tbuckley/cabot-search huggingface dataset:
MicroRNA Sequence and Expression Analysis in Breast Tumors by Deep Sequencing
Authors: Thalia A. Farazi, Hugo M. Horlings, Jelle J. ten Hoeve, Aleksandra Mihailovic, Hans Halfwerk, Pavel Morozov, Miguel Brown, Markus Hafner, Fabien Reyal, Marieke van Kouwenhove, Bas Kreike, Daoud Sie, Volker Hovestadt, Lodewyk F.A. Wessels, Marc J. van de Vijver, Thomas Tuschl
Journal: Cancer Research (2011)

MicroRNAs (miRNA) regulate many genes critical for tumorigenesis. We profiled miRNAs from 11 normal breast tissues, 17 noninvasive, 151 invasive breast carcinomas, and 6 cell lines by in-house-developed barcoded Solexa sequencing. miRNAs were organized in genomic clusters representing promoter-controlled miRNA expression and sequence families representing seed sequence-dependent miRNA target regulation. Unsupervised clustering of samples by miRNA sequence families best reflected the clustering based on mRNA expression available for this sample set. Clustering and comparative analysis of miRNA read frequencies showed that normal breast samples were separated from most noninvasive ductal carcinoma in situ and invasive carcinomas by increased miR-21 (the most abundant miRNA in carcinomas) and multiple decreased miRNA families (including miR-98/let-7), with most miRNA changes apparent already in the noninvasive carcinomas. In addition, patients that went on to develop metastasis showed increased expression of mir-423, and triple-negative breast carcinomas were most distinct from other tumor subtypes due to upregulation of the mir~17-92 cluster. However, absolute miRNA levels between normal breast and carcinomas did not reveal any significant differences. We also discovered two polymorphic nucleotide variations among the more abundant miRNAs miR-181a (T19G) and miR-185 (T16G), but we did not identify nucleotide variations expected for classical tumor suppressor function associated with miRNAs. The differentiation of tumor subtypes and prediction of metastasis based on miRNA levels is statistically possible but is not driven by deregulation of abundant miRNAs, implicating far fewer miRNAs in tumorigenic processes than previously suggested.
Comparison of proportional assist ventilation and pressure support ventilation in chronic respiratory failure due to neuromuscular and chest wall deformity
Authors: N Hart
Journal: Thorax (2002)

<b>Background:</b> The physiological and symptomatic effects of proportional assist ventilation (PAV) and pressure support ventilation (PSV) were compared in stable awake patients with neuromuscular and chest wall deformity (NMCWD). <b>Methods:</b> Oxygen saturation (Sao<sub>2</sub>), transcutaneous carbon dioxide (Tcco<sub>2</sub>), minute ventilation (Ve), tidal volume (Vt), respiratory rate (RR), and diaphragm electromyography (EMGdi) were measured in 15 patients during both modes. Subjective effort of breathing and synchrony with the ventilator were assessed using visual analogue scales. <b>Results:</b> Three of 15 patients failed to trigger the ventilator in either mode and were excluded. In the 12 remaining patients there were similar improvements in Sao<sub>2</sub>, Tcco<sub>2</sub>, Ve, Vt, and RR during both modes. The mean (SD) percentage fall in EMGdi was greater during PSV (–80.5 (10.7)%) than during PAV (–41.3 (35.2)%; p= 0.01). Effort of breathing (p=0.004) and synchrony with the ventilator (p=0.004) were enhanced more with PSV than with PAV. <b>Conclusion:</b> Both PSV and PAV produced similar improvements in physiological parameters. However, greater diaphragm unloading was observed with PSV than with PAV, associated with greater symptomatic benefit. These findings suggest that tolerance to PAV may be compromised in patients with NMCWD.
A Tissue Culture Study of the Chick Fibroblast in Relation to Streptococcal Filtrates and Rheumatic Heart Disease
Authors: ROBERT J. BOUCEK, GLADYS CAMERON, VINCENT R. SAURINO, ROBERT CHAMBERS
Journal: Circulation Research (1954)

Marked degeneration and disintegration of the chick embryo fibroblast was observed in tissue cultures after their exposure to sera of patients with active or inactive rheumatic heart disease or to the filtrates of beta hemolytic streptococci. Some tissue specificity was demonstrated; sera of the patients or the filtrates of the streptococci failed to affect contractility of the myocardial cells or secretion of the mesonephros. Sera of normal control humans or of patients with other so-called collagen diseases did not seriously affect the fibroblasts. Filtrates of nine other bacteria failed to alter the morphology of the fibroblasts unless severe toxicity was present and the tissue culture died.
Presence of plasma cells binding autologous antibody during an immune response.
Authors: S Jackson, J Mestecky
Journal: The Journal of Experimental Medicine (1979)

Spleen and other lymphoid tissues of rabbits immunized with human serum albumin (HSA) and human lactoferrin (LF) were examined for the presence of cells forming anti-idiotype antibodies. To detect these cells, IgG, F(ab')2, or Fab' of specific antibodies were isolated, fluorochrome-tagged with tetramethylrhodamine isothiocyanate, and used as an idiotypic marker to detect splenic plasma cells that are producing anti-idiotypic antibody. By this procedure, we were able to demonstrate anti-idiotypic cells in surprisingly high numbers. For example, in six rabbits immunized with HSA for periods ranging from 36 to 542 d, the percentage of Ig-positive cells that stained with autologous idiotype ranged from 0.7 to 44; furthermore, cross-reactivity was observed among seven different anti-HSA preparations and two anti-LF antisera. The isotype of anti-idiotypic cells, determined by costaining with fluorescein isothiocyanate-labeled goat Fc-specific anti-rabbit Ig, was shown to be predominantly IgG. These findings provide evidence of the presence of plasma cells producing antibody to autologous idiotype during a vigorous immune response.
Television Viewing and Low Leisure-Time Physical Activity in Adolescence Independently Predict the Metabolic Syndrome in Mid-Adulthood
Authors: Patrik Wennberg, Per E. Gustafsson, David W. Dunstan, Maria Wennberg, Anne Hammarström
Journal: Diabetes Care (2013)

OBJECTIVE We investigated whether television (TV) viewing and low leisure-time physical activity in adolescence predict the metabolic syndrome in mid-adulthood. RESEARCH DESIGN AND METHODS TV viewing habits and participation in leisure-time physical activity at age 16 years were assessed by self-administered questionnaires in a population-based cohort in Northern Sweden. The presence of the metabolic syndrome at age 43 years was ascertained in 888 participants (82% of the baseline sample) using the International Diabetes Federation criteria. Odds ratios (ORs) and CIs were calculated using logistic regression. RESULTS The overall prevalence of the metabolic syndrome at age 43 years was 26.9%. Adjusted OR for the metabolic syndrome at age 43 years was 2.14 (95% CI 1.24–3.71) for those who reported “watching several shows a day” versus “one show/week” or less and 2.31 (1.13–4.69) for leisure-time physical activity “several times/month” or less compared with “daily” leisure-time physical activity at age 16 years. TV viewing at age 16 years was associated with central obesity, low HDL cholesterol, and hypertension at age 43 years, whereas low leisure-time physical activity at age 16 years was associated with central obesity and triglycerides at age 43 years. CONCLUSIONS Both TV viewing and low leisure-time physical activity in adolescence independently predicted the metabolic syndrome and several of the metabolic syndrome components in mid-adulthood. These findings suggest that reduced TV viewing in adolescence, in addition to regular physical activity, may contribute to cardiometabolic health later in life.
Effect of dietary protein on rat renin and angiotensinogen gene expression.
Authors: M E Rosenberg, D Chmielewski, T H Hostetter
Journal: Journal of Clinical Investigation (1990)

Plasma renin activity varies with the level of dietary protein, being higher on a high protein diet. To explore the molecular mechanisms underlying this relationship we first examined the effect of dietary protein on renin and angiotensinogen gene expression at the level of steady state mRNA in male Sprague-Dawley rats. Renal renin mRNA was higher on a 50% (high) compared to a 6% (low) protein diet both 3 d (9.4 +/- 1.1 vs. 5.3 +/- 0.4 pg/micrograms of total RNA; P less than 0.02) and 21 d (6.8 +/- 1.0 vs. 3.5 +/- 0.4 pg/micrograms of total RNA; P less than 0.02) after dietary change. No change occurred in either renal or liver angiotensinogen mRNA. When three levels of dietary protein were examined, renal renin mRNA was elevated on a 50% and lowered on a 6% protein diet compared to a more standard 20% protein diet. Kidney weights and renal protein, RNA, and RNA/DNA increased with the level of dietary protein reflecting protein-induced renal hypertrophy. Uninephrectomy resulted in no change in renin mRNA compared to sham operation (3.7 +/- 0.1 vs. 3.4 +/- 0.1 pg/micrograms RNA; P = NS) despite renal growth in the uninephrectomy group implicating dietary protein and not hypertrophy as the major factor for stimulating renin mRNA. In conclusion, the level of dietary protein is a novel and specific stimulus for changes in renal renin mRNA. The increased plasma renin activity on a high protein diet is due at least in part to increased renin synthesis.
Differential disease restriction of Moloney and Friend murine leukemia viruses by the mouse Rmcf gene is governed by the viral long terminal repeat.
Authors: B K Brightman, Q X Li, D J Trepp, H Fan
Journal: The Journal of Experimental Medicine (1991)

Neonatal CxD2 (Rmcfr) and Balb/c (Rmcfs) mice inoculated with Moloney murine leukemia virus (M-MuLV) exhibited approximately equivalent time course and pathology for disease. CxD2 mice showed only slightly reduced presence of Moloney mink cell focus-forming virus (M-MCF) provirus as seen by Southern blot analysis compared to Balb/c mice. This lack of restriction for disease and spread of MCF was in sharp contrast to that seen for CxD2 mice inoculated with Friend murine leukemia virus (F-MuLV), where incidence of disease and propagation of MCFs were severely restricted, as previously reported. Inoculation of CxD2 mice with FM-MuLV, a recombinant F-MuLV virus containing M-MuLV LTR sequences (U3 and R), resulted in T cell disease of time course equal to that seen in Balb/c mice; there also was little restriction for propagation of MCFs. This indicated that presence of the M-MuLV long terminal repeat (LTR) was sufficient for propagation of MCFs in CxD2 mice. Differing restriction for F-MuLV vs. M-MuLV in CxD2 mice was explained on the basis of different "MCF propagator cells" for the two viruses. It was suggested that cells propagating F-MCF (e.g., erythroid progenitors) are blocked by endogenous MCF-like gp70env protein, whereas cells propagating M-MCF (e.g., lymphoid) do not express this protein on their surface. F-MuLV disease in CxD2 mice was greatly accelerated when neonates were inoculated with a F-MuLV/F-MCF pseudotypic mixture. However, F-MCF provirus was not detectable or only barely detectable in F-MuLV/F-MCF-induced tumors, suggesting that F-MCF acted indirectly in induction of these tumors.
Erythropoietin-Mobilized Endothelial Progenitors Enhance Reendothelialization via Akt-Endothelial Nitric Oxide Synthase Activation and Prevent Neointimal Hyperplasia
Authors: Norifumi Urao, Mitsuhiko Okigaki, Hiroyuki Yamada, Yasushi Aadachi, Kuniharu Matsuno, Akihiro Matsui, Shinsaku Matsunaga, Kento Tateishi, Tetsuya Nomura, Tomosaburo Takahashi, Tetsuya Tatsumi, Hiroaki Matsubara
Journal: Circulation Research (2006)

We investigated whether the mobilization of endothelial progenitor cells (EPCs) by exogenous erythropoietin (Epo) promotes the repair of injured endothelium. Recombinant human Epo was injected (1000 IU/kg for the initial 3 days) after wire injury of the femoral artery of mice. Neointimal formation was inhibited by Epo to 48% of the control (P<0.05) in an NO-dependent manner. Epo induced a 1.4-fold increase in reendothelialized area of day 14 denuded vessels, 55% of which was derived from bone marrow (BM) cells. Epo increased the circulating Sca-1(+)/Flk-1(+) EPCs (2.0-fold, P<0.05) with endothelial properties NO dependently. BM replacement by GFP- or beta-galactosidase-overexpressing cells showed that Epo stimulated both differentiation of BM-derived EPCs and proliferation of resident ECs. BM-derived ECs increased 2.2- to 2.7-fold (P<0.05) in the Epo-induced neoendothelium, where the expression of Epo receptor was upregulated. Epo induced Akt/eNOS phosphorylation and NO synthesis on EPCs and exerted an antiapoptotic action on wire-injured arteries. In conclusion, Epo treatment inhibits the neointimal hyperplasia after arterial injury in an NO-dependent manner by acting on the injured vessels and mobilizing EPCs to the neo-endothelium.
What's App? Sports medicine physicians should not talk double Dutch: Figure 1
Authors: Johannes Zwerver, Adam Weir, Johannes L Tol
Journal: British Journal of Sports Medicine (2012)

The 1928 Olympic Games held in Amsterdam was notable for a number of firsts—the first time the Olympic flame was lit in the stadium, the first time the parade of Nations started with Greece, the first time women participated in gymnastics, the first time a strict schedule of 16 days was introduced and the first appearance of Coca-Cola as a sponsor. Queen Wilhelmina refused to come back from holiday in Norway to open the Games, Tarzan (Johnny Weissmuller) won two gold medals in swimming and the very first World Congress of Sports Medicine was held in conjunction with the Games. Hosting the Olympics gave both Dutch sporting infrastructure and also sports and exercise medicine a major boost. Exactly a century later, the power of the Olympics inspires our nation once again to bid for the 2028 Olympic Games. We are eager to harness the impetus provided by the Olympic Games to build a far-reaching legacy—improving the health of the population through sports and exercise. Building a nation where the population is healthy and fit!

Sports medicine in the Netherlands has responded swiftly to this call for action. In Cockney rhyming slang, ‘stairs’ are referred to as ‘apples and pears’ and ‘taking the stairs’ has long been a maxim to improve the health of sedentary elevator users. Every new technology now has an App that you can download onto your mobile phone and the Dutch start utilising this tool for promoting physical activity. …
Distal common bile duct metastasis from hepatocellular carcinoma
Authors: Young Chul Kim, Mi-Suk Park
Journal: Hepatology (2011)

A 60-year-old female was admitted to our hospital because of obstructive jaundice. She had undergone a right hepatectomy resulting from a single small (approximately 3 cm) hepatocellular carcinoma (HCC) 6 months previously. Laboratory data values were abnormally increased as follows: serum bilirubin level, 7.7 mg/dL (normal, <1.0 mg/dL); serum alkaline phosphatase, 295 IU/L (normal, 20-120); aspartate aminotransferase, 55 (normal, 5-40); gamma-glutamyl transferase, 318 (normal, 10-66); amylase, 165 (normal, 28-116); lipase, 78 (normal, 0-60), white blood cell count, 16,400 cells/mm3 (normal, 3.9-9.7 × 103); and alfa-fetoprotein, 10.82 ng/mL (normal, 0-6). Levels of all other serum tumor markers, including carcinoembryonic antigen, carbohydrate antigen (CA) 125, and CA 19-9, were within normal limits. CA, carbohydrate antigen; CBD, common bile duct; HCC, hepatocellular carcinoma; iHCC, icteric hepatocellular carcinoma. A dynamic series of computed tomography scans revealed a polypoid lesion in the distal common bile duct (CBD), which showed early enhancement on the arterial phase and washout on the portal venous phase (Fig. A). Endoscopic retrograde cholangiopancreatography showed marked CBD dilatation with a round filling defect in the distal CBD (Fig. B). On endoscopy, a whitish polypoid lesion was visible in the distal CBD (Fig. C). There were no other abnormal lesions in the abdomen. A lesion specimen, obtained by an endoscopy-guided biopsy in the distal CBD, displayed tumor cells proliferating in a trabecular-to-compact manner without glandular differentiation or mucin-containing cells (hematoxylin and eosin; magnification, ×10 and ×100; Fig. D). The tumor was diagnosed as metastatic HCC without a choloangiocellular carcinoma component. HCC commonly occurs in a cirrhotic liver, and invasion of the intrahepatic bile duct is not rare.1 Icteric HCC (iHCC) might invade the biliary tree by three different mechanisms of action: direct tumor infiltration to the biliary tree, infiltration from a periportal tumor, and intraductal tumor growth. 2 There were several reports about radiographic findings of biliary invasion from HCC. 3 However, to the best of our knowledge, endoscopic presentation of intraductal metastasis into the distal CBD from HCC has not previously been reported. On various imaging modalities, iHCC appears as an expansile soft-tissue mass that causes dilatation of the bile duct. 1 Our case mimicked the intraductal mass-forming type of cholangiocarcinoma. Presentation of the clinical and radiologic characteristics of iHCC may help narrow the differential diagnoses for this condition. However, the radiological findings are nonspecific, and a biopsy may be required to achieve a conclusive histopathological diagnosis.
Defective interleukin 2 production and responsiveness in human pulmonary tuberculosis.
Authors: Z Toossi, M E Kleinhenz, J J Ellner
Journal: The Journal of Experimental Medicine (1986)

Patients with newly diagnosed, pulmonary tuberculosis had a tuberculin-specific defect in IL-2 production. Mean PPD-induced IL-2 activity was 81.2% lower in patients as compared with healthy tuberculin reactors. PPD-induced expression of T cell IL-2 receptors was 5.9 times less in peripheral blood mononuclear cells of patients with tuberculosis as compared with healthy tuberculin reactors. Furthermore, purified IL-2 failed to correct PPD-induced blastogenesis in patients. Suppression by adherent cells was operative in one group of patients; adherent cell depletion increased their T cell production of IL-2 7.2-fold. A second group of patients with low IL-2 production did not have suppressor adherent cells and were clinically distinct, with more extensive disease on chest x ray. The basis for low IL-2 production in such individuals is unknown. Disordered regulation of IL-2 metabolism may be a key feature in the depressed cellular immune response of tuberculosis.
Blood flow resistance during hemodilution: effect of plasma composition
Authors: A Pries
Journal: Cardiovascular Research (1998)

Objectives: To investigate the causes of wide variations in reported effects of hemodilution on flow resistance of vascular beds. Methods: (a) In a meta-analysis of 28 prior studies, resistance values at hematocrits of zero (R0) and 0.45 (R0.45) were derived. Study design characteristics (presence of vasodilatory reserve or leukocytes, species, tissue, hemodiluent) were tested by ANOVA for their relation to the ratio R0/R0.45. (b) Experiments were performed to determine flow resistance during hemodilution in the rat mesentery with (n = 8) and without (n = 11) pretreatment with heparinase, which modifies the endothelial glycocalyx. (c) A mathematical flow simulation for mesenteric microvascular networks was used to predict resistance effects of hemodilution and of a hypothetical layer on the endothelial surface. Results: (a) In prior studies using native plasma for hemodilution R0 averaged 59±8% of R0.45, while in studies using artificial solutions R0 averaged 32±12% of R0.45. The larger reduction of flow resistance upon dilution with artificial media is independent of viscosity and oncotic pressure. Other design characteristics did not show strong significant effects. (b) Present experiments showed large reductions of flow resistance with saline hemodilution which were nearly halved after heparinase pretreatment. (c) Resistance effects of hemodilution with plasma or after heparinase treatment agree with model predictions based on tube flow rheology of blood. The larger resistance effects of dilution with artificial media can be explained by the removal of an endothelial surface layer of ∼1.5 μm thickness. Conclusions: The results imply that changes of plasma composition, due to use of artificial infusion media, influence peripheral resistance and tissue perfusion. They are consistent with the hypothesis that interactions between endothelial glycocalyx structures and plasma components lead to formation of a thick layer at the endothelial surface which increases flow resistance.
Resolution of<i>Clostridium difficile</i>–Associated Diarrhea in Patients With Cancer Treated With Fidaxomicin or Vancomycin
Authors: Oliver A. Cornely, Mark A. Miller, Bruno Fantin, Kathleen Mullane, Yin Kean, Sherwood Gorbach
Journal: Journal of Clinical Oncology (2013)

Purpose Patients with cancer are at increased risk for Clostridium difficile–associated diarrhea (CDAD). Little is known about treatment response. Patients and Methods Two double-blind trials randomly allocated 1,105 patients with CDAD to fidaxomicin or vancomycin treatment (modified intent-to-treat [mITT]), and 183 of these had cancer. Univariate and multivariate post hoc analyses compared effects of treatment and patient characteristics on cure, recurrence, and sustained response after 4 weeks. Time to resolution of diarrhea (TTROD) was also evaluated. Results Patients with cancer had a lower cure rate and longer TTROD than patients without cancer. Recurrence rates were similar. Cure was more likely with fidaxomicin than vancomycin (odds ratio [OR] 2.0; P = .065), recurrence was less likely (OR = 0.37; P = .018), and sustained response more frequent (OR = 2.56; P = .003). Under vancomycin, median TTROD was longer in patients with cancer than in those without (123 v 58 hours; log-rank P &lt; .001). With fidaxomicin, median TTROD was not significantly affected by presence of cancer (74 v 54 hours; log-rank P = .145). In the full mITT population, age, hypoalbuminemia, and cancer were inversely associated with clinical cure by multivariate analysis. Study treatment with vancomycin was a significant predictor of recurrence (P &lt; .001). Within the cancer population, low albumin was negatively and fidaxomicin was positively associated with improved cure. Conclusion For patients with cancer, fidaxomicin treatment was superior to vancomycin, resulting in higher cure and sustained response rates, shorter TTROD, and fewer recurrences.