tbuckley/cabot-search huggingface dataset:
Antileucoprotease in the developing fetal lung.
Authors: L N Willems, J A Kramps, P K Jeffery, J H Dijkman
Journal: Thorax (1988)

The distribution of antileucoprotease in the lungs of 25 fetuses of 9-40 weeks' gestation was studied with monoclonal antibodies and an indirect immunoperoxidase technique. Antileucoprotease was detected from 16 weeks in submucosal glands and collecting ducts in the trachea and main and lobar bronchi: it was also found in the surface epithelium of the trachea at 20 weeks, in main and lobar bronchi at 20 weeks, and in smaller bronchi at 20-25 weeks. Non-ciliated cells containing antileucoprotease were observed in the bronchiolar epithelium at 36 and 40 weeks. The results of this study indicate that antileucoprotease is available from birth. It may therefore form part of the first line of defence of the lung.
Moderators of the intention-behaviour relationship in the physical activity domain: a systematic review
Authors: Ryan E Rhodes, Leanne Dickau
Journal: British Journal of Sports Medicine (2012)

Intention is theorised as the proximal determinant of behaviour in many leading theories and yet intention-behaviour discord is prevalent. The purpose of this review was to retrieve, theme and appraise the variables that have been evaluated as the potential moderators of the intention-behaviour relationship in the physical activity (PA) domain. Eligible studies were selected from English peer-reviewed journals and had to report an empirical test of moderation of intention-PA (I-PA) with a third variable. Fifty-seven studies passed the inclusion criteria and these represented 38 different potential moderators of I-PA. Intention stability proved to be the most consistent moderator of I-PA, suggesting that much of the discordance may be from motivational flux between initial intention and eventual behaviour. Anticipated regret and conscientiousness also had evidence as the moderators of I-PA. Perceived control/self-efficacy, planning, extraversion, habit and environmental proximity to recreation showed some evidence for moderation, while gender, agreeableness, openness, body mass index and ethnicity did not appear to moderate I-PA. The findings demonstrate that traditional intention theories may need augmentation to better account for the evidence present in I-PA discordance.
Vasculitis in patients with systemic sclerosis and severe digital ischaemia requiring amputation.
Authors: A L Herrick, P K Oogarah, A J Freemont, R Marcuson, M Haeney, M I Jayson
Journal: Annals of the Rheumatic Diseases (1994)

OBJECTIVES--To document the incidence of histological vasculitis in amputation specimens from patients with severe digital ischaemia secondary to systemic sclerosis (SSc), and to look for an association between anticardiolipin (aCL) antibodies and severe digital ischaemia in SSc. METHODS--This was a retrospective review of patients with SSc who underwent amputation for digital ischaemia over a three year period. RESULTS--Five of nine patients had histological vasculitis, four of whom had aCL antibodies, although these were not present in high titre. CONCLUSION--Vasculitis does occur in SSc, at least in that subgroup with severe peripheral ischaemia. These findings could have implications for treatment of this subgroup of patients with SSc.
Positive Selection and Gene Conversion in SPP120, a Fertilization-Related Gene, during the East African Cichlid Fish Radiation
Authors: Dave T. Gerrard, Axel Meyer
Journal: Molecular Biology and Evolution (2007)

The ability to infer historical natural selection from sequence data aides in finding genes that might be important in adaptation and the formation of new species. As the fastest evolving and largest known vertebrate radiation, the cichlid fish of the African Great Lakes exhibit a wide range of recent morphological diversification. We used DNA databases, mostly of expressed sequence tags, to find candidate orthologous coding sequences from 2 tribes of cichlids and, using an automated procedure, scanned these sequence pairs for high dN/dS, the signal of positive selection and protein adaptation. The results included vertebrate genes commonly found to be under selection (e.g., major histocompatibility complex [MHC] loci) as well as genes known to be important specifically in the cichlid radiation (e.g., long-wave-sensitive opsins). Further investigation focused on a gene encoding a fertilization-related protein, SPP120, which was previously known only from cichlids. Using maximum likelihood analysis on novel SPP120 cDNA sequences from a range of African cichlids, we demonstrate the influence of positive selection in a specific subregion of the protein. We also show that SPP120 is a tandemly arranged, multicopy gene evolving with occasional interlocus gene conversion. A search of the Medaka genome database also revealed a tandem arrangement of multiple SPP120 copies and evolutionary rate differences between Medaka gene subregions mirroring those found for cichlids. Combined, these results suggest that SPP120 has been under repeated diversifying selection for over 100 Myr.
Impaired endothelium-dependent vasodilation in type 2 diabetes mellitus and the lack of effect of simvastatin
Authors: M van de Ree
Journal: Cardiovascular Research (2001)

Objective: Although type 2 diabetes is recognized as an independent risk factor for cardiovascular disease and cardiovascular disease is associated with endothelial dysfunction, the influence of type 2 diabetes per se on the endothelial function is controversial. HMG-CoA-reductase inhibitors have been shown to have short-term beneficial effects on endothelial dysfunction among patients with dyslipidemia or cardiovascular disease. The effect of HMG-CoA reductase inhibitors on the endothelial function in diabetes is largely unknown. Methods: Seventeen patients with type 2 diabetes, free of cardiovascular disease and no other cardiovascular risk factors, except for dyslipidemia, were studied together with ten healthy volunteers. The effect of 5-hydroxytryptamine, as an endothelium-dependent vasodilator, and sodium nitroprusside, as an endothelium-independent vasodilator, on the forearm blood flow was measured using venous occlusion plethysmography. Results: 5-Hydroxytryptamine and sodium nitroprusside, infused in the brachial artery, caused a dose-dependent vasodilation. The vasodilator response to 5-hydroxytryptamine was significantly lower among the diabetic patients, 42 and 56%, than among the controls, 73 and 103%, at a dose of 0.3 and 0.9 ng/kg/min, respectively (P<0.05 and P<0.001). Vasodilator responses to sodium nitroprusside were comparable among the diabetic patients and controls. A 6-week treatment with simvastatin 40 mg once daily did not change the vasodilator responses to 5-hydroxytryptamine or sodium nitroprusside among the patients with diabetes. Conclusions: The results of this study indicate that the endothelial function is impaired in type 2 diabetes and is not restored after a 6-week treatment period with simvastatin 40 mg.
Impaired skeletal muscle function in patients with congestive heart failure. Relationship to systemic exercise performance.
Authors: J R Minotti, I Christoph, R Oka, M W Weiner, L Wells, B M Massie
Journal: Journal of Clinical Investigation (1991)

In patients with congestive heart failure (CHF), the poor relationship between systemic exercise performance and cardiac function, together with morphologic and metabolic abnormalities in skeletal muscle, raises the possibility that skeletal muscle function may be impaired and limit systemic exercise performance. We assessed strength and endurance of the knee extensors during static and dynamic exercise in 16 patients with Class I-IV CHF and eight age-matched sedentary controls and related these measurements to systemic exercise performance. To assess skeletal muscle function independent of peripheral blood flow, endurance was repeated under ischemic conditions. Strength was not significantly different in the two groups. Dynamic endurance, quantified as the decline in peak torque during 15 successive isokinetic knee extensions, was significantly reduced in the patients compared to controls during aerobic (peak torque 65 vs. 86% of initial for exercise at 90 deg/s and 60 vs. 85% for exercise at 180 deg/s; P less than 0.002 for both), and during ischemic exercise (56 vs. 76% of initial torque; P less than 0.01). Static endurance, defined as the time required for force during a sustained maximal voluntary contraction to decline to 60% of maximal, was reduced in the patients compared to controls (40 +/- 14 vs. 77 +/- 29 s; P less than 0.02). There were highly significant relationships between systemic exercise performance and skeletal muscle endurance at 90 and 180 deg/s in the patients with CHF (r = 0.90 and 0.66, respectively). These findings indicate that skeletal muscle endurance is impaired in patients with CHF, that this abnormality is in part independent of limb blood flow, and that these changes may be important determinants of systemic exercise performance.
AN EXPERIMENTAL CONTRIBUTION TO THE STUDY OF CARDIAC HYPERTROPHY
Authors: Hugh A. Stewart
Journal: The Journal of Experimental Medicine (1911)

1. Hypertrophy induced by the production of aortic insufficiency involves all the chambers of the heart. The greatest absolute increase in weight is in the left ventricle. The remaining segments, arranged in the order of decreasing increments are septum, right ventricle, and auricles. The greatest relative increase is also in the left ventricle, but the auricles show a relative hypertrophy greater than that of the septum or right ventricle. 2. The co-hypertrophy of the auricles is not due to an altered venous pressure, but results from an increased force of auricular systole. 3. The heart shows an increase in weight within one week after the production of aortic insufficiency. The increase in weight is due only in part to an increased water content.
RANDOMIZED PHASE II STUDY OF FIRST-LINE EVEROLIMUS (EVE) + BEVACIZUMAB (BEV) VERSUS INTERFERON ALFA-2A (IFN) + BEV IN PATIENTS (PTS) WITH METASTATIC RENAL CELL CARCINOMA (MRCC): RECORD-2
Authors: A. Ravaud, C. Barrios, Ö. Anak, D. Pelov, A. Louveau, B. Alekseev, T. M-H, S.S. Agarwala, S. Yalcin, B. Melichar
Journal: Annals of Oncology (2012)
Screening for Intimate Partner Violence and Abuse of Elderly and Vulnerable Adults: U.S. Preventive Services Task Force Recommendation Statement
Authors: Virginia A. Moyer
Journal: Annals of Internal Medicine (2013)

Chinese translation Description: Update of the 2004 U.S. Preventive Services Task Force (USPSTF) recommendation statement on screening for family and intimate partner violence (IPV). Methods: The USPSTF commissioned a systematic evidence review on screening women for IPV and elderly and vulnerable adults for abuse and neglect. This review examined the accuracy of screening tools for identifying IPV and the benefits and harms of screening women of childbearing age and elderly and vulnerable adults. Population: These recommendations apply to asymptomatic women (women who do not have signs or symptoms of abuse) of reproductive age and elderly and vulnerable adults. Recommendation: The USPSTF recommends that clinicians screen women of childbearing age for IPV, such as domestic violence, and provide or refer women who screen positive to intervention services (B recommendation). The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening all elderly or vulnerable adults (physically or mentally dysfunctional) for abuse and neglect (I statement).
Hydroxylation of d-phenylalanine as a novel approach to detect hydroxyl radicals: Application to cardiac pathophysiology
Authors: R BIONDI, G AMBROSIO, T LIEBGOTT, A CARDOUNEL, M BETTINI, I TRITTO, J ZWEIER
Journal: Cardiovascular Research (2006)

Research in the pathophysiology of ischemia/reperfusion or redox signaling is hindered by lack of simple methodology to measure short-lived oxygen radicals. In the presence of hydroxyl radical ((*)OH), d-phenylalanine (d-Phe) yields para-, meta- and ortho-tyrosine. We have previously demonstrated that d-Phe can accurately detect (*)OH formation in chemical, enzymatic and cellular systems by simple HPLC methodology [Anal Biochem 290:138;2001]. In the present study, we tested whether d-Phe hydroxylation can be used to detect (*)OH formation in intact organs.Rat hearts were perfused with buffer containing 5 mM d-Phe and subjected to 30 min of total global ischemia at 37 degrees C followed by 45 min of reperfusion. Quantitative analysis of the three hydroxytyrosine isomers was achieved by HPLC-based electrochemical detection of cardiac venous effluent, with the analytical cells operating in the oxidative mode. The detection limit of this assay was <10 fmol.Under baseline conditions, hydroxytyrosine release from the heart was very low ( congruent with0.8 nmol/min/g). However, a prominent tyrosine burst occurred immediately upon post-ischemic reflow. In cardiac effluent collected 40 s into reperfusion, the hydroxytyrosine concentration was more than 40 times greater than at baseline; hydroxytyrosine concentration then progressively declined, to return to pre-ischemic values by 5 min of reperfusion. In parallel experiments, formation of hydroxytyrosines was markedly reduced in hearts reperfused in the presence of the (*)OH scavenger mannitol. Inclusion of 5 mm d-Phe in the perfusion medium altered neither basal cardiac function nor coronary vascular tone, but it enhanced recovery of myocardial function during post-ischemic reperfusion, consistent with direct reaction with (*)OH.Our results demonstrate that d-Phe is a sensitive method for detection of (*)OH generation in the heart. Since d-Phe is not a substrate for endogenous enzymes, it can be exploited as a reliable method to measure (*)OH formation under a variety of pathophysiological conditions.
Rethinking Risk-Benefit Assessment for Phase I Cancer Trials
Authors: Steven Joffe, Franklin G. Miller
Journal: Journal of Clinical Oncology (2006)

Although vital to developing new cancer treatments, phase I trials in oncology remain ethically controversial. Classically, they involve the initial administration of new antineoplastic agents to patient-participants, based on apparent safety and potential for efficacy in in vitro and animal studies. Participants, though not imminentlydying,generallyhaveadvancedcancer,haveexhausted establishedanticancertreatments,andareineligibleforlater-phase
Concurrent Chemoradiotherapy for Unresectable Stage III Non–Small Cell Lung Cancer
Authors: Everett E. Vokes, Jeffrey Crawford, Jeffrey Bogart, Mark A. Socinski, Gerald Clamon, Mark R. Green
Journal: Clinical Cancer Research (2005)

Abstract Over the last two decades, several approaches to multimodality therapy have been investigated in patients with advanced unresectable non–small cell lung cancer. These include induction chemotherapy and concurrent chemoradiotherapy. Both approaches have been shown to be superior to radiation therapy alone. However, in several randomized trials, concomitant chemoradiotherapy was shown to be superior to the induction chemotherapy approach. It has been hypothesized that the addition of systemic dose sequential chemotherapy to concurrent chemoradiotherapy, either as induction or as consolidation chemotherapy, might further improve survival rates. Recently, the Cancer and Leukemia Group B reported on a randomized phase III trial directly evaluating the addition of two cycles of carboplatin and paclitaxel to concurrent chemoradiotherapy. In this study, induction chemotherapy failed to further improve survival rates of concurrent chemoradiotherapy. A previously conducted randomized phase II study also suggested no benefit from the addition of induction chemotherapy to concomitant chemoradiotherapy. Favorable phase II data have been published supporting the use of consolidation chemotherapy. However, to date, no large randomized study evaluating a possible benefit from consolidation chemotherapy has been completed. In addition to evaluating optimal sequencing strategies of combined modality therapy, current investigations are also focusing on the integration of novel agents, including chemotherapeutic and targeted therapies. Currently ongoing trials involving novel approaches are reviewed here.
Xenografted Human Amniotic Membrane–Derived Mesenchymal Stem Cells Are Immunologically Tolerated and Transdifferentiated Into Cardiomyocytes
Authors: Hiroko Tsuji, Shunichiro Miyoshi, Yukinori Ikegami, Naoko Hida, Hironori Asada, Ikuko Togashi, Junshi Suzuki, Masaki Satake, Hikaru Nakamizo, Mamoru Tanaka, Taisuke Mori, Kaoru Segawa, Nobuhiro Nishiyama, Junko Inoue, Hatsune Makino, Kenji Miyado, Satoshi Ogawa, Yasunori Yoshimura, Akihiro Umezawa
Journal: Circulation Research (2010)

Rationale : Amniotic membrane is known to have the ability to transdifferentiate into multiple organs and is expected to stimulate a reduced immunologic reaction. Objective : Determine whether human amniotic membrane–derived mesenchymal cells (hAMCs) can be an ideal allograftable stem cell source for cardiac regenerative medicine. Methods and Results : We established hAMCs. After cardiomyogenic induction in vitro, hAMCs beat spontaneously, and the calculated cardiomyogenic transdifferentiation efficiency was 33%. Transplantation of hAMCs 2 weeks after myocardial infarction improved impaired left ventricular fractional shortening measured by echocardiogram (34±2% [n=8] to 39±2% [n=11]; P &lt;0.05) and decreased myocardial fibrosis area (18±1% [n=9] to 13±1% [n=10]; P &lt;0.05), significantly. Furthermore hAMCs transplanted into the infarcted myocardium of Wistar rats were transdifferentiated into cardiomyocytes in situ and survived for more than 4 weeks after the transplantation without using any immunosuppressant. Immunologic tolerance was caused by the hAMC-derived HLA-G expression, lack of MHC expression of hAMCs, and activation of FOXP3-positive regulatory T cells. Administration of IL-10 or progesterone, which is known to play an important role in feto-maternal tolerance during pregnancy, markedly increased HLA-G expression in hAMCs in vitro and, surprisingly, also increased cardiomyogenic transdifferentiation efficiency in vitro and in vivo. Conclusions : Because hAMCs have a high ability to transdifferentiate into cardiomyocytes and to acquire immunologic tolerance in vivo, they can be a promising cellular source for allograftable stem cells for cardiac regenerative medicine.
Nitric oxide contributes to estrogen-induced vasodilation of the ovine uterine circulation.
Authors: C R Rosenfeld, B E Cox, T Roy, R R Magness
Journal: Journal of Clinical Investigation (1996)

Estradiol-17beta (E2beta), a potent vasodilator, has its greatest effects on the uterine vasculature, blood flow (UBF) increasing > or = 10-fold. The mechanism(s) responsible for E2beta-induced vasodilation is unclear. We determined if nitric oxide (NO)-induced increases in cGMP modulate estrogen-induced increases in UBF, and if cyclooxygenase inhibition modifies E2beta responses. Nonpregnant (n = 15) and pregnant (n = 8) ewes had flow probes implanted on main uterine arteries and catheters in branches of the uterine vein and artery bilaterally for blood sampling and infusion of the NO synthase inhibitor L-nitro-arginine methyl ester (L-NAME), respectively. In nonpregnant ewes E2beta (1 microg/kg) caused parallel increases (P < 0.001) in UBF (15+/-3 to 130+/-16 ml/min) and uterine cGMP secretion (23+/-10 to 291+/-38 pmol/min); uterine venous cGMP also rose (4.98+/-1.4 to 9.43+/-3.2 pmol/ml; P < 0.001). Intra-arterial L-NAME partially inhibited increases in UBF dose-dependently (r = 0.66, n = 18, P < 0.003) while completely inhibiting cGMP secretion (P = 0.025). Indomethacin, 2 mg/kg intravenously, did not alter E2beta-induced responses. After E2beta-induced increases in UBF, intraarterial L-NAME partially decreased UBF dose dependently (r = 0.73, n = 46, P < 0.001) while inhibiting cGMP secretion (178+/-48 to 50+/-24 pmol/min; n = 5, P = 0.006); both were reversed by L-arginine. In pregnant ewes, E2beta increased UBF and venous cGMP (9.1+/-0.96 to 13.2+/-0.96 pmol/ml, P < 0.01); however, intraarterial L-NAME decreased basal cGMP secretion 66% (P = 0.02), but not UBF. Acute estrogen-induced increases in UBF are associated with NO-dependent increases in cGMP synthesis, but other mechanisms may also be involved. However, vasodilating prostanoids do not appear to be important. In ovine pregnancy NO is not essential for maintaining uteroplacental vasodilation.
Introduction of a novel magnetic resonance imaging tenosynovitis score for rheumatoid arthritis: reliability in a multireader longitudinal study
Authors: E. A Haavardsholm, M. Ostergaard, B. J Ejbjerg, N. P Kvan, T. K Kvien
Journal: Annals of the Rheumatic Diseases (2007)

<b>Objectives:</b> To describe a novel scoring system for the assessment of tenosynovitis by magnetic resonance imaging (MRI) in patients with rheumatoid arthritis, and assess its intra- and inter-reader reliability in a multireader, longitudinal setting. <b>Methods:</b> Flexor and extensor tenosynovitis were evaluated at the level of the wrist in 10 different anatomical areas, graded semi-quantitatively from grade 0 to 3 (total score 0–30), based on the maximum width of post-contrast enhancement within each anatomical area on axial T1-weighted MR images. Ten sets of baseline and 1-year follow-up MR images of the wrists of patients with rheumatoid arthritis with early and established disease were scored independently by four readers twice on 2 consecutive days. Intra- and inter-reader agreements were evaluated. <b>Results:</b> The intrareader intraclass correlation coefficients (ICCs) were high for status scores (median ICCs 0.84–0.88) and slightly lower for change score (0.74). The smallest detectable difference (SDD) in % of the maximum score was 11.2–11.5% for status scores and 13.3% for change scores. Inter-reader single-measure ICCs were acceptable for both status scores (median 0.73–0.74) and change scores (0.67), while average-measures ICCs were very high for both status and change score (all ⩾0.94). The median scoring time per patient (baseline and follow-up images) was 7 min (range 3–10). <b>Conclusions:</b> The introduced tenosynovitis scoring system demonstrates a high degree of multireader reliability, is feasible, and may be used as an adjuvant to the existing OMERACT RAMRIS score, allowing improved quantification of inflammatory soft tissue changes in patients with rheumatoid arthritis.
Targeting the renin-angiotensin system in patients with renal disease
Authors: M. A J Devonald, F. E Karet
Journal: Journal of the Royal Society of Medicine (2002)

The rationale for use of angiotensin-converting enzyme (ACE) inhibitors in patients with proteinuria or established renal impairment is in general twofold—first, to slow the progression of renal disease, by reducing blood pressure (BP) and proteinuria or by other renoprotective mechanisms; second, to lessen the risk of cardiovascular morbidity and mortality associated with chronic renal disease and with one of its leading causes, diabetes. This review highlights the evidence for and against targeting the renin-angiotensin system in the treatment of patients with different types of nephropathy. Findings from the major studies are summarized in Table 1.



Table 1

Summary of major trials investigating renoprotective effect of ACE inhibitors and ARBs