tbuckley/cabot-search huggingface dataset:
P3-07-13: Validation and Comparison of Models To Predict Nonsentinel Lymph Node Metastasis in Chinese Breast Cancer Patients with Positive Sentinel Lymph Nodes.
Authors: K Chen, W Jia, Y Zeng, M Fan, F Su, S Li
Journal: Cancer Research (2011)

Abstract Background: Several models for predicting the risk of nonsentinel lymph node (NSLN) metastasis in breast cancer patients with positive sentinel lymph nodes (SLNs) have been developed. Independent validation of these models in different populations is necessary before clinical application. This study aimed to validate and compare these models in Chinese patients. Patients and Methods: A total of 159 breast cancer patients with positive SLNs treated at our institution were included. Chi-squared tests, RP-ROC, CART and multivariate logistic regression were used to analyze the risk factors for NSLN involvement in our population. ROC curves, calibration plots and false-negative (FN) rates were evaluated for 11 reported models. The threshold of each model for classifying patients into the low-risk group was adjusted to render the FN rate close to 10%. Results: In total, 81 (50.9%) patients had at least one NSLN involvement. Univariate and multivariate analyses revealed that the number of negative SLNs (P&amp;lt;0.01, HR=0.63) and the metastasis size of the positive SLNs (P&amp;lt;0.01, HR=1.15) independently predicted the NSLN status in our population. The Cambridge and Mou models outperformed the others, both with AUCs of 0.73. The other models performed as follows: the Mayo, Tenon, MDA, MSKCC, Ljubljana, SNUH and Louisville models had AUCs of 0.68, 0.66, 0.66, 0.64, 0.62, 0.61 and 0.60, respectively. The Stanford and Saidi models did not present any discriminative capabilities, with AUCs of 0.54 and 0.50, respectively. The Cambridge, MSKCC and Mayo models were well calibrated. The Ljubljana model did not calibrate well. With adjusted thresholds, the Mayo model outperformed the others by classifying the highest proportion of patients (20%) into the low-risk group. The Cambridge, Mou and MDA models defined 17.0%, 14.5% and 15.1% of patients as low-risk, respectively. Conclusion: The Cambridge and Mou models performed well in Chinese patients. ROC curves, calibration plots and FN rates should be used together for the accurate evaluation of prediction models. The analysis of the clinicopathological features of the targeted population is critical for the selection of the most appropriate model. The models specifically designed for patients with micrometastases or macrometastases of SLNs are needed in the future. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-13.
'Funny' current: If heart rate slowing is not the best answer, what might be?
Authors: H. Gewirtz
Journal: Cardiovascular Research (2009)

DiFrancesco first described an ion current in the sinoatrial node (SAN) of the rabbit which was thought ‘funny’, as is unusual, since it was hyperpolarization-activated and carried by both sodium and potassium ions.1,2 Hence, its name I f. The current is active in diastole between roughly −50 and −20 mV when it shuts down and is followed by the activation of the T-channel calcium current, which continues the process of diastolic depolarization. Accordingly, I f contributes significantly to spontaneous pacemaker activity in the mammalian heart.1 The gene encoding the channel was first discovered in the mouse brain.3 Subsequently, in the cardiac tissue, four isoforms of the hyperpolarization-activated, cyclic nucleotide-gating channel protein (HCN 1,2,3,4) were identified.1,4 The channel's operating range and activity are sensitive to cAMP (second messenger role) and so autonomic tone, both sympathetic and parasympathetic.1 The distribution of isoforms in the rabbit heart also is variable, with HCN4 greater than HCN1 in SAN, whereas much lower levels of HCN2 are found in ventricular myocardium,5 but given the very large mass of myocytes vs. SAN tissue, HCN2 likely is the dominant isoform on a mass basis.5 Finally, the I f current is active at a threshold of −45 mV in the rabbit SAN but is only faint at hyperpolarization to −150 mV in rabbit myocytes.5 However, it is readily apparent at −100 mV in … 

*Corresponding author. Tel: +1 617 724 3650; fax: +1 617 724 3636/3600. E-mail address : hgewirtz{at}partners.org; gewirtz.henry{at}mgh.harvard.edu
Estimation of thyroxine and triiodothyronine distribution and of the conversion rate of thyroxine to triiodothyronine in man.
Authors: M Inada, K Kasagi, S Kurata, Y Kazama, H Takayama, K Torizuka, M Fukase, T Soma
Journal: Journal of Clinical Investigation (1975)

Studies on peripheral metabolism of simultaneously administered 125-I-labeled L-thyroxine ([125-I]T4) and 131-I labeled L-trilodothyronine ([131-I]T3) were performed in five normal subjects, in four patients with untreated hypothyroidism, and in 3 hypothyroid patients made euthyroid by the administration of T4. The fractional turnover rate (lambda 03) of thyroid hormones irreversibly leaving the site of degradation and the volumes of pool 1 (serum V1) of pool (interstitial fluid, V2), and of pool 3 (all tissues, V3)were obtained by using a three-compartment analysis. In addition to the turnover studies, the ratios for the in vivo T4 to T3 conversion were determined by paper chromatographic study in sera obtained 4, 7, and 10 daysafter the injection. The rate (K12) of the extrathyroidal conversion of T4 to T3 was also estimated by the compartment analysis. The T3 distribution volume (V3) of pool 3, in which T3 is utilized and degraded, was about 60% of totaldistribution volume (V=V1+V2+V3) in normal subjects, whereas only about 25% of the extrathyroidal T4 pool was in the intracellular compartment, indicating that T3 is predominantly an intracellular hormone..
Free Fatty Acid (FFA) and Hydroxy Carboxylic Acid (HCA) Receptors
Authors: Stefan Offermanns
Journal: The Annual Review of Pharmacology and Toxicology (2013)

Saturated and unsaturated free fatty acids (FFAs), as well as hydroxy carboxylic acids (HCAs) such as lactate and ketone bodies, are carriers of metabolic energy, precursors of biological mediators, and components of biological structures. However, they are also able to exert cellular effects through G protein–coupled receptors named FFA1–FFA4 and HCA1–HCA3. Work during the past decade has shown that these receptors are widely expressed in the human body and regulate the metabolic, endocrine, immune and other systems to maintain homeostasis under changing dietary conditions. The development of genetic mouse models and the generation of synthetic ligands of individual FFA and HCA receptors have been instrumental in identifying cellular and biological functions of these receptors. These studies have produced strong evidence that several FFA and HCA receptors can be targets for the prevention and treatment of various diseases, including type 2 diabetes mellitus, obesity, and inflammation.
Expression of p160erbB-3 and p185erbB-2 in Prostatic Intraepithelial Neoplasia and Prostatic Adenocarcinoma
Authors: R. B. Myers, S. Srivastava, D. K. Oelschlager, W. E. Grizzle
Journal: JNCI Journal of the National Cancer Institute (1994)

Background : Although prostatic adenocarcinoma is the most frequent malignancy among American men, little is known concerning the roles of growth factors, growth factor receptors, or proto-oncogene products in the development and progression of this malignancy. Purpose : We examined and compared the expression and cellular distribution of the erbB-3 protein (p160 erbB-3 ) and the erbB-2 protein (p185 erbB-2 ) in various stages of development and progression of prostatic adenocarcinoma. Methods : Immunoperoxidase staining was used to determine the expression of p160 erbB-3 and p185 erbB-2 in benign prostatic epithelium, prostatic intraepithelial neoplasia, localized adenocarcinomas (pathologic stages B and C) as well as matching primary and lymph node lesions from patients with stage D adenocarcinoma. In order to test antibody specificity, we used Western blot analysis to examine the expression of p160 erbB-3 and p185 erbB-2 in selected prostatic adenocarcinomas. Results : Within benign glands, immunostaining for p160 erbB-3 or p185 erbB-2 was strongest in the basal cells and was typically absent or weak in the luminal (secretory) cells. Expression of both proteins within luminal cells was localized to cell membranes. We examined the expression of p160 erbB-3 and p185 erbB-2 in the prostatic intraepithelial neoplastic lesions of 22 radical prostatectomy specimens. Like benign glands, the basal cells of these neoplastic lesions typically demonstrated strong to moderate immunostaining when stained with either antibody. In contrast to benign glands, moderate to strong immunostaining for p160 erbB-3 and p185 erbB-2 was frequently observed within the cytoplasm and cell membranes of the prostatic intraepithelial neoplastic luminal cells. p160 erbB-3 and p185 erbB-2 were detected within the malignant cells in 28 and 29 of 29 localized adenocarcinomas, respectively. Immunostaining with either antibody was typically moderate to strong in the malignant cells. Both proteins were expressed on the cellular membranes as well as in the cytoplasm of malignant cells. Immunostaining for p160 erbB-3 was detected in the matching primary and metastatic lesions (lymph nodes) in 10 of 11 patients with stage D adenocarcinoma. Immunostaining for p185 erbB-2 was detected in matching primary and metastatic lesions (lymph nodes) obtained from 16 patients with stage D adenocarcinoma. Western blot analysis confirmed the specificity of the antibodies. Conclusions : These results suggest that increased expression and changes in the subcellular distribution of both p160 erbB-3 and p185 erbB-2 represent early events in the development and progression of prostatic adenocarcinomas. The high expression and distribution of both p160 erbB-3 and p185 erbB-2 are retained both in advanced-stage primary and metastatic tumors.
Production, degradation, and circulating levels of 1,25-dihydroxyvitamin D in health and in chronic glucocorticoid excess.
Authors: E Seeman, R Kumar, G G Hunder, M Scott, H Heath, B L Riggs
Journal: Journal of Clinical Investigation (1980)

The decreased intestinal absorption of calcium and accelerated bone loss associated with chronic glucocorticoid excess may be mediated by changes in vitamin D metabolism, leading to decreased availability of circulating 1,25-dihydroxyvitamin D. This hypothesis was examined in 14 patients with either endogenous or exogenous glucocorticoid excess. Analysis of paired serum samples (mean +/- SE) in 13 patients during euglucocorticoidism and during hyperglucocorticoidism showed that glucocorticoid excess resulted in small decreases of plasma 25-hydroxy-vitamin D concentrations (22 +/- 2- 18 +/- 2 ng/ml; P < 0.05) but no significant changes in plasma 1,25-dihydroxyvitamin D (32 +/- 8- 23 +/- 6 pg/ml) or serum immunoreactive parathyroid hormone (21 +/- 2- 18 +/- 2 muleq/ml). Additionally, we studied plasma kinetics of [3H]1,25-dihydroxyvitamin D3 after intravenous bolus administration in 10 hyperglucocorticoid patients and in 14 normal controls. Assessment with a three-compartment model showed no significant abnormalities in production rates (hyperglucocorticoid patients 1.2 +/- 0.3 micrograms/d, controls 1.5 +/- 0.2 micrograms/d) or metabolic clearance rates (hyperglucocorticoid patients, 18 +/- 2%; controls, 14 +/- 2%) or feces (hyperglucocorticoid patients, 60 +/- 9%, controls, 54 +/- 6%). We conclude that glucocorticoid excess does not effect plasma levels, production, or degradation of 1,25(OH)2D in humans. Thus, other mechanisms must be postulated to explain satisfactorily the abnormalities of bone structure and intestinal calcium absorption that may occur after chronic glucocorticoid therapy.
Patency of the ductus arteriosus after balloon dilatation: an experimental study.
Authors: G Lund, A Cragg, J Rysavy, F Castaneda, E Salomonowitz, Z Vlodaver, W Casteneda-Zuniga, K Amplatz
Journal: Circulation (1983)

Balloon dilatation of the ductus arteriosus was carried out in vivo in newborn pigs and on postmortem specimens from humans and piglets. The ductus was functionally closed in all newborn animals but patency resulted in all animals after balloon dilatation. Left-to-right shunts of 50% to 70% were found with anatomic lumen sizes of 3 to 5 mm. Patency was demonstrated up to 6 weeks after dilatation. Histologic examination showed splitting of the internal elastic layer and media, areas of hemorrhage confined to the media, and preservation of the adventitia. Mediastinal hemorrhage did not occur. This new technique is useful as an animal model of patent ductus arteriosus and could theoretically be used for palliative treatment of ductus-dependent congenital heart disease.
Effect of Histamine and of the Anaphylactic Reaction on Isolated Guinea Pig Atria
Authors: MARIO PENNA, ALEJANDRO ILLANES, MARIO UBILLA, SERGIO MUJICA
Journal: Circulation Research (1959)

Addition of specific antigen to the isolated atria of sensitized guinea pigs and of histamine to those of nonsensitized animals resulted in an increase of both frequency and amplitude of contraction and in the appearance of rhythmic activity in the isolated left atrium. On a quantitative basis the anaphylactic response looks like the effects of histamine in concentrations between 10 -3 and 10 -2 mM/L. No qualitative differences between the effects of histamine and those of the anaphylactic reaction were observed. Since isolated atria thus are seen to participate in tissue sensitization, the heart should be considered as a potential shock organ in the anaphylactic reaction.
Diversification of Bitter Taste Receptor Gene Family in Western Chimpanzees
Authors: T. Sugawara, Y. Go, T. Udono, N. Morimura, M. Tomonaga, H. Hirai, H. Imai
Journal: Molecular Biology and Evolution (2010)

In mammals, bitter taste is mediated by T2R genes, which belong to the large family of seven transmembrane G protein–coupled receptors. Because T2Rs are directly involved in the interaction between mammals and their dietary sources, it is likely that these genes evolved to reflect species' specific diets during mammalian evolution. Here, we investigated the sequences of all 28 putative functional chimpanzee T2R genes (cT2Rs) in 46 western chimpanzees to compare the intraspecies variations in chimpanzees to those already known for all 25 human functional T2R genes (hT2Rs). The numbers of functional genes varied among individuals in western chimpanzees, and most chimpanzees had two or three more functional genes than humans. Similarly to hT2Rs, cT2Rs showed high nucleotide diversity along with a large number of amino acid substitutions. Comparison of the nucleotide substitution patterns in cT2Rs with those in five cT2R pseudogenes and 14 autosomal intergenic noncoding regions among the same individuals revealed that the evolution of cT2R genes was almost identical to that of putative neutral regions with slight but significantly positive Tajima's D values, suggesting that selective constraint on these genes was relaxed with weak balancing selection. These trends have resulted in the occurrence of various divergent alleles of T2Rs within the western chimpanzee populations and in heterozygous individuals who might have the ability to taste a broader range of substances.
Retrospective survey of the management of miliary tuberculosis in South and West Wales, 1976-8.
Authors: R D Monie, A M Hunter, K M Rocchiccioli, J P White, I A Campbell, G S Kilpatrick
Journal: Thorax (1983)

In a survey of 1000 patients with tuberculosis 28 were found to have miliary disease. Half of these patients were over 60 years old. Anorexia and weight loss were present in 19 (70%) and pyrexia in 17 (63%). A factor predisposing to tuberculosis or a history of recent contact was found in 12 (43%), and 21 (75%) had positive cultures. Seventeen (61%) had classical miliary shadowing while four (14%) had cryptic miliary tuberculosis with no radiological evidence of tuberculosis. The remaining seven patients (25%) had radiological changes consistent with pulmonary tuberculosis, but no miliary shadows. Of those who completed chemotherapy, only five (42%) received 18 months9 treatment. Nine patients (32%) died from their miliary tuberculosis. Failure to consider the diagnosis, leading to a delay in starting chemotherapy, appeared to be a major problem.
Predictive value of interleukin 1 gene polymorphisms for surgery
Authors: Anne Crilly, Nicola Maiden, Hilary A Capell, Rajan Madhok
Journal: Annals of the Rheumatic Diseases (2000)

<h3>OBJECTIVES</h3> To determine the influence of interleukin 1α (IL1α), IL1β, and IL1 receptor antagonist gene polymorphisms on disease outcome as assessed by the need for major joint surgery within 15 years of diagnosis. <h3>PATIENTS AND METHODS</h3> 50 patients with rheumatoid arthritis (RA) who required major joint surgery (hip, knee, or shoulder arthroplasty) within a 15 year period of disease diagnosis and 50 patients with RA with disease duration greater than 15 years and no major surgery were recruited together with 66 normal west of Scotland controls. Genomic DNA and polymerase chain reaction were used to determine polymorphisms in the genes for IL1α, IL1β, and IL1 receptor antagonist. For all patients with RA recruited to the study, HLA-DR β1 gene status was recorded as was the erythrocyte sedimentation rate (ESR) at the first ever clinic visit. <h3>RESULTS</h3> No difference in the allele frequencies or genotypes of the IL1α and IL1 receptor antagonist gene polymorphisms was found between the controls and patients with RA, with or without previous surgery. IL1β allele 2 was overrepresented in patients with RA who had undergone surgery compared with patients who had not (40% <i>v</i> 27%, χ<sup>2</sup>=4, 1df, p=0.04). ESR at the first ever clinic visit was significantly higher in those carrying allele 2 (36 mm/1st h<i>v</i> 22 mm/1st h, p=0.04). When patients, with or without previous surgery, who did not carry two disease associated HLA-DR β1 alleles were compared, an increase in allele 2 was observed in the surgery cohort (42% <i>v</i> 25%, χ<sup>2</sup>=4.8, 1df, p=0.03). <h3>CONCLUSIONS</h3> Patients who require major joint surgery were found to carry the IL1β allele 2 more often than expected. Patients with this allele also had a higher initial ESR. This may be useful in predicting early surgery in patients who do not carry two disease associated HLA-DR β1 alleles. Although these findings are interesting, further functional and epidemiological studies to confirm these observations are required.
Update in Respiratory Infections 2011
Authors: Richard G. Wunderink, Michael S. Niederman
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Respiratory tract infections again featured prominently in the Journal and other publications in 2011.We will discuss updates in respiratory tract infections, classified by the traditional breakdowns by site of acquisition, type of infection, and to a certain extent, causative organisms.Publications addressing cystic fibrosis are the subject of a separate update.Full understanding of infections of the lower respiratory tract requires knowledge of the normal flora of the respiratory tract.An extremely careful study of the distal lung microbiota (sampled by bronchoalveolar lavage and protected specimen brush) in healthy volunteers contradicts the general assumption that the distal lung is sterile.After careful control for contamination of the bronchoscope during insertion, Charlson and colleagues found that the distal respiratory tract contained an almost identical spectrum of bacteria as the upper respiratory tract but at roughly 2-4 logs lower quantitative counts (1).Distal lung-only isolates were rare and varied from person to person but did include pathogens associated with nosocomial pneumonia.Although study of the lung microbiome is just beginning, changes in the microbiome at this site are likely to have important effects on risk of pneumonia and possibly other respiratory illnesses, similar to those demonstrated for alterations in the gut microbiome (2).
Estimation of genetic distance and coefficient of gene diversity from single-probe multilocus DNA fingerprinting data.
Authors: L Jin, R Chakraborty
Journal: Molecular Biology and Evolution (1994)

DNA fingerprinting exhibits multilocus genotypes of individuals, detected by the use of a single multilocus probe. Consequently, population data on DNA fingerprinting do not provide a complete characterization of the genetic variation in terms of allele-frequency distributions, since neither the number of loci nor the locus affiliation of alleles is directly observable. Yet DNA fingerprinting has been proved to be a cost-effective method of detecting hypervariable polymorphisms in several organisms, where the traditional loci fail to detect enough variation for microevolutionary studies. In the present paper we demonstrate that the above-mentioned features of DNA fingerprinting data do not cause any serious problem when they are used in evolutionary studies. Bias-corrected estimators of Nei's standard and minimum genetic distances are derived, and, by an application of this theory to data on seven short tandem repeat loci in three major human populations, it is shown that these modified measures of genetic distances based on DNA fingerprint patterns are quite close to Nei's distances based on locus-specific allele frequencies. Empirical as well as theoretical support of the adequacy of such genetic distances from DNA fingerprinting data is also discussed, and it indicates that the technical limitations of DNA fingerprinting should not deter the use of the method for short-term evolutionary studies.
Randomized multicenter phase II trial of cisplatin and ifosfamide with or without paclitaxel in recurrent or metastatic carcinoma of the uterine cervix: a Hellenic Cooperative Oncology Group (HeCOG) study
Authors: G. Mountzios, M.A. Dimopoulos, A. Bamias, G. Vourli, H. Kalofonos, G. Aravantinos, G. Fountzilas, C.A. Papadimitriou
Journal: Annals of Oncology (2009)
Comparison of incremental and constant load tests of inspiratory muscle endurance in COPD
Authors: K. Hill, S. C. Jenkins, D. L. Philippe, K. L. Shepherd, D. R. Hillman, P. R. Eastwood
Journal: European Respiratory Journal (2007)

The aim of the present study was to determine the relative value of incremental and constant load tests in detecting changes in inspiratory muscle endurance following high-intensity inspiratory muscle training (H-IMT) in chronic obstructive pulmonary disease. In total, 16 subjects (11 males; forced expiratory volume in one second (FEV(1)) 37.4+/-12.5%) underwent H-IMT. In addition, 17 subjects (11 males; FEV(1) 36.5+/-11.5%) underwent sham inspiratory muscle training (S-IMT). Training took place three times a week for 8 weeks. Baseline and post-training measurements were obtained of maximum threshold pressure sustained during an incremental load test (P(th,max)) and time breathing against a constant load (t(lim)). Breathing pattern was unconstrained. H-IMT increased P(th,max) and t(lim) relative to baseline and to any change seen following S-IMT. The effect size for P(th,max) was greater than for t(lim). Post-training tests were accompanied by changes in breathing pattern, including decreased duty cycle, which may have served to decrease inspiratory work and thereby contribute to the increase in P(th,max) and t(lim) in both groups. When assessing inspiratory muscle function in chronic obstructive pulmonary disease via tests in which the pattern of breathing is unconstrained, the current authors recommend incremental load tests be used in preference to constant load tests. However, to attribute changes in these tests to improvements in inspiratory muscle endurance, breathing pattern should be controlled.