tbuckley/cabot-search huggingface dataset:
Cardiovascular Adaptation to Partial Heart-Lung Bypass
Authors: PIERRE M. GALLETTI, GERHARD A. BRECHER
Journal: Circulation Research (1960)

Partial heart-lung bypass was performed in open-chest dogs, using the gravity arterial in-fusion technique. Arterial infusion pressure, venous suction and pressures in the left ventricle, aortic arch, and airways were phasically recorded. The mean flow in the aortic arch and the blood content of the extracorporeal circuit were continuously recorded. According to the height of the bag oxygenator above the heart level, partial heart-lung bypass resulted in a shift of blood either from the extracorporeal circuit into the animal or vice versa. When the body blood volume was increased by the bypass procedure, the cardiac output decreased only slightly. When the body blood volume was diminished by the bypass procedure, the cardiac output dropped markedly. It was found that when the systemic arterial pressure was maintained at approximately normal levels, independent of cardiac output, the change in cardiac output was proportional to the change in the body blood volume.
Stereotactic core-needle biopsy of the breast: a report of the Joint Task Force of the American College of Radiology, American College of Surgeons, and College of American Pathologists
Authors: L. Bassett, D. P. Winchester, R. B. Caplan, D. D. Dershaw, K. Dowlatshahi, W. P. Evans, L. L. Fajardo, P. L. Fitzgibbons, D. E. Henson, R. V. Hutter, M. Morrow, J. R. Paquelet, S. E. Singletary, J. Curry, P. Wilcox-Buchalla, M. Zinninger
Journal: CA A Cancer Journal for Clinicians (1997)

A national task force consisting of members from the American College of Radiology, the American College of Surgeons, and the College of American Pathologists examined the issues surrounding stereotactic core-needle biopsy for occult breast lesions. Their report includes indications and contraindications, informed consent, specimen handling, and management of indeterminate, atypical, or discordant lesions.
A Critical Role for Natural Killer T Cells in Immunosurveillance of Methylcholanthrene-induced Sarcomas
Authors: Nadine Y. Crowe, Mark J. Smyth, Dale I. Godfrey
Journal: The Journal of Experimental Medicine (2002)

Natural killer (NK) T cells initiate potent antitumor responses when stimulated by exogenous factors such as interleukin (IL)-12 or alpha-galactosylceramide (alpha-GalCer), however, it is not clear whether this reflects a physiological role for these cells in tumor immunity. Through adoptive transfer of NK T cells from wild-type to NK T cell-deficient (T cell receptor [TCR] Jalpha281-/-) mice, we demonstrate a critical role for NK T cells in immunosurveillance of methylcholanthrene (MCA)-induced fibrosarcomas, in the absence of exogenous stimulatory factors. Using the same approach with gene-targeted and/or antibody-depleted donor or recipient mice, we have shown that this effect depends on CD1d recognition and requires the additional involvement of both NK and CD8+ T cells. Interferon-gamma production by both NK T cells and downstream, non-NK T cells, is essential for protection, and perforin production by effector cells, but not NK T cells, is also critical. The protective mechanisms in this more physiologically relevant system are distinct from those associated with alpha-GalCer-induced, NK T cell-mediated, tumor rejection. This study demonstrates that, in addition to their importance in tumor immunotherapy induced by IL-12 or alpha-GalCer, NK T cells can play a critical role in tumor immunosurveillance, at least against MCA-induced sarcomas, in the absence of exogenous stimulation.
Contractile Fatigue, Muscle Morphometry, and Blood Lactate in Chronic Obstructive Pulmonary Disease
Authors: Didier Saey, Annie Michaud, Annabelle Couillard, Claude H. Côté, M. Jeffery Mador, Pierre LeBlanc, Jean Jobin, François Maltais
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

We hypothesized that patients with chronic obstructive pulmonary disease developing contractile fatigue of the quadriceps during cycle exercise may have characteristic metabolic and muscle features that could increase their susceptibility to fatigue, thus differentiating them from those who do not develop fatigue. We examined, in 32 patients, the fiber-type proportion, enzymatic activities, and capillary density in the vastus lateralis and the arterial blood lactate level during constant work-rate cycling exercise. Contractile fatigue was defined as a postexercise fall in quadriceps twitch force greater than 15% of resting values. Twenty-two patients developed contractile fatigue after exercise. No significant differences were found between fatiguers and non-fatiguers for the endurance time, fiber-type proportion, and oxidative enzyme activities. The lactate dehydrogenase activity was significantly higher (p < 0.05) and muscle capillarization significantly reduced in fatiguers (p < 0.05). Compared with non-fatiguers, the arterial lactate level during exercise was significantly higher in fatiguers (p < 0.001). A significant relationship was found between the fall in quadriceps twitch force and lactate dehydrogenase activity, capillary/fiber ratio, and blood lactate level. We conclude that changes in muscle enzymatic profile and capillarization with a greater reliance on glycolytic metabolism during exercise are associated with contractile fatigue in patients with chronic obstructive pulmonary disease.
Copy number variations and cancer
Authors: Adam Shlien, David Malkin
Journal: Genome Medicine (2009)

DNA copy number variations (CNVs) are an important component of genetic variation, affecting a greater fraction of the genome than single nucleotide polymorphisms (SNPs). The advent of high-resolution SNP arrays has made it possible to identify CNVs. Characterization of widespread constitutional (germline) CNVs has provided insight into their role in susceptibility to a wide spectrum of diseases, and somatic CNVs can be used to identify regions of the genome involved in disease phenotypes. The role of CNVs as risk factors for cancer is currently underappreciated. However, the genomic instability and structural dynamism that characterize cancer cells would seem to make this form of genetic variation particularly intriguing to study in cancer. Here, we provide a detailed overview of the current understanding of the CNVs that arise in the human genome and explore the emerging literature that reveals associations of both constitutional and somatic CNVs with a wide variety of human cancers.
Functional Neuroanatomy of Grief: An fMRI Study
Authors: Harald Gündel, Mary-Frances O’Connor, Lindsey Littrell, Carolyn Fort, Richard D. Lane
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: In this study the authors examined the functional neuroanatomy of grief, which to their knowledge has not been studied previously in functional neuroimaging research. METHOD: Grief was elicited in eight bereaved women through photographs of the deceased versus a stranger, combined with words specific to the death event versus neutral words. Use of both pictures and words resulted in a 2×2 factorial design. RESULTS: Three brain regions were independently activated by the picture and word factors: posterior cingulate cortex, medial/superior frontal gyrus, and cerebellum. The two factors also activated distinct regions: for the picture factor, they were the cuneus, superior lingual gyrus, insula, dorsal anterior cingulate cortex, inferior temporal gyrus, and fusiform gyrus; and for the word factor, they were the precuneus, precentral gyrus, midbrain, and vermis. The interaction of the two factors showed significant activation in the cerebellar vermis. CONCLUSIONS: Grief is mediated by a distributed neural network that subserves affect processing, mentalizing, episodic memory retrieval, processing of familiar faces, visual imagery, autonomic regulation, and modulation/coordination of these functions. This neural network may account for the unique, subjective quality of grief and provide new leads in understanding the health consequences of grief and the neurobiology of attachment.
Lung function impairment, COPD hospitalisations and subsequent mortality
Authors: J. Garcia-Aymerich, I. Serra Pons, D. M. Mannino, A. K. Maas, D. P. Miller, K. J. Davis
Journal: Thorax (2011)

<h3>Background</h3> Hospitalisations and their sequelae comprise key morbidities in the natural history of chronic obstructive pulmonary disease (COPD). A study was undertaken to examine the associations between lung function impairment and COPD hospitalisation, and COPD hospitalisation and mortality. <h3>Methods</h3> The analysis included a population-based sample of 20 571 participants with complete demographic, lung function, smoking, hospitalisation and mortality data, with 10-year median follow-up. Participants were classified by prebronchodilator lung function according to the modified Global Initiative on Obstructive Lung Disease (GOLD) criteria. Hospitalisations were defined by the presence of a COPD discharge diagnosis (ICD-9 codes 490–496). Incidence rate ratios (IRR) of COPD admissions and hazard ratios (HR) of mortality with respective 95% CI were calculated, adjusted for potential confounders. <h3>Results</h3> The prevalence of modified GOLD categories was normal (36%), restricted (15%), GOLD stage 0 (22%), GOLD stage 1 (13%), GOLD stage 2 (11%) and GOLD stages 3 or 4 (3%). Adjusted IRRs (and 95% CI) indicated an increased risk of COPD hospitalisation associated with each COPD stage relative to normal lung function: 4.7 (3.7 to 6.1), 2.1 (1.6 to 2.6), 3.2 (2.6 to 4.0), 8.0 (6.4 to 10.0) and 25.5 (19.5 to 33.4) for the restricted, GOLD stage 0, GOLD stage 1, GOLD stage 2 and GOLD stages 3 or 4, respectively. Hospitalisation for COPD increased the risk of subsequent mortality (HR 2.7, 95% CI 2.5 to 3.0), controlling for severity, number of prior hospitalisations and other potential confounders. The increase in mortality associated with admission was very similar across the modified GOLD stages. <h3>Conclusions</h3> COPD severity was associated with a higher rate of severe exacerbations requiring hospitalisation, although severe exacerbations at any stage were associated with a higher risk of short-term and long-term all-cause mortality.
PD-L2 is a second ligand for PD-1 and inhibits T cell activation
Authors: Yvette Latchman, Clive R. Wood, Tatyana Chernova, Divya Chaudhary, Madhuri Borde, Irene Chernova, Yoshiko Iwai, Andrew J. Long, Julia A. Brown, Raquel Nunes, Edward A. Greenfield, Karen Bourque, Vassiliki A. Boussiotis, Laura L. Carter, Beatriz M. Carreno, Nelly Malenkovich, Hiroyuki Nishimura, Taku Okazaki, Tasuku Honjo, Arlene H. Sharpe, Gordon J. Freeman
Journal: Nature Immunology (2001)
Potassium secretion in rat distal colon during dietary potassium loading: role of pH regulated apical potassium channels
Authors: G I Sandle, I Butterfield
Journal: Gut (1999)

Chronic dietary K+ loading increases the abundance of large conductance (210 pS) apical K+ channels in surface cells of rat distal colon, resulting in enhanced K+ secretion in this epithelium. However, the factors involved in the regulation of these K+ channels are at present unclear.To evaluate the effect of dietary K+ loading on intracellular pH and its relation to large conductance apical K+ channel activity in surface cells of rat distal colon.As assessed by fluorescent imaging, intracellular pH was higher in K+ loaded animals (7.48 (0.09)) than in controls (7.07 (0.04); p<0.01) when surface cells were bathed in NaCl solution, and a similar difference in intracellular pH was observed when cells were bathed in Na2SO4 solution (7.67 (0.09) and 6.92 (0.05) respectively; p<0.001). Ethylisopropylamiloride (EIPA; an inhibitor of Na+-H+ exchange; 1 microM) decreased intracellular pH when surface cells from K+ loaded animals were bathed in either solution, although the decrease was greater when the solution contained NaCl (DeltapH 0.50 (0.03)) rather than Na2SO4 (DeltapH 0. 18 (0.02); p<0.05). In contrast, EIPA had no effect in cells from control animals. As assessed by patch clamp recording techniques, the activity of large conductance K+ channels in excised inside-out membrane patches from distal colonic surface cells of K+ loaded animals increased twofold when the bath pH was raised from 7.40 to 7. 60. As assessed by cell attached patches in distal colonic surface cells from K+ loaded animals, the addition of 1 M EIPA decreased K+ channel activity by 50%, consistent with reversal of Na+-H+ exchange mediated intracellular alkalinisation.Intracellular alkalinisation stimulates pH sensitive large conductance apical K+ channels in rat distal colonic surface cells as part of the K+ secretory response to chronic dietary K+ loading. Intracellular alkalinisation seems to reflect an increase in EIPA sensitive Na+-H+ exchange, which may be a manifestation of the secondary hyperaldosteronism associated with this model of colonic K+ adaptation.
Proportional assist ventilation as an aid to exercise training in severe chronic obstructive pulmonary disease
Authors: P Hawkins, Lorna Johnson, D Nikoletou, C H Hamnegard, R Sherwood, M I Polkey, John Moxham
Journal: Thorax (2002)

The effects of providing ventilatory assistance to patients with severe chronic obstructive pulmonary disease (COPD) during a high intensity outpatient cycle exercise programme were examined.Nineteen patients (17 men) with severe COPD (mean (SD) forced expiratory volume in 1 second (FEV(1)) 27 (7)% predicted) underwent a 6 week supervised outpatient cycle exercise programme. Ten patients were randomised to exercise with ventilatory assistance using proportional assist ventilation (PAV) and nine (two women) to exercise unaided. Before and after training patients performed a maximal symptom limited incremental cycle test to determine peak work rate (Wpeak) followed by a constant work rate (CWR) test at 70% of Wpeak achieved in the baseline incremental test. Minute ventilation (VE), heart rate, and arterialised venous plasma lactate concentration [La(+)] were measured before and after each test.Mean training intensity (Wt/Wpeak) at 6 weeks was 15.2% (95% CI 3.2 to 27.1) higher in the group that used ventilatory assistance (p=0.016). Peak work rate after training was 18.4% (95% CI 6.4 to 30.5) higher (p=0.005) in the assisted group (p=0.09). [La(+)] at an identical workload after training was reduced by 30% (95% CI 16 to 44) in the assisted group (p=0.002 compared with baseline) and by 11% (95% CI -7 to 31) (p=0.08 compared with baseline) in the unassisted group (mean difference 18.4% (95% CI 3.3 to 40), p=0.09). A significant inverse relationship was found between reduction in plasma lactate concentration (DeltaL) at an equivalent workload after training during the CWR test and Wt/Wpeak achieved during the last week of training (r=-0.7, p=0.0006).PAV enables a higher intensity of training in patients with severe COPD, leading to greater improvements in maximum exercise capacity with evidence of true physiological adaptation.
The Revisited Classification of GN in SLE at 10 Years
Authors: Suzanne Wilhelmus, Charles E Alpers, H Terence Cook, Franco Ferrario, Agnes B Fogo, Mark Haas, Kensuke Joh, Laure-Hélène Noël, Surya V Seshan, Jan A Bruijn, Ingeborg M Bajema
Journal: Journal of the American Society of Nephrology (2015)

Over 10 years have passed since the latest revision of the histopathologic classification of lupus nephritis. This revision was a significant improvement compared with the previous version, mainly because of clearer and more concise definitions and the elimination of mixed subclasses. Despite these improvements, there are still some difficulties in the classification for lupus nephritis, many of which are in the definitions provided. In this review, we focus on the difficulties surrounding the evaluation of classes III and IV lesions, particularly the definitions of endocapillary and extracapillary proliferation, the use of the terms endocapillary proliferation and hypercellularity, the clinical relevance of segmental and global subdivision in class IV, and the value of distinguishing lesions that indicate activity and chronicity. Vascular and tubulointerstitial lesions are also discussed. Furthermore, we give an overview of the history of the classification to provide background on the origin and development of the definitions in lupus nephritis. The issues raised in this review as well as the suggestions for improvements may assist with a revision of the lupus nephritis classification in the near future.
Elevated Serum Angiopoietin-like Protein 2 Correlates with the Metastatic Properties of Colorectal Cancer: A Serum Biomarker for Early Diagnosis and Recurrence
Authors: Yuji Toiyama, Koji Tanaka, Takahito Kitajima, Tadanobu Shimura, Mikio Kawamura, Aya Kawamoto, Yoshinaga Okugawa, Susumu Saigusa, Junichiro Hiro, Yasuhiro Inoue, Yasuhiko Mohri, Ajay Goel, Masato Kusunoki
Journal: Clinical Cancer Research (2014)

Angiopoietin-like protein 2 (ANGPTL2) is a mediator of chronic inflammation and inflammatory carcinogenesis. The biologic and clinical significance of ANGPTL2 remains unknown in human cancer. Therefore, we investigated the function of ANGPTL2 and evaluated its clinical significance in both primary tumors and matched sera in patients with colorectal cancer.A colorectal cancer cell line was transfected with siRNA against ANGPTL2 for the assessment of its function. We examined ANGPTL2 expression in colorectal cancer tissues (n = 195) by immunohistochemistry. Finally, we screened serum ANGPTL2 levels from 32 colorectal cancers and 23 normal controls (NC), and validated these results in serum samples obtained from 195 colorectal cancers and 45 NCs by ELISA.Knockdown of ANGPTL2 in vitro significantly inhibited cell proliferation, migration, and invasion, whereas it enhanced anoikis. ANGPTL2 was overexpressed in colorectal cancer tissues, and was significantly associated with advanced T stage, lymph node, and liver metastasis. Likewise, serum ANGPTL2 levels in colorectal cancers were significantly higher than NCs (P < 0.01), and allowed distinguishing of colorectal cancers from NCs with high accuracy (AUC = 0.837). The subsequent validation step confirmed that serum ANGPTL2 levels in colorectal cancers were significantly higher than in NCs (P < 0.0001), and had a high AUC value (0.885) for distinguishing colorectal cancers from NCs. High serum ANGPTL2 was significantly associated with advanced T stage, lymph node and liver metastasis, early relapse, and poor prognosis in colorectal cancers.Serum ANGPTL2 is a novel diagnostic and recurrence-predictive biomarker in patients with colorectal cancer.
Who should be blinded?
Authors: C Gissane
Journal: British Journal of Sports Medicine (2000)

Bone density in elderly womenEDITOR,-In the article by Rhodes et al 1 "EVects of one year of resistance training on the relation between muscular strength and bone density in elderly women", I was surprised to see no mention of HRT status in the women in the trial.Given the relatively small number of women taking part, surely this is quite an important variable?
Direct effect of acebutolol on force generation in immature and adult myocardium
Authors: D. SHERIDAN, M. TYNAN
Journal: Cardiovascular Research (1977)

The effect of acebutolol on active isometric force generation has been studied in isolated papillary muscle preparations from adult cats and kittens less than 24 h old. Statistically significant reduction in active force occurred at a concentration of 0.27 mmol·litre−1 in the adult preparations and at 1.34 mmol·litre−1 in the infant ones. At 2.86 mmol·litre−1 active force had fallen to 43.4% ±2.2 (SEM) of the control value in the adults and to 52.4% ±3.3 (SEM) in the infants. These results suggest that the infant myocardium is no more sensitive to the negative inotropic effect of acebutolol than is the adult myocardium.
Clostridium difficile toxin A stimulates intracellular calcium release and chemotactic response in human granulocytes.
Authors: C Pothoulakis, R Sullivan, D A Melnick, G Triadafilopoulos, A S Gadenne, T Meshulam, J T LaMont
Journal: Journal of Clinical Investigation (1988)

Clostridium difficile, a common enteric pathogen, mediates tissue damage and intestinal fluid secretion by release of two protein exotoxins: toxin A, an enterotoxin, and toxin B, a cytotoxin. Because toxin A elicits an intense inflammatory reaction in vivo, we studied the effects of highly purified C. difficile toxins on activation of human granulocytes. Toxin A at concentrations of 10(-7) to 10(-6) M, but not toxin B, elicited a significant chemotactic and chemokinetic response by granulocytes that was comparable with that induced by the chemotactic factor N-FMLP (10(-7) M). Neither toxin stimulated release of superoxide anion from granulocytes. Toxin A produced a rapid, transient rise in cytosolic [Ca2+]i, as measured by quin 2 fluorescence. Pertussis toxin and depletion of intra- and extracellular calcium blocked the toxin A effect on cytosolic [Ca2+]i. These findings suggest that the inflammatory effects of C. difficile toxin A in the intestine may be related to its ability to mobilize intracellular Ca2+ and elicit a chemotactic response by granulocytes.
Nur77 Activated by Hypoxia-Inducible Factor-1α Overproduces Proopiomelanocortin in von Hippel-Lindau-Mutated Renal Cell Carcinoma
Authors: Ji-Woong Choi, Sang Chul Park, Gyeong Hoon Kang, Jun O. Liu, Hong-Duk Youn
Journal: Cancer Research (2004)

Abstract Mutation in the von Hippel-Lindau (VHL) protein associated with renal cell carcinoma causes hypoxia-inducible factor (HIF) to stabilize and consequently to induce various HIF-targeting proteins. In this study, we found that proopiomelanocortin (POMC), an adrenocorticotropic hormone precursor, is up-regulated constitutively in VHL-mutated renal cell carcinoma. A critical transcription factor responsible for POMC overproduction was identified as Nur77, a member of the orphan steroid receptor superfamily. Little is known about how VHL mutation leads to activation of Nur77. We report that Nur77 is directly regulated by HIF. We show that HIF-1α, but not HIF-2α, binds to a putative HIF responsive element in the Nur77 promoter, activating the expression of Nur77. Mutation or deletion of the HIF binding site in the Nur77 promoter abrogates activation of a luciferase reporter gene under the control of Nur77 promoter by HIF-1α. The treatment of Nur77 antisense oligonucleotide reduces POMC transcription under hypoxic conditions. We confirmed that Nur77 and POMC are up-regulated in VHL-mutated renal cell carcinoma. In this study, we provide the first molecular evidence that Nur77 activated by HIF under hypoxic conditions regulates production of the peptide hormone precursor POMC.