tbuckley/cabot-search huggingface dataset:
Modulation of Endothelial Cell Growth Arrest and Apoptosis by Vascular Endothelial Growth Inhibitor
Authors: Jingyi Yu, Song Tian, Linda Metheny-Barlow, Li-Jin Chew, Andrew J. Hayes, Hongguang Pan, Guo-Liang Yu, Lu-Yuan Li
Journal: Circulation Research (2001)

Vascular endothelial growth inhibitor (VEGI), a new member of the tumor necrosis factor family, is an endothelial cell–specific gene and a potent inhibitor of endothelial cell proliferation, angiogenesis, and tumor growth. We report here that VEGI mediates the following two activities in endothelial cells: early G 1 arrest in G 0 /G 1 cells responding to growth stimuli, and programmed death in proliferating cells. G 0 /G 1 -synchronized bovine aortic endothelial cells were treated with VEGI before and after the onset of the growth cycle. When the cells were stimulated with growth conditions but treated simultaneously with VEGI, a reversible, early-G 1 growth arrest occurred, evidenced by the lack of late G 1 markers such as hyperphosphorylation of the retinoblastoma gene product and upregulation of the c-myc gene. Additionally, VEGI treatment led to inhibition of the activities of cyclin-dependent kinases CDK2, CDK4, and CDK6. In contrast, VEGI treatment of cells that had entered the growth cycle resulted in apoptotic cell death, as evidenced by terminal deoxytransferase labeling of fragmented DNA, caspase 3 activation, and annexin V staining, all of which were lacking in nonproliferating cells treated with VEGI. Additionally, stress-signaling proteins p38 and JNK were not as fully activated by VEGI in quiescent as compared with proliferating populations. These findings suggest a dual role for VEGI, the maintenance of growth arrest and induction of apoptosis, in the modulation of the endothelial cell cycle.
Consensus on biomarkers for neuroendocrine tumour disease
Authors: Kjell Oberg, Irvin M Modlin, Wouter De Herder, Marianne Pavel, David Klimstra, Andrea Frilling, David C Metz, Anthony Heaney, Dik Kwekkeboom, Jonathan Strosberg, Timothy Meyer, Steven F Moss, Kay Washington, Edward Wolin, Eric Liu, James Goldenring
Journal: The Lancet Oncology (2015)
Racial and Ethnic Differences in Health Care Access and Health Outcomes for Adults With Type 2 Diabetes
Authors: Maureen I. Harris
Journal: Diabetes Care (2001)

OBJECTIVE—To evaluate health care access and utilization and health status and outcomes for type 2 diabetic patients according to race and ethnicity and to determine whether health status is influenced by health care access and utilization. RESEARCH DESIGN AND METHODS—National samples of Caucasians, African-Americans, and Mexican-Americans were studied in the third National Health and Nutrition Examination Survey. Information on medical history and treatment of diabetes, health care access and utilization, and health status and outcomes was obtained by structured questionnaires and by clinical and laboratory assessments. RESULTS—Almost all patients in each race and ethnic group had one primary source of ambulatory medical care (92–97%), saw one physician at this source (83–92%), and had at least semiannual physician visits (83–90%). Almost all patients ≥65 years of age had health insurance (99–100%), and for those patients &amp;lt;65 years of age, Caucasians (91%) and African-Americans (89%) had higher rates of coverage than Mexican-Americans (66%). Rates of treatment with insulin or oral agents (71–78%), eye examination in the previous year (61–70%), blood pressure check in the previous 6 months (83–89%), and the proportion of hypertension that was diagnosed (84–91%) were similar for each race and ethnic group. Lower proportions of African-Americans and Mexican-Americans self-monitored their blood glucose (insulin-treated, 27 vs. 44% of Caucasians), had their cholesterol checked (62–68 vs. 81%), and had their dyslipidemia diagnosed (45 vs. 58%). African-American and Mexican-American patients had a somewhat higher proportion than Caucasian patients, with HbA1c ≥7% (58–66 vs. 55%), blood pressure ≥140/90 mmHg among those with diagnosed hypertension (60–65 vs. 55%), and clinical proteinuria (11–14 vs. 5%). In contrast, they had better levels of total cholesterol (≥240 mg/dl) (28–30 vs. 34%) and HDL cholesterol (≥45 mg/dl) (46–59 vs. 38%), and African-American and Mexican-American men were less overweight than Caucasian men (BMI ≥30) (34–37 vs. 44%), although the opposite was true for women. LDL cholesterol levels and the proportion of patients who smoked cigarettes or were hospitalized in the past year were similar among all three groups. In logistic regression analysis, there was little evidence that levels of blood glucose, blood pressure, lipids, or albuminuria were associated with access to or utilization of health care or with socioeconomic status. CONCLUSIONS—There are some differences by race and ethnicity in health care access and utilization and in health status and outcomes for adults with type 2 diabetes. However, the magnitude of these differences pale in comparison with the suboptimal health status of all three race and ethnic groups relative to established treatment goals. Health status does not appear to be influenced by access to health care.
Signaling effectors underlying pathologic growth and remodeling of the heart
Authors: Jop H. van Berlo, Marjorie Maillet, Jeffery D. Molkentin
Journal: Journal of Clinical Investigation (2013)

Cardiovascular disease is the number one cause of mortality in the Western world. The heart responds to many cardiopathological conditions with hypertrophic growth by enlarging individual myocytes to augment cardiac pump function and decrease ventricular wall tension. Initially, such cardiac hypertrophic growth is often compensatory, but as time progresses these changes become maladaptive. Cardiac hypertrophy is the strongest predictor for the development of heart failure, arrhythmia, and sudden death. Here we discuss therapeutic avenues emerging from molecular and genetic studies of cardiovascular disease in animal models. The majority of these are based on intracellular signaling pathways considered central to pathologic cardiac remodeling and hypertrophy, which then leads to heart failure. We focus our discussion on selected therapeutic targets that have more recently emerged and have a tangible translational potential given the available pharmacologic agents that could be readily evaluated in human clinical trials.
Transplantation of mouse HSCs genetically modified to express a CD4-restricted TCR results in long-term immunity that destroys tumors and initiates spontaneous autoimmunity
Authors: Sung P. Ha, Nicholas D. Klemen, Garrett H. Kinnebrew, Andrew G. Brandmaier, Jon Marsh, Giao Hangoc, Douglas C. Palmer, Nicholas P. Restifo, Kenneth Cornetta, Hal E. Broxmeyer, Christopher E. Touloukian
Journal: Journal of Clinical Investigation (2010)

The development of effective cancer immunotherapies has been consistently hampered by several factors, including an inability to instigate long-term effective functional antitumor immunity. This is particularly true for immunotherapies that focus on the adoptive transfer of activated or genetically modified mature CD8+ T cells. In this study, we sought to alter and enhance long-term host immunity by genetically modifying, then transplanting, mouse HSCs. We first cloned a previously identified tumor-reactive HLA-DR4–restricted CD4+ TCR specific for the melanocyte differentiation antigen tyrosinase-related protein 1 (Tyrp1), then constructed both a high-expression lentivirus vector and a TCR-transgenic mouse expressing the genes encoding this TCR. Using these tools, we demonstrated that both mouse and human HSCs established durable, high-efficiency TCR gene transfer following long-term transplantation into lethally irradiated mice transgenic for HLA-DR4. Recipients of genetically modified mouse HSCs developed spontaneous autoimmune vitiligo that was associated with the presence of a Th1-polarized memory effector CD4+ T cell population that expressed the Tyrp1-specific TCR. Most importantly, large numbers of CD4+ T cells expressing the Tyrp1-specific TCR were detected in secondary HLA-DR4–transgenic transplant recipients, and these mice were able to destroy subcutaneously administered melanoma cells without the aid of vaccination, immune modulation, or cytokine administration. These results demonstrate the creation of what we believe to be a novel translational model of durable lentiviral gene transfer that results in long-term effective immunity.
Evolution of Ancient Functions in the Vertebrate Insulin-Like Growth Factor System Uncovered by Study of Duplicated Salmonid Fish Genomes
Authors: Daniel J. Macqueen, Daniel Garcia de la serrana, Ian A. Johnston
Journal: Molecular Biology and Evolution (2013)

Whole-genome duplication (WGD) was experienced twice by the vertebrate ancestor (2 rounds; 2R), again by the teleost fish ancestor (3R) and most recently in certain teleost lineages (4R). Consequently, vertebrate gene families are often expanded in 3R and 4R genomes. Arguably, many types of "functional divergence" present across 2R gene families will exceed that between 3R/4R paralogs of genes comprising 2R families. Accordingly, 4R offers a form of replication of 2R. Examining whether this concept has implications for molecular evolutionary research, we studied insulin-like growth factor (IGF) binding proteins (IGFBPs), whose six 2R family members carry IGF hormones and regulate interactions between IGFs and IGF1-receptors (IGF1Rs). Using phylogenomic approaches, we resolved the complete IGFBP repertoire of 4R-derived salmonid fishes (19 genes; 13 more than human) and established evolutionary relationships/nomenclature with respect to WGDs. Traits central to IGFBP action were determined for all genes, including atomic interactions in IGFBP-IGF1/IGF2 complexes regulating IGF-IGF1R binding. Using statistical methods, we demonstrate that attributes of these protein interfaces are overwhelming a product of 2R IGFBP family membership, explain 49-68% of variation in IGFBP mRNA concentration in several different tissues, and strongly predict the strength and direction of IGFBP transcriptional regulation under differing nutritional states. The results support a model where vertebrate IGFBP family members evolved divergent structural attributes to provide distinct competition for IGFs with IGF1Rs, predisposing different functions in the regulation of IGF signaling. Evolution of gene expression then acted to ensure the appropriate physiological production of IGFBPs according to their structural specializations, leading to optimal IGF-signaling according to nutritional-status and the endocrine/local mode of action. This study demonstrates that relatively recent gene family expansion can facilitate inference of functional evolution within ancient genetic systems.
Management of Skin Abscesses in the Era of Methicillin-Resistant <i>Staphylococcus aureus</i>
Authors: Adam J. Singer, David A. Talan
Journal: New England Journal of Medicine (2014)

The incidence of abscesses is increasing, and community-acquired methicillin-resistant Staphylococcus aureus (MRSA) has become common. This review explains the role of ultrasonography and provides guidance on the management of skin abscesses and the use of antibiotics.
Elevated Biomarkers of Inflammation Are Associated With Reduced Survival Among Breast Cancer Patients
Authors: Brandon L. Pierce, Rachel Ballard-Barbash, Leslie Bernstein, Richard N. Baumgartner, Marian L. Neuhouser, Mark H. Wener, Kathy B. Baumgartner, Frank D. Gilliland, Bess E. Sorensen, Anne McTiernan, Cornelia M. Ulrich
Journal: Journal of Clinical Oncology (2009)

PURPOSE Chronic inflammation is believed to contribute to the development and progression of breast cancer. Systemic C-reactive protein (CRP) and serum amyloid A (SAA) are measures of low-grade chronic inflammation and potential predictors of cancer survival. PATIENTS AND METHODS We evaluated the relationship between circulating markers of inflammation and breast cancer survival using data from the Health, Eating, Activity, and Lifestyle (HEAL) Study (a multiethnic prospective cohort study of women diagnosed with stage 0 to IIIA breast cancer). Circulating concentrations of CRP and SAA were measured approximately 31 months after diagnosis and tested for associations with disease-free survival (approximately 4.1 years of follow-up) and overall survival (approximately 6.9 years of follow-up) in 734 disease-free breast cancer survivors. Cox proportional hazards models were used with adjustment for potential confounding factors to generate hazard ratios (HRs) and 95% CIs. Results Elevated SAA and CRP were associated with reduced overall survival, regardless of adjustment for age, tumor stage, race, and body mass index (SAA P trend < .0001; CRP P trend = .002). The HRs for SAA and CRP tertiles suggested a threshold effect on survival, rather than a dose-response relationship (highest v lowest tertile: SAA HR = 3.15; 95% CI, 1.73 to 5.65; CRP HR = 2.27; 95% CI, 1.27 to 4.08). Associations were similar and still significant after adjusting for self-reported history of cardiovascular events and censoring cardiovascular disease deaths. Elevated CRP and SAA were also associated with reduced disease-free survival, although these associations were of borderline significance (SAA P trend = .04; CRP P trend = .07). CONCLUSION Circulating SAA and CRP may be important prognostic markers for long-term survival in breast cancer patients, independent of race, tumor stage, and body mass index.
Indolent CD8-positive lymphoid proliferation of acral sites: identifying the sheep in wolf's clothing
Authors: J.R. Goodlad
Journal: British Journal of Dermatology (2015)

ORIGINAL ARTICLE, p 1573 In 2007, Petrella et al. described four patients, all presenting with a CD8+ T‐cell lymphoproliferative disorder affecting the skin of the ear.1 Despite displaying morphological, phenotypical and genotypical features of aggressive lymphoma, all pursued a remarkably indolent course, and an entity entitled 'indolent CD8+ lymphoid proliferation of the ear' was proposed.1 Since this original publication, somewhere in the region of 40 additional cases have been reported, all with similar pathological and clinical features, although the distribution of lesions has been broadened to include elsewhere on the face, particularly the nose, and other acral sites. Thus, the currently preferred nomenclature is 'indolent CD8+ lymphoid proliferation of acral sites'.2 The histology is of a monotonous, diffuse, nonepidermotropic dermal infiltrate of intermediate‐to‐large lymphoid cells with blast‐like morphology. By definition, the constituent T cells are CD8+ and usually also express cytotoxic granule‐associated RNA binding protein 1 (TIA1). Cases are clonal and usually have an aberrant phenotype, being deficient in one or more of the pan‐T‐cell antigens CD2, CD3, CD5 and CD7. They are typically negative for CD30, CD56 and Epstein–Barr virus.1 2 3 4 5 6 7 8 Despite these features of malignancy, and regardless of the blast cell morphology and frequent association of a cytotoxic T‐cell phenotype with aggressive clinical behaviour, this is an indolent process. Patients treated with only locally directed therapy, including biopsy or excision alone, almost invariably go into complete remission and, although relapses may occur, no disease‐related deaths have yet been reported.1 2 3 4 5 6 7 8
Angiotensin-converting enzyme overexpression in myelomonocytes prevents Alzheimer’s-like cognitive decline
Authors: Kenneth E. Bernstein, Yosef Koronyo, Brenda C. Salumbides, Julia Sheyn, Lindsey Pelissier, Dahabada H.J. Lopes, Kandarp H. Shah, Ellen A. Bernstein, Dieu-Trang Fuchs, Jeff J.-Y. Yu, Michael Pham, Keith L. Black, Xiao Z. Shen, Sebastien Fuchs, Maya Koronyo-Hamaoui
Journal: Journal of Clinical Investigation (2014)

Cognitive decline in patients with Alzheimer's disease (AD) is associated with elevated brain levels of amyloid β protein (Aβ), particularly neurotoxic Aβ(1-42). Angiotensin-converting enzyme (ACE) can degrade Aβ(1-42), and ACE overexpression in myelomonocytic cells enhances their immune function. To examine the effect of targeted ACE overexpression on AD, we crossed ACE(10/10) mice, which overexpress ACE in myelomonocytes using the c-fms promoter, with the transgenic APP(SWE)/PS1(ΔE9) mouse model of AD (AD⁺). Evaluation of brain tissue from these AD⁺ACE(10/10) mice at 7 and 13 months revealed that levels of both soluble and insoluble brain Aβ(1-42) were reduced compared with those in AD⁺ mice. Furthermore, both plaque burden and astrogliosis were drastically reduced. Administration of the ACE inhibitor ramipril increased Aβ levels in AD⁺ACE(10/10) mice compared with the levels induced by the ACE-independent vasodilator hydralazine. Overall, AD⁺ACE(10/10) mice had less brain-infiltrating cells, consistent with reduced AD-associated pathology, though ACE-overexpressing macrophages were abundant around and engulfing Aβ plaques. At 11 and 12 months of age, the AD⁺ACE(10/WT) and AD⁺ACE(10/10) mice were virtually equivalent to non-AD mice in cognitive ability, as assessed by maze-based behavioral tests. Our data demonstrate that an enhanced immune response, coupled with increased myelomonocytic expression of catalytically active ACE, prevents cognitive decline in a murine model of AD.
Long-Term Effect of Shoyu (Japanese Soy Sauce) on the Gastric Mucosa of the Rat 2
Authors: W. C. MacDonald, J. W. Dueck
Journal: JNCI Journal of the National Cancer Institute (1976)

The long-term effect of shoyu (Japanese soy sauce) on the gastric mucosa was assessed in intact rats and in those with a fundusectomy. One hundred female 4-month-old Wistar rats were divided into 4 groups: intact and operated rats on a control diet and intact and operated rats on the same diet saturated with shoyu. The animals given shoyu were smaller than the controls; 15 intact rats receiving the sauce were healthy at 33 months compared with 7 controls. Only 9 of 50 operated rats lived 33 months. Breast tumors developed in 10 control rats but in none given shoyu. The distribution of other tumors was the same. Two malignant neoplasms appeared to originate in the perigastric tissues of operated rats: a reticulum cell sarcoma in the shoyu group and a lymphosarcoma in the control group. None involved the gastric mucosa. Most of the operated rats (with or without shoyu) developed small benign gastric tumors. Mucosal histology was well preserved in 22 intact rats on shoyu: In 15 it was normal, in 7 there was mucus loss and nuclear changes in the cells of the gastric pits; 2 of the 7 had mild gastritis. One intact control showed patchy mucus loss. Shoyu did not appear to be a carcinogen in the rat; its prolonged use impaired neither health nor longevity. Long-term use was associated with gastric mucus loss and nuclear changes in a few rats, occasionally with a mild gastritis.
Impact of Coronary Heart Disease on World Leaders
Authors: Alyce M. Girardi, Leslie R. Pyenson, Jon Morris, Francis X. Brickfield
Journal: Annals of Internal Medicine (2001)

Previous studies have shown that from 1965 to 1996, coronary heart disease was a frequent natural cause of death among world leaders.To assess incidence of and death from coronary heart disease among world leaders and to determine the effect of this disease on office-holding ability.Archive search of worldwide English-language and translated press and media reports from 1970 to 1999 for reference to coronary events.U.S. federal government medical analytic unit.National principal decision makers in countries with populations greater than 250 000.Reports of angina, heart attack, myocardial infarction, and arrhythmia attributed to coronary artery disease; use of cardiac procedures; receipt of foreign care; death; and removal from office.64 leaders had initial coronary heart disease events while holding their nation's highest office. Initial event rates decreased from the 1970s to the 1990s (1.9 events per 100 person-years vs. 1.1 events per 100 person-years). Survival, use of procedures, and receipt of foreign care increased over time. Most leaders who survived an acute event continued to function in office.Incidence of and death from coronary heart disease among office-holding world leaders has decreased over the past 30 years, possibly because of increased use of cardiac procedures. A coronary event in a world leader is unlikely to presage a change in government.
Two Cases of Lymphosarcoma in Channel Catfish Exposed to &lt;italic&gt;N&lt;/italic&gt;-Methyl-&lt;italic&gt;N′&lt;/italic&gt;-nitro-&lt;italic&gt;N&lt;/italic&gt;-nitrosoguanidine&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: H H Chen, M R Brittelli, C F Muska
Journal: JNCI Journal of the National Cancer Institute (1985)

Of 158 channel catfish (Ictalurus punctatus) exposed to N-methyl-N'-nitro-N-nitrosoguanidine [(MNNG) CAS:70-25-7] in water for 28 days, 2 developed disseminated lymphosarcoma. One fish was necropsied at 12 months and another at 18 months following exposure. Both fish had a massive neoplastic infiltration of the bilateral pairs of head and trunk kidneys from which the neoplastic cells appeared to originate. The neoplastic infiltration was also observed in the following: thymus, gills, oral mucosa, liver, skin, skeletal muscle of head-neck region, and to a lesser extent spleen and bone marrow. This is probably the first report of lymphosarcoma in channel catfish. Although the occurrence of lymphosarcoma in these 2 catfish appeared to be related to exposure to MNNG, the exact role MNNG played in the tumor formation was not determined.
Hospital Volume and the Outcomes of Mechanical Ventilation
Authors: Jeremy M. Kahn, Christopher H. Goss, Patrick J. Heagerty, Andrew A. Kramer, Chelsea R. O'Brien, Gordon D. Rubenfeld
Journal: New England Journal of Medicine (2006)

An increased volume of patients is associated with improved survival in numerous high-risk medical and surgical conditions. The relationship between the number of patients admitted (hospital volume) and outcome among patients with critical illnesses is unknown.
Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECT): a randomised, double-blind, placebo-controlled trial
Authors: Ralf Gold, Gavin Giovannoni, Krzysztof Selmaj, Eva Havrdova, Xavier Montalban, Ernst-Wilhelm Radue, Dusan Stefoski, Randy Robinson, Katherine Riester, Jitesh Rana, Jacob Elkins, Gilmore O'Neill
Journal: The Lancet (2013)