified between MCS grade, histological grade (p = 0.001) and mucosal IL8 activity (p<0.001). Multivariate proportional hazard model analysis showed that MCS grade was a significant predictor of relapse (relative risk 2.06, p = 0.001). Kaplan-Meier estimate of relapse during 12 months of follow-up was found to increase with increasing MCS grade, with values of 0% for grade 1, 21% for grade 2, 43% for grade 3 and 60% for grade 4.MCS grading is associated with the degree of histological inflammation and mucosal IL8 activity in patients with quiescent ulcerative colitis, and may predict the probability of subsequent disease relapse in patients with ulcerative colitis in remission.
The Gift of Laughter
Authors: R. Dale Liechty
Journal: JAMA (1979)

Hence loathed Melancholy... Haste thee nymph, and bring with thee Jest and youthful Jollity, Quips and Cranks, and wanton Wiles... Sport that wrinkled Care derides, And Laughter, holding both his sides.  THREE centuries ago, John Milton thus invoked the laughing good times in L'Allegro . Today, in much the same spirit, albeit in less majestic words, we hear the familiar Thank God it's Friday. Regardless of the words or the era that spoke them, people have always needed laughter. Distinguishing man from all the other animals, the belly laugh is innately human.  In his introduction to Loren Eiseley's The Star Thrower , W. H. Auden puts laughter—the spirit of carnival—into perspective. According to Auden, successful lives must pay respect to three worlds: Work, Worship, and Carnival. Most important, the three must balance. Without Worship and Work, Laughter turns ugly and humor grubby and pornographic, the ultimate downfall of many comics. Without Laughter
Geographical and socioeconomic variation in the prevalence of asthma symptoms in English and Scottish children
Authors: E Duran-Tauleria, R J Rona
Journal: Thorax (1999)

<h3>BACKGROUND</h3> There has been controversy over the relation between poverty and asthma in the community. The aim of this analysis was to disentangle geographical and socioeconomic variation in asthma symptoms. <h3>METHODS</h3> The analysis is based on parental reports of symptoms from data collected in 1990 and 1991. Children aged 5–11 years from three populations (English representative sample, Scottish representative sample, and an English inner city sample) were included. Of 17 677 eligible children, between 14 490 (82.0%) and 15 562 (88.0%) children were available for analysis according to symptom group. <h3>RESULTS</h3> Wheezy symptoms were less prevalent in the Scottish sample than in the English samples and asthma attacks were most prevalent in the English representative sample. Asthma attacks were less prevalent in inner city areas than in the English representative sample (OR 0.79, 95% CI 0.66 to 0.95), but persistent wheeze and other respiratory symptoms were more prevalent (OR 1.95, 95% CI 1.65 to 2.32 and OR 1.67, 95% CI 1.52 to 1.84, respectively). The prevalence of persistent wheeze was higher in children whose father's social class was low and in those living in areas with a high Townsend score (an index of poverty) than in other children (p&lt;0.001). Of the 14 areas with the highest Townsend score, 13 had an OR above 1 and six had an OR significantly higher than the reference area. <h3>CONCLUSIONS</h3> Persistent wheeze is more prevalent in poor areas than in less deprived areas. This may indicate that poverty is associated with severe asthma or that a high percentage of persistent asthma symptoms in inner city areas are unrecognised and untreated.
Beyond the blot: cutting edge tools for genomics, proteomics and metabolomics analyses and previous successes
Authors: A.B. Kimball, R.A. Grant, F. Wang, R. Osborne, J.P. Tiesman
Journal: British Journal of Dermatology (2012)

Journal Article Beyond the blot: cutting edge tools for genomics, proteomics and metabolomics analyses and previous successes Get access A.B. Kimball, A.B. Kimball Harvard Medical School, Boston, MA, U.S.A Search for other works by this author on: Oxford Academic Google Scholar R.A. Grant, R.A. Grant The Procter & Gamble Company, Miami Valley Innovation Center, PO Box 538707, Cincinnati, OH 45253‐8707, U.S.A Search for other works by this author on: Oxford Academic Google Scholar F. Wang, F. Wang The Procter & Gamble Company, Miami Valley Innovation Center, PO Box 538707, Cincinnati, OH 45253‐8707, U.S.A Search for other works by this author on: Oxford Academic Google Scholar R. Osborne, R. Osborne The Procter & Gamble Company, Miami Valley Innovation Center, PO Box 538707, Cincinnati, OH 45253‐8707, U.S.A Search for other works by this author on: Oxford Academic Google Scholar J.P. Tiesman J.P. Tiesman The Procter & Gamble Company, Miami Valley Innovation Center, PO Box 538707, Cincinnati, OH 45253‐8707, U.S.A Jay P. Tiesman. E‐mail: tiesman.jp@pg.com Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 166, Issue s2, 1 June 2012, Pages 1–8, https://doi.org/10.1111/j.1365-2133.2012.10859.x Published: 01 June 2012 Article history Accepted: 19 September 2011 Published: 01 June 2012
Mice with a “Monoclonal Nose”: Perturbations in an Olfactory Map Impair Odor Discrimination
Authors: Alexander Fleischmann, Benjamin M. Shykind, Dara L. Sosulski, Kevin M. Franks, Meredith E. Glinka, Dan Feng Mei, Yonghua Sun, Jennifer Kirkland, Monica Mendelsohn, Mark W. Albers, Richard Axel
Journal: Neuron (2008)
Philosophy in medicine
Authors: A. K Demetriades, C. K Demetriades
Journal: Journal of the Royal Society of Medicine (2003)

Dr Harper should be congratulated for his attempt to entice physicians to philosophical values (January 2003 JRSM1). His article touches on several aspects of philosophy that can be viewed on a par with medicine. Philosophy (from the Greek for love of wisdom/knowledge) was the unifying theme in classical education. It encouraged the quest for why and how things come to be and provided a mechanism for reasoning that could be applied to any academic discipline. In modern times, when medicine is threatened by information-overload, the philosophical process (inquiry, critical reasoning, analysis) can offer valuable insights for practice. However, as Dr Harper indicates, acceptance demands an end to the misconception that philosophy is incompatible with practical science.

The general view is that, while science has answers that command widespread agreement, philosophy is interested in matters on which there is less consensus. By challenging concepts and assumptions, the philosophical approach can generate new perspectives in science. Advances in genomic biotechnology, for instance, illustrate the difficulty of deciding what to do with scientific discoveries. We need to consider what society we wish to have and our relationships with each other and our surroundings, which depend on our conception of ourselves as human beings at societal level.

This is where, in our opinion, Dr Harper's article is overambitious in scope. In trying to cover a large area, he omits certain issues that are important in explicating/exploring the common ground between philosophy and medicine; for example, how should ethics be applied in the medical arena, or how does morality ethically connect with human society? His choice of philosophers was necessarily limited, but in an article about science as applied to medicine we would have included the following: Thales of Miletus, the first natural scientist and analytical philosopher in Western intellectual history; Aristotle, for his observation, methodological classification and empirical analysis; Bertrand Russell, for his logical analysis;2 and Michel Foucault, for his insightful analysis of scientific knowledge and social control.3