tbuckley/cabot-search huggingface dataset:
Changes in Levels of Urinary Estrogen Metabolites After Oral Indole-3-Carbinol Treatment in Humans
Authors: J. J. Michnovicz, H. Adlercreutz, H. L. Bradlow
Journal: JNCI Journal of the National Cancer Institute (1997)

Background: The oxidative metabolism of estrogens in humans is mediated primarily by cytochrome P450, many isoenzymes of which are inducible by dietary and pharmacologic agents. One major pathway, 2-hydroxylation, is induced by dietary indole-3-carbinol (I3C), which is present in cruciferous vegetables (e.g., cabbage and broccoli). Purpose: Because the pool of available estrogen substrates for all pathways is limited, we hypothesized that increased 2-hydroxylation of estrogens would lead to decreased activity in competing metabolic pathways. Methods: Urine samples were collected from subjects before and after oral ingestion of I3C (6–7 mg/kg per day). In the first study, seven men received I3C for 1 week; in the second study, 10 women received I3C for 2 months. A profile of 13 estrogens was measured in each sample by gas chromatography-mass spectrometry. Results: In both men and women, I3C significantly increased the urinary excretion of C-2 estrogens. The urinary concentrations of nearly all other estrogen metabolites, including levels of estradiol, estrone, estriol, and 16α-hydroxyestrone, were lower after I3C treatment. Conclusions: These findings support the hypothesis that I3Cinduced estrogen 2-hydroxylation results in decreased concentrations of several metabolites known to activate the estrogen receptor. This effect may lower estrogenic stimulation in women. Implications: I3C may have chemopreventive activity against breast cancer in humans, although the long-term effects of higher catechol estrogen levels in women require further investigation.
Local Tissue Interactions across the Dorsal Midline of the Forebrain Establish CNS Laterality
Authors: Miguel L Concha, Claire Russell, Jennifer C Regan, Marcel Tawk, Samuel Sidi, Darren T Gilmour, Marika Kapsimali, Lauro Sumoy, Kim Goldstone, Enrique Amaya, David Kimelman, Teresa Nicolson, Stefan Gründer, Miranda Gomperts, Jonathan D.W Clarke, Stephen W Wilson
Journal: Neuron (2003)
KPNA2 Expression Is an Independent Adverse Predictor of Biochemical Recurrence after Radical Prostatectomy
Authors: Ashkan Mortezavi, Thomas Hermanns, Hans-Helge Seifert, Martin K. Baumgartner, Maurizio Provenzano, Tullio Sulser, Maximilian Burger, Matteo Montani, Kristian Ikenberg, Ferdinand Hofstädter, Arndt Hartmann, Rolf Jaggi, Holger Moch, Glen Kristiansen, Peter J. Wild
Journal: Clinical Cancer Research (2011)

To analyze rates of expression of karyopherin alpha 2 (KPNA2) in different prostate tissues and to evaluate the prognostic properties for patients with primary prostate cancer.Tissue microarrays (TMA) contained 798 formalin-fixed, paraffin-embedded prostate tissue cores from two different institutes of pathology. TMAs were stained immunohistochemically for KPNA2 and NBS1. SiRNA technologies were used to inhibit KPNA2 expression in vitro, and the effect of this inhibition on cellular viability was determined. Efficiency of knockdown experiments was determined by Western blot analysis.KPNA2 expression was significantly upregulated in carcinomas of the prostate, especially in metastatic and castration-resistant prostate cancer samples. Positive nuclear KPNA2 immunoreactivity was identified as a novel predictor of biochemical recurrence after radical prostatectomy (n = 348), and was independent of the well-established predictive factors preoperative PSA value, Gleason score, tumor stage, and surgical margin status. These results were validated by analyzing a second and independent prostate cancer cohort (n = 330). Further, in vitro experiments showed that the cell proliferation and viability of PC3 cells was significantly reduced when KPNA2 expression was inhibited. KPNA2 knockdown did not induce PARP cleavage as marker for apoptosis. No significantly increased sub-G(1) fraction could be found by FACS analysis.KPNA2 is a novel independent prognostic marker for disease progression after radical prostatectomy. This allows to identify patients who need more aggressive treatment. It can moreover be speculated that patients not suited for surveillance regimens might be identified at initial biopsy by a positive KPNA2 immunohistochemistry.
moral heuristics and the means/end distinction
Authors: barbara h. fried
Journal: Behavioral and Brain Sciences (2005)

a mental heuristic is a shortcut (means) to a desired end. in the moral (as opposed to factual) realm, the means/end distinction is not self-evident: how do we decide whether a given moral intuition is a mere heuristic to achieve some freestanding moral principle, or instead a freestanding moral principle in its own right? i discuss sunstein's solution to that threshold difficulty in translating “heuristics” to the moral realm.
Pushing the Limits of Glioma Resection Using Electrophysiologic Brain Mapping
Authors: Pedro R. Lowenstein, Maria G. Castro
Journal: Journal of Clinical Oncology (2012)

proposes that intraoperative stimulatory mapping to determine the location of eloquent brain areas during glioma resection provides increased volume of resection and is associated with reduced late severe neurologic deficits. The report is based on a retrospective systematic meta-analysis of 90 publications describing 8,091 patients with glioma. Because extent of resection and neurologic status are two crucial predictors of longer survival in patients with glioblastoma, the authors propose that intraoperative surgical mapping should become part of the standard of care for resective neurosurgery of high-grade brain gliomas. The current standard of care for the treatment of high-grade gliomas is neurosurgical resection, followed by radiation and chemotherapy. If tumors can be resected at all, the aim is for the resection to be as complete as possible. Radiation treatment has been standardized for some time now, and the current chemotherapy of choice is temozolomide administered in various regimes that have been optimized over the last 5 years. Because long-term survival ( 2 years) continues to be low, experimental therapies are administered in tandem with the primary standard of care or on tumor recurrence, which occurs in almost 100% of cases. 2-4 Two-year survival in patients with high-grade gliomas at the highest-complexity medical centers, with optimized standard of care, is 38.4%, and median survival is 18 to 21 months. 5 Longer-term survival of the majority of patients continues to be an elusive goal. Predictors of long-term survival continue to be classical clinical categories: younger patients (age 35 years), with high Karnofsky performance score at presentation, and a tumor that in principle is susceptible to complete neurosurgical excision. Even in these cases, 5-year survival remains below 5%. 4,6-8
Speaking for the Evidence: Colonoscopy vs Computed Tomographic Colonography
Authors: Russell Harris
Journal: JNCI Journal of the National Cancer Institute (2010)

At a recent National Institutes of Health State-of-the-Science Conference on “Enhancing the Use and Quality of Colorectal Cancer Screening,” the final discussion period was dominated by an animated debate between optical colonoscopists and computed tomographic (CT) colonographers about the relative merits of their respective screening tests (optical colonoscopy and CT colonography). A similar exchange between gastroenterology and radiology specialty societies occurred in strongly worded letters to the White House after President Obama had CT colonography for colorectal cancer screening during his annual physical examination. Gastroenterologists claimed that optical colonoscopy is the “gold standard” test; radiologists claimed that Medicare unfairly excludes reimbursement for CT colonography as a screening test (1).
Multiple Roles of Antimicrobial Defensins, Cathelicidins, and Eosinophil-Derived Neurotoxin in Host Defense
Authors: De Yang, Arya Biragyn, David M. Hoover, Jacek Lubkowski, Joost J. Oppenheim
Journal: Annual Review of Immunology (2004)

Mammals generate a diverse array of antimicrobial proteins, largely represented by defensins or cathelicidins. The direct in vitro microbicidal activity of antimicrobial proteins has long been considered an important innate immune defense, although the in vivo relevance has only very recently been established for certain defensins and cathelicidins. Mammalian defensins and cathelicidins have also been shown to have multiple receptor-mediated effects on immune cells. Beta-defensins interact with CCR6; murine beta-defensin-2 in addition activates TLR4. Cathelicidins act on FPRL1-expressing cells. Furthermore, several defensins have considerable immunoenhancing activity. Thus, it appears that mammalian antimicrobial proteins contribute to both innate and adaptive antimicrobial immunity.
Parasympathetic nervous system dysfunction in primary Sjogren's syndrome
Authors: A Hocevar
Journal: Annals of the Rheumatic Diseases (2003)

In the past sicca syndromes were attributed to destruction of glandular tissue. It is now thought that cytokines, autoantibodies, and parasympathetic nervous system dysfunction all have an important role in the xerostomia and xerophthalmia in Sjögren's syndrome.
Severe novel influenza A (H1N1) infection in cancer patients
Authors: L.A. Hajjar, T. Mauad, F.R.B.G. Galas, A. Kumar, L.F.F. da Silva, M. Dolhnikoff, T. Trielli, J.P. Almeida, M.R.L. Borsato, E. Abdalla, L. Pierrot, R. Kalil Filho, J.O.C. Auler, P.H.N. Saldiva, P.M. Hoff
Journal: Annals of Oncology (2010)

The natural history and consequences of severe H1N1 influenza infection among cancer patients are not yet fully characterized. We describe eight cases of H1N1 infection in cancer patients admitted to the intensive care unit of a referral cancer center.Clinical data from all patients admitted with acute respiratory failure due to novel viral H1N1 infection were reviewed. Lung tissue was submitted for viral and bacteriological analyses by real-time RT-PCR, and autopsy was conducted on all patients who died.Eight patients were admitted, with ages ranging from 55 to 65 years old. There were five patients with solid organ tumors (62.5%) and three with hematological malignancies (37.5%). Five patients required mechanical ventilation and all died. Four patients had bacterial bronchopneumonia. All deaths occurred due to multiple organ failure. A milder form of lung disease was present in the three cases who survived. Lung tissue analysis was performed in all patients and showed diffuse alveolar damage in most patients. Other lung findings were necrotizing bronchiolitis or extensive hemorrhage.H1N1 viral infection in patients with cancer can cause severe illness, resulting in acute respiratory distress syndrome and death. More data are needed to identify predictors of unfavorable evolution in these patients.
Suppression of aggregate formation and apoptosis by transglutaminase inhibitors in cells expressing truncated DRPLA protein with an expanded polyglutamine stretch
Authors: Shuichi Igarashi, Reiji Koide, Takayoshi Shimohata, Mitsunori Yamada, Yasuko Hayashi, Hiroki Takano, Hidetoshi Date, Mutsuo Oyake, Toshiya Sato, Aki Sato, Shigekimi Egawa, Takeshi Ikeuchi, Hajime Tanaka, Ryoichi Nakano, Keiko Tanaka, Isao Hozumi, Takashi Inuzuka, Hitoshi Takahashi, Shoji Tsuji
Journal: Nature Genetics (1998)
Impact of tumour necrosis factor inhibitor treatment on radiographic progression in rheumatoid arthritis patients in clinical practice: results from the nationwide Danish DANBIO registry
Authors: Lykke Midtbøll Ørnbjerg, Mikkel Østergaard, Pernille Bøyesen, Niels Steen Krogh, Anja Thormann, Ulrik Tarp, Uta Engling Poulsen, Jakob Espesen, Vibeke Stevenius Ringsdal, Niels Graudal, Gina Kollerup, Dorte Vendelbo Jensen, Ole Rintek Madsen, Bente Glintborg, Torben Christensen, Hanne Lindegaard, Ditte Dencker, Annette Hansen, Anne Rødgaard Andersen, Merete Lund Hetland
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objectives</h3> To compare radiographic progression during treatment with disease-modifying antirheumatic drugs (DMARD) and subsequent treatment with tumour necrosis factor α inhibitors (TNF-I) in rheumatoid arthritis (RA) patients in clinical practice. <h3>Methods</h3> Conventional radiographs (x-rays) of hands and wrists were obtained ∼2 years before start (prebaseline), at baseline and ∼2 years after start (follow-up) of TNF-I. Clinical data were obtained from the DANBIO registry and the patient files. x-Rays were scored blinded to chronology according to the Sharp/van der Heijde method. Annual radiographic progression rates during the DMARD (prebaseline to baseline x-ray) and TNF-I (baseline to follow-up x-ray) periods were calculated. <h3>Results</h3> 517 RA patients (76% women, 80% IgM rheumatoid factor positive, 65% anticyclic citrullinated peptide positive, 40% current smokers, age 54 years (range 21–86), median disease duration 5 years (range 0–57)) were included. Patients were treated with infliximab (61%), etanercept (15%) or adalimumab (24%). During the DMARD period 85% of patients received methotrexate, 51% sulphasalazine and 78% prednisolone. The median DMARD period was 733 days (IQR 484–1002) and the median TNF-I period was 562 days (IQR 405–766). The median radiographic progression rate decreased from 0.7 (IQR 0–2.9) total Sharp score units/year (dTSS) in the DMARD period to 0 (0–0.9) units/year in the TNF-I period (p&lt;0.0001, Wilcoxon). Corresponding mean dTSS values were 2.1 (SD 3.7) versus 0.7 (SD 2.3) units/year (p&lt;0.0001, paired t test). 305 patients progressed (dTSS &gt;0) in the DMARD period compared with 158 patients in the TNF-I period (p&lt;0.0001, χ<sup>2</sup>). <h3>Conclusion</h3> This nationwide observational study of RA patients documented significantly reduced radiographic progression during TNF-I treatment compared with the previous period of DMARD treatment.
Association Between Brain Tumors and Menopausal Status
Authors: B. Schlehofer, M. Blettner, J. Wahrendorf
Journal: JNCI Journal of the National Cancer Institute (1992)

Several lines of evidence have implicated female hormones in the etiology of human brain tumors, meningiomas in particular.To investigate the relationship between brain tumor development and the hormonal changes manifested during pregnancy and menopause, we analyzed data from female participants in a population-based case-control study of adult brain tumors. This study was conducted in 1987-1988 in the Rhein-Neckar-Odenwald area of the Federal Republic of Germany.The study population consisted of 127 women with meningiomas, gliomas, and acoustic neuromas (case patients) and 233 control women who were selected from the general population and frequency-matched by age to the case patients. Information on parity, menopausal status, and previous gynecologic surgeries was obtained through a standardized questionnaire. Case patients and control subjects were compared with the use of the unconditional maximum likelihood estimation of the parameters in a logistic regression model.Our results were not statistically significant; nevertheless, they revealed some interesting trends. No association was found between parity and the development of any of the three histological subtypes of brain tumor (relative risk [RR] = 1.31; 95% confidence interval [CI] = 0.51-2.07). Menopausal women had a greatly reduced risk of developing meningiomas (RR = 0.58; 95% CI = 0.18-1.90), and this effect was most pronounced when menopause had been surgically induced by bilateral oophorectomy (RR = 0.12; 95% CI = 0.01-1.30). Menopausal women had a greater risk of developing gliomas or acoustic neuromas (RR = 1.77; 95% CI = 0.67-4.68), except when menopause was surgically induced, in which case the risk was reduced (RR = 0.33; 95% CI = 0.04-3.09). Oophorectomy after menopause did not appear to influence risk.Since the onset of menopause is accompanied by cessation of estrogen production, our results support the notion that female hormones play a role in the development of brain tumors.
Morphological changes in peripheral blood cells and skin in amiodarone-treated patients
Authors: K. RAPPERSBERGER, K. KONRAD, E. WIESER, H. WEBER, K. WOLFF
Journal: British Journal of Dermatology (1986)

Amiodarone, used in the treatment of cardiac arrhythmia, may lead to severe discolouration of sun-exposed skin. The lysosomal storage of a lipid-like material has been shown to be the morphological substrate for this cutaneous hyperpigmentation. Examination of peripheral white blood cells of amiodarone-treated patients disclosed identical lysosomal structures indicating that amiodarone treatment leads to a more generalized lysosomal storage of lipids and of amiodarone and its metabolites.
Exercise tolerance with helium-hyperoxia<i>versus</i>hyperoxia in hypoxaemic patients with COPD
Authors: Fernando Queiroga, Marcos Nunes, Ethiane Meda, Gaspar Chiappa, Maria Christina Machado, Luiz Eduardo Nery, J. Alberto Neder
Journal: European Respiratory Journal (2012)

The purpose of this study was to investigate whether helium-hyperoxia (HeHOx) would allow greater tolerance to maximal and submaximal exercise compared to hyperoxia (HOx) on isolation in hypoxaemic chronic obstructive pulmonary disease (COPD) patients under long-term oxygen therapy. In a double-blind study, 24 males in the Global Initiative for Chronic Obstructive Lung Disease functional class IV (forced expiratory volume in 1 s 35.2±10.1% predicted and arterial oxygen tension 56.2±7.5 mmHg) were submitted to incremental and constant load cycling at 70–80% peak work rate while breathing HOx (60% nitrogen and 40% oxygen) or HeHOx (60% helium and 40% oxygen). HeHOx improved resting airflow obstruction and lung hyperinflation in all but two patients (p&lt;0.05). Peak work rate and time to exercise intolerance were higher with HeHOx than HOx in 17 (70.8%) out of 24 patients and 14 (66.6%) out of 21 patients, respectively (p&lt;0.05). End-expiratory lung volumes were lower with HeHOx, despite a higher ventilatory response (p&lt;0.05). HeHOx speeded on-exercise oxygen uptake kinetics by ∼30%, especially in more disabled and hyperinflated patients. Fat-free mass was the only independent predictor of higher peak work rate with HeHOx (r<sup>2</sup> = 0.66, p&lt;0.001); in contrast, none of the resting characteristics or exercise responses were related to improvements in time to exercise intolerance (p&gt;0.05). Helium is a valuable ergogenic aid when added to HOx for most long-term oxygen therapy-dependent patients with advanced COPD.
Hemodynamic Effects of Peritoneal Dialysis Solutions on the Rat Peritoneal Membrane
Authors: Siska Mortier, An S. De Vriese, Johan Van de Voorde, Thomas P. Schaub, Jutta Passlick-Deetjen, Norbert H. Lameire
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Conventional peritoneal dialysis fluids (PDF) are unphysiologic because of their hypertonicity, high glucose and lactate concentrations, acidic pH, and presence of glucose degradation products (GDP). Long-term exposure to conventional PDF may cause functional and structural alterations of the peritoneal membrane. New PDF have a neutral pH, a low GDP content, and contain bicarbonate or lactate as the buffer. Intravital microscopy was used to analyze the vasoactive effects of conventional and new PDF on the rat peritoneal membrane. A conventional, acidic pH, lactate-buffered 4.25% glucose PDF induced maximal vasodilation of mesenteric arteries, resulting in a doubling of the arteriolar flow and a 20% increase of the perfused capillary length per area. The hemodynamic effects of conventional PDF were similar after pH-adjustment with NaOH, indicating that acidity per se is not essential for the changes. Superfusion by a pH-neutral, lactate-buffered PDF with low GDP content caused only a transient arterial vasodilation despite continuous exposure, with a commensurate effect on arteriolar flow and capillary recruitment. Application of a pH-neutral, bicarbonate-buffered PDF with low GDP content did not affect the hemodynamic parameters. Resterilization of the bicarbonate solution increased GDP levels and completely restored the vasodilatory capacity. The corresponding 1.5% glucose PDF induced similar but less pronounced changes. Conventional PDF have important vasoactive effects on the peritoneal circulation, mainly because of the presence of GDP and transiently because of high lactate concentrations. Capillary recruitment may increase effective peritoneal vascular surface area. In addition, chronic vasodilation may induce structural adaptations in the blood vessel wall, contributing to vascular sclerosis. PDF with reduced GDP content induce no major hemodynamic effects and may thus have the potential to better preserve peritoneal vascular integrity.
THE TREATMENT OF HAEMORRHOIDS BY SUBMUCOUS INJECTIONS OF CHEMICALS
Authors: H. G. Anderson
Journal: BMJ (1924)

r VXTD BOITNA Andrews of Chicago, which rather emphasizes the handicap of not having access to Sir Berkeley Moyinihan's book on the subject of duodenal hernia.My case seems to support Dr. Andrews's theory that these cases are of congenital origin.
Phenotyping male infertility in the mouse: how to get the most out of a 'non-performer'
Authors: C. L. Borg, K. M. Wolski, G. M. Gibbs, M. K. O'Bryan
Journal: Human Reproduction Update (2009)

Functional male gametes are produced through complex processes that take place within the testis, epididymis and female reproductive tract. A breakdown at any of these phases can result in male infertility. The production of mutant mouse models often yields an unexpected male infertility phenotype. It is with this in mind that the current review has been written. The review aims to act as a guide to the 'non-reproductive biologist' to facilitate a systematic analysis of sterile or subfertile mice and to assist in extracting the maximum amount of information from each model. This is a review of the original literature on defects in the processes that take a mouse spermatogonial stem cell through to a fully functional spermatozoon, which result in male infertility. Based on literature searches and personal experience, we have outlined a step-by-step strategy for the analysis of an infertile male mouse line. A wide range of methods can be used to define the phenotype of an infertile male mouse. These methods range from histological methods such as electron microscopy and immunohistochemistry, to hormone analyses and methods to assess sperm maturation status and functional competence. With the increased rate of genetically modified mouse production, the generation of mouse models with unexpected male infertility is increasing. This manuscript will help to ensure that the maximum amount of information is obtained from each mouse model and, by extension, will facilitate the knowledge of both normal fertility processes and the causes of human infertility.
Dual effects of macrophage inflammatory protein-1α on osteolysis and tumor burden in the murine 5TGM1 model of myeloma bone disease
Authors: Babatunde O. Oyajobi, Giovanni Franchin, Paul J. Williams, Donna Pulkrabek, Anjana Gupta, Steve Munoz, Barry Grubbs, Ming Zhao, Di Chen, Barbara Sherry, Gregory R. Mundy
Journal: Blood (2003)
MPs propose toning down aspects of health bill that increase competition in NHS
Authors: A. O'Dowd
Journal: BMJ (2011)

Competition in the NHS in England should be not allowed, as it will fatally damage some health services, doctors’ leaders have claimed, with the support of some MPs. The BMA has issued a warning in a briefing paper that the NHS should not be run like a privatised industry such as water, gas, and telecommunications.

The briefing paper for MPs was published on 10 March to coincide with MPs debating sections of the Health and Social Care Bill relating to new powers to enforce competition in the NHS in England.

Many of the amendments the BMA would like to see made to the bill, which is currently being scrutinised by MPs before proceeding through parliament, were proposed by MPs during their meeting on 10 March. The amendments will …