tbuckley/cabot-search huggingface dataset:
Matrix metalloproteinase-2 mediates cytokine-induced myocardial contractile dysfunction
Authors: Cindy Qun Gao, Grzegorz Sawicki, Wilma L Suarez-Pinzon, Tamás Csont, Mieczyslaw Wozniak, Péter Ferdinandy, Richard Schulz
Journal: Cardiovascular Research (2003)

Pro-inflammatory cytokines depress myocardial contractile function by enhancing peroxynitrite production, yet the mechanism by which peroxynitrite does this is unknown. As matrix metalloproteinases (MMPs) can be activated by peroxynitrite and can proteolytically cleave troponin I in hearts, we determined whether this occurs in cytokine-induced myocardial dysfunction.Isolated working rat hearts were perfused with buffer containing interleukin-1 beta, interferon-gamma, and tumor necrosis factor-alpha.Cytokines induced a marked decline in mechanical function during 60-120 min of perfusion. This decline was accompanied by increased myocardial inducible NO synthase activity and perfusate dityrosine (a marker of peroxynitrite), compared to control hearts. Before the decline in mechanical function there was enhanced MMP-2 activity in the perfusate. This was accompanied by decreased tissue levels of MMP-2, tissue inhibitor of matrix metalloproteinases-4 and troponin I in cytokine-treated hearts. The collagen content of the heart was not affected by cytokine treatment. A neutralizing anti-MMP-2 antibody or the MMP inhibitors Ro31-9790 or PD166793 attenuated the decline in myocardial function. Moreover, the MMP-2 antibody prevented the decline in myocardial MMP-2 and troponin I levels.Myocardial contractile dysfunction caused by pro-inflammatory cytokines results in MMP-2 activation and a decline in tissue inhibitor of matrix metalloproteinases-4 in the heart. Troponin I is also a target for the proteolytic action of MMP-2 during acute heart failure triggered by pro-inflammatory cytokines. Inhibition of MMPs may be a novel pharmacological strategy for the treatment of acute inflammatory heart disease.
DIETARY FAT AND HYPERCHOLESTEREMIA IN THE CEBUS MONKEY
Authors: Oscar W. Portman, Leonardo Sinisterra
Journal: The Journal of Experimental Medicine (1957)

A series of studies of cholesterol metabolism in the Cebus monkey were carried out in an attempt to understand the mechanisms responsible for the great differences in serum cholesterol levels when different dietary fats were used. Three groups of monkeys, one fed diets including 45 per cent of calories as corn oil, a second corn oil plus cholesterol (0.1 gm./100 calories), and a third lard plus cholesterol for 5 months (mean serum cholesterol values were 237, 268, and 601 mg. per cent, respectively) were injected with emulsions of cholesterol-4-C14. The mean biological half-lives for the disappearance of serum radiocholesterol were 8.8, 8.4, and 6.6 days respectively. Esterification of radiocholesterol as measured by equilibration of specific activities of serum-free cholesterol and total cholesterol was delayed in the monkeys fed lard plus cholesterol. When cholesterol-4-C-14-stearate was given intravenously to a series of monkeys, an erratic non-exponential biological decay curve resulted. Specific activity for free serum cholesterol was greater than that for total cholesterol within 1 hour after the injection. After 7 months on experimental diets including corn oil with added cholesterol and lard with added cholesterol the levels of lipides in most tissues were not different for the two dietary groups, nor were they appreciably elevated above previous control figures for monkeys not fed cholesterol. Total lipide levels in the adrenals of monkeys fed corn oil were twice those of monkeys fed lard. Monkeys were fasted before and after intragastric administration of cholesterol-4-C14 in small formula meals including various fats and fatty acids. The disappearance of total cholesterol from the serum consisted of a rapid followed by a slow exponential function. The type of fat and fatty acid appeared to influence the rate of disappearance of radiocholesterol. There was a broad range of apparent activity of the different fats and fatty acids in promoting cholesterol absorption.
Mammography, Breast Ultrasound, and Magnetic Resonance Imaging for Surveillance of Women at High Familial Risk for Breast Cancer
Authors: Christiane K. Kuhl, Simone Schrading, Claudia C. Leutner, Nuschin Morakkabati-Spitz, Eva Wardelmann, Rolf Fimmers, Walther Kuhn, Hans H. Schild
Journal: Journal of Clinical Oncology (2005)

To compare the effectiveness of mammography, breast ultrasound, and magnetic resonance imaging (MRI) for surveillance of women at increased familial risk for breast cancer (lifetime risk of 20% or more).We conducted a surveillance cohort study of 529 asymptomatic women who, based on their family history and/or mutational analysis, were suspected or proven to carry a breast cancer susceptibility gene (BRCA). A total of 1,542 annual surveillance rounds were completed with a mean follow-up of 5.3 years. Diagnostic accuracies of the three imaging modalities used alone or in different combinations were compared.Forty-three breast cancers were identified in the total cohort (34 invasive, nine ductal carcinoma-in-situ). Overall sensitivity of diagnostic imaging was 93% (40 of 43 breast cancers); overall node-positive rate was 16%, and one interval cancer occurred (one of 43 cancers, or 2%). In the analysis by modality, sensitivity was low for mammography (33%) and ultrasound (40%) or the combination of both (49%). MRI offered a significantly higher sensitivity (91%). The sensitivity of mammography in the higher risk groups was 25%, compared with 100% for MRI. Specificity of MRI (97.2%) was equivalent to that of mammography (96.8%).Mammography alone, and also mammography combined with breast ultrasound, seems insufficient for early diagnosis of breast cancer in women who are at increased familial risk with or without documented BRCA mutation. If MRI is used for surveillance, diagnosis of intraductal and invasive familial or hereditary cancer is achieved with a significantly higher sensitivity and at a more favorable stage.
Joint Fluid Pressure in Chronic Knee Effusions
Authors: D. E. Caughey, E. G. L. Bywaters
Journal: Annals of the Rheumatic Diseases (1963)

<h3>ABSTRACT</h3> The accumulated number of COVID-19 cases per capita is an important characteristic of the pandemic dynamics that may also indicate the effectiveness of quarantine, testing and vaccination. As this value increases monotonically over time, the end of June 2021 was chosen, when the growth rate in Ukraine and the vast majority of European countries was small. This allowed us to draw some intermediate conclusions about the influence of the volume of population, its density, and the level of urbanization on the accumulated number of laboratory-confirmed cases per capita in European countries and regions of Ukraine. A simple analysis showed that the number of cases per capita does not depend on these demographic factors, although it may differ by about 4 times for different regions of Ukraine and more than 9 times for different European countries. The number of COVID-19 per capita registered in Ukraine is comparable with the same characteristic in other European countries but much higher than in China, South Korea and Japan.
Reducing Unnecessary Biopsy During Prostate Cancer Screening Using a Four-Kallikrein Panel: An Independent Replication
Authors: Andrew Vickers, Angel Cronin, Monique Roobol, Caroline Savage, Mari Peltola, Kim Pettersson, Peter T. Scardino, Fritz Schröder, Hans Lilja
Journal: Journal of Clinical Oncology (2010)

Purpose We previously reported that a panel of four kallikrein forms in blood—total, free, and intact prostate-specific antigen (PSA) and kallikrein-related peptidase 2 (hK2)—can reduce unnecessary biopsy in previously unscreened men with elevated total PSA. We aimed to replicate our findings in a large, independent, representative, population-based cohort. Patients and Methods The study cohort included 2,914 previously unscreened men undergoing biopsy as a result of elevated PSA (≥ 3 ng/mL) in the European Randomized Study of Screening for Prostate Cancer, Rotterdam, with 807 prostate cancers (28%) detected. The cohort was randomly divided 1:3 into a training and validation set. Levels of kallikrein markers were compared with biopsy outcome. Results Addition of free PSA, intact PSA, and hK2 to a model containing total PSA and age improved the area under the curve from 0.64 to 0.76 and 0.70 to 0.78 for models without and with digital rectal examination results, respectively (P &lt; .001 for both). Application of the panel to 1,000 men with elevated PSA would reduce the number of biopsies by 513 and miss 54 of 177 low-grade cancers and 12 of 100 high-grade cancers. Findings were robust to sensitivity analysis. Conclusion We have replicated our previously published finding that a panel of four kallikreins can predict the result of biopsy for prostate cancer in men with elevated PSA. Use of this panel would dramatically reduce biopsy rates. A small number of men with cancer would be advised against immediate biopsy, but these men would have predominately low-stage, low-grade disease.
Clinical Depression Versus Distress Among Patients With Type 2 Diabetes: Not Just a Question of Semantics
Authors: Norbert Hermanns, Thomas Kubiak, Berndhard Kulzer, Thomas Haak
Journal: Diabetes Care (2007)

We read with interest the recent article by Fisher et al. (1) that concluded that subthreshold de-pression could be regarded as a proxy marker of diabetes-related distress rather than a proxy marker of clinical depression. Fisher et al. support their conclusion by referring to two key findings of their study. Their first finding was a markedly higher correlation between diabetes-related distress and the intensity of depressive symptoms than that between diabetes-related distress and clinical depression. Their second finding was significant associations between subthreshold …
Somatostatin and somatostatin analogues--are they indicated in the management of acute pancreatitis?
Authors: C J McKay, C W Imrie, J N Baxter
Journal: Gut (1993)

Somatostatin was first suggested for the treatment of acute pancreatitis more than 15 years ago but despite many studies, its role in the management of this condition remains unclear. The experimental and clinical studies are reviewed and the physiological actions of somatostatin, which may influence the course of acute pancreatitis are examined. It is concluded that although some reports suggest a trend towards improved survival and lessened complication rate with somatostatin treatment, insufficient evidence of benefit exists to support the use of somatostatin or its analogue in the treatment or prophylaxis against acute pancreatitis in routine clinical practice.
Unexpected Proatherogenic Properties of p21
Authors: Vicente Andrés
Journal: Circulation (2004)

therosclerosis is an inflammatory disease that involves the interplay between endothelial cells, smooth muscle cells (SMCs), and immune cells. 1,2arious atherogenic stimuli lead to endothelial damage, which in turn triggers the adhesion and extravasation of circulating monocytes and lymphocytes into the artery wall.Resident immune cells produce a plethora of inflammatory mediators that exacerbate leukocyte recruitment and proliferation and promote SMC growth and migration from the underlying media toward the developing atheroma.Abnormal cell proliferation and migration are also a hallmark of neointimal thickening during postangioplasty restenosis, transplant vasculopathy, and graft atherosclerosis. 1,3 See p 3830Mammalian cell cycle progression is governed by the concerted activation of holoenzymes composed of a catalytic cyclin-dependent protein kinase (CDK) and a regulatory subunit named cyclin.Cell proliferation is constrained by the interaction of CDK/cyclin holoenzymes with members of the Cip/Kip (for CDK interacting protein/kinase inhibitory protein) and Ink4 (for inhibitor of CDK4) families of CDK inhibitory proteins (CKIs). 4Ink4 proteins (p16 Ink4a , p15 Ink4b , p18 Ink4c , p19 Ink4d ) are thought to be specific for cyclin D-associated CDKs, whereas Cip/Kip proteins (p21 Cip1/Waf1/Sdi1 , p27 Kip1 , p57 Kip2 ) bind to and inhibit a wide spectrum of CDK/cyclin complexes.
Functional Roles of Cardiac and Vascular ATP-Sensitive Potassium Channels Clarified by Kir6.2-Knockout Mice
Authors: Masashi Suzuki, Ronald A. Li, Takashi Miki, Hiroko Uemura, Naoya Sakamoto, Yuki Ohmoto-Sekine, Masaji Tamagawa, Takehiko Ogura, Susumu Seino, Eduardo Marbán, Haruaki Nakaya
Journal: Circulation Research (2001)

Abstract —ATP-sensitive potassium (K ATP ) channels were discovered in ventricular cells, but their roles in the heart remain mysterious. K ATP channels have also been found in numerous other tissues, including vascular smooth muscle. Two pore-forming subunits, Kir6.1 and Kir6.2, contribute to the diversity of K ATP channels. To determine which subunits are operative in the cardiovascular system and their functional roles, we characterized the effects of pharmacological K + channel openers (KCOs, ie, pinacidil, P-1075, and diazoxide) in Kir6.2-deficient mice. Sarcolemmal K ATP channels could be recorded electrophysiologically in ventricular cells from Kir6.2 +/+ (wild-type [WT]) but not from Kir6.2 −/− (knockout [KO]) mice. In WT ventricular cells, pinacidil induced an outward current and action potential shortening, effects that were blocked by glibenclamide, a K ATP channel blocker. KO ventricular cells exhibited no response to KCOs, but gene transfer of Kir6.2 into neonatal ventricular cells rescued the electrophysiological response to P-1075. In terms of contractile function, pinacidil decreased force generation in WT but not KO hearts. Pinacidil and diazoxide produced concentration-dependent relaxation in both WT and KO aortas precontracted with norepinephrine. In addition, pinacidil induced a glibenclamide-sensitive current of similar magnitude in WT and KO aortic smooth muscle cells and comparable levels of hypotension in anesthetized WT and KO mice. In both WT and KO aortas, only Kir6.1 mRNA was expressed. These findings indicate that the Kir6.2 subunit mediates the depression of cardiac excitability and contractility induced by KCOs; in contrast, Kir6.2 plays no discernible role in the arterial tree.
Prevalence of Diabetes and Impaired Fasting Glucose in Adults in the U.S. Population
Authors: Catherine C. Cowie, Keith F. Rust, Danita D. Byrd-Holt, Mark S. Eberhardt, Katherine M. Flegal, Michael M. Engelgau, Sharon H. Saydah, Desmond E. Williams, Linda S. Geiss, Edward W. Gregg
Journal: Diabetes Care (2006)

The purpose of this study was to examine the prevalences of diagnosed and undiagnosed diabetes, and impaired fasting glucose (IFG) in U.S. adults during 1999-2002, and compare prevalences to those in 1988-1994.
Consultant shortage is fatal thorn in side of emergency services, say MPs
Authors: A. O'Dowd
Journal: BMJ (2014)

A serious shortage of expertise in the form of emergency consultants is hampering hospital emergency departments in England from providing an adequate service, MPs have concluded.

MPs on the influential House of Commons Public Accounts Committee have raised several concerns over the state of emergency services in England in a highly critical report published on 4 March.1

The committee said that the government currently had no clear strategy for tackling what it called a “chronic” shortage of emergency consultants. In 2012 almost a fifth of consultant posts in emergency departments were either vacant or filled by locums.

The report explains how there were 5.3 million emergency admissions to hospitals in England in 2012-13, an increase of 47% over the …
Vaccination of Patients with Advanced Ovarian Carcinoma with the Anti-Idiotype ACA125
Authors: Silke Reinartz, Siegmund Köhler, Harald Schlebusch, Karl Krista, Patrick Giffels, Kirsten Renke, Jens Huober, Volker Möbus, Rolf Kreienberg, Andreas duBois, Paul Sabbatini, Uwe Wagner
Journal: Clinical Cancer Research (2004)

Abstract Purpose: A Phase I/IIb multicenter study was conducted to evaluate the safety and immunogenicity of the anti-idiotypic antibody vaccine ACA125 that functionally imitates the tumor antigen CA125 in 119 patients with advanced ovarian carcinoma. A preliminary report on the initial 42 patients demonstrated safety and immunogenicity. Experimental Design: Using the complete intention-to-treat population (n = 119) who received a mean of 9.7 ACA125 applications, survival was analyzed with respect to immunological responses. Results: In 81 patients (68.1%), a specific anti-anti-idiotypic antibody (Ab3) response could be induced. Additionally, the development of CA125-specific antibodies (Ab1′) and antibody-dependent cell-mediated cytotoxicity of CA125-positive tumor cells was observed in 50.4% and 26.9% of patients, respectively. The median survival of all patients was 19.4 months (range, 0.5–56.1 months). Ab3-positive patients showed a significantly longer survival (median, 23.4 months; P &amp;lt; 0.0001) as compared with Ab3-negative patients (median, 4.9 months). A positive Ab3 response remained associated with longer survival when controlling for other prognostic factors including FIGO (International Federation of Gynecologists and Obstetricians) stage, response to and type of first-line chemotherapy, number of previous treatments, or concomitant antitumor therapy. With regard to safety, repeated vaccination was well tolerated. No serious adverse events related to the application of ACA125 occurred. Conclusions: Although the uncontrolled design of this study prevents definitive conclusions with respect to subgroups, the data support a relationship between Ab3 response and survival time. Thus, the need for further randomized, controlled clinical trials to establish efficacy of the vaccine ACA125 seems to be indicated.
Aerobic capacity and peak power output of elite quadriplegic games players
Authors: V Goosey-Tolfrey, P Castle, N Webborn
Journal: British Journal of Sports Medicine (2006)

Background: Participation in wheelchair sports such as tennis and rugby enables people with quadriplegia to compete both individually and as a team at the highest level. Both sports are dominated by frequent, intermittent, short term power demands superimposed on a background of aerobic activity. Objective: To gain physiological profiles of highly trained British quadriplegic athletes, and to examine the relation between aerobic and sprint capacity. Methods: Eight male quadriplegic athletes performed an arm crank exercise using an ergometer fitted with a Schoberer Rad Messtechnik (SRM) powermeter. The sprint test consisted of three maximum-effort sprints of five seconds duration against a resistance of 2%, 3%, and 4% of body mass. The highest power output obtained was recorded (PPO). Peak oxygen consumption (V̇ o 2peak ), peak heart rate (HR peak ), and maximal power output (PO aer ) were determined. Results: Mean PO aer was 67.7 (16.2) W, mean V̇ o 2peak was 0.96 (0.17) litres/min, and HR peak was 134 (19) beats/min for the group. There was high variability among subjects. Peak power over the five second sprint for the group was 220 (62) W. There was a significant correlation between V̇ o 2peak (litres/min) and PO aer (W) ( r = 0.74, p&lt;0.05). Conclusions: These British quadriplegic athletes have relatively high aerobic fitness when compared with the available literature. Moreover, the anaerobic capacity of these athletes appeared to be relatively high compared with paraplegic participants.
Electronic tagging of people with dementia who wander
Authors: J. C Hughes
Journal: BMJ (2002)

Once again the issue of using electronic tagging to safeguard older people who wander has attracted media attention.1 It is tempting to see the arguments as simply two sided—one side stressing the need to ensure safety and the other waving the banners of civil liberties and human rights. We think that this is not simply a factual matter but one that touches important values to do with respect for people. The correct position, therefore, is to face the complex dilemma. Decisions about limiting a person's liberty should remain a matter of ethical concern even when technology finally makes the practical management of wandering easier.In electronic tagging the tag is usually a wristband. The circuitry in the tag may either set off a boundary alarm or emit a radio signal that allows the wearer to be tracked down by means of a hand held detector.

The problem of wandering in dementia is not trivial. It causes stress to carers, referrals to psychiatric services and hospital admissions, problems in the hospital …
Efficacy and Mechanism-of-Action of a Novel Superagonist Interleukin-15: Interleukin-15 Receptor αSu/Fc Fusion Complex in Syngeneic Murine Models of Multiple Myeloma
Authors: Wenxin Xu, Monica Jones, Bai Liu, Xiaoyun Zhu, Christopher B. Johnson, Ana C. Edwards, Lin Kong, Emily K. Jeng, Kaiping Han, Warren D. Marcus, Mark P. Rubinstein, Peter R. Rhode, Hing C. Wong
Journal: Cancer Research (2013)

Abstract ALT-803, a complex of an interleukin (IL)-15 superagonist mutant and a dimeric IL-15 receptor αSu/Fc fusion protein, was found to exhibit significantly stronger in vivo biologic activity on NK and T cells than IL-15. In this study, we show that a single dose of ALT-803, but not IL-15 alone, eliminated well-established 5T33P and MOPC-315P myeloma cells in the bone marrow of tumor-bearing mice. ALT-803 treatment also significantly prolonged survival of myeloma-bearing mice and provided resistance to rechallenge with the same tumor cells through a CD8+ T-cell–dependent mechanism. ALT-803 treatment stimulated CD8+ T cells to secrete large amounts of IFN-γ and promoted rapid expansion of CD8+CD44high memory T cells in vivo. These memory CD8+ T cells exhibited ALT-803–mediated upregulation of NKG2D (KLRK1) but not PD-1 (PDCD1) or CD25 (IL2RA) on their cell surfaces. ALT-803–activated CD8+ memory T cells also exhibited nonspecific cytotoxicity against myeloma and other tumor cells in vitro, whereas IFN-γ had no direct effect on myeloma cell growth. ALT-803 lost its antimyeloma activity in tumor-bearing IFN-γ knockout mice but retained the ability to promote CD8+CD44high memory T-cell proliferation, indicating that ALT-803–mediated stimulation of CD8+CD44high memory T cells is IFN-γ–independent. Thus, besides well-known IL-15 biologic functions in host immunity, this study shows that IL-15–based ALT-803 could activate CD8+CD44high memory T cells to acquire a unique innate-like phenotype and secrete IFN-γ for nonspecific tumor cell killing. This unique immunomodulatory property of ALT-803 strongly supports its clinical development as a novel immunotherapeutic agent against cancer and viral infections. Cancer Res; 73(10); 3075–86. ©2013 AACR.