tbuckley/cabot-search huggingface dataset:
Imatinib Mesylate May Improve Fasting Blood Glucose in Diabetic Ph+ Chronic Myelogenous Leukemia Patients Responsive to Treatment
Authors: M. Breccia, M. Muscaritoli, Z. Aversa, F. Mandelli, G. Alimena
Journal: Journal of Clinical Oncology (2004)

coverage of the screening program.One explanation is the ever increasing use of imaging techniques as "opportunistic" clinical tools. 7he present data show the large increase in the incidence of breast cancer in the screened population of women.A proportion of the increase is undoubtedly due to changing risk factors related to fertility and child bearing (early menarche, late first pregnancy, low parity), but the main part is likely to be due to mammographic screening, used by a majority of the target population of women.Even though there is no noticeable decrease in incidence at older age, which would be predicted by an effective screening, there is no increase either.As such, these types of ecological data do not allow conclusions about the benefits of screening, particularly, because we do not know how the incidence would have changed without screening.However, a drastic remodeling of the age-incidence relationship in breast cancer has taken place, and the change is likely to continue.Undoubtedly, opportunistic screening will have similar effects, which will be noted in all developed countries when the proportion of screened women will increase.Breast cancer will definitely become a disease of middleaged women.
Clinical and Cardiodynamic Effects of Adrenocortical
Authors: MURRAY A. GREENE, ARTHUR GORDON, ADOLPH J. BOLTAX
Journal: Circulation (1960)

This study is concerned with the effects of adrenocortical steroids in patients with congestive heart failure. Nine adults with heart failure were studied during a steady clinical state (5 to 7 days), during administration for 13 to 16 days of prednisome (6 patients) or triamcinolone (3 patients) and in some subjects following steroid withdrawal. Daily determinations of fluid balances were made. Standard right heart catheterizations and measurements of blood volumes were performed prior to and at the termination of therapy. Three types of responses to steroids occurred. In 5 patients increases in subjective and objective manifestations of heart failure and increased fluid retention occurred. Four of them developed precarious clinical conditions during steroid therapy, requiring mercurial diuretics, but with poor results. In general, cardiodynamic status at the termination of steroid therapy correlated well with clinical status. In 3 patients the clinical status did not change. Some depression in urinary sodium and chloride excretions were noted during therapy. Cardiodynamics were unaltered, except for an unexplained decrease in right ventricular end-diastolic pressure in 1 patient. In 1 patient clinical and cardiodynamic state improved, despite positive fluid balance. This was the only subject with primary lung disease (emphysema) and cor pulmonale. These studies suggest that corticosteroids are generally detrimental in uncomplicated congestive heart failure. Greater deterioration appeared in subjects having the more severe degrees of decompensation, suggesting that exogenous fluid-retaining influences were added to endogenous fluid-retaining forces, resulting in further accumulation of fluid in a circulatory system already burdened by hypervolemia.
Stage IA-IIB Hodgkin's disease: staging and treatment of patients with large mediastinal adenopathy.
Authors: K A Leopold, G P Canellos, D Rosenthal, L N Shulman, H Weinstein, P Mauch
Journal: Journal of Clinical Oncology (1989)

Ninety-two patients with clinically staged (CS) IA-IIB Hodgkin's disease (HD) with large mediastinal adenopathy (LMA) underwent three different staging and treatment approaches between April 1969 and December 1984. These approaches included: (1) staging laparotomy followed by radiation therapy (RT) alone; (2) staging laparotomy followed by combined RT and chemotherapy (CMT); or (3) clinical staging followed by CMT. Patients treated with CMT were more likely to have "B" symptoms, extension into extranodal sites, or stage III disease. Patients treated with RT alone had a significantly higher risk of relapse as compared to patients receiving CMT. No overall survival differences were seen between the three groups of patients. For patients treated with CMT without RT to the spleen or abdominal nodes, the risk of relapse in the abdomen was low (4%). These data suggest that for those CS I-II HD patients with LMA who are treated with CMT, the role for staging laparotomy and abdominal irradiation is limited. RT alone remains an option for some patients with LMA, but careful assessment of the anatomic extent of thoracic disease as well as staging laparotomy is essential if such treatment is recommended.
MRI study of the size, symmetry and function of the trunk muscles among elite cricketers with and without low back pain
Authors: J Hides, W Stanton, M Freke, S Wilson, S McMahon, C Richardson
Journal: British Journal of Sports Medicine (2007)

To determine if asymmetry of trunk muscles and deficits of motor control exist among elite cricketers with and without low back pain (LBP).Single-blinded observational quasi-experimental design studyAssessments were conducted in a hospital setting.Among a total eligible sample of 26 male elite cricketers (mean age 21.2 (SD 2.0) years), selected to attend a national training camp, 21 participated in the study.The independent variables were 'group' (LBP or asymptomatic) and 'cricket position' (fast bowler versus the rest of the squad).The dependent variables were the cross-sectional areas (CSA) of the quadratus lumborum (QL), lumbar erector spinae plus multifidus (LES + M) and psoas muscles, the thickness of the internal oblique (IO) and transversus abdominis (TrA) muscles, and the amount of lateral slide of the anterior abdominal fascia.The QL and LES + M muscles were larger ipsilateral to the dominant arm. In the subgroup of fast bowlers with LBP, the asymmetry in the QL muscle was the greatest. The IO muscle was larger on the side contralateral to the dominant arm. No difference between sides was found for the psoas and TrA muscles. Cricketers with LBP showed a reduced ability to draw in the abdominal wall and contract the TrA muscle independently of the other abdominal muscles.This study provides new insights into trunk muscle size and function in elite cricketers, and evidence of impaired motor control in elite cricketers with LBP. Rehabilitation using a motor control approach has been shown to be effective for subjects with LBP, and this may also benefit elite cricketers.
CXCR3+CCR5+ T cells and autoimmune diseases: guilty as charged?
Authors: Charles R. Mackay
Journal: Journal of Clinical Investigation (2014)

Prior to the 1990s, genetic analyses indicated that many autoimmune diseases are driven by T cell responses; however, the identity of the pathogenic T cell populations responsible for dysfunctional autoimmune responses remained unclear. Some 20 years ago, the discovery of numerous chemokines and their receptors along with the development of specific mAbs to these provided a distinct advance. These new tools revealed a remarkable dichotomy and disclosed that some chemokine receptors guided the constitutive migration of T cells through lymphoid tissues, whereas others, such as CCR5 and CXCR3, guided effector and memory T cell migration to inflammatory lesions. These T cell markers enabled a new understanding of immune responses and the types of T cells involved in different inflammatory reactions.
The secretory IgA system of lung secretions in chronic obstructive bronchitis: comparison of sputum with secretions obtained during fibreoptic bronchoscopy.
Authors: J Wiggins, S L Hill, R A Stockley
Journal: Thorax (1984)

The constituents of the secretory immunoglobulin A system (dimeric IgA, total secretory component and free secretory component) were measured in sputum sol phase, tracheal aspirates, and bronchoalveolar lavage fluids from 15 patients undergoing fibreoptic bronchoscopy. All of the proteins showed a progressive decrease in concentration from sputum to the bronchoalveolar lavage fluids (2p less than 0.001). Standardisation of samples by means of protein concentration ratios showed that all secretions were generally similar in respect of their secretory IgA profiles, although major differences remained in some individual patients. The between patient variability of the results was generally reduced by the use of protein concentration ratios, allowing closer comparison between subjects. When the secretion albumin concentration was used as a standard, however, it increased the variability of the sputum sol phase IgA components (2p less than 0.01), whereas it decreased the variability of the IgA components in the bronchoalveolar lavage fluid (2p less than 0.05). The role of albumin as a standard protein for assessing the secretory IgA system in lung secretions remains uncertain.
Vascular calcification: expression patterns of the osteoblast-specific gene core binding factor α-1 and the protective factor matrix gla protein in human atherogenesis
Authors: M Engelse
Journal: Cardiovascular Research (2001)

Increasing evidence suggests that vascular calcification is a regulated process. We studied the vascular expression pattern of a key factor in mineralization and a counteracting, protective factor. Based on the phenotype of null mice, Core binding factor alpha-1 (Cbfa-1) plays a pivotal role in bone formation, whereas Matrix Gla Protein (MGP) is a potent inhibitor of vascular calcification.We investigated the expression of MGP and Cbfa-1 in cultured, human monocytic cells, endothelial cells and smooth muscle cells (SMC), as well as in normal and atherosclerotic vessel specimens.In cultured cells MGP is expressed in endothelial cells and SMC, whereas Cbfa-1 mRNA is predominantly present in macrophages and to a lesser extent in SMC. In the normal vessel wall MGP expression is high at the luminal side and declines toward the center of the media, whereas Cbfa-1 is absent. Moderate, diffuse calcification of the aorta media was observed only in those regions where MGP is low or absent. In atherosclerotic lesions MGP is expressed in endothelial cells and SMC that form fibrous caps, but is never present in macrophages. Cbfa-1 is synthesized in regions without MGP, it is associated with calcified areas and Cbfa-1 may be considered a marker for osteoprogenitor-like cells in the vessel wall.Our observations on MGP expression confirm and extend published data and are consistent with a protective function of MGP. Cbfa-1 expression is absent in normal medial SMC and co-localizes with neointimal macrophages and focal calcifications.
Decreased Neprilysin and Pulmonary Vascular Remodeling in Chronic Obstructive Pulmonary Disease
Authors: Marilee J. Wick, Erica J. Buesing, Carol A. Wehling, Zoe L. Loomis, Carlyne D. Cool, Martin R. Zamora, York E. Miller, Sean P. Colgan, Louis B. Hersh, Norbert F. Voelkel, Edward C. Dempsey
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Rationale: Studies with genetically engineered mice showed that decreased expression of the transmembrane peptidase neprilysin (NEP) increases susceptibility to hypoxic pulmonary vascular remodeling and hypertension; in hypoxic wild-type mice, expression is decreased early in distal pulmonary arteries, where prominent vascular remodeling occurs. Therefore, in humans with smoke- and hypoxia-induced vascular remodeling, as in chronic obstructive pulmonary disease (COPD), pulmonary activity/expression of NEP may likewise be decreased.Objectives: To test whether NEP activity and expression are reduced in COPD lungs and pulmonary arterial smooth muscle cells (SMCs) exposed to cigarette smoke extract or hypoxia and begin to investigate mechanisms involved.Methods: Control and advanced COPD lung lysates (n = 13–14) were analyzed for NEP activity and protein and mRNA expression. As a control, dipeptidyl peptidase IV activity was analyzed. Lung sections were assessed for vascular remodeling and oxidant damage. Human pulmonary arterial SMCs were exposed to cigarette smoke extract, hypoxia, or H2O2, and incubated with antioxidants or lysosomal/proteasomal inhibitors.Measurements and Main Results: COPD lungs demonstrated areas of vascular rarification, distal muscularization, and variable intimal and prominent medial/adventitial thickening. NEP activity was reduced by 76%; NEP protein expression was decreased in alveolar walls and distal vessels; mRNA expression was also decreased. In SMCs exposed to cigarette smoke extract, hypoxia, and H2O2, NEP activity and expression were also reduced. Reactive oxygen species inactivated NEP activity; NEP protein degradation appeared to be substantially induced.Conclusions: Mechanisms responsible for reduced NEP activity and protein expression include oxidative reactions and protein degradation. Maintaining or increasing lung NEP may protect against pulmonary vascular remodeling in response to chronic smoke and hypoxia.
Activated Ca2+/Calmodulin-Dependent Protein Kinase IIγ Is a Critical Regulator of Myeloid Leukemia Cell Proliferation
Authors: Jutong Si, Steven J. Collins
Journal: Cancer Research (2008)

Abstract Ca2+ signaling is an important component of signal transduction pathways regulating B and T lymphocyte proliferation, but the functional role of Ca2+ signaling in regulating myeloid leukemia cell proliferation has been largely unexplored. We observe that the activated (autophosphorylated) Ca2+/calmodulin-dependent protein kinase IIγ (CaMKIIγ) is invariably present in myeloid leukemia cell lines as well as in the majority of primary acute myelogenous leukemia patient samples. In contrast, myeloid leukemia cells induced to terminally differentiate or undergo growth arrest display a marked reduction in this CaMKIIγ autophosphorylation. In cells harboring the bcr-abl oncogene, the activation (autophosphorylation) of CaMKIIγ is regulated by this oncogene. Moreover, inhibition of CaMKIIγ activity with pharmacologic agents, dominant-negative constructs, or short hairpin RNAs inhibits the proliferation of myeloid leukemia cells, and this is associated with the inactivation/down-regulation of multiple critical signal transduction networks involving the mitogen-activated protein kinase, Janus-activated kinase/signal transducers and activators of transcription (Jak/Stat), and glycogen synthase kinase (GSK3β)/β-catenin pathways. In myeloid leukemia cells, CaMKIIγ directly phosphorylates Stat3 and enhances its transcriptional activity. Thus, CaMKIIγ is a critical regulator of multiple signaling networks regulating the proliferation of myeloid leukemia cells. Inhibiting CaMKIIγ may represent a novel approach in the targeted therapy of myeloid leukemia. [Cancer Res 2008;68(10):3733–42]
ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation
Authors: Valentin Fuster, Lars E. Rydén, David S. Cannom, Harry J. Crijns, Anne B. Curtis, Kenneth A. Ellenbogen, Jonathan L. Halperin, Jean-Yves Le Heuzey, G. Neal Kay, James E. Lowe, S. Bertil Olsson, Eric N. Prystowsky, Juan Luis Tamargo, Samuel Wann, Sidney C. Smith, Alice K. Jacobs, Cynthia D. Adams, Jeffery L. Anderson, Elliott M. Antman, Jonathan L. Halperin, Sharon Ann Hunt, Rick Nishimura, Joseph P. Ornato, Richard L. Page, Barbara Riegel, Silvia G. Priori, Jean-Jacques Blanc, Andrzej Budaj, A. John Camm, Veronica Dean, Jaap W. Deckers, Catherine Despres, Kenneth Dickstein, John Lekakis, Keith McGregor, Marco Metra, Joao Morais, Ady Osterspey, Juan Luis Tamargo, José Luis Zamorano
Journal: Circulation (2006)
Joffe will amend role for doctors in new bill on assisted dying
Authors: Adrian O'Dowd
Journal: BMJ (2005)

Joel Joffe, the cross bench peer who introduced a parliamentary bill on assisted dying last year, announced this week that he intends to modify his original proposals on the role of doctors in helping the terminally ill to die.

During a debate on the issue in the House of Lords on Monday, Lord Joffe announced a number of amendments to his initial Assisted Dying for the Terminally Ill Bill that would allow doctors to prescribe drugs to patients who wish to use them to die, but not to administer them.

The debate, featuring more than 70 speakers, centred on a report produced in April by the House of Lords select committee that considered the issues raised by Lord Joffe's original bill, which ran out of parliamentary time before it could …
Prolonged Cell Cycle Response of HeLa Cells to Low-Level Alkylation Exposure
Authors: Allen G. Schroering, Anbarasi Kothandapani, Steve M. Patrick, Saravanan Kaliyaperumal, Vishal P. Sharma, Kandace J. Williams
Journal: Cancer Research (2009)

Abstract Alkylation chemotherapy has been a long-standing treatment protocol for human neoplasia. N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) is a direct-acting monofunctional alkylator. Temozolomide is a clinical chemotherapeutic equivalent requiring metabolic breakdown to the alkylating agent. Both chemicals have similar mechanistic efficacy against DNA mismatch repair–proficient tumor cells that lack expression of methylguanine methyltransferase. Clinically relevant concentrations of both agents affect replicating cells only after the first cell cycle. This phenomenon has been attributed to replication fork arrest at unrepaired O6-methyldeoxyguanine lesions mispaired with thymine during the first replication cycle. Here, we show, by several different approaches, that MNNG-treated tumor cells do not arrest within the second cell cycle. Instead, the population slowly traverses through mitosis without cytokinesis into a third cell cycle. The peak of both ssDNA and dsDNA breaks occurs at the height of the long mitotic phase. The majority of the population emerges from mitosis as multinucleated cells that subsequently undergo cell death. However, a very small proportion of cells, &amp;lt;1:45,000, survive to form new colonies. Taken together, these results indicate that multinucleation within the third cell cycle, rather than replication fork arrest within the second cell cycle, is the primary trigger for cell death. Importantly, multinucleation and cell death are consistently avoided by a small percentage of the population that continues to divide. This information should prove clinically relevant for the future design of enhanced cancer chemotherapeutics. [Cancer Res 2009;69(15):6307–14]
The Polycomb Gene Product BMI1 Contributes to the Maintenance of Tumor-Initiating Side Population Cells in Hepatocellular Carcinoma
Authors: Tetsuhiro Chiba, Satoru Miyagi, Atsunori Saraya, Ryutaro Aoki, Atsuyoshi Seki, Yohei Morita, Yutaka Yonemitsu, Osamu Yokosuka, Hideki Taniguchi, Hiromitsu Nakauchi, Atsushi Iwama
Journal: Cancer Research (2008)

Side population (SP) cell analysis and sorting have been successfully applied to hepatocellular carcinoma (HCC) cell lines to identify a minor cell population with cancer stem cell properties. However, the molecular mechanisms operating in SP cells remain unclear. The polycomb gene product BMI1 plays a central role in the self-renewal of somatic stem cells in a variety of tissues and organs and seems to be implicated in tumor development. In this study, we determined the critical role of BMI1 in the maintenance of cancer stem cells with the SP phenotype in HCC cell lines. BMI1 was preferentially expressed in SP cells in Huh7 and PLC/PRF/5 HCC cells compared with the corresponding non-SP cells. Lentiviral knockdown of BMI1 considerably decreased the number of SP cells in both Huh7 and PLC/PRF/5 cells. Long-term culture of purified SP cells resulted in a drastic reduction in the SP subpopulation upon the BMI1 knockdown, indicating that BMI1 is required for the self-renewal of SP cells in culture. More importantly, the BMI1 knockdown abolished the tumor-initiating ability of SP cells in nonobese diabetic/severe combined immunodeficiency mice. Derepression of the INK4A and ARF genes that are major targets for BMI1 was not necessarily associated with impaired self-renewal of SP cells caused by BMI1 knockdown. In conclusion, our findings define an important role for BMI1 in the maintenance of tumor-initiating SP cells in HCC. BMI1 might be a novel therapeutic target for the eradication of cancer stem cells in HCC.
Serotonergic modulation of hypercapnia induced respiratory plasticity - changes in phrenic nerve activity
Authors: Maja Valic, Renata Pecotic, Ivana Pavlinac Dodig, Zoran Dogas
Journal: European Respiratory Journal (2014)

Intermittent hypercapnia, along with hypoxia, is a concomitant feature seen in obstructive sleep apnea patients. Intermittent hypercapnia can evoke long-term depression of phrenic nerve activity, but inconsistency in its manifestation, indicates involvement of additional factors.  This study was performed to investigate effects of episodic hypercapnia, and the role of intravenous injection of 5-HT receptors antagonist methysergide on phrenic nerve activity after exposures to intermittent hypercapnic stimulus.  Twelve, male, urethane anesthetized, vagotomized, paralyzed, mechanically ventilated Sprague-Dawley rats, were exposed to the acute intermittent hypercapnia protocol. Protocol consisted of 5 hypercapnic episodes (15% CO2), each lasting for 3 min (HC, control group, N=7). Experimental group (MeHC group, N=5) received an intravenous injection of methysergide, before the onset of the first hypercapnia.Peak phrenic nerve amplitude (pPNA), burst frequency, and breathing rhythm parameters were analyzed during the first hypercapnia, at 15, 30, and 60 minutes after the end of the last hypercapnia, and compared to the baseline values.  In HC group, non-significant changes of the pPNA were observed 15, 30 and 60 minutes after the last hypercapnia (pPNA was 107.3±16.6%, 84.1±21.0% and 92.5±18.5%, respectively, p>0.999). In MeHC group, significant decrease of pPNA 15, 30 and 60 min after the last hypercapnia was observed (64.1±5.0%, 57.9±6.8% and 49.6±6.7%, respectively, p  Administration of methysergide prior to the onset of the hypercapnia protocol intensified depression of the phrenic nerve activity following intermittent hypercapnia exposure.  HRZZ 09/165.
On the Role of the Kidney during Nephrotic Edema: Potassium Excretion and Sodium Retention 1
Authors: Jack Metcoff, Nobuyuki Nakasone, C. Phillips Rance
Journal: Journal of Clinical Investigation (1954)

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