tbuckley/cabot-search huggingface dataset:
Comparison of hemodynamic determinants for myocardial oxygen consumption under different contractile states in human ventricle.
Authors: H Takaoka, M Takeuchi, M Odake, Y Hayashi, K Hata, M Mori, M Yokoyama
Journal: Circulation (1993)

BACKGROUND Recently, several indexes such as tension-time index (TTI), tension-time or force-time integral (FTI), rate-pressure product (RPP), pressure-work index (PWI), and systolic pressure-volume area (PVA) have been developed as predictors of myocardial oxygen consumption in experimental and clinical studies. However, it is still unclear whether these indexes are reliable predictors of myocardial oxygen consumption under various contractile states in human hearts. METHODS AND RESULTS We assessed the relation between TTI, FTI, RPP, PWI, and PVA and myocardial oxygen consumption per beat (VO2) in 13 patients with heart disease during volume loading. Left ventricular (LV) volume and pressure were measured simultaneously by the conductance catheter with the tipped micromanometer technique. VO2 was calculated from arterial coronary sinus oxygen content difference, and coronary sinus blood flow was measured by the thermodilution method. After z transformation of the correlation coefficients, mean z value for the VO2-PVA relation (1.83 +/- 0.60) was greater than those for the VO2-TTI relation (1.22 +/- 0.66; p &lt; 0.005), VO2-FTI relation (1.18 +/- 0.61; p &lt; 0.05), VO2-RPP relation (0.95 +/- 0.65; p &lt; 0.05), and VO2-PWI relation (1.24 +/- 0.58; p &lt; 0.05). During dobutamine infusion (5 micrograms.kg-1.min-1) in five of the 13 patients, VO2 also correlated best with PVA (z = 1.70 +/- 0.89) compared with TTI (z = 1.43 +/- 0.86), FTI (z = 1.48 +/- 0.95), RPP (z = 1.00 +/- 0.53), and PWI (z = 0.88 +/- 0.80). The contractile efficiency (38 +/- 14% to 38 +/- 20%), the reciprocal of the slope of the VO2-PVA relation, remained unchanged, whereas the VO2,PVA 0.8 (VO2 at PVA = 0.8 J per beat/100 g LV) increased from 1.48 +/- 1.16 to 2.06 +/- 1.13 J per beat/100 g LV (p &lt; 0.05). These results show the parallel upward shift of the VO2-PVA relation during dobutamine infusion. Because increases in the VO2-intercept represent the VO2 for the increased excitation-contraction (E-C) coupling associated with the augmented contractile state, the parallelism of the VO2-PVA relation could discriminate between VO2 for mechanical work (PVA-dependent VO2) and VO2 for E-C coupling (PVA-independent VO2). CONCLUSIONS The results of the present study indicate that PVA is a reliable and valuable predictor of myocardial oxygen consumption under different contractile states in human hearts. The VO2-PVA relation could provide useful information about mechanoenergetics in diseased human hearts.
Management of Breast Cancer in the Genome Era
Authors: Phuong Khanh H. Morrow, Gabriel N. Hortobagyi
Journal: Annual Review of Medicine (2009)

The genomic era has been characterized by an exponential increase in the number of targets in the management of breast cancer. Prognostic profiling has helped to determine which tumors are more likely to be associated with poor disease-free survival. Gene expression profiles are being studied in order to improve predictions of response and toxicity. Epigenetics is being evaluated for its ability to influence estrogen receptor expression. However, these fields require further validation. This review discusses the advances in the management of breast cancer through genomic evaluation.
Can NO diffusion predict desaturation during maximal exercise
Authors: Eline Oppersma, W.J.C. van Beurden, M. Brusse-Keizer, P.D.L.P.M. van der Valk, F.H.C. de Jongh
Journal: European Respiratory Journal (2011)

Introduction:  Desaturation during maximal exercise can be caused by several problems; decreased diffusing capacity, leading to an increased Alveolar-arterial (A-a) oxygen gradient, or V/Q mismatch or a contact time problem. The present method to establish decreased diffusing capacity is the measurement of diffusing capacity for carbon monoxide (TLCO). We hypothesize that the diffusing capacity for nitric oxide (TLNO) is more accurate than TLCO.   Aim:  The aim of this study is to find out whether diffusing capacity for NO, as a marker for the membrane component of diffusion, can be a more accurate predictor of the A-a gradient at maximal exercise, compared to diffusing capacity for CO, as a marker for the membrane and hemodynamic component of diffusion.   Methods:  15 patients with pulmonary complaints (mean age 58 years) performed a combined single breath TLNO/TLCO measurement and a maximal exercise test. We constructed a model to predict the A-a gradient at maximal exercise.   Results:  The A-a gradient at maximal exercise can be predicted by TLCO%R, and resulted in an R 2  (coefficient of determination) of 0.64. TLNO%R predicted the A-a gradient at maximal exercise with an R 2  of 0.81 (see figure).   Conclusion:  The diffusing capacity for NO is a more accurate predictor of the A-a gradient at maximal exercise than the diffusing capacity for CO, and thereby a more accurate predictor of desaturation during exercise.   Reference:   1Lee, I van der  Resp Med  2007;101:1579-84.
Neoadjuvant Therapy With Trastuzumab, Paclitaxel and Epirubicin for HER-2–Positive Operable Breast Cancer
Authors: Manmeet S. Ahluwalia, Hamed A. Daw
Journal: Journal of Clinical Oncology (2005)

difficult to interpret.Nonetheless, the selection of patients who were more likely to have an inferior treatment outcome is a potential drawback of our study, as this could have reduced the observed magnitude of benefit to cetuximab and carboplatin.There is no published experience on the re-treatment of patients with platinum within 6 months of completing prior platinum in metastatic NPC.However, if we may draw an analogy with ovarian cancer, in which a platinum-free interval of Յ 6 months predicts inferior response to platinum retreatment, 10 the platinum-free interval reported in the study should adequately reflect the "platinum-refractoriness" of most patients.As described, the median platinum-free interval, defined as the period from the time platinum was last received to the first dose of cetuximab, was 3.8 months (116 days), and most patients experienced progressive disease within 6.7 months during platinum-chemotherapy (203 days) in this study.Therefore, the chance of recruiting patients who might still be sensitive to platinum should be small.Licitra et al have raised an interesting point about the need to maintain homogeneity when selecting patients for clinical trials based on recognized prognostic factors of NPC.Works from our institution and from others have identified several key prognostic factors for advanced NPC, including plasma Epstein-Barr virus level 11 and isolated intrathoracic metastasis. 12,13 It would be more relevant to incorporate some of these prognostic markers in a phase III setting in order to allow stratified randomization and/or analysis of results according to specific prognostic subgroups.Furthermore, at the time of this study, the influence of molecular heterogeneity in diluting the response to novel therapies in clinical trials had not been recognized. 14 Therefore, the design of future studies on EGFR inhibitors should take into account the known molecular factors that may predict response to these novel agents.
Lipid phosphate phosphatase-3 regulates tumor growth via β-catenin and Cyclin-D1 signaling
Authors: Ishita Chatterjee, Joseph O Humtsoe, Erin E Kohler, Claudio Sorio, Kishore K Wary
Journal: Molecular Cancer (2011)

Abstract Background The acquisition of proliferative and invasive phenotypes is considered a hallmark of neoplastic transformation; however, the underlying mechanisms are less well known. Lipid phosphate phosphatase-3 (LPP3) not only catalyzes the dephosphorylation of the bioactive lipid sphingosine-1-phosphate (S1P) to generate sphingosine but also may regulate embryonic development and angiogenesis via the Wnt pathway. The goal of this study was to determine the role of LPP3 in tumor cells. Results We observed increased expression of LPP3 in glioblastoma primary tumors and in U87 and U118 glioblastoma cell lines. We demonstrate that LPP3 -knockdown inhibited both U87 and U118 glioblastoma cell proliferation in culture and tumor growth in xenograft assays. Biochemical experiments provided evidence that LPP3 -knockdown reduced β-catenin, CYCLIN-D1, and CD133 expression, with a concomitant increase in phosphorylated β-catenin. In a converse experiment, the forced expression of LPP3 in human colon tumor (SW480) cells potentiated tumor growth via increased β-catenin stability and CYCLIN-D1 synthesis. In contrast, elevated expression of LPP3 had no tumorigenic effects on primary cells. Conclusions These results demonstrate for the first time an unexpected role of LPP3 in regulating glioblastoma progression by amplifying β-catenin and CYCLIN-D1 activities.
STUDIES ON ENDEMIC PNEUMONIA OF THE ALBINO RAT
Authors: John B. Nelson
Journal: The Journal of Experimental Medicine (1946)

A specific disease entity was established in white mice by the nasal instillation of lung and exudate suspensions from each of 14 adult albino rats affected with endemic pneumonia. The induced disease was characterized by pneumonia (96 per cent), otitis media (94 per cent), and rhinitis (30 per cent). It progressed slowly after an incubation period of 7 to 14 days and was attended by a variable mortality which reached 33 per cent in 22 weeks. Maintenance of the disease was regularly accomplished by direct transmission from mouse to mouse but only by the nasal route and only from the three foci of involvement. It was also transmissible by direct contact but required a prolonged period of exposure. The relation of the disease to infectious catarrh, which it closely resembles, is discussed.
Vaccination with Tumor Lysate-Pulsed Dendritic Cells Elicits Antigen-Specific, Cytotoxic T-Cells in Patients with Malignant Glioma
Authors: John S. Yu, Gentao Liu, Han Ying, William H. Yong, Keith L. Black, Christopher J. Wheeler
Journal: Cancer Research (2004)

Abstract The primary goal of this Phase I study was to assess the safety and bioactivity of tumor lysate-pulsed dendritic cell (DC) vaccination to treat patients with glioblastoma multiforme and anaplastic astrocytoma. Adverse events, survival, and cytotoxicity against autologous tumor and tumor-associated antigens were measured. Fourteen patients were thrice vaccinated 2 weeks apart with autologous DCs pulsed with tumor lysate. Peripheral blood mononuclear cells were differentiated into phenotypically and functionally confirmed DCs. Vaccination with tumor lysate-pulsed DCs was safe, and no evidence of autoimmune disease was noted. Ten patients were tested for the development of cytotoxicity through a quantitative PCR-based assay. Six of 10 patients demonstrated robust systemic cytotoxicity as demonstrated by IFN-γ expression by peripheral blood mononuclear cells in response to tumor lysate after vaccination. Using HLA-restricted tetramer staining, we identified a significant expansion in CD8+ antigen-specific T-cell clones against one or more of tumor-associated antigens MAGE-1, gp100, and HER-2 after DC vaccination in four of nine patients. A significant CD8+ T-cell infiltrate was noted intratumorally in three of six patients who underwent reoperation. The median survival for patients with recurrent glioblastoma multiforme in this study (n = 8) was 133 weeks. This Phase I study demonstrated the feasibility, safety, and bioactivity of an autologous tumor lysate-pulsed DC vaccine for patients with malignant glioma. We demonstrate for the first time the ability of an active immunotherapy strategy to generate antigen-specific cytotoxicity in brain tumor patients.
Minoxidil in patients with chronic left heart failure: contrasting hemodynamic and clinical effects in a controlled trial.
Authors: J A Franciosa, R A Jordan, M M Wilen, C L Leddy
Journal: Circulation (1984)

Minoxidil, a potent predominant arterial dilator, improves hemodynamics over the short term in patients with heart failure. In random double-blind fashion 17 patients with chronic left heart failure were given minoxidil (nine patients) or placebo (eight patients) in addition to digoxin and diuretics for 3 months. Cardiac index and heart rate increased and mean arterial pressure and systemic vascular resistance fell within 4 hr of minoxidil administration. Right heart and pulmonary arterial pressures were unchanged over the short term but rose after long-term minoxidil. After 3 months of minoxidil treatment, systemic vascular resistance was still reduced (11.7 +/- 6.3[SD] vs 17.1 +/- 3.1 U at baseline; p less than .05). Hemodynamics were similar at baseline and remained unchanged during placebo treatment. Mean left ventricular ejection fraction rose from 29.6 +/- 17.7% to 42.7 +/- 22.3% (p less than .05) after 3 months of minoxidil treatment (this result was influenced largely by responses in two patients), and remained unchanged (at 25.1 +/- 16.6%) after 3 months of placebo. Exercise duration and maximal oxygen uptake during exercise were unchanged during minoxidil or placebo treatment. Total clinical events, including increased need for diuretics, angina, ventricular arrhythmias, worsening heart failure, and death were all more frequent during minoxidil vs placebo administration (21 vs seven total events; p less than .01). Thus, despite improving hemodynamics and left ventricular function, long-term minoxidil administration was associated with a poorer clinical course in patients with chronic left ventricular failure. Furthermore, this experience demonstrates that improvement of left ventricular function alone cannot be reliably interpreted as proof of clinical efficacy of therapeutic interventions in patients with heart failure.
ADRB2 (Adrenergic B2 Receptor Agonist Gene) Arg 16 Allele and Effect of LABA Withdrawal in Patients with Moderate to Severe Asthma
Authors: M.L. Slankard, S. Canfield, M. Michelis, M. Mansukhani, B. McGoey, A. Paige, D.J. Lederer, E.A. DiMango
Journal: Journal of Allergy and Clinical Immunology (2011)
Change in Lung Function and Morbidity from Chronic Obstructive Pulmonary Disease in α<sub>1</sub>-Antitrypsin <i>MZ</i> Heterozygotes: A Longitudinal Study of the General Population
Authors: Morten Dahl, Anne Tybjærg-Hansen, Peter Lange, Jørgen Vestbo, Børge G. Nordestgaard
Journal: Annals of Internal Medicine (2002)

Background: A deteriorating effect of severe α1-antitrypsin deficiency (ZZ genotype) on lung function is well known, whereas the role of intermediate deficiency (MZ genotype) remains uncertain. Objective: To test the hypothesis that MZ intermediate α1-antitrypsin deficiency affects pulmonary function and disease. Design: Population-based cohort study with 21-year follow-up. Setting: Copenhagen, Denmark. Participants: 9187 adults randomly selected from the Danish general population. Measurements: Plasma α1-antitrypsin levels, annual decrease in FEV1, airway obstruction, and hospitalization and mortality from chronic obstructive pulmonary disease (COPD). Results: 451 participants (4.9%) carried the MZ genotype. Plasma α1-antitrypsin levels were 31% lower in MZ heterozygotes than in persons with the MM genotype (Student t-test, P < 0.001). Annual decrease in FEV1 was 25 mL in MZ heterozygotes and 21 mL in persons with the MM genotype (t-test, P = 0.048). Airway obstruction was found in 19% of MZ heterozygotes compared with 15% of MM carriers (chi-square test, P = 0.023); in a logistic regression analysis adjusted for age, sex, and tobacco consumption, the corresponding odds ratio was 1.3 (CI, 1.0 to 1.7). The incidence of hospitalization and mortality from COPD was 32 cases per 10 000 person-years in persons with the MZ genotype and 22 cases per 10 000 person-years in those with the MM genotype (log-rank test, P = 0.063). In a Cox regression model adjusted for age, sex, tobacco use, and FEV1 at study entry, relative risk for COPD outcomes in persons with the MZ genotype versus persons with the MM genotype was 1.5 (CI, 1.0 to 2.3). All these results were independent of the S and E alleles in this gene and were not affected by cystic fibrosis ΔF508 heterozygosity. Conclusions: MZ heterozygotes had a slightly greater rate of decrease in FEV1 and were modestly over-represented among persons with airway obstruction and COPD. In the population at large, MZ heterozygosity may account for a fraction of COPD cases—on the order of 2%, similar to the percentage of persons with COPD who have the severe but rare ZZ genotype.
Characterisation of long-term non-progression of HIV-1 infection after seroconversion: a cohort study
Authors: Jannie J van der Helm, Ronald Geskus, Sara Lodi, Laurence Meyer, Hanneke Schuitemaker, Barbara Gunsenheimer-Bartmeyer, Antonella d'Arminio Monforte, Ashley Olson, Giota Touloumi, Caroline Sabin, Kholoud Porter, Maria Prins
Journal: The Lancet HIV (2014)
Failure of Routine HIV-1 Tests in a Case Involving Transmission With Preseroconversion Blood Components During the Infectious Window Period
Authors: Ai Ee Ling
Journal: JAMA (2000)

Current screening practices for blood donations have been successful in reducing human immunodeficiency virus (HIV) transmission through receipt of contaminated blood products. However, HIV-infected blood donations made prior to seroconversion and before high levels of viral replication occur could test negative using both serologic antigen and antibody tests. Testing based on nucleic acid amplification (NAT) is being implemented to screen for HIV-infected blood donated during this period, yet the issue of single vs minipool donation screening remains unresolved.To determine HIV-1 genetic linkage between virus in 2 HIV-1-infected recipients of blood components and virus in the donor, who was HIV antigen and antibody negative at the time of donation; to screen the blood donor's plasma with HIV NAT assays, including those currently proposed for use in US blood donation screening.Case study conducted in October 1997 involving the Communicable Disease Centre, Singapore General Hospital, and the Singapore Blood Transfusion Service, Singapore.The blood donor and the 2 recipients of donor platelets and red blood cells.Genetic analysis of the HIV-1 p17 coding region of gag and the C2V5 region of env to determine the genetic relatedness of virus from the donor and recipients; reactivity in quantitative and qualitative assays, and reactivity in donor screening HIV NAT assays in single donation and minipool screening contexts.Direct DNA sequencing demonstrated identical HIV-1 subtype E viral sequences in the donor and recipients. Based on comparisons of a qualitative and quantitative assay for HIV-1 RNA levels, a low level of viremia (range, 5-39 copies/mL in plasma) was estimated to be in the donor's undiluted blood at the time of donation. Additional testing using donor-screening NAT assays showed consistent detection of HIV RNA in the undiluted donor plasma whereas detection was inconsistent at the 1:16 and 1:24 dilution levels currently used in minipool screening of blood donations in the United States.Transmission of HIV from a blood donor to a platelet recipient and a red blood cell recipient occurred in the preseroconversion infectious window period. The viral load in the implicated donation was estimated to be less than 40 copies/mL of plasma. Current US minipool HIV NAT screening protocols may not be sufficiently sensitive to detect all infectious window-period donations. JAMA. 2000;284:210-214
Brain imaging studies of appetite in the context of obesity and the menstrual cycle
Authors: D. A. Van Vugt
Journal: Human Reproduction Update (2009)

Obesity affects many aspects of health, including reproduction. Despite unrelenting warnings about the health consequences of obesity, its prevalence continues to rise. Beginning with the discovery of leptin in 1994, the endocrinology of energy homeostasis has been significantly advanced. More recently, brain imaging studies have been providing novel insights into homeostatic and hedonic aspects of human ingestive behavior. A comprehensive MEDLINE search was conducted on the topic of neuroendocrine control of ingestive behavior with an emphasis on functional magnetic resonance imaging studies. Additional articles were collected by hand searching the bibliographies of all relevant articles retrieved. This review describes recent advances in our understanding of endocrine signals that respond to acute and chronic energy states and regulate ingestive behavior so as to achieve a balance between energy intake and energy expenditure. Recently published brain imaging studies, describing the neural networks that process endocrine signals of energy state and hedonic cues associated with highly palatable foods, are highlighted. Brain responses to food cues are described in the context of appetite changes during the menstrual cycle both in normal physiology and under the conditions anorexia nervosa and bulimia nervosa. The prevalence of obesity belies the plethora of endocrine signals in place to ensure energy homeostasis. However, satiety signals appear to be counteracted by hedonic signals derived from highly palatable foods typical of today's diet. A better understanding of the interaction between homeostatic and hedonic signals is needed to devise effective strategies for dealing with obesity. Menstrual cycle dependent changes in brain responses to food cues may provide insight into the normal physiological control of ingestive behavior as well as dysfunctional regulation associated with disordered eating.
A new method for the determination of steroid sulphatase activity in leukocytes in X-linked recessive ichthyosis
Authors: A.C. JOBSIS, W.P. GROOT, A.E.F.H. MEIJER, C.M. LOOS
Journal: British Journal of Dermatology (1983)

The diagnosis of X-linked ichthyosis can now be reliably established by using a non-radioactive method to detect steroid sulphatase deficiency in leukocytes. This new method yields the same results with leukocytes as with cultured fibroblasts. The second type of microsomal arylsulphatase previously described in cultured fibroblasts is also present in leukocytes.
A Prospective PCR-Based Screening for the <i>EML4-ALK</i> Oncogene in Non–Small Cell Lung Cancer
Authors: Manabu Soda, Kazutoshi Isobe, Akira Inoue, Makoto Maemondo, Satoshi Oizumi, Yuka Fujita, Akihiko Gemma, Yoshihiro Yamashita, Toshihide Ueno, Kengo Takeuchi, Young Lim Choi, Hitoshi Miyazawa, Tomoaki Tanaka, Koichi Hagiwara, Hiroyuki Mano
Journal: Clinical Cancer Research (2012)

EML4-ALK is a lung cancer oncogene, and ALK inhibitors show marked therapeutic efficacy for tumors harboring this fusion gene. It remains unsettled, however, how the fusion gene should be detected in specimens other than formalin-fixed, paraffin-embedded tissue. We here tested whether reverse transcription PCR (RT-PCR)-based detection of EML4-ALK is a sensitive and reliable approach.We developed a multiplex RT-PCR system to capture ALK fusion transcripts and applied this technique to our prospective, nationwide cohort of non-small cell lung cancer (NSCLC) in Japan.During February to December 2009, we collected 916 specimens from 853 patients, quality filtering of which yielded 808 specimens of primary NSCLC from 754 individuals. Screening for EML4-ALK and KIF5B-ALK with our RT-PCR system identified EML4-ALK transcripts in 36 samples (4.46%) from 32 individuals (4.24%). The RT-PCR products were detected in specimens including bronchial washing fluid (n = 11), tumor biopsy (n = 8), resected tumor (n = 7), pleural effusion (n = 5), sputum (n = 4), and metastatic lymph node (n = 1). The results of RT-PCR were concordant with those of sensitive immunohistochemistry with ALK antibodies.Multiplex RT-PCR was confirmed to be a reliable technique for detection of ALK fusion transcripts. We propose that diagnostic tools for EML4-ALK should be selected in a manner dependent on the available specimen types. FISH and sensitive immunohistochemistry should be applied to formalin-fixed, paraffin-embedded tissue, but multiplex RT-PCR is appropriate for other specimen types.