tbuckley/cabot-search huggingface dataset:
Autonomic dysfunction and urinary albumin excretion rate are associated with an abnormal blood pressure pattern in normotensive normoalbuminuric type 1 diabetic patients.
Authors: M Pecis, M J Azevedo, R S Moraes, E L Ferlin, J L Gross
Journal: Diabetes Care (2000)

OBJECTIVE: To analyze the role of autonomic function and other possible factors associated with a blunted fall in nocturnal blood pressure. RESEARCH DESIGN AND METHODS: A total of 39 normotensive normnoalbuminuric type 1 diabetic patients were studied. Glomerular filtration rate (51Cr-EDTA technique), extracellular volume (51Cr-EDTA distribution volume), and urinary albumin excretion rate (UAER) (by radioimmunoassay) were measured. The subjects' 24-h ambulatory blood pressure and a 24-h electrocardiogram were recorded simultaneously Heart rate variability was calculated in the time domain for 24 h, in the frequency domain at night, at rest in the supine position, and during tilt. Patients were classified according to diastolic blood pressure (dBP) night/day ratio as dipper patients (&amp;lt; or =0.9) and nondipper patients (&amp;gt;0.9). RESULTS: Nondipper patients presented a higher low-frequency (LF) component (a sympathetic index) and higher LF/high-frequency (HF) ratio during sleep than dipper patients (0.29 +/- 0.12 vs. 0.19 +/- 0.10 normalized units [n.u.], P = 0.008; and 0.98 +/- 0.53 vs. 0.55 +/- 0.45 n.u., P = 0.007, respectively). At rest, the LF component in nondipper patients (0.38 +/- 0.13 n.u.) was higher than in dipper patients (0.27 +/- 0.12 n.u., P = 0.04). After the tilt, nondipper patients did not show an increase in the LF component (P = 0.32), but in dipper patients, the increase was significant (P = 0.001). In both groups, tilting promoted a decrease in the HF component (a parasympathetic index). In a stepwise multiple linear regression analysis, the LF component during sleep and the UAER accounted for 24% of the variability in the dBP night/day ratio. CONCLUSIONS: The predominance of sympathetic activity and increased levels of UAER, although within the normal range, are associated with a blunted fall in nocturnal dBP in normoalbuminuric normotensive type 1 diabetic patients.
Prevalence and Correlates of Depressive Symptoms Among Rural Older African Americans, Native Americans, and Whites With Diabetes
Authors: Ronny A. Bell, Shannon L. Smith, Thomas A. Arcury, Beverly M. Snively, Jeanette M. Stafford, Sara A. Quandt
Journal: Diabetes Care (2005)

OBJECTIVE—Depression is associated with morbidity, mortality, and decreased quality of life and is a well-established complication among people with diabetes. Little is known about the prevalence and correlates of depressive symptoms among older adults living in rural communities, particularly among ethnic minority groups, who are at increased risk of developing diabetes and complications. RESEARCH DESIGN AND METHODS—Data were analyzed from the ELDER (Evaluating Long-term Diabetes Self-management Among Elder Rural Adults) diabetes study in which face-to-face interviews were conducted with 696 older (≥65 years of age) African-American, Native American, and white men and women in two rural counties in central North Carolina. RESULTS—Using a criterion of ≥9 on a modified CES-D (Center for Epidemiologic Study of Depression) scale, 15.8% of the sample had depressive symptoms. In bivariate analyses, depressive symptomatology was more common among women and individuals who were unmarried and had less than a high school education, fewer financial resources, more chronic conditions, more prescription medications, and lower physical functioning. In multivariate analyses, sex, education, living arrangement, BMI, number of prescription medications, number of chronic conditions, and physical functioning remained significant. CONCLUSIONS—These results show that older rural adults with diabetes are at high risk for depressive symptoms, regardless of their ethnic group, and that certain demographic and health characteristics are important factors in this association. These findings add to the limited body of knowledge of comorbid depression in this population. Greater attention should be paid to diagnosing and treating this condition by those who provide care to these populations.
Précis of <i>The Modularity of Mind</i>
Authors: Jerry A. Fodor
Journal: Behavioral and Brain Sciences (1985)

Abstract The Modularity of Mind proposes an alternative to the “New Look” or “interaetionist” view of cognitive architecture that has dominated several decades of cognitive science. Whereas interactionism stresses the continuity of perceptual and cognitive processes, modularity theory argues for their distinctness. It is argued, in particular, that the apparent plausibility of New Look theorizing derives from the failure to distinguish between the (correct) claim that perceptual processes are inferential and the (dubious) claim that they are unencapsidated , that is, that they are arbitrarily sensitive to the organism's beliefs and desires. In fact, according to modularity theory, perceptual processes are computationally isolated from much of the background knowledge to which cognitive processes have access. The postulation of autonomous, domain-specific psychological mechanisms underlying perceptual integration connects modularity theory with the tradition of faculty psychology, in particular, with the work of Franz Joseph Call. Some of these historical affinities, and some of the relations between faculty psychology and Cartesianism, are discussed in the book.
Natural killer clones derived from fetal (25 wk) blood. Probing the human T cell receptor with WT31 monoclonal antibody.
Authors: A Nowill, P Moingeon, A Ythier, M Graziani, F Faure, L Delmon, M Rainaut, F Forrestier, C Bohuon, T Hercend
Journal: The Journal of Experimental Medicine (1986)

We have conducted a phenotypic and functional analysis of 19 cloned cell lines generated after allogeneic stimulation of circulating lymphocytes from a normal human fetus aged 25 wk. Using a limited series of mAbs (Anti-T3, WT31, T4, T8, and NKH1A), cloned cells were found to fall in three groups. Three clones have a conventional "inducer" phenotype. Three clones have a phenotype (T3+, WT31+, T8+, and NKH1A+) similar to that of certain NK active mature T lymphocytes present in adult peripheral blood. In contrast, 13 cell lines display surface characteristics that have not been described previously. Indeed, they express T3 proteins but not the WT31 determinant. In light of previous studies, these results show that WT31 mAb is a unique reagent directed at an invariant epitope of the human T cell receptor that is not present on all circulating T3+ fetal lymphocytes. Functionally the T3+, WT31+, and NKH1A+ clones were found to kill immunizing LAZ 388 cells, as well as K562, while T3+, WT31- and NKH1A+ clones display NK-like function exclusively. Moreover, only WT31+ lymphocytes present in the cell line used for cloning experiments have the capacity to recognize alloantigen-bearing cells. Together, these data suggest that expression of WT31 may be necessary for recognition of alloantigens, while NK reactions mediated by T3+ lymphocytes are WT31-independent.
Left Ventricular Geometry and Hypotension in End-Stage Renal Disease
Authors: Giovanni de Simone
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Hemodynamic and nonhemodynamic factors are implicated in the maintenance and aggravation of left ventricular (LV) hypertrophy in ESRD. Functional consequences of LV geometry are of substantial importance in patients who undergo dialysis and may contribute to explain the negative outcome related to LV hypertrophy, also in patients without overt coronary heart disease (CHD). Whereas most patients with eccentric LV hypertrophy have systolic dysfunction and the underlying CHD imposes progression of their disease, when overt CHD does not occur to remodel left ventricle, concentric LV geometry is more prevalent in ESRD and functional consequences are different. Concentric LV geometry is very sensitive to abrupt changes of cardiac loading conditions because of increased LV stiffness. Dialysis-related decrease in LV filling pressure reduces Starling forces recruitment and causes a fall in stroke volume as a result of reduced preload. This fall cannot be compensated by increased contractility, as myocardial mechanics is impaired in concentric LV geometry and no functional reserve can be used. When adequate increase in heart rate is not achieved to compensate reduced stroke volume, cardiac output substantially decreases and hypotension occurs. Occurrence of hypotension in the context of concentric LV geometry might contribute to reduce repeatedly coronary blood flow supply in the stiff and thick myocardium and might accelerate myocardial structural deterioration seen in ESRD. E-mail: [email protected]
Monitoring Intervention Coverage in the Context of Universal Health Coverage
Authors: Ties Boerma, Carla AbouZahr, David Evans, Tim Evans
Journal: PLoS Medicine (2014)

As part of the Universal Health Coverage Collection, Ties Boerma and colleagues discuss monitoring intervention coverage related to the full spectrum of UHC, including health promotion and disease prevention, treatment, rehabilitation, and palliation. Please see later in the article for the Editors' Summary
A HaemAtlas: characterizing gene expression in differentiated human blood cells
Authors: Nicholas A. Watkins, Arief Gusnanto, Bernard de Bono, Subhajyoti De, Diego Miranda-Saavedra, Debbie L. Hardie, Will G. J. Angenent, Antony P. Attwood, Peter D. Ellis, Wendy Erber, Nicola S. Foad, Stephen F. Garner, Clare M. Isacke, Jennifer Jolley, Kerstin Koch, Iain C. Macaulay, Sarah L. Morley, Augusto Rendon, Kate M. Rice, Niall Taylor, Daphne C. Thijssen-Timmer, Marloes R. Tijssen, C. Ellen van der Schoot, Lorenz Wernisch, Thilo Winzer, Frank Dudbridge, Christopher D. Buckley, Cordelia F. Langford, Sarah Teichmann, Berthold Göttgens, Willem H. Ouwehand
Journal: Blood (2009)

Abstract Hematopoiesis is a carefully controlled process that is regulated by complex networks of transcription factors that are, in part, controlled by signals resulting from ligand binding to cell-surface receptors. To further understand hematopoiesis, we have compared gene expression profiles of human erythroblasts, megakaryocytes, B cells, cytotoxic and helper T cells, natural killer cells, granulocytes, and monocytes using whole genome microarrays. A bioinformatics analysis of these data was performed focusing on transcription factors, immunoglobulin superfamily members, and lineage-specific transcripts. We observed that the numbers of lineage-specific genes varies by 2 orders of magnitude, ranging from 5 for cytotoxic T cells to 878 for granulocytes. In addition, we have identified novel coexpression patterns for key transcription factors involved in hematopoiesis (eg, GATA3-GFI1 and GATA2-KLF1). This study represents the most comprehensive analysis of gene expression in hematopoietic cells to date and has identified genes that play key roles in lineage commitment and cell function. The data, which are freely accessible, will be invaluable for future studies on hematopoiesis and the role of specific genes and will also aid the understanding of the recent genome-wide association studies.
Analysis of CUL-5 expression in breast epithelial cells, breast cancer cell lines, normal tissues and tumor tissues.
Authors: Michael J Fay, Kenneth A Longo, George A Karathanasis, David M Shope, Craig J Mandernach, Jason R Leong, Alfred Hicks, Kenneth Pherson, Amyna Husain
Journal: Molecular Cancer (2003)

The chromosomal location of CUL-5 (11q 22-23) is associated with LOH in breast cancer, suggesting that CUL-5 may be a tumor suppressor. The purpose of this research was to determine if there is differential expression of CUL-5 in breast epithelial cells versus breast cancer cell lines, and normal human tissues versus human tumors. The expression of CUL-5 in breast epithelial cells (HMEC, MCF-10A), and breast cancer cells (MCF-7, MDA-MB-231) was examined using RT-PCR, Northern blot analysis, and Western blot analysis. The expression of mRNA for other CUL family members (CUL-1, -2, -3, -4A, and -4B) in these cells was evaluated by RT-PCR. A normal human tissue expression array and a cancer profiling array were used to examine CUL-5 expression in normal human tissues and matched normal tissues versus tumor tissues, respectively. CUL-5 is expressed at the mRNA and protein levels by breast epithelial cells (HMEC, MCF-10A) and breast cancer cells (MCF-7, MDA-MB-231). These cells also express mRNA for other CUL family members. The normal human tissue expression array revealed that CUL-5 is widely expressed. The cancer profiling array revealed that 82% (41/50) of the breast cancers demonstrated a decrease in CUL-5 expression versus the matched normal tissue. For the 50 cases of matched breast tissue there was a statistically significant ~2.2 fold decreased expression of CUL-5 in tumor tissue versus normal tissue (P < 0.0001). The data demonstrate no apparent decrease in CUL-5 expression in the breast cancer cell lines (MCF-7, MDA-MB-231) versus the breast epithelial cells (HMEC, MCF-10A). The decrease in CUL-5 expression in breast tumor tissue versus matched normal tissue supports the hypothesis that decreased expression of CUL-5 may play a role in breast tumorigenesis.
Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) - classification, diagnosis and management: review of the EAACI/ENDA# and GA2LEN/HANNA*
Authors: M. L. Kowalski, J. S. Makowska, M. Blanca, S. Bavbek, G. Bochenek, J. Bousquet, P. Bousquet, G. Celik, P. Demoly, E. R. Gomes, E. Niżankowska-Mogilnicka, A. Romano, M. Sanchez-Borges, M. Sanz, M. J. Torres, A. De Weck, A. Szczeklik, K. Brockow
Journal: Allergy (2011)

Nonsteroidal anti-inflammatory drugs (NSAIDs) are responsible for 21-25% of reported adverse drug events which include immunological and nonimmunological hypersensitivity reactions. This study presents up-to-date information on pathomechanisms, clinical spectrum, diagnostic tools and management of hypersensitivity reactions to NSAIDs. Clinically, NSAID hypersensitivity is particularly manifested by bronchial asthma, rhinosinusitis, anaphylaxis or urticaria and variety of late cutaneous and organ-specific reactions. Diagnosis of hypersensitivity to a NSAID includes understanding of the underlying mechanism and is necessary for prevention and management. A stepwise approach to the diagnosis of hypersensitivity to NSAIDs is proposed, including clinical history, in vitro testing and/or provocation test with a culprit or alternative drug depending on the type of the reaction. The diagnostic process should result in providing the patient with written information both on forbidden and on alternative drugs.
Genetic variants associated with warfarin dose in African-American individuals: a genome-wide association study
Authors: Minoli A Perera, Larisa H Cavallari, Nita A Limdi, Eric R Gamazon, Anuar Konkashbaev, Roxana Daneshjou, Anna Pluzhnikov, Dana C Crawford, Jelai Wang, Nianjun Liu, Nicholas Tatonetti, Stephane Bourgeois, Harumi Takahashi, Yukiko Bradford, Benjamin M Burkley, Robert J Desnick, Jonathan L Halperin, Sherief I Khalifa, Taimour Y Langaee, Steven A Lubitz, Edith A Nutescu, Matthew Oetjens, Mohamed H Shahin, Shitalben R Patel, Hersh Sagreiya, Matthew Tector, Karen E Weck, Mark J Rieder, Stuart A Scott, Alan HB Wu, James K Burmester, Mia Wadelius, Panos Deloukas, Michael J Wagner, Taisei Mushiroda, Michiaki Kubo, Dan M Roden, Nancy J Cox, Russ B Altman, Teri E Klein, Yusuke Nakamura, Julie A Johnson
Journal: The Lancet (2013)
Gain in Patients' Knowledge of Diabetes Management Targets Is Associated With Better Glycemic Control
Authors: Padmalatha Berikai, Peter M. Meyer, Rasa Kazlauskaite, Barbara Savoy, Kelly Kozik, Leon Fogelfeld
Journal: Diabetes Care (2007)

Optimal glycemic, lipid, and blood pressure control has been shown to decrease the microvascular and macrovascular complications of diabetes (1–10). However, the status of control of these cardiovascular risk factors in individuals with diabetes is far from optimal (11,12). Lack of patients' knowledge of the targets of diabetes care might be one of the reasons for the low level of control of risk factors. Some studies showed that only 23–25% of individuals with diabetes know what the target A1C level is (<7%), and about the same percent of patients know how to interpret A1C values in relation to their own glycemic control (13,14). Improving patients' knowledge might help attain the goals of diabetes management, but the supporting studies are limited (14–18).

We investigated whether the gain in the knowledge of the targets of diabetes care after receiving diabetes self-management education (DSME) predicts the achievement of target A1C levels (<7%) at 6 months.

This is a retrospective study of adult diabetic subjects who received DSME in the American Diabetes Association–certified Diabetes Center of John H. Stroger, Jr. Hospital of Cook County between 2001 and 2004.

Patients with baseline A1C levels ≥7% measured within 1 month of receiving DSME and with an ∼6-month follow-up A1C measurement (ranging 3–12 months and at least 3 months from the baseline A1C) were selected for this study. A1C was measured by the high-performance liquid chromatography method throughout the study period. After the educational sessions, patients received follow-up medical care by endocrinologists in conjunction with their primary …
Heat Shock Protein 90 Inhibitor 17-Dimethylaminoethylamino-17-Demethoxygeldanamycin Enhances EphA2+ Tumor Cell Recognition by Specific CD8+ T Cells
Authors: Mayumi Kawabe, Maja Mandic, Jennifer L. Taylor, Cecilia A. Vasquez, Amy K. Wesa, Leonard M. Neckers, Walter J. Storkus
Journal: Cancer Research (2009)

Abstract EphA2, a member of the receptor tyrosine kinase family, is commonly expressed by a broad range of cancer types, where its level of (over)expression correlates with poor clinical outcome. Because tumor cell expressed EphA2 is a nonmutated “self” protein, specific CD8+ T cells are subject to self-tolerance mechanisms and typically exhibit only moderate-to-low functional avidity, rendering them marginally competent to recognize EphA2+ tumor cells in vitro or in vivo. We have recently reported that the ability of specific CD8+ T cells to recognize EphA2+ tumor cells can be augmented after the cancer cells are pretreated with EphA2 agonists that promote proteasomal degradation and up-regulated expression of EphA2/class I complexes on the tumor cell membrane. In the current study, we show that treatment of EphA2+ tumor cells with the irreversible heat shock protein 90 inhibitor, 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), similarly enhances their recognition by EphA2-specific CD8+ T-cell lines and clones in vitro via a mechanism that is dependent on proteasome and transporter-associated protein function as well as the retrotranslocation of EphA2 into the tumor cytoplasm. When 17-DMAG and agonist anti-EphA2 monoclonal antibodies are coapplied, T-cell recognition of tumor cells is further increased over that observed for either agent alone. These studies suggest that EphA2 represents a novel heat shock protein 90 client protein and that the treatment of cancer patients with 17-DMAG–based “pulse” therapy may improve the antitumor efficacy of CD8+ T effector cells reactive against EphA2-derived epitopes. [Cancer Res 2009;69(17):6995–7003]
ACE Inhibitors Improve Diabetic Nephropathy Through Suppression of Renal MCP-1
Authors: Berthold Amann, Ralph Tinzmann, Bernhard Angelkort
Journal: Diabetes Care (2003)

OBJECTIVE—Chemokines play an important role in the pathogenesis of diabetic nephropathy. Angiotensin II induces several fibrogenic chemokines, namely monocyte chemoattractant protein-1 (MCP-1) and transforming growth factor-β. The progression of diabetic nephropathy can be retarded by ACE inhibitors (ACEIs) in patients with type 1 and type 2 diabetes. We examined if blockade of the renin-angiotensin system lowered urinary levels of the chemokine MCP-1 and correlated urinary MCP-1 (uMCP-1) with parameters of renal function and glucose and lipid metabolism before and after 1 year of treatment with an ACE inhibitor. RESEARCH DESIGN AND METHODS—In 22 patients with type 2 diabetes and diabetic nephropathy in stages 3–5, treatment with the ACEI lisinopril was initiated. Before treatment and after 12 months of continuous therapy, proteinuria, creatinine clearance, uMCP-1 levels, BMI, HbA1c, and serum cholesterol were assessed. RESULTS—Lisinopril treatment improved renal function. Proteinuria decreased from 410 ± 662 mg per 24 h to 270 ± 389 mg per 24 h. Creatinine clearance rose from 61 ± 26 to 77 ± 41 ml/min. Urinary MCP-1 levels decreased from 0.456 ± 0.22 ng/mg creatinine to 0.08 ± 0.096 ng/mg creatinine. The change in uMCP-1 correlated significantly (r = 0.61, P &amp;lt; 0.001) with the change in proteinuria. No other parameter correlated with the improvement in renal function. CONCLUSIONS—Blockade of the renin-angiotensin system in type 2 diabetic patients with diabetic nephropathy reduces uMCP-1 levels and improves renal function. Because MCP-1 induces monocyte immigration and differentiation to macrophages, which augment extracellular matrix production and tubulointerstitial fibrosis, pharmacological reduction of angiotensin II may also exert its beneficial effects in diabetic nephropathy by downregulation of renal MCP-1.
Expression of Liver Phenotypes in Cultured Mouse Hepatoma Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Gretchen J. Darlington, Hans Peter Bernhard, Richard A. Miller, Frank H. Ruddle
Journal: JNCI Journal of the National Cancer Institute (1980)

Mouse hepatoma cells were established in vitro as a permanently growing line designated Hepa. The mass population and a subclone were characterized for their karyotype and their retention of liver-specific properties. An examination of 17 hepatic traits revealed that the cell lines secreted several serum proteins. The activities of a number of liver-specific enzymes, however, appeared to be absent in these cells. The identification of differentiated properties of cultured hepatoma cells permits the use of these lines in a variety of studies such as cell hybridization, biochemical analysis of tissue-specific gene products, and the modulation of expression of genes governing differentiated phenotypes. This report presents the analysis of a broad spectrum of characteristics and thereby describes one of the most fully defined hepatoma cell lines of murine origin in the literature.
A call for action. The Pepper Commission's blueprint for health care reform
Authors: J. D. Rockefeller
Journal: JAMA (1991)

After a year of deliberation and investigation, the Pepper Commission recommended action to ensure that all Americans would have health insurance protection in an efficient, effective health care system. Because it believes that action is urgent, the commission would build universal coverage by securing, improving, and extending the combination of job-based and public coverage we now have. Reform would entail the following elements: a combination of incentives and requirements that would guarantee all workers (with their nonworking dependents) insurance coverage through their jobs; replacement of Medicaid with a new federal program that would cover all those not covered through the workplace and workers whose employers find public coverage more affordable; guaranteed affordable coverage for employers--through reform of private insurance, tax credits for small employers, and the opportunity to purchase public coverage; a minimum benefit standard for private and public plans that would cover preventive and primary services as well as catastrophic care and would include cost sharing, subject to ability to pay; and a combination of public and private sector initiatives to promote quality and contain costs.