tbuckley/cabot-search huggingface dataset:
Castration resistance in human prostate cancer is conferred by a frequently occurring androgen receptor splice variant
Authors: Shihua Sun, Cynthia C.T. Sprenger, Robert L. Vessella, Kathleen Haugk, Kathryn Soriano, Elahe A. Mostaghel, Stephanie T. Page, Ilsa M. Coleman, Holly M. Nguyen, Huiying Sun, Peter S. Nelson, Stephen R. Plymate
Journal: Journal of Clinical Investigation (2010)

Progression of prostate cancer following castration is associated with increased androgen receptor (AR) expression and signaling despite AR blockade. Recent studies suggest that these activities are due to the generation of constitutively active AR splice variants, but the mechanisms by which these splice variants could mediate such effects are not fully understood. Here we have identified what we believe to be a novel human AR splice variant in which exons 5, 6, and 7 are deleted (ARv567es) and demonstrated that this variant can contribute to cancer progression in human prostate cancer xenograft models in mice following castration. We determined that, in human prostate cancer cell lines, ARv567es functioned as a constitutively active receptor, increased expression of full-length AR (ARfl), and enhanced the transcriptional activity of AR. In human xenografts, human prostate cancer cells transfected with ARv567es cDNA formed tumors that were resistant to castration. Furthermore, the ratio of ARv567es to ARfl expression within the xenografts positively correlated with resistance to castration. Importantly, we also detected ARv567es frequently in human prostate cancer metastases. In summary, these data indicate that constitutively active AR splice variants can contribute to the development of castration-resistant prostate cancers and may serve as biomarkers for patients who are likely to suffer from early recurrence and are candidates for therapies directly targeting the AR rather than ligand.
OBSERVATIONS ON SOME PATHOLOGIC CONDITIONS OF THE NASO-PHARYNX.
Authors: EMMA E. MUSSON
Journal: JAMA (1898)

Believing that the presentation of cases having either special pathologic features or dependent on unusual causes, or amenable only to special lines of treatment, would be of interest. I have selected from my case book several groups of cases which have come under my observation during the past two years. The first group comprises a number of cases of hypertrophied lymphoid tissue in the vault of the pharynx, all of which required for their relief operative interference. The points of interest in these cases, relate to the age and the character of the symptoms. Out of the last 230 patients in my case book, 34 had hypertrophy of the third or Luschka's tonsil. Of this number eleven were from 15 to 20 years of age; eleven from 20 to 25; eleven from 25 to 35, and one 40 years of age. The age of the majority of these patients attracted
Exercise and coronary heart disease
Authors: J N Morris
Journal: BMJ (1987)

cant," this equates to a bacterial density of 200/ml.This "sensitive" diagnostic criterion was proposed by Stamm for patients with frequency ofmicturition, not pregnant women.3Moreover, criticisms4 of Stamm's hypothesis have not been rebutted.The absurdity of regarding a single colony on the culture plate as "significant" is illustrated by the appearance of Candida albicans as a cause of bacteriuria at Northwick Park.For the same reason it becomes difficult to discern how many women with asymptomatic "bacteriuria" were genuinely infected.It was wrong, however, to suggest that previous workers examined only one urine and therefore treated uninfected women, giving artificially high success rates.At least two25 or three6 specimens were cultured.It is Dr M E Foley and coworkers (25 July, p 270) who could be criticised on this account, so their reported incidence of pyelo- nephritis in women with untreated bacteriuria may well be spuriously low.Moreover, the "low" (12-5%) incidence of pyelonephritis in such women at North- wick Park was extrapolated from just one case out of eight.The 95% confidence interval for the real incidence in such a small sample is 0 to 35%.In other words, there is no significant difference between the incidence of pyelonephritis at Northwick Park and that reported previously.256Finally, the four cases of pyelonephritis which occurred after treatment were in women who were recognised either to have relapsed or to have become reinfected.If no further treatment was given it is hardly surprising that they developed complications.
Palmitoleate attenuates palmitate-induced Bim and PUMA up-regulation and hepatocyte lipoapoptosis
Authors: Yuko Akazawa, Sophie Cazanave, Justin L. Mott, Nafisa Elmi, Steven F. Bronk, Shigeru Kohno, Michael R. Charlton, Gregory J. Gores
Journal: Journal of Hepatology (2010)
Effects of high glucose on the production of heparan sulfate proteoglycan by mesangial and epithelial cells
Authors: Nicole F. van Det, Jacob van den Born, Jouke T. Tamsma, Nicole A.M. Verhagen, Jo H.M. Berden, Jan A. Bruijn, Mohamed R. Daha, Fokko J. van der Woude
Journal: Kidney International (1996)
Swimming reduces the severity of atherosclerosis in apolipoprotein E deficient mice by antioxidant effects
Authors: T OKABE, K SHIMADA, M HATTORI, T MURAYAMA, M YOKODE, T KITA, C KISHIMOTO
Journal: Cardiovascular Research (2007)

It was shown that aerobic exercise training may protect against the development of atherosclerosis. However, the precise mechanisms are still unknown. We assessed the hypothesis that exercise training reduced the severity of experimental atherosclerosis in apolipoprotein (apo) E-deficient mice by antioxidant effects.Exercise training (45 min swimming, 3 times/week) was conducted on apo E-deficient mice fed a high fat diet. Over 8 and 16 weeks on alternate days, mice were treated with and without exercise, and additional exercise-treated mice were orally given 25 mg/kg/day of NG-nitro-L-arginine methylester (L-NAME), an inhibitor of nitric oxide synthase (NOS). In addition, the effect of L-arginine against L-NAME was also tested.Fatty streak formation at 8 weeks and fibrofatty plaques at 16 weeks developed in apo E-deficient mice fed a high fat diet, and were suppressed in mice treated with swimming for 8 and 16 weeks. In contrast, atherosclerotic lesions were not ameliorated in mice treated with exercise training associated with oral L-NAME. However, in mice treated with swimming associated with L-NAME and L-arginine, the atherosclerotic lesions were reduced. Immunohistochemical analysis revealed that macrophage and CD4+ cell accumulation in the fatty streak lesions was suppressed in mice treated with exercise, but not in those treated with exercise associated with L-NAME administration. The severity of atherosclerotic lesions was inversely correlated with the endothelial NOS expression and the expression of an endogenous antioxidant protein, thioredoxin. Namely, the expression of thioredoxin in mice treated with exercise was suppressed compared with mice without exercise. Plasma thiobarbituric acid-reactive substance levels were significantly lower in groups with exercise than in those without exercise or with exercise associated with L-NAME administration, suggesting exercise-induced less lipid peroxidation. Differences in lesion area did not correlate with any significant alterations in serum lipid levels. The exercise load used in the current study did not affect energy metabolism efficacies in the hearts.Exercise training, in which the load did not affect energy metabolism efficacy of the heart, suppressed atherosclerosis by antioxidant effects via the vascular NO system.
Incidence and Prognosis of Transient Neurological Attacks
Authors: Michiel J. Bos, Marie Josee E. van Rijn, Jacqueline C. M. Witteman, Albert Hofman, Peter J. Koudstaal, Monique M. B. Breteler
Journal: JAMA (2007)

Transient neurological attacks (TNAs) are attacks with temporary (<24 hours) neurological symptoms. These symptoms can be focal, nonfocal, or a mixture of both. The prognostic significance of TNAs with focal symptoms (better known as transient ischemic attacks [TIAs]) is well understood. Conversely, hardly anything is known about the prognostic significance of TNAs with nonfocal or mixed symptoms.To study the incidence and prognosis of focal TNAs (or TIAs), nonfocal TNAs, and mixed TNAs.The study population comprised 6062 community-dwelling Rotterdam Study participants who were aged 55 years or older and free from stroke, myocardial infarction, and dementia at baseline (1990-1993). They were followed up for events until January 1, 2005. We analyzed the associations between incident TNAs and subsequent adverse events with age- and sex-adjusted Cox regression models.Stroke, ischemic heart disease, or dementia.During 60 535 person-years, 548 participants developed TNA (282 focal, 228 nonfocal, and 38 mixed). The incidence rate per 1000 person-years was 4.7 (95% confidence interval [CI], 4.1-5.2) for focal TNA, 3.8 (95% CI, 3.3-4.3) for nonfocal TNA, and 0.6 (95% CI, 0.4-0.9) for mixed TNA. Participants with focal TNA were at higher risk of subsequent stroke than participants without TNA (n = 46 vs 540; hazard ratio [HR], 2.14; 95% confidence interval [CI]; 1.57-2.91) but had an equal risk of ischemic heart disease and dementia. Nonfocal TNA patients were at higher risk of stroke (27 vs 540; HR, 1.56; 95% CI, 1.08-2.28) and dementia (30 vs 552; HR, 1.59; 95% CI, 1.11-2.26) than participants without TNA. Mixed TNA patients were at higher risk of stroke (6 vs 540; HR, 2.48; 95% CI, 1.11-5.56), ischemic heart disease (8 vs 779; HR, 2.26; 95% CI, 1.07-4.78), vascular death (8 vs 594; HR, 2.54; 95% CI, 1.31-4.91), and dementia (7 vs 552; HR, 3.46; 95% CI, 1.72-6.98) than participants without TNA.Patients who experience nonfocal TNAs, and especially those with mixed TNAs, have a higher risk of major vascular diseases and dementia than persons without TNA.
Hot Nose after 1-131 Sodium Iodide Thyroablation Therapy
Authors: HEE-MYUNG PARK, H N WELLMAN
Journal: Clinical Nuclear Medicine (1992)

A 41-year-old man presented with a cystic mass. Ultrasound of the left lower neck revealed a papillary carcinoma of the thyroid. He underwent a total thyroidectomy and modified left neck dissection. He received 98.4 mCi of 1-131 as sodium iodide for ablation of the residual thyroid tissue, which was documented on a diagnostic survey scan using 0.3 mCi of 1-131. A therapy scan obtained 24 hours later showed a hot nose caused by the radioactive mucus in his nose. This was confirmed by a repeat image obtained after he blew his nose.
Common genetic variants regulating ADD3 gene expression alter biliary atresia risk
Authors: Guo Cheng, Clara Sze-Man Tang, Emily Hoi-Man Wong, William Wai-Chun Cheng, Man-Ting So, Xiaoping Miao, Ruizhong Zhang, Long Cui, Xuelai Liu, Elly Sau-Wai Ngan, Vincent Chi-Hang Lui, Patrick Ho-Yu Chung, Ivy Hau-Yee Chan, Juncheng Liu, Wei Zhong, Huimin Xia, Jiakang Yu, Xiu Qiu, Xuan-Zhao Wu, Bin Wang, Xiao Dong, Jinfa Tou, Liuming Huang, Bin Yi, Hongxia Ren, Edwin Kin-Wai Chan, Kenny Ye, Paul F. O′Reilly, Kenneth Kak-Yuen Wong, Pak-Chung Sham, Stacey S. Cherny, Paul Kwong-Hang Tam, Maria-Mercè Garcia-Barceló
Journal: Journal of Hepatology (2013)
Distinct Effects of Leukocyte and Cardiac Phosphoinositide 3-Kinase γ Activity in Pressure Overload–Induced Cardiac Failure
Authors: Federico Damilano, Irene Franco, Cinzia Perrino, Katrin Schaefer, Ornella Azzolino, Daniela Carnevale, Giuseppe Cifelli, Pierluigi Carullo, Riccardo Ragona, Alessandra Ghigo, Alessia Perino, Giuseppe Lembo, Emilio Hirsch
Journal: Circulation (2011)

Signaling from phosphoinositide 3-kinase γ (PI3Kγ) is crucial for leukocyte recruitment and inflammation but also contributes to cardiac maladaptive remodeling. To better understand the translational potential of these findings, this study investigates the role of PI3Kγ activity in pressure overload-induced heart failure, addressing the distinct contributions of bone marrow-derived and cardiac cells.After transverse aortic constriction, mice knock-in for a catalytically inactive PI3Kγ (PI3Kγ KD) showed reduced fibrosis and normalized cardiac function up to 16 weeks. Accordingly, treatment with a selective PI3Kγ inhibitor prevented transverse aortic constriction-induced fibrosis. To define the cell types involved in this protection, bone marrow chimeras, lacking kinase activity in the immune system or the heart, were studied after transverse aortic constriction. Bone marrow-derived cells from PI3Kγ KD mice were not recruited to wild-type hearts, thus preventing fibrosis and preserving diastolic function. After prolonged pressure overload, chimeras with PI3Kγ KD bone marrow-derived cells showed slower development of left ventricular dilation and higher fractional shortening than controls. Conversely, in the presence of a wild-type immune system, KD hearts displayed bone marrow-derived cell infiltration and fibrosis at early stages but reduced left ventricular dilation and preserved contractile function at later time points.Together, these data demonstrate that, in response to transverse aortic constriction, PI3Kγ contributes to maladaptive remodeling at multiple levels by modulating both cardiac and immune cell functions.
Neostigmine reversal doesn't improve postoperative respiratory safety
Authors: M. J. Meyer, B. T. Bateman, T. Kurth, M. Eikermann
Journal: BMJ (2013)

We recently reported an association between the intraoperative administration of intermediate acting non-depolarizing neuromuscular blocking agents and severe postoperative respiratory complications (oxygen desaturation, reintubation, and unplanned admission to intensive care).1 In secondary analyses we examined standard techniques to abate the effects of postoperative residual neuromuscular blockade—neostigmine administration and neuromuscular transmission monitoring. We found that their use did not reduce the risk of respiratory outcomes.

In the main and secondary analyses we used propensity score matching to control for confounding factors associated with the use of neuromuscular blocking agents. However, our methods did not account for confounding factors related to the use of neostigmine.

We conducted additional analyses to evaluate whether these recommended strategies to reduce the risk of residual neuromuscular blockade help …
Dermatitis Herpetiformis
Authors: John B. Kalis
Journal: JAMA (1983)

The early 19th century marked the birth of dermatology as a specialty in Europe. Postgraduate training in dermatology was available only in the European capitals. When Louis Duhring returned to his native Philadelphia after two years of specialty training in London, Paris, and Vienna, he established a private practice and a public dispensary devoted to the diagnosis and treatment of skin disorders. Duhring's keen clinical sense, pragmatic approach, clarity of prose, and thorough knowledge of the literature soon gained him local recognition. In 1873, he was appointed as a lecturer on skin disorders at the University of Pennsylvania, Philadelphia. In 1875, at the age of 35 years, he was appointed the first professor of dermatology at the University of Pennsylvania, a post he held for 35 years. His excellent textbooks, widely read here and in Europe, and his establishment of dermatitis herpetiformis (DH) as a distinct disease entity soon led
The efficacy and tolerability of doxycycline and mefloquine in malaria prophylaxis of the ISAF troops in Afghanistan
Authors: Alper Sonmez, Ali Harlak, Selim Kilic, Zülfikar Polat, Levent Hayat, Ozcan Keskin, Teoman Dogru, M. Ilker Yilmaz, Cengiz Han Acikel, Ismail H. Kocar
Journal: Journal of Infection (2005)
Genome-wide analysis of functional sirtuin chromatin targets in yeast
Authors: Mingguang Li, Veena Valsakumar, Kunal Poorey, Stefan Bekiranov, Jeffrey S Smith
Journal: Genome biology (2013)

The sirtuins are a conserved family of NAD⁺-dependent histone/protein deacetylases that regulate numerous cellular processes, including heterochromatin formation and transcription. Multiple sirtuins are encoded by each eukaryotic genome, raising the possibility of cooperativity or functional overlap. The scope and variety of chromatin binding sites of the sirtuins in any specific organism remain unclear.Here we utilize the ChIP-seq technique to identify and functionally characterize the genome-wide targets of the sirtuins, Sir2, Hst1 to Hst4, and the DNA binding partner of Hst1, Sum 1, in Saccharomyces cerevisiae. Unexpectedly, Sir2, Hst1 and Sum1, but not the other sirtuins, exhibit co-enrichment at several classes of chromatin targets. These include telomeric repeat clusters, tRNA genes, and surprisingly, the open reading frames (ORFs) of multiple highly expressed RNA polymerase II-transcribed genes that function in processes such as fermentation, glycolysis, and translation. Repression of these target genes during the diauxic shift is specifically dependent on Sir2/Hst1/Sum1 binding to the ORF and sufficiently high intracellular NAD⁺ concentrations. Sir2 recruitment to the ORFs is independent of the canonical SIR complex and surprisingly requires Sum1. The shared Sir2/Hst1/Sum1 targets also significantly overlap with condensin and cohesin binding sites, where Sir2, Hst1, and Sum1 were found to be important for condensin and cohesin deposition, suggesting a possible mechanistic link between metabolism and chromatin architecture during the diauxic shift.This study demonstrates the existence of overlap in sirtuin function, and advances our understanding of conserved sirtuin-regulated functions, including the regulation of glycolytic gene expression and condensin loading.
Diligentiae Defensio Fortissima
Authors: Edward K. Markell
Journal: JAMA (1964)

<h3>To the Editor:—</h3> In their recent discussion of schistosomiasis in American tourists (<i>JAMA</i><b>186</b>:453 [Nov 2] 1963), Drs. Most and Levine quote Professor Brian Maegraith, whose lead article in the Feb 23 issue of<i>The Lancet</i>(<b>1</b>:401, 1963) was entitled "Unde Venis?" They politely refrain from calling attention to the fact that Professor Maegraith's translation of "Unde Venis?" was faulty. In both papers, the translation is given as "Where have you been?" whereas, if my memory serves me right, it should be "Whence comest thou?" or, less elegantly perhaps, "Where do you come from?" This is not a world-shaking matter, and Drs. Maegraith, Most, and Levine have rendered a real service to the profession by emphasizing the importance of a geographical history. However, looseness in translation weakens the purpose when Latin is relied upon for a precise transmission of ideas.
Mice Lacking Inducible Nitric Oxide Synthase Have Improved Left Ventricular Contractile Function and Reduced Apoptotic Cell Death Late After Myocardial Infarction
Authors: Flora Sam, Douglas B. Sawyer, Zhonglin Xie, Donny L.F. Chang, Soeun Ngoy, Daniel A. Brenner, Deborah A. Siwik, Krishna Singh, Carl S. Apstein, Wilson S. Colucci
Journal: Circulation Research (2001)

Nitric oxide produced by inducible nitric oxide synthase (NOS2) has been implicated in the pathophysiology of chronic myocardial remodeling and failure. We tested the role of NOS2 in left ventricular (LV) remodeling early (1 month) and late (4 months) after myocardial infarction (MI) in mice lacking NOS2. MI size measured 7 days, 1 month, and 4 months after MI was the same in NOS2 knockout (KO) and wild-type (WT) mice. The LV end-diastolic pressure-volume relationship measured by the isovolumic Langendorff technique showed a progressive rightward shift from 1 to 4 months after MI in WT mice. LV developed pressure measured over a range of LV volumes was reduced at 1 and 4 months after MI in WT mice (P<0.05 and P<0.01 versus shams, respectively). In KO mice, the rightward shift was similar to that in WT mice at 1 and 4 months after MI, as was peak LV developed pressure at 1 month after MI. In contrast, at 4 months after MI, peak LV developed pressure in KO mice was higher than in WT mice (P<0.05 versus WT) and similar to that in sham-operated mice. At 1 month after MI, the frequency of terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive myocytes in the remote myocardium was increased to a similar extent in WT and KO mice. At 4 months after MI, the frequency of apoptotic myocytes was increased in WT mice but not in KO mice (P<0.05 versus WT). Improved contractile function and reduced apoptosis were associated with reduced mortality rate in KO mice at 4 months after MI. Thus, NOS2 does not play an important role in determining infarct size or early LV remodeling during the first month after MI. In contrast, during late (ie, 4 months after MI) remodeling, NOS2 in remote myocardium contributes to decreased contractile function, increased myocyte apoptosis in remote myocardium, and reduced survival.
Multicentre, phase II trial on the safety and efficacy of topical tacrolimus ointment for the treatment of lichen sclerosus
Authors: U.R. Hengge, W. Krause, H. Hofmann, R. Stadler, G. Gross, M. Meurer, T. Brinkmeier, P. Frosch, I. Moll, P. Fritsch, K. Müller, N. Meykadeh, A. Marini, T. Ruzicka, H. Gollnick
Journal: British Journal of Dermatology (2006)

Lichen sclerosus is a chronic inflammatory autoimmune disease causing significant sclerosis, atrophy and pruritus. Treatment remains unsatisfactory, with potent corticosteroids being the most effective therapy.To conduct a multicentre, phase II trial to assess the safety and efficacy of tacrolimus ointment 0.1% for the treatment of lichen sclerosus with a follow-up period of 18 months at 10 university and teaching hospitals in Germany and Austria.Eighty-four patients (49 women, 32 men and three girls) aged between 5 and 85 years with long-standing, active lichen sclerosus (79 with anogenital and five with extragenital localization) were treated with topical tacrolimus ointment 0.1% twice daily for 16 weeks. Computerized analysis of the lesional area was performed. The primary endpoint was clearance of active lichen sclerosus. Secondary endpoints were time to optimal response, reduction of sclerosis and duration of remission.The primary endpoint (clearance of active lichen sclerosus) was reached by 43% of patients at 24 weeks of treatment. Partial resolution was reached in 34% of patients. Maximal effects occurred between week 10 and 24 of therapy. Treatment led to a significant reduction of the total lesional area (P < 0.01) and to a significant decline in the total symptom score (P < 0.005). Symptoms (e.g. itching) and findings (erythema, erosions and induration) showed significant improvement. No serious adverse events were observed. There were three (9%) recurrences during the follow-up period.Topical tacrolimus ointment 0.1% was safe and effective for the treatment of long-standing active lichen sclerosus.