tbuckley/cabot-search huggingface dataset:
Alcohol and Postmenopausal Breast Cancer Risk Defined by Estrogen and Progesterone Receptor Status: A Prospective Cohort Study
Authors: Reiko Suzuki, Weimin Ye, Tove Rylander-Rudqvist, Shigehira Saji, Graham A. Colditz, Alicja Wolk
Journal: JNCI Journal of the National Cancer Institute (2005)

Background: Alcohol intake has been reported to be positively associated with an increased risk of postmenopausal breast cancer; however, the association with the estrogen receptor (ER) and progesterone receptor (PR) status of the breast tumors remains unclear. Methods: Self-reported data on alcohol consumption were collected in 1987 and 1997 from 51 847 postmenopausal women in the population-based Swedish Mammography Cohort. Through June 30, 2004, 1188 invasive breast cancer case patients with known ER and PR status were identified during an average 8.3-year follow-up. We used Cox proportional hazards models to estimate multivariable relative risks (RRs) of breast cancer, adjusting for age; family history of breast cancer; body mass index; height; parity; age at menarche, first birth, and menopause; education level; use of postmenopausal hormones; and diet. Heterogeneity among groups was evaluated using the Wald test. All statistical tests were two-sided. Results : Alcohol consumption was associated with an increased risk for the development of ER-positive (+) tumors, irrespective of PR status (highest intake [≥10 g of alcohol per day] versus nondrinkers, multivariable RR = 1.35, 95% confidence interval [CI] = 1.02 to 1.80; Ptrend <.049 for ER+PR+ tumors; and RR = 2.36, 95% CI = 1.56 to 3.56; Ptrend <.001 for ER+PR− tumors). The absolute rate of ER+ breast cancer (standardized to the age distribution of person-years experienced by all study participants using 5-year age categories) was 232 per 100 000 person-years among women in the highest category of alcohol intake, and 158 per 100 000 person-years among nondrinkers. No association was observed between alcohol intake and the risk of developing ER− tumors. Furthermore, we observed a statistically significant interaction between alcohol intake and the use of postmenopausal hormones on the risk for ER+PR+ tumors ( Pinteraction = .039). Conclusion : The observed association between risk of developing postmenopausal ER+ breast cancer and alcohol drinking, especially among those women who use postmenopausal hormones, may be important, because the majority of breast tumors among postmenopausal women overexpress ER.
Immunity to Influenza. Preventing Infection and Regulating Disease
Authors: E. Kaitlynn Allen, Paul G. Thomas
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Although mortality is less, two recent reports indicate that contemporary characterization of children with sepsis may be insufficient (11,12).In one study, protocolized fluid boluses such as those commonly recommended in the developed world increased mortality compared with usual care by local practitioners (11).In the other study, protocolized fluid regimens appeared to increase mortality in children with concomitant respiratory failure (12).The reasons for these unfortunate outcomes are not understood, but it is precisely that knowledge gap (and its consequences) that should direct us away from consensus-type definitions of fatal illness and point us instead toward placing our patients on the potentially firmer footing of biologic insight.In summary, the big lesson from the paper by Wong and colleagues is that biologic insights into how (and who) septic shock can kill might soon be applied to the advantage of individual patients (1).In an age of consensus, guidelines, and big data, it is easy to forget that the biology of the individual patient matters; important work such as this reminds us that in pediatric septic shock, it almost certainly does.
NEUROPSYCHIATRIC CONSEQUENCES OF STROKE
Authors: Robert G. Robinson, MD
Journal: Annual Review of Medicine (1997)

▪ Abstract Numerous emotional and behavioral disorders occur following cerebrovascular lesions. Depression is the most common of these, affecting up to 40% of patients. Clinical correlates of post-stroke depression include severity of physical and cognitive impairment as well as location of brain injury. Perhaps the most compelling reason to identify post-stroke depression, however, is its substantial impact on recovery in activities of daily living, cognitive function, and survival. Antidepressant medication has been shown to effectively treat depression, although its administration may require careful clinical monitoring. Other post-stroke emotional/behavioral disorders include mania, bipolar disorder, anxiety disorder, apathy, and pathological crying. Controlled studies have not documented the effect of these disorders on long-term recovery, but the potential impact of syndromes such as mania and apathy on rehabilitation efforts or pathological crying on social functioning are evident. With the exception of pathological crying, which has been shown to respond to antidepressant drug therapy, the other post-stroke emotional/behavioral disorders need to be evaluated in controlled treatment trials for response to therapy.
Partial deficiency of protein 4.1 in hereditary elliptocytosis
Authors: S. Lambert, S. Zail
Journal: American Journal of Hematology (1987)

Abstract Protein 4.1, an important component of the red cell membrane skeleton, was quantitated relative to protein 3 after sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS‐PAGE) of membranes isolated from red cells of members of 14 kindreds with hereditary elliptocytosis (HE) who reside in South Africa. A partial deficiency of protein 4.1 (mean 30% reduction) was inherited in autosomal dominant fashion in five white kindreds giving a frequency of 0.36 of HE families studied. Immunoblots of membrane proteins separated by SDS‐PAGE and probed with a monoclonal antibody to protein 4.1 did not reveal any proteolytic fragments in the 4.1‐deficient subjects that could account for the reduction of this protein. These studies draw attention to the relatively high frequency of this condition as a cause of HE in white subjects in this country.
Assessment of lung function in pre-school children with cystic fibrosis by nitrogen washout
Authors: Jacquelyn Zirbes, Dario Prais, Colleen Dunn, Carlos Milla
Journal: European Respiratory Journal (2012)

Pulmonary function in young children can identify the early manifestations of diseases like cystic fibrosis (CF) and prompt to early intervention. We evaluated in pre-school age children the performance of ventilatory indices obtained from N2 washout (FRC, LCI, Scond, Sacin) as to their feasibility and ability to detect differences between disease and control groups. N2 washout was performed with a novel system that utilizes an ultrasonic flow sensor as well as O2 and CO2 sensors (Exhalyzer, EcoMedics AG). N2 washout was performed during tidal breathing and using 100% Oxygen. Three maneuvers free of artifact were obtained whenever possible and allowing for 2-times the washout time to lapse between maneuvers. This was followed by spirometry and aiming to obtain at least 3 valid flow volume loops. Study groups included children ages 3 to 6 year old with CF (n=20) and asthma (AS, n=15), as well as a group of healthy controls (HC, free from history of respiratory disease or cigarette smoke exposure). Children were studied at a period of freedom from any acute symptomatology. Research quality Nitrogen washout could be completed in 90% of CF, 75% of AS and 70% of HC. FRC was comparable between the groups (p=0.1). The LCI from the N2 washout was elevated in CF with a mean of 10.4 ± 2.6, as well as Scond 0.05 ± 0.03 and Sacin 0.5 ± 0.5, which was statistically significant from the other 2 groups (p
The regulation of toll-like receptor 2 by miR-143 suppresses the invasion and migration of a subset of human colorectal carcinoma cells
Authors: Haiyan Guo, Ying Chen, Xiaobo Hu, Guanxiang Qian, Shengfang Ge, Jianjun Zhang
Journal: Molecular Cancer (2013)

The Toll-like receptor 2 (TLR2)-driven tissue response may promote neoangiogenesis and tumour growth by mechanisms that are poorly understood. We investigated the expression levels of TLR2 and associated-miRNAs in colorectal carcinoma (CRC) tissues and cell lines using real-time PCR, northern blotting and western blotting. Survival curver was generated by Log-Rank test and the role of TLR2 signalling in tumour invasion and migration was determined by transwell analysis kits. We observed that the tissues from CRC patients express relatively high levels of TLR2. Targeting TLR2 markedly reduces the invasion and migration of CRC cells. We also found that miR-143, a putative tumour suppressor that is down-regulated in CRC tissues, reduces the invasion and migration of CRC cells primarily via TLR2. Utilising a xenograft mouse model, we demonstrated that re-expression of miR-143 inhibits CRC cell colonisation in vivo. miR-143 blocks the TLR2 signalling pathway in human CRC cells. This knowledge may pave the way for new clinical applications utilising miR-143 mimics in the treatment of patients with CRC.
Protein Phosphatase-1α Regulates Centrosome Splitting through Nek2
Authors: Jun Mi, Changyue Guo, David L. Brautigan, James M. Larner
Journal: Cancer Research (2007)

Abstract ATM is a central mediator of the cellular response to the DNA damage produced by ionizing radiation. We recently showed that protein phosphatase 1 (PP1) is activated by ATM. Because Nek2 is activated by autophosphorylation, and because its dephosphorylation is catalyzed by PP1, we asked if the radiation damage signal to Nek2 was mediated by PP1. Overexpression of Nek2 induces premature centrosome splitting probably by phosphorylating centrosome cohesion proteins C-Nap1 and Rootletin. In this study, we show isoform specificity of PP1 binding and regulation of Nek2. Although both PP1α and PP1γ coimmunoprecipitated with Nek2, only PP1α regulated Nek2 function. Ionizing radiation inhibited Nek2 activity, and this response was dependent on ATM and on PP1 binding to Nek2 and coincident with Thr320 dephosphorylation of PP1. Radiation-induced inhibition of centrosome splitting was abrogated in cells expressing Nek2 mutated in the PP1-binding motif outside the kinase domain. Conversely, cells depleted of PP1α by small interfering RNA showed enhanced centrosome splitting and loss of radiation-induced inhibition of centrosome splitting. The identification of a PP1-specific isoform mediating a checkpoint response opens up the possibility of selectively targeting phosphatases as novel radiation sensitizers. [Cancer Res 2007;67(3):1082–9]
Different Versions of the Dayhoff Rate Matrix
Authors: Carolin Kosiol, Nick Goldman
Journal: Molecular Biology and Evolution (2004)

Many phylogenetic inference methods are based on Markov models of sequence evolution. These are usually expressed in terms of a matrix (Q) of instantaneous rates of change but some models of amino acid replacement, most notably the PAM model of Dayhoff and colleagues, were originally published only in terms of time-dependent probability matrices (P(t)). Previously published methods for deriving Q have used eigen-decomposition of an approximation to P(t). We show that the commonly used value of t is too large to ensure convergence of the estimates of elements of Q. We describe two simpler alternative methods for deriving Q from information such as that published by Dayhoff and colleagues. Neither of these methods requires approximation or eigen-decomposition. We identify the methods used to derive various different versions of the Dayhoff model in current software, perform a comparison of existing and new implementations, and, to facilitate agreement among scientists using supposedly identical models, recommend that one of the new methods be used as a standard.
FAMILIAL MAMMARY TUMORS IN THE RABBIT
Authors: Harry S. N. Greene
Journal: The Journal of Experimental Medicine (1940)

A series of experiments is described in which fragments derived from two mammary tumors of distinct types were transferred at different developmental stages to the anterior chamber of the eye of normal rabbits. It was found that the ability to survive and to grow progressively after transplantation was not immediately related to anaplastic cellular changes. On the other hand, there existed a definite correlation between the success of transplantation and the morphological relationship of tumor cells and the normal cells of the host. Transplantation to normal animals could not be effected during stages of local tissue invasion but was successfully performed as soon as the tumor cells manifested the ability to invade foreign tissues or to metastasize in the spontaneous host. It was concluded, therefore, that neither anaplasia nor local tissue invasion represented autonomy but, rather, stages in its development and that the final attainment of this condition was only evidenced by metastasis or by invasion in foreign tissues. The tumors were successfully transplanted to normal animals during this series of experiments and have been carried by serial transfer to the present time. The most outstanding feature in the transplantation of the papillary type tumor was the marked difference in susceptibility exhibited by the two sexes. The acinar type tumor was distinguished by high transplantability, an extremely rapid growth rate and early regression.
CHEMICAL INVESTIGATIONS ON THE ACTIVE PRINCIPLES OF THE PHENOMENON OF LOCAL SKIN REACTIVITY TO BACTERIAL FILTRATES
Authors: Gregory Shwartzman, Sam Morell, Harry Sobotka
Journal: The Journal of Experimental Medicine (1937)

A quantitative biological assay of the products obtained from the dialysis of B. typhosus, meningococcus, and B. coli culture filtrates has been undertaken. It was found that the active principles of the phenomenon of local skin reactivity to bacterial filtrates were retained by cellophane membranes. An appreciable purification was thus effected, amounting, on the average, to about a threefold increase in reacting potency per milligram of dry weight and of nitrogen. Attempts to purify bacterial filtrates by the fractional precipitation of their concentrates with dilute alkali, acid, and alcohol were unsuccessful.
Cystic fibrosis patients and families support cross-infection measures
Authors: Amanda L Griffiths, David Stuart Armstrong, Rosemary Carzino, Philip Robinson
Journal: European Respiratory Journal (2004)

A clonal strain of <i>Pseudomonas aeruginosa</i> (PA) was isolated in 1999 at the Royal Children9s Hospital, Melbourne, Australia, after five unrelated children with cystic fibrosis (CF) died from severe lung disease aged &lt;5 yrs. Subsequently, more than half of the patients in the clinic with PA were found to harbour this strain, and segregation measures were instituted at the hospital to prevent further spread. The aim of this study was to assess CF parent and patient responses to the segregation measures to determine overall support. A questionnaire was sent out to the families of 291 CF children treated at the centre. A 65% response rate was obtained. The majority of parents (85%) and patients ≥12 yrs old (63%) were positive about the segregation measures instituted. A total of 11% of parents and 25% of patients were unsure, and 4% of parents and 12% of children gave negative responses. Those who were not happy listed reasons such as concerns about the emotional impact of not socialising with other CF children, inconclusive evidence about person–person spread of infection and feelings of alienation created in the clinic by the separation. In conclusion, the majority of responding cystic fibrosis patients and their families understand and are supportive of infection control measures instituted at the Royal Children9s Hospital, Melbourne, Australia.
Surgical Diseases of the Pancreas
Authors: C D JOHNSON
Journal: Gut (1999)

Surgical Diseases of the Pancreas . Howard J, Idezuki Y, Ihse I, Prinz R. (Pp 868; illustrated; £115.00.) Williams and Wilkins, 1998. ISBN 0-683-18019-3.

This book is a delight to own. It has already become my first choice for seeking out detailed information about obscure topics in pancreatic disease. The scope is defined by its title, and in a field where there are two three other similar volumes, this book stands …
Infiltrating Macrophages Promote Prostate Tumorigenesis via Modulating Androgen Receptor-Mediated CCL4–STAT3 Signaling
Authors: Lei-Ya Fang, Kouji Izumi, Kuo-Pao Lai, Liang Liang, Lei Li, Hiroshi Miyamoto, Wen-Jye Lin, Chawnshang Chang
Journal: Cancer Research (2013)

Abstract Infiltrating macrophages are a key component of inflammation during tumorigenesis, but the direct evidence of such linkage remains unclear. We report here that persistent coculturing of immortalized prostate epithelial cells with macrophages, without adding any carcinogens, induces prostate tumorigenesis and that induction involves the alteration of signaling of macrophage androgen receptor (AR)-inflammatory chemokine CCL4–STAT3 activation as well as epithelial-to-mesenchymal transition and downregulation of p53/PTEN tumor suppressors. In vivo studies further showed that PTEN+/− mice lacking macrophage AR developed far fewer prostatic intraepithelial neoplasia (PIN) lesions, supporting an in vivo role for macrophage AR during prostate tumorigenesis. CCL4-neutralizing antibody effectively blocked macrophage-induced prostate tumorigenic signaling and targeting AR via an AR-degradation enhancer, ASC-J9, reduced CCL4 expression, and xenografted tumor growth in vivo. Importantly, CCL4 upregulation was associated with increased Snail expression and downregulation of p53/PTEN in high-grade PIN and prostate cancer. Together, our results identify the AR-CCL4-STAT3 axis as key regulators during prostate tumor initiation and highlight the important roles of infiltrating macrophages and inflammatory cytokines for the prostate tumorigenesis. Cancer Res; 73(18); 5633–46. ©2013 AACR.
Effects of obstructive sleep apnoea on heart rhythm
Authors: Valentina A. Rossi, John R. Stradling, Malcolm Kohler
Journal: European Respiratory Journal (2012)

Symptomatic obstructive sleep apnoea (OSA) has been proven to be a risk factor for hypertension and vascular dysfunction, and has been proposed to be causally related with cardiac arrhythmias and sudden cardiac death. Searches of bibliographical databases revealed that several mechanisms seem to underpin the association between OSA and cardiac arrhythmias: intermittent hypoxia associated with autonomic nervous system activation and increased oxidative stress, which may lead to cardiac cellular damage and alteration in myocardial excitability; recurrent arousals, resulting in sympathetic activation and coronary vasoconstriction; and increased negative intrathoracic pressure which may mechanically stretch the myocardial walls and, thus, promote acute changes in myocardial excitability as well as structural remodelling of the myocardium. Findings from cross-sectional studies suggest a high prevalence of cardiac arrhythmias in patients with OSA and a high prevalence of OSA in those with cardiac arrhythmias. Preliminary evidence from uncontrolled interventional studies suggests that treatment of OSA may prevent cardiac arrhythmias. In conclusion, there is preliminary evidence that OSA is associated with the development of cardiac arrhythmias. Data from randomised controlled studies are needed to definitively clarify the role of OSA in arrhythmogenesis.
Humoral and cellular immune responses to gliadin in inhalant wheat allergy and in wheat-dependent, exercise-induced anaphylaxis
Authors: Maili Lehto, Kati Palosuo, Elina Varjonen, Marja-Leena Majuri, Ulpu Andersson, Timo Reunala, Harri Tapio Alenius
Journal: Journal of Allergy and Clinical Immunology (2002)
Ion Channels and Transporters in Cancer: Pathophysiology, Regulation, and Clinical Potential
Authors: Stine Falsig Pedersen, Christian Stock
Journal: Cancer Research (2013)

Abstract Over the last 15 years it has become increasingly clear that dysregulated expression, splicing, and/or function of ion channels and transporters (ICT) occur in all cancers. Being linked to the widely accepted hallmarks of cancer, ICTs represent novel therapeutic, diagnostic, and prognostic targets. To discuss the current status of the field, a colloquium on “Ion Transport and Cancer” was held, covering the roles of ICTs in cancer cell proliferation, apoptosis, motility, and invasion, and in both the generation of and the interaction of the cancer cells with the tumor environment. Additional sessions dealt with pancreatic ductal adenocarcinoma and transport protein–based therapeutic and diagnostic concepts. There was overall consensus that essential contributions of ICT dysregulation to the cancer process have been demonstrated. Future research should be directed toward further elucidating the mechanisms and developing therapeutic applications. Cancer Res; 73(6); 1658–61. ©2012 AACR.
Inhibition of Cardiac Delayed Rectifier K <sup>+</sup> Current by Overexpression of the Long-QT Syndrome HERG G628S Mutation in Transgenic Mice
Authors: Philip Babij, G. Roger Askew, Bart Nieuwenhuijsen, Chien-Min Su, Terry R. Bridal, Brian Jow, Thomas M. Argentieri, John Kulik, Louis J. DeGennaro, Walter Spinelli, Thomas J. Colatsky
Journal: Circulation Research (1998)

Mutations in the HERG gene are linked to the LQT2 form of the inherited long-QT syndrome. Transgenic mice were generated expressing high myocardial levels of a particularly severe form of LQT2-associated HERG mutation (G628S). Hearts from G628S mice appeared normal except for a modest enlargement seen only in females. Ventricular myocytes isolated from adult wild-type hearts consistently exhibited an inwardly rectifying E-4031-sensitive K+ current resembling the rapidly activating cardiac delayed rectifier K+ current (Ikr) in its time and voltage dependence; this current was not found in cells isolated from G628S mice. Action potential duration was significantly prolonged in single myocytes from G628S ventricle (cycle length=1 second, 26 degrees C) but not in recordings from intact ventricular strips studied at more physiological rates and temperature (200 to 400 bpm, 37 degrees C). ECG intervals, including QT duration, were unchanged, although minor aberrancies were noted in 20% (16/80) of the G628S mice studied, primarily involving the QRS complex and, more rarely, T-wave morphology. The aberrations were more commonly observed in females than males but could not be correlated with sex-based differences in action potential duration. These results establish the presence of IKr in the adult mouse ventricle and demonstrate the ability of the G628S mutation to exert a dominant negative effect on endogenous IKr in vivo, leading to the expected LQT2 phenotype of prolonged repolarization at the single cell level but not QT prolongation in the intact animal. The model may be useful in dissecting repolarization currents in the mouse heart and as a means of examining the mechanism(s) by which the G628S mutation exerts its dominant negative effect on native cardiac cells in vivo.