tbuckley/cabot-search huggingface dataset:
Changes in Cardiac Output with Age
Authors: MARTIN BRANDFONBRENER, MILTON LANDOWNE, NATHAN W. SHOCK
Journal: Circulation (1955)

In the first of two papers, the details and results of a systematic, carefully standardized application of dye dilution technic to the measurement of cardiac output are reported. A substantially reduced output was a consistent finding in older subjects. Factors responsible for this are analyzed in this article, and further interpretations are made in the succeeding article. One result of the analysis of time-concentration curves of dye provides an interesting relationship to clinical estimates of circulation time.
Rat Liver Regeneration After 90% Partial Hepatectomy
Authors: Johannes Gaub, Johan Iversen
Journal: Hepatology (1984)

In previous studies, 90% partial hepatectomy in the rat was invariably accompanied by 100% mortality within 40 hr. This paper describes a technique by which 90% of the liver mass can be removed with only 14% mortality, provided that rats have free access to glucose-containing drinking water. Measurements of total liver DNA, [ 3 H]thymidine labeling index and mitotic index suggest rapid cell proliferation, commensurate with a powerful regenerative stimulus. In the presence of normoglycemia, peripheral insulin and glucagon concentrations were elevated to levels normally observed in the portal vein.
Increased Glutamine in Patients Undergoing Long-term Treatment for Schizophrenia
Authors: Juan R. Bustillo, Hongji Chen, Thomas Jones, Nicholas Lemke, Christopher Abbott, Clifford Qualls, Jose Canive, Charles Gasparovic
Journal: JAMA Psychiatry (2014)

The N-methyl-d-aspartic acid receptor hypofunction model of schizophrenia predicts a paradoxical increase in synaptic glutamate release. In vivo measurement of glutamatergic neurotransmission in humans is challenging, but glutamine, the principal metabolite of synaptic glutamate, can be quantified with proton magnetic resonance spectroscopy (1H-MRS). Although a few studies have measured glutamate, glutamine, and glutamine to glutamate ratio, it is not clear which of these 1H-MRS indices of glutamatergic neurotransmission is altered in schizophrenia.To examine glutamine, glutamate, and glutamine to glutamate ratio in the dorsal anterior cingulate, as well as their relationships with symptoms and cognition in schizophrenia.Cross-sectional design using 3-T 1H-MRS in participants recruited from university-based psychiatric outpatient clinics who underwent neuroimaging at an affiliated research facility. Participants were 84 patients with a DSM-IV-TR diagnosis of schizophrenia and 81 psychiatrically healthy volunteers, matched in age, sex, ethnicity, and occupational level to the head of household of family of origin.Glutamine, glutamate, and glutamine to glutamate ratio. Also symptoms and cognition.Glutamine was increased in the schizophrenia group (P = .01) as well as the glutamine to glutamate ratio (P = .007) but not glutamate (P = .89). Glutamine levels were positively correlated with severity of psychotic symptoms (P = .02). Choline was also increased in schizophrenia (P = .002).Elevated glutamine, which was directly related to psychotic symptoms, is consistent with increased glutamatergic synaptic release in schizophrenia, as predicted by the N-methyl-d-aspartic acid receptor hypofunction model. Further understanding the underlying mechanism of glutamatergic dysfunction in schizophrenia may lead to new pharmacological strategies to treat psychosis.
Exacerbation of Cerebral Injury in Mice That Express the P-Selectin Gene
Authors: E. S. Connolly, C. J. Winfree, C. J. Prestigiacomo, S. C. Kim, T. F. Choudhri, B. L. Hoh, Y. Naka, R. A. Solomon, D. J. Pinsky
Journal: Circulation Research (1997)

Abstract There is currently a stark therapeutic void in the treatment of evolving stroke. Although P-selectin is rapidly expressed by hypoxic endothelial cells in vitro, the functional significance of P-selectin expression in stroke remains unexplored. In order to identify the pathophysiological consequences of P-selectin expression and to identify P-selectin blockade as a potential new approach for the treatment of stroke, experiments were performed using a murine model of focal cerebral ischemia and reperfusion. Early P-selectin expression in the postischemic cerebral cortex was demonstrated by the specific accumulation of radiolabeled anti-murine P-selectin IgG, with the increased P-selectin expression localized to the ipsilateral cerebral microvascular endothelial cells by immunohistochemistry. In experiments designed to test the functional significance of increased P-selectin expression in stroke, neutrophil accumulation in the ischemic cortex of mice expressing the P-selectin gene (PS +/+) was demonstrated to be significantly greater than that in homozygous P-selectin–null mice (PS −/−). Reduced neutrophil influx was accompanied by greater postischemic cerebral reflow (measured by laser Doppler) in the PS −/− mice. In addition, PS −/− mice demonstrated smaller infarct volumes (5-fold reduction, P &lt;.05) and improved survival compared with PS +/+ mice (88% versus 44%, P &lt;.05). Functional blockade of P-selectin in PS +/+ mice using a monoclonal antibody directed against murine P-selectin also improved early reflow and stroke outcome compared with control mice, with reduced cerebral infarction volumes noted even when the blocking antibody was administered after occlusion of the middle cerebral artery. These data are the first to demonstrate a pathophysiological role for P-selectin in stroke and suggest that P-selectin blockade may represent a new therapeutic target in the treatment of stroke.
Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013
Authors: A. Goldhirsch, E.P. Winer, A.S. Coates, R.D. Gelber, M. Piccart-Gebhart, B. Thürlimann, H.-J. Senn, Kathy S. Albain, Fabrice André, Jonas Bergh, Hervé Bonnefoi, Denisse Bretel-Morales, Harold Burstein, Fatima Cardoso, Monica Castiglione-Gertsch, Alan S. Coates, Marco Colleoni, Alberto Costa, Giuseppe Curigliano, Nancy E. Davidson, Angelo Di Leo, Bent Ejlertsen, John F. Forbes, Richard D. Gelber, Michael Gnant, Aron Goldhirsch, Pamela Goodwin, Paul E. Goss, Jay R. Harris, Daniel F. Hayes, Clifford A. Hudis, James N. Ingle, Jacek Jassem, Zefei Jiang, Per Karlsson, Sibylle Loibl, Monica Morrow, Moise Namer, C. Kent Osborne, Ann H. Partridge, Frédérique Penault-Llorca, Charles M. Perou, Martine J. Piccart-Gebhart, Kathleen I. Pritchard, Emiel J.T. Rutgers, Felix Sedlmayer, Vladimir Semiglazov, Zhi-Ming Shao, Ian Smith, Beat Thürlimann, Masakazu Toi, Andrew Tutt, Michael Untch, Giuseppe Viale, Toru Watanabe, Nicholas Wilcken, Eric P. Winer, William C. Wood
Journal: Annals of Oncology (2013)

The 13th St Gallen International Breast Cancer Conference (2013) Expert Panel reviewed and endorsed substantial new evidence on aspects of the local and regional therapies for early breast cancer, supporting less extensive surgery to the axilla and shorter durations of radiation therapy. It refined its earlier approach to the classification and management of luminal disease in the absence of amplification or overexpression of the Human Epidermal growth factor Receptor 2 (HER2) oncogene, while retaining essentially unchanged recommendations for the systemic adjuvant therapy of HER2-positive and 'triple-negative' disease. The Panel again accepted that conventional clinico-pathological factors provided a surrogate subtype classification, while noting that in those areas of the world where multi-gene molecular assays are readily available many clinicians prefer to base chemotherapy decisions for patients with luminal disease on these genomic results rather than the surrogate subtype definitions. Several multi-gene molecular assays were recognized as providing accurate and reproducible prognostic information, and in some cases prediction of response to chemotherapy. Cost and availability preclude their application in many environments at the present time. Broad treatment recommendations are presented. Such recommendations do not imply that each Panel member agrees: indeed, among more than 100 questions, only one (trastuzumab duration) commanded 100% agreement. The various recommendations in fact carried differing degrees of support, as reflected in the nuanced wording of the text below and in the votes recorded in supplementary Appendix S1, available at Annals of Oncology online. Detailed decisions on treatment will as always involve clinical consideration of disease extent, host factors, patient preferences and social and economic constraints.
Interferon gamma inhibits apoptotic cell death in B cell chronic lymphocytic leukemia.
Authors: M Buschle, D Campana, S R Carding, C Richard, A V Hoffbrand, M K Brenner
Journal: The Journal of Experimental Medicine (1993)

The malignant, CD5+ B lymphocytes of B cell chronic lymphocytic leukemia (B-CLL) die by apoptosis in vitro. This is in contrast to the prolonged life span of the leukemic cells in vivo and likely reflects the lack of essential growth factors in the tissue culture medium. We found that interferon gamma (IFN-gamma) inhibits programmed cell death and promotes survival of B-CLL cells in culture. This effect may also be important in vivo: increased serum levels of IFN-gamma, ranging from 60 to &amp;gt; 2,200 pg/ml, were found in 7 of 10 B-CLL samples tested, whereas the sera of 10 healthy individuals did not contain detectable levels of this cytokine (&amp;lt; 20 pg/ml). High levels of IFN-gamma message were detected in RNA from T cell-depleted B-CLL peripheral blood samples by Northern blot analysis. Synthesis of IFN-gamma by B-CLL lymphocytes was confirmed by in situ hybridization and flow cytometry. The majority of B-CLL cells (74-82%) expressed detectable levels of IFN-gamma mRNA, and CD19+ B-CLL cells were labeled with anti-IFN-gamma monoclonal antibodies. These results show that IFN-gamma inhibits programmed cell death in B-CLL cells and suggest that the malignant cells are able to synthesize this cytokine. By delaying apoptosis, IFN-gamma may extend the life span of the malignant cells and thereby contribute to their clonal accumulation.
Uses and abuses of recovery: implementing recovery-oriented practices in mental health systems
Authors: Mike Slade, Michaela Amering, Marianne Farkas, Bridget Hamilton, Mary O'Hagan, Graham Panther, Rachel Perkins, Geoff Shepherd, Samson Tse, Rob Whitley
Journal: World Psychiatry (2014)

An understanding of recovery as a personal and subjective experience has emerged within mental health systems. This meaning of recovery now underpins mental health policy in many countries. Developing a focus on this type of recovery will involve transformation within mental health systems. Human systems do not easily transform. In this paper, we identify seven mis-uses ("abuses") of the concept of recovery: recovery is the latest model; recovery does not apply to "my" patients; services can make people recover through effective treatment; compulsory detention and treatment aid recovery; a recovery orientation means closing services; recovery is about making people independent and normal; and contributing to society happens only after the person is recovered. We then identify ten empirically-validated interventions which support recovery, by targeting key recovery processes of connectedness, hope, identity, meaning and empowerment (the CHIME framework). The ten interventions are peer support workers, advance directives, wellness recovery action planning, illness management and recovery, REFOCUS, strengths model, recovery colleges or recovery education programs, individual placement and support, supported housing, and mental health trialogues. Finally, three scientific challenges are identified: broadening cultural understandings of recovery, implementing organizational transformation, and promoting citizenship.
Indoor air pollution and the lung in low- and medium-income countries
Authors: Om P. Kurmi, Kin Bong Hubert Lam, Jon G. Ayres
Journal: European Respiratory Journal (2012)

Over half the world's population, mostly from developing countries, use solid fuel for domestic purposes and are exposed to very high concentrations of harmful air pollutants with potential health effects such as respiratory problems, cardiovascular problems, infant mortality and ocular problems. The evidence also suggests that, although the total percentage of people using solid fuel is decreasing, the absolute number is currently increasing. Exposure to smoke from solid fuel burning increases the risk of chronic obstructive pulmonary disease (COPD) and lung cancer in adults, and acute lower respiratory tract infection/pneumonia in children. Despite the heterogeneity among studies, the association between COPD and exposure to smoke produced by burning different types of solid fuel is consistent. However, there is strong evidence that while coal burning is a risk factor for lung cancer, exposure to other biomass fuel smoke is less so. There is some evidence that reduction of smoke exposure using improved cooking stoves reduces the risk of COPD and, possibly, acute lower respiratory infection in children, so approaches to reduce biomass smoke exposure are likely to result in reductions in the global burden of respiratory disease.
Sensory Function and Albumin Excretion According to Diagnostic Criteria for Diabetes
Authors: Jay M. Sosenko, Martha Kato, Ronald B. Goldberg
Journal: Diabetes Care (2004)

The purpose of this study was to examine sensory function and albumin excretion according to categories of glucose tolerance in individuals undergoing screening for diabetes.Sensory function and albumin excretion measurements were obtained in 636 individuals at the time of screening for diabetes according to American Diabetes Association glucose tolerance criteria. Sensory thresholds were measured by forced-choice techniques. Albumin-to-creatinine ratios were calculated from spot urine samples.Of 90 individuals whose glucose levels were in the range for diabetes, 65 had fasting glucose values >or=126 mg/dl, whereas 25 had 2-h glucose values >or=200 mg/dl, with fasting glucose values <126 mg/dl. In covariance analyses, those with fasting glucose levels >or=126 mg/dl had higher vibration (P < 0.01) and thermal (P < 0.05 for cool and warm) thresholds than those with normal glucose tolerance. This pattern was also evident for albumin-to-creatinine ratios (P < 0.001). In contrast, those with 2-h glucose values >or=200 mg/dl and fasting glucose values <126 mg/dl had sensory threshold and albumin-to-creatinine ratio values similar to those of the normal group. Individuals with fasting glucose levels >or=126 mg/dl had higher vibration threshold and albumin-to-creatinine ratio values (<0.05 and <0.01, respectively) than those with levels <126 mg/dl.Sensory threshold and albumin excretion values already tend to be greater than normal at screening in individuals with fasting glucose levels >or=126 mg/dl, but not in those with levels <126 mg/dl. A reliance on fasting glucose levels >or=126 mg/dl for screening might not be sufficient for early intervention and the optimal prevention of diabetes complications.
A myelin basic protein peptide is recognized by cytotoxic T cells in the context of four HLA-DR types associated with multiple sclerosis.
Authors: R Martin, M D Howell, D Jaraquemada, M Flerlage, J Richert, S Brostoff, E O Long, D E McFarlin, H F McFarland
Journal: The Journal of Experimental Medicine (1991)

We have examined previously the peptide specificity of the T cell response to myelin basic protein (MBP) in patients with multiple sclerosis (MS) and healthy controls, and demonstrated that an epitope spanning amino acids 87-106 was frequently recognized. Because this region is encephalitogenic in some experimental animals, it has been postulated that the response to the epitope may have relevance to MS. In this study, the fine specificity of this response is studied using four well-characterized, monospecific T cell lines from three MS patients and an identical twin of a patient. Each of the lines recognized a peptide with the same core sequence, amino acids 89-99, although the responses were affected to various degrees by truncations at the COOH- or NH2 terminal ends of the 87-106 epitope. Importantly, the epitope was recognized in conjunction with four different HLA-DR molecules. Also, the T cell receptor beta chain usage was heterogeneous, and each line expressed a different VDJ sequence. The four HLA-DR molecules restricting the response to this epitope have been shown to be overrepresented in MS populations in various geographic areas, suggesting that the response to this region of the MBP molecule may be relevant to the pathogenesis of MS. These findings may have important implications in designing therapeutic strategies for the disease.
Sleep-disordered breathing and hormones
Authors: T. Saaresranta, O. Polo
Journal: European Respiratory Journal (2003)

Sleep-disordered breathing (SDB) is not only a problem of the upper airway but is a systemic condition with endocrine and metabolic interactions. The accumulating body of evidence shows that SDB induces changes in the serum levels or secretory patterns of several hormones. Conversely, various endocrine disorders and hormone therapies may induce, exacerbate or alleviate SDB. Much of the understanding of the interactions between hormones and sleep-disordered breathing derive from intervention studies with nasal continuous positive airway pressure therapy. Better understanding of hormones and breathing may open new perspectives in developing strategies to prevent, alleviate or cure sleep-disordered breathing and its systemic consequences.
Capecitabine in combination with preoperative radiation therapy in locally advanced, resectable, rectal cancer: a multicentric phase II study
Authors: A. De Paoli, S. Chiara, G. Luppi, M.L. Friso, G.D. Beretta, S. Del Prete, L. Pasetto, M. Santantonio, E. Sarti, G. Mantello, R. Innocente, S. Frustaci, R. Corvò, R. Rosso
Journal: Annals of Oncology (2005)
The Relationship of Reticular Basement Membrane Thickness to Airway Wall Remodeling in Asthma
Authors: Alan L. James, Peta S. Maxwell, Gladys Pearce-Pinto, John G. Elliot, Neil G. Carroll
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Assessment of airway wall remodeling in asthma is difficult in vivo. The thickness of deposited extracellular matrix proteins below the epithelium, the reticular basement membrane, can be assessed by bronchial biopsy of proximal airways. The aim of this study was to determine the relationship between the thickness of the reticular basement membrane in a sample equivalent to a central airway biopsy and the dimensions of the airway wall measured on transverse sections of both central and peripheral airways. Large and small cartilaginous and membranous airways from persons who had died from asthma (fatal asthma, n = 5) or from nonrespiratory causes with asthma (nonfatal asthma, n = 5) or without asthma (control subjects, n = 5) were studied. Reticular basement membrane thickness correlated with the percentage of smooth muscle, submucosal mucous gland, and inner wall area (p < 0.05) in large cartilaginous airways, and with inner wall area and area of smooth muscle (p < 0.01) in small cartilaginous airways, but was not related to airway wall dimensions in membranous airways. These findings show that reticular basement membrane thickness of central airways, which may be assessed by endobronchial biopsy, is correlated with airway remodeling in cartilaginous airways but not with airway wall dimensions of membranous airways.
Adherence of pilus- Opa+ gonococci to epithelial cells in vitro involves heparan sulfate.
Authors: T Chen, R J Belland, J Wilson, J Swanson
Journal: The Journal of Experimental Medicine (1995)

Neisseria gonorrhoeae attaches to host epithelial cells via pili and opacity-associated (Opa) outer membrane proteins. Pilus- gonococci (Gc) of strain MS11 adhere to both human and nonhuman cells, but only when particular Opa proteins are expressed; OpaA+ variants adhere best, OpaC+ variants are next best, and the seven other Opa+ variants adhere poorly or not at all. The adherence of OpaA+ Gc to Chinese hamster ovary (CHO) cells is inhibited by heparin or heparan sulfate (HS), but not by chondroitin sulfate. OpaA+ Gc do not adhere to CHO cells devoid of HS proteoglycans; low concentrations of heparin restore OpaA+ Gc adherence to these HS-deficient CHO cells and high concentrations inhibit it. 3H-heparin binding to whole Gc parallels their adherence abilities (OpaA+ > OpaC+ > OpaH+ >> Opas B, D, E, F, G, I = Opa- = 0). Opa proteins separated by SDS-PAGE also bind 3H-heparin. These data suggest that adherence of pilus-, Opa+ Gc involves HS-proteoglycan of eukaryotic cells.
Hormonal replacement therapy may reduce the risk for RA in women with early arthritis who carry HLA-DRB1 *01 and/or *04 alleles by protecting against the production of anti-CCP: results from the ESPOIR cohort
Authors: C. Salliot, C. Bombardier, A. Saraux, B. Combe, M. Dougados
Journal: Annals of the Rheumatic Diseases (2009)

Objective To assess the effect of reproductive factors, especially hormone replacement therapy (HRT) and its interaction with HLA-DRB1 *01 and/or *04 alleles on the diagnosis of rheumatoid arthritis (RA) and the presence of anti-cyclic citrullinated peptide (CCP) antibodies in women included in the ESPOIR cohort (early arthritis cohort). Methods 568 patients were included in the analyses, which were performed using logistic regression. Results HRT reduced the risk of RA due to the HLA-DRB1 *01 and/or *04 alleles from OR 1.88 (95% CI 1.32 to 2.68, p<0.000) for HLA-DRB1 *01 and/or *04 alleles alone to OR 1.07 (95% CI 0.51 to 2.26, p=0.85) in women with HLA-DRB1 *01 and/or *04 alleles who received HRT. One explanation might be the protective effect of HRT on the presence of anti-CCP antibodies (OR 0.43, 95% CI 0.24 to 0.77, p<0.006). Other reproductive factors such as the number of pregnancies, menopause and age at menopause, age at menarche and a history of pregnancy with poor outcome were not associated with the diagnosis of RA and the presence of anti-CCP antibodies. Conclusion HRT may reduce the risk of RA due to HLA-DRB1 *01 and/or *04 alleles by protecting against the production of anti-CCP antibodies.
The Role of the ErbB Family Members in Non–Small Cell Lung Cancers Sensitive to Epidermal Growth Factor Receptor Kinase Inhibitors
Authors: Jeffrey A. Engelman, Lewis C. Cantley
Journal: Clinical Cancer Research (2006)

Abstract Inhibitors targeting the epidermal growth factor receptor (EGFR) are effective in a subset of non–small cell lung cancers. Such cancers often harbor EGFR mutations and/or amplification. These cancers require EGFR activity for the maintenance of critical intracellular survival and growth signaling pathways. Evidence is now accruing that EGFR works in concert with other ErbB family members, particularly HER2 and ErbB3, to activate these signaling pathways in lung cancers. These findings have important implications regarding the biology of these cancers and may lead to improved methods for identifying tumors that are responsive to EGFR kinase inhibitors and alternative therapies to treat cancers driven by ErbB signaling.