tbuckley/cabot-search huggingface dataset:
Breakdown and Release of Myofilament Proteins During Ischemia and Ischemia/Reperfusion in Rat Hearts
Authors: Jennifer E. Van Eyk, Francis Powers, William Law, Catherine Larue, Robert S. Hodges, R. John Solaro
Journal: Circulation Research (1998)

Our objective in experiments reported here was to identify myofilament proteins of rat hearts either lost or degraded by cardiac ischemia (15- or 60-minute duration) with and without 45 minutes of reperfusion. We correlated these changes with alterations in myofilament sensitivity to Ca2+ and maximum force generation. Protein degradation and loss were assessed by high-performance liquid chromatography, SDS-PAGE, Western blotting analysis, and amino acid sequencing. Compared with nonischemic control hearts, bundles of skinned fibers from hearts subjected to ischemia alone demonstrated a decrease in maximum force generation and an increase in sensitivity to Ca2+. These changes in function were increased with the duration of the ischemia and with reperfusion. With increasing duration of ischemia, there was an increased loss and degradation of myofibrillar alpha-actinin and troponin I (TnI) at its C-terminus. Alpha-actinin and TnI were most susceptible to ischemia, but with 60 minutes of ischemia/reperfusion, there was also degradation of myosin light chain-1 (MLC1) involving a clip of residues 1 to 19. The MLC1 degradation product was detected in the reperfusion effluent (along with troponin T, tropomyosin, and alpha-actinin) but not in the tissue with 60 minutes of ischemia with no reperfusion. Moreover, with ischemia the following proteins became associated with the myofibrils: GAPDH and proteins of the mitochondrial ATP synthase complex. Our results provide new evidence regarding the mechanism by which ischemia/reperfusion causes myocardial injury and support the hypothesis that an important element in the injury is altered activity and structure of the myofilaments.
Thalamocortical Disconnection in the Orbitofrontal Region Associated With Cortical Thinning in Schizophrenia
Authors: Manabu Kubota, Jun Miyata, Akihiko Sasamoto, Genichi Sugihara, Hidefumi Yoshida, Ryosaku Kawada, Shinsuke Fujimoto, Yusuke Tanaka, Nobukatsu Sawamoto, Hidenao Fukuyama, Hidehiko Takahashi, Toshiya Murai
Journal: JAMA Psychiatry (2012)

Dysfunction of the thalamocortical pathway has been proposed as a putative underlying pathology of schizophrenia. Although the mechanisms involved remain unclear, postmortem studies suggest the involvement of altered neural projections from the thalamus to layers within the prefrontal cortex.To investigate thalamocortical connectivity in schizophrenia and to examine its possible association with cortical thinning in vivo.Case-control cross-sectional study.Department of Psychiatry at Kyoto University Hospital, Japan.A total of 37 patients with schizophrenia and 36 age-, sex-, and education-matched healthy controls recruited from the local community underwent diffusion-weighted imaging and T1-weighted 3-dimensional magnetic resonance imaging.Probabilistic tractography was performed to investigate thalamocortical pathways. Group differences in mean fractional anisotropy (FA) values were examined in the entire thalamocortical pathway, the thalamolateral prefrontal pathway, the thalamomedial prefrontal pathway, and the thalamo-orbitofrontal pathway. Surface-based analysis was performed to investigate cortical thickness, and the correlation between FA values and cortical thickness was examined.The patient group exhibited reduced FA values within the right thalamo-orbitofrontal pathway (P < .05 for the 8 group comparisons of FA, Bonferroni correction). In the patient group only, the mean FA value for this pathway was positively correlated with thickness of the right frontal polar and lateral orbitofrontal cortices (P < .05, clusterwise correction).These results suggest that, in schizophrenia, regional thalamocortical white matter pathology is specifically associated with cortical pathology in regions where fibers connect.
Effects of digoxin on the control of heart rate and atrioventricular conduction in the dog
Authors: D. WALLICK, S. L STUESSE, Y. MASUDA, M. N LEVY
Journal: Cardiovascular Research (1983)

Journal Article Effects of digoxin on the control of heart rate and atrioventricular conduction in the dog Get access DON WALLICK, DON WALLICK * From the Department of Surgery, Cleveland Metropolitan General Hospital; Division of Investigative Medicine, Mt. Sinai Hospital; and Case Western Reserve University, Cleveland, Ohio *Address for reprint requests: Don W Wallick, PhD, Department of Surgery, Cleveland Metropolitan General Hospital, 3395 Scranton Road, Cleveland, Ohio 44109, USA. Search for other works by this author on: Oxford Academic PubMed Google Scholar SHERRY L STUESSE, SHERRY L STUESSE From the Department of Surgery, Cleveland Metropolitan General Hospital; Division of Investigative Medicine, Mt. Sinai Hospital; and Case Western Reserve University, Cleveland, Ohio Search for other works by this author on: Oxford Academic PubMed Google Scholar YUKITAKA MASUDA, YUKITAKA MASUDA From the Department of Surgery, Cleveland Metropolitan General Hospital; Division of Investigative Medicine, Mt. Sinai Hospital; and Case Western Reserve University, Cleveland, Ohio Search for other works by this author on: Oxford Academic PubMed Google Scholar MATTHEW N LEVY MATTHEW N LEVY From the Department of Surgery, Cleveland Metropolitan General Hospital; Division of Investigative Medicine, Mt. Sinai Hospital; and Case Western Reserve University, Cleveland, Ohio Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 17, Issue 7, July 1983, Pages 400–406, https://doi.org/10.1093/cvr/17.7.400 Published: 01 July 1983
Venous Thromboembolism Prophylaxis in Hospitalized Patients: A Clinical Practice Guideline From the American College of Physicians
Authors: Physicians Qaseem, Roger Chou, Linda L. Humphrey, Melissa Starkey, Paul Shekelle
Journal: Annals of Internal Medicine (2011)

Description: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on prophylaxis of venous thromboembolism for hospitalized nonsurgical patients (medical patients and patients with acute stroke). Methods: This guideline is based on published literature on the topic from 1950 through April 2011 that was identified by using MEDLINE, the Cochrane Library, and reference lists of pertinent randomized trials and systematic reviews to identify additional reports. Searches were limited to randomized trials and English-language publications. The primary outcome for this guideline was total mortality up to 120 days after randomization. Secondary outcomes included symptomatic deep venous thrombosis; all pulmonary embolisms; fatal pulmonary embolism; all bleeding events; major bleeding events; and, for mechanical prophylaxis, effects on skin. This guideline grades the evidence and recommendations by using the ACP's clinical practice guidelines grading system. Recommendation 1: ACP recommends assessment of the risk for thromboembolism and bleeding in medical (including stroke) patients prior to initiation of prophylaxis of venous thromboembolism (Grade: strong recommendation, moderate-quality evidence). Recommendation 2: ACP recommends pharmacologic prophylaxis with heparin or a related drug for venous thromboembolism in medical (including stroke) patients unless the assessed risk for bleeding outweighs the likely benefits (Grade: strong recommendation, moderate-quality evidence). Recommendation 3: ACP recommends against the use of mechanical prophylaxis with graduated compression stockings for prevention of venous thromboembolism (Grade: strong recommendation, moderate-quality evidence). Policy Implication: ACP does not support the application of performance measures in medical (including stroke) patients that promotes universal venous thromboembolism prophylaxis regardless of risk.
Respiratory function in healthy young children using forced oscillations
Authors: G. L Hall, P. D Sly, T. Fukushima, M. M Kusel, P. J Franklin, F. Horak, H. Patterson, C. Gangell, S. M Stick
Journal: Thorax (2007)

Monitoring of respiratory function is important in the diagnosis and management of respiratory disease. The forced oscillation technique requires minimal patient cooperation and is ideal for the determination of respiratory function in young children. This study aimed to develop reference ranges and to document the repeatability in healthy young children using commercially available forced oscillation equipment.The forced oscillation technique, which uses a pseudo-random noise forcing signal between 4 and 48 Hz, was used to measure respiratory function in healthy young children. Repeatability over a 15 min period was also assessed. Regression equations and standardised Z scores were determined for respiratory resistance (Rrs) and reactance (Xrs) at 6, 8 and 10 Hz.Respiratory function was obtained in 158 healthy children aged two to seven years and between 92 and 127 cm in height. Oscillatory respiratory mechanics exhibited linear relationships with height. Within-test variability for resistance ranged between 6% and 9% and between 17% and 20% for reactance. Resistance and reactance did not change significantly over a 15 min period.Reference ranges for respiratory impedance variables in healthy children aged two to seven years are presented. The short-term repeatability of forced oscillatory variables in this age group is reported, allowing appropriate cut-off values for therapeutic interventions to be defined.
Timing: A missing key ingredient in typical fMRI studies of emotion
Authors: Christian E. Waugh, James A. Schirillo
Journal: Behavioral and Brain Sciences (2012)

Abstract Lindquist et al. provide a compelling summary of the brain bases of the onset of emotion. Their conclusions, however, are constrained by typical fMRI techniques that do not assess a key ingredient in emotional experience – timing. We discuss the importance of timing in theories of emotion as well as the implications of neural temporal dynamics for psychological constructionism.
Thoracoscopy assisted pulmonary lobectomy.
Authors: W S Walker, F M Carnochan, M Tin
Journal: Thorax (1993)

This report describes a preliminary experience with six patients undergoing video imaged thoracoscopic pulmonary lobectomy.Three left upper lobectomies, and one each of right upper, right lower and left lower lobectomy were undertaken. The resections were performed as orthodox dissectional lobectomy procedures but were carried out under videothoracoscopic imaging with instruments introduced through two stab incisions. The entire resected lobe was delivered through a 7 cm submammary intercostal incision.There were no operative deaths or complications attributable to the technique. In three other patients conversion to an open thoracotomy was required because of bleeding (two cases) or obscure anatomy (one case). Post-operative pain in those undergoing thoracoscopic resection was less than that encountered with standard thoracotomy and early clinic review showed the patients to be pain free with excellent shoulder movement.Major pulmonary resection according to standard cancer practices is feasible with videothoracoscopic techniques. This approach is likely to offer considerable functional benefit to patients. Specimen delivery through the submammary incision imposes a 5 cm primary lesion size limitation. Detailed mediastinal assessment is necessary to exclude N2 status before undertaking thoracoscopic surgery.
Ty3/Gypsy Retrotransposons: Description of New Arabidopsis thaliana Elements and Evolutionary Perspectives Derived from Comparative Genomic Data
Authors: Ignacio Marín, Carlos Lloréns
Journal: Molecular Biology and Evolution (2000)

We performed a comprehensive analysis of the evolution of the Ty3/Gypsy group of long-terminal-repeat retrotransposons (also known as Metaviridae). Exhaustive database searches allowed us to detect novel elements of this group. In particular, the Arabidopsis thaliana and Drosophila melanogaster genome sequencing projects have recently disclosed a large number of new Ty3/Gypsy sequences. So far, elements of three different Ty3/Gypsy lineages had been described for A. thaliana. Here, we describe six new lineages, which we have called Tit-for-tat1, Tit-for-tat2, Gimli, Gloin, Legolas, and Little Athila. We confirm that plant Ty3/Gypsy elements form two main monophyletic groups. Moreover, our results suggest that at least four independent ancestral lineages existed before the monocot-dicot split, about 200 MYA. Twelve sequences from D. melanogaster that may correspond to new elements are also described. Some of these sequences are similar to those of Osvaldo and Ulysses, two elements of the Osvaldo clade that had never before been described for D. melanogaster. Comparative analyses of multiple organisms, some of them with completely sequenced genomes, show that the number of lineages of Ty3/Gypsy elements is very variable. Thus, while only 1 lineage is present in Saccharomyces cerevisiae, at least 6 exist in Caenorhabditis elegans, at least 9 are present in the A. thaliana, and perhaps 20 are present in D. melanogaster. Finally, we suggest that the presence of a chromodomain-containing integrase, a feature of some closely related Ty3/Gypsy elements of fungi, plants, and animals, may be used to define a new Metaviridae genus.
EFFECTS OF ZIDOVUDINE IN 365 CONSECUTIVE PATIENTS WITH AIDS OR AIDS-RELATED COMPLEX
Authors: E. Dournon, W. Rozenbaum, C. Michon, C. Perronne, P. De Truchis, E. Bouvet, M. Levacher, S. Matheron, S. Gharakhanian, P.M. Girard, D. Salmon, C. Leport, M.C. Dazza, B. Regnier
Journal: The Lancet (1988)
Infusion of Pharmaceutical-Grade Natural Human C-Reactive Protein Is Not Proinflammatory in Healthy Adult Human Volunteers
Authors: Thirusha Lane, Nancy Wassef, Stephen Poole, Yogesh Mistry, Helen J. Lachmann, Julian D. Gillmore, Philip N. Hawkins, Mark B. Pepys
Journal: Circulation Research (2013)

Rationale : Baseline circulating concentrations of C-reactive protein (CRP) are significantly associated with cardiovascular disease risk in general populations. This modest association has been inappropriately conflated with causality, and it has been claimed that CRP is proatherogenic. Most of the known causative factors for atherosclerosis stimulate increased CRP production, but comprehensive genetic epidemiology studies provide no support for a pathogenic role of CRP. The reported proinflammatory effects of human CRP preparations on healthy cells in vitro and in healthy animals in vivo have all been produced by poorly characterized CRP preparations, demonstrably caused by impurities, or elicited by CRP made in recombinant Escherichia coli not by humans. None of the in vitro or animal findings have been reproduced with pure natural human CRP. Nevertheless, the strong proinflammatory effects of infusing recombinant bacterial CRP into humans have still been inappropriately ascribed to CRP. Objective : To investigate the effects of infusion into healthy adult human volunteers of pure natural human CRP. Methods and Results : Comprehensively characterized, pharmaceutical-grade, endotoxin-free, purified CRP, prepared to GMP standard from pooled normal human donor plasma was infused as an intravenous bolus in 7 healthy adult human volunteers at ≤2 mg/kg to provide circulating CRP concentrations ≤44 mg/L. No recipient showed any significant clinical, hematologic, coagulation, or biochemical changes, or any increase in proinflammatory cytokines or acute phase proteins. Conclusions : The human CRP molecule itself is not proinflammatory in healthy human adults.
Locus for Atrial Fibrillation Maps to Chromosome 6q14–16
Authors: Patrick T. Ellinor, Jordan T. Shin, Rachel K. Moore, Danita M. Yoerger, Calum A. MacRae
Journal: Circulation (2003)

Atrial fibrillation (AF), the most common clinical arrhythmia, is a major cause of morbidity and mortality. Although AF is often associated with other cardiovascular conditions, many patients present without an obvious etiology. Inherited forms of AF exist, but the causative gene has been defined only in a single family. We have identified a large family (family FAF-1) in which AF segregates as a Mendelian trait.Thirty-four family members were evaluated by 12-lead ECG, echocardiogram, 24-hour Holter monitoring, and laboratory studies. Individuals with electrocardiographically documented AF were defined as affected. Subjects were considered unaffected if they were >60 years of age, had no personal history of AF, and had no offspring with a history of AF. DNA was extracted and genotypic analyses were performed using polymorphic microsatellite markers. Evidence of linkage was obtained on chromosome 6, with a peak 2-point logarithm of the odds (LOD) score of 3.63 (theta=0) at the marker D6S1021. A maximal multipoint LOD score of 4.9 was obtained between D6S286 and D6S1021, indicating odds of approximately 100 000:1 in favor of this interval as the location of the gene defect responsible for AF in this family. The LOD scores were robust to changes in penetrance and allele frequency. Haplotype analyses further supported this minimal genetic interval.We have mapped a novel locus for AF to chromosome 6q14-16. The identification of the causative gene in this interval will be an important step in understanding the fundamental mechanisms of AF.
The isoflavone metabolite 6-methoxyequol inhibits angiogenesis and suppresses tumor growth
Authors: Sofia Bellou, Evdoxia Karali, Eleni Bagli, Nawaf Al-Maharik, Lucia Morbidelli, Marina Ziche, Herman Adlercreutz, Carol Murphy, Theodore Fotsis
Journal: Molecular Cancer (2012)

Increased consumption of plant-based diets has been linked to the presence of certain phytochemicals, including polyphenols such as flavonoids. Several of these compounds exert their protective effect via inhibition of tumor angiogenesis. Identification of additional phytochemicals with potential antiangiogenic activity is important not only for understanding the mechanism of the preventive effect, but also for developing novel therapeutic interventions.In an attempt to identify phytochemicals contributing to the well-documented preventive effect of plant-based diets on cancer incidence and mortality, we have screened a set of hitherto untested phytoestrogen metabolites concerning their anti-angiogenic effect, using endothelial cell proliferation as an end point. Here, we show that a novel phytoestrogen, 6-methoxyequol (6-ME), inhibited VEGF-induced proliferation of human umbilical vein endothelial cells (HUVE) cells, whereas VEGF-induced migration and survival of HUVE cells remained unaffected. In addition, 6-ME inhibited FGF-2-induced proliferation of bovine brain capillary endothelial (BBCE) cells. In line with its role in cell proliferation, 6-ME inhibited VEGF-induced phosphorylation of ERK1/2 MAPK, the key cascade responsible for VEGF-induced proliferation of endothelial cells. In this context, 6-ME inhibited in a dose dependent manner the phosphorylation of MEK1/2, the only known upstream activator of ERK1/2. 6-ME did not alter VEGF-induced phosphorylation of p38 MAPK or AKT, compatible with the lack of effect on VEGF-induced migration and survival of endothelial cells. Peri-tumor injection of 6-ME in A-431 xenograft tumors resulted in reduced tumor growth with suppressed neovasularization compared to vehicle controls (P < 0.01).6-ME inhibits VEGF- and FGF2-induced proliferation of ECs by targeting the phosphorylation of MEK1/2 and it downstream substrate ERK1/2, both key components of the mitogenic MAPK pathway. Injection of 6-ME in mouse A-431 xenograft tumors results to tumors with decreased neovascularization and reduced tumor volume suggesting that 6-ME may be developed to a novel anti-angiogenic agent in cancer treatment.
Nitrate tolerance in vivo is not associated with depletion of arterial or venous thiol levels.
Authors: S Boesgaard, J Aldershvile, H E Poulsen, S Loft, M E Anderson, A Meister
Journal: Circulation Research (1994)

Results from in vitro experiments suggest that development of nitrate tolerance is due to a depletion of vascular thiol compounds (ie, cysteine and glutathione [GSH]) necessary for the bioconversion of organic nitrates. However, it is unknown whether in vivo tolerance development is associated with changes in thiol levels. This study measures plasma and vessel tissue GSH and cysteine levels in nontolerant rats, nitrate-tolerant rats, and rats treated with the two characteristically different thiol donors N-acetyl-L-cysteine and L-2-oxothiazolidine-4-carboxylic acid (OXO). Chronically catheterized conscious rats received an intravenous infusion of either nitroglycerin (NTG, 0.2 mg/h) or matching placebo for 3 days. At day 3, the hypotensive effect of 2.5 mg NTG/kg was decreased by 74 +/- 6% (mean +/- SEM, P < .05) in the NTG-treated group (n = 7), indicating the development of tolerance. No change in the hypotensive effect of NTG was seen in the placebo group (n = 6, P > .05). Hemodynamic tolerance is not associated with changes in aorta cysteine or GSH levels as compared with the placebo group (cysteine, 77 +/- 14 versus 57 +/- 11 [mean + SEM] nmol/g; GSH, 414 +/- 62 versus 399 +/- 89 nmol/g; P > .05). However, the increase in vascular thiol levels seen after OXO treatment in nontolerant rats is completely absent in nitrate-tolerant animals.(ABSTRACT TRUNCATED AT 250 WORDS)
The human rights of women with intellectual disability
Authors: Ashwin Roy, Ameeta Roy, Meera Roy
Journal: Journal of the Royal Society of Medicine (2012)

The universal human rights ‘to marry and found a family’ and to not be ‘subjected to torture or degrading treatment or punishment’ as affirmed by the United Nations Universal Declaration of Human Rights are breached when people with intellectual disability lacking capacity to consent are sterilized. In this paper the authors review the practices of contraceptive sterilization for people with intellectual disability in different countries including the United Kingdom United States Canada Australia Germany Belgium Scandinavia South Africa Japan China India and Taiwan. After conducting an extensive literature review the authors found that hysterectomies continue to be performed for menstrual management in several countries. In a few notable cases the rights of the person with intellectual disability can be superseded by interests of caregivers. It appears that worldwide there is a slow but definite move to uphold the rights of people with intellectual disability in line with Universal Human Rights with consideration of their capacity to consent and their best interest. It is important that gynecologists and psychiatrists are aware of these issues and the practice of using the least restrictive contraceptive option when dealing with women with intellectual disabilities.