tbuckley/cabot-search huggingface dataset:
A Natural History of FUT2 Polymorphism in Humans
Authors: A. Ferrer-Admetlla, M. Sikora, H. Laayouni, A. Esteve, F. Roubinet, A. Blancher, F. Calafell, J. Bertranpetit, F. Casals
Journal: Molecular Biology and Evolution (2009)

Because pathogens are powerful selective agents, host-cell surface molecules used by pathogens as identification signals can reveal the signature of selection. Most of them are oligosaccharides, synthesized by glycosyltransferases. One known example is balancing selection shaping ABO evolution as a consequence of both, A and B antigens being recognized as receptors by some pathogens, and anti-A and/or anti-B natural antibodies produced by hosts conferring protection against the numerous infectious agents expressing A and B motifs. These antigens can also be found in tissues other than blood if there is activity of another enzyme, FUT2, a fucosyltransferase responsible for ABO biosynthesis in body fluids. Homozygotes for null variants at this locus present the nonsecretor phenotype (se), because they cannot express ABO antigens in secretions. Multiple independent mutations have been shown to be responsible for the nonsecretor phenotype, which is coexisting with the secretor phenotype in most populations. In this study, we have resequenced the coding region of FUT2 in 732 individuals from 39 worldwide human populations. We report a complex pattern of natural selection acting on the gene. Although frequencies of secretor and nonsecretor phenotypes are similar in different populations, the point mutations at the base of the phenotypes are different, with some variants showing a long history of balancing selection among Eurasian and African populations, and one recent variant showing a fast spread in East Asia, likely due to positive selection. Thus, a convergent phenotype composition has been achieved through different mutations with different evolutionary histories.
Intracranial arterial dolichoectasia in autosomal dominant polycystic kidney disease.
Authors: W I Schievink, V E Torres, D O Wiebers, J Huston
Journal: Journal of the American Society of Nephrology (1997)

Autosomal dominant polycystic kidney disease (ADPKD) is a systemic disorder with a variety of cardiovascular manifestations. This study presents a group of patients with ADPKD who had intracranial arterial dolichoectasia. One hundred seventy-eight ADPKD patients were screened with magnetic resonance angiography, 40 ADPKD patients had conventional angiography, and 98 ADPKD patients underwent a brain autopsy. For comparison, 360 patients without ADPKD who had magnetic resonance angiography and conventional angiography or brain autopsy were also studied. The prevalence of asymptomatic intracranial arterial dolichoectasia was 2.2% (4 of 178), 2.5% (1 of 40), and 2.0% (2 of 98) in the three ADPKD groups, respectively. None of the patients without ADPKD had intracranial arterial dolichoectasia. In addition to the seven patients with asymptomatic disease, two ADPKD patients with vertebrobasilar dolichoectasia had posterior circulation ischemic symptoms. The mean age of the nine patients (five men and four women) was 56.6 yr (range, 41 to 67 yr). The posterior circulation was involved in five patients, the anterior circulation was involved in two patients, and both were involved in two patients. Arterial dissection was believed to have caused middle cerebral artery dolichoectasia in one patient, and intracranial arterial dissections were strongly suspected in two other patients. Six of the nine patients with intracranial arterial dolichoectasia had additional vascular manifestations of ADPKD. Some patients with ADPKD are at an increased risk of developing intracranial arterial dolichoectasia and dissections. Recognizing this association is important because (1) it may be a cause of stroke; (2) it may mimic a saccular aneurysm on radiographic studies; and (3) it suggests that the arteriopathy of ADPKD may be more generalized than previously believed.
Remission is the goal for cardiovascular risk management in patients with rheumatoid arthritis: a cross-sectional comparative study
Authors: S. A. Provan, A. G. Semb, J. Hisdal, E. Stranden, S. Agewall, H. Dagfinrud, K. Angel, D. Atar, T. K. Kvien
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objectives</h3> To compare markers of cardiovascular disease (CVD) risk between patients with rheumatoid arthritis (RA) in an active disease state and those with RA in remission, and to compare both groups with community controls. <h3>Methods</h3> 113 patients with RA and 86 community controls were assessed across a panel of biomarkers for CVD. RA in remission was defined as Clinical Disease Activity Index ≤2.8. Community controls were selected at random by Statistics Norway, and controls were matched with patients in the cohorts in strata using details of age, sex and residential area. A panel of biomarkers (N-terminal pro-brain natriuretic peptide (NT-proBNP), total cholesterol, reactive hyperaemia index (RHI), pressure measurements, measures of arterial stiffness and intima-media thickness) were compared between patients with active RA and those with RA in remission. Both groups were compared with controls. In addition, biomarker levels were compared across subgroups based on anticyclic citrullinated peptide status, level of joint destruction and presence of extra-articular manifestations. <h3>Results</h3> Patients with active RA had significantly higher levels of NT-proBNP, brachial systolic pressure, augmentation index and central systolic pressure but lower cholesterol than patients in remission and controls. In addition, patients with active RA had significantly higher levels of pulse wave velocity and worse RHI than patients in remission. Comparison across other subgroups gave less consistent differentiations in levels of CVD risk markers. <h3>Conclusion</h3> Patients with active RA, but not those in remission, had significantly increased levels of CVD risk markers. These results link inflammatory activity to markers of CVD risk in patients with RA and may indirectly support the notion that remission in RA confers diminished cardiovascular morbidity.
Therapeutic equivalence of inhaled salbutamol
Authors: S. J FOWLER
Journal: Thorax (2000)

The meta-analysis by Hughes et al was hindered by difficulties in comparing trials that were often flawed and of varied design.1 The authors correctly pointed out that, in most of the studies, the use of equivalence as the null hypothesis was invalid. In addition, all but two of the studies looked at the bronchodilator effects in the presence of basal airway tone, when the top of the dose response curve for bronchodilator response occurs in mild to moderate asthma at a salbutamol dose of approximately 200 μg for chlorofluorocarbon (CFC) or hydrofluoralkane (HFA) pressurised metered dose inhalers (pMDIs).2 To construct a proper dose response curve to estimate relative bronchodilator potency would therefore necessitate the use of doses much lower than …
Repeated allergen exposure enhances excitatory nonadrenergic noncholinergic nerve-mediated bronchoconstriction in sensitized guinea-pigs
Authors: N. Kageyama, M. Ichinose, A. Igarashi, M. Miura, H. Yamauchi, Y. Sasaki, J. Ishikawa, M. Tomaki, K. Shirato
Journal: European Respiratory Journal (1996)

The effect of repeated allergen inhalation challenge on the airway excitatory nonadrenergic noncholinergic (e-NANC) nerve-mediated bronchoconstrictor response was studied in ovalbumin (OA) sensitized guinea-pigs. Three weeks after sensitization, OA inhalation, 0.03% for 3 min (challenged group), or saline inhalation (control group) was repeated every day for 4 weeks. The e-NANC nerve function was examined in vitro by means of isometric tension measurement of main bronchi. After pretreatment with atropine (10(-6) M) and propranolol (10(-6) M), we performed electrical field stimulation (EFS) or exogenous neurokinin A (NKA) administration. In the challenged group, EFS-induced main bronchial contraction was significantly greater than that of the control group (p < 0.05 or p < 0.01), but exogenous NKA-mediated responses were almost the same in both groups. The e-NANC-induced main bronchial contractions after EFS were enhanced by pretreatment with the neutral endopeptidase inhibitor, phosphoramidon, to the same degree in the control and challenged groups, indicating that the peptide degradation mechanisms were not impaired even in the challenged group. Substance P immunoreactivities in the lung of the challenged group were significantly higher than those of the control group. These results suggest that chronic airway inflammation after repeated allergen challenge increases excitatory nonadrenergic noncholinergic nerve function, possibly by enhancing sensory neuropeptide production and/or release.
Patterns of gold levels in urine, serum, and saliva in patients with rheumatoid arthritis undergoing chrysotherapy.
Authors: M J Heath, G T Gillett, A J Swannell, C R Williams, T Palmer
Journal: Annals of the Rheumatic Diseases (1987)

Twenty patients undergoing treatment with aurothiomalate for rheumatoid arthritis (RA) were studied for the presence of gold in all urine specimens passed over four days and for gold in the serum of blood drawn by venous section at 10.00, 16.00, and 22.00 hours on a single day of the study. Specimens of saliva collected at the same times as the blood specimens were also analysed for (total) gold content. Eighteen patients showed rhythmic urinary gold excretion. Variations were observed in the serum levels for total, free, and protein bound gold at different times of the day and night together with similar variations in the salivary total gold levels. It was established that a possible relation exists between urinary gold, serum gold, and salivary gold such that at times of higher urinary gold excretion the serum gold levels (total, free, and protein bound) and the total salivary gold levels were decreased. Conversely, at times of lower urinary gold excretion serum and salivary gold levels were increased.
ET-65 * THE KETOGENIC DIET REDUCES CARBONIC ANHYDRASE 9 AND ALTERS THE EXPRESSION OF PROTEINS INVOLVED WITH GLIOMA GROWTH AND PROGRESSION IN HYPOXIC CONDITIONS
Authors: E. C. Woolf, K. L. Curley, R. Vatsa, J. A. Charlton, C. J. Woodrow, A. C. Scheck
Journal: Neuro-Oncology (2014)

Patients with malignant gliomas have a median survival of approximately 15 months following diagnosis, regardless of currently available treatments which include surgery, radiation and chemotherapy. Improvement in the survival of these patients requires the design of new therapeutic modalities that take advantage of common phenotypes. One such phenotype is metabolic dysregulation - a hallmark of cancer cells. It has been postulated that one approach to treating gliomas may be by metabolic alteration such as that which occurs through the use of the ketogenic diet (KD). The KD is high-fat, low-carbohydrate diet that induces ketosis and has been utilized for the non-pharmacologic treatment of refractory epilepsy. We and others have shown that this diet enhances survival and potentiates standard therapy in mouse models of glioma, yet the anti-tumor mechanisms are not fully understood. We have previously shown that the KD reduces peritumoral edema and tumor vasculature in a mouse model of glioma. We now show that tumors from animals fed the KD show reduced expression of the hypoxia marker carbonic anhydrase 9 (CA9) when compared to animals fed a standard rodent diet (SD). Protein analyses showed that the KD alters the expression of the tight junction protein zona occludens 1 (ZO-1), and the membrane water channel aquaporin-4 (AQPN4), which are regulated by tumor hypoxia and have been implicated in peritumoral edema. We also see a reduction in phosphorylated NF-κB which may result in reduced transcription of hypoxia-related genes. Further analysis showed that the KD reduced expression of vascular endothelial growth factor receptor 2 (VEGFR2), which plays a key role in hypoxia-induced angiogenesis. Taken together our data offers insight into the anti-edema and anti-angiogenic mechanisms underlying the KD. A greater understanding of the effects of the KD as an adjuvant therapy will allow for a more rational approach to its clinical use.
P107 Long-term adherence to exercise after pulmonary rehabilitation: Understanding the motivations and barriers to exercise?
Authors: C Lee, S Elkin
Journal: Thorax (2012)

<h3>Introduction</h3> Adherence to exercise after PR is known to be low and the role of motivation/barriers in this population remains unclear. This study aimed to further investigate the role of motivation and barriers to exercise and specifically profiling trends that may guide/assist maintenance strategies. <h3>Method</h3> 112 (58=M) patients who completed &gt;50% of a PR programme over a 3 year period, were sent a postal survey. Data collected included; demographics, co-morbidities, MRC, physical activity/exercise and motivation (21 items) and barriers (14 items) to exercise quantified along a 5 point-likert scale (Newson and Kemps, 2007). <h3>Results</h3> 51.8% (n=58) responded; mean age 71.72, MRC dyspnoea 2.86 and co-morbidities 1.09, COPD=87.9%. Motivation and barriers were analysed separately, as mean motivation/barriers weren’t significantly correlated. Mean barrier was significant correlated with MRC dyspnoea (p=0.003), co-morbidities (p&lt;0.001) and intent to exercise (p&lt;0.001), but not with motivation. Sub-analyses identified those who exercised regularly (currently at least once a week most weeks) rated motivations and barriers significantly different to those who didn’t. Exercisers had significantly higher mean motivation (p=0.023) and deemed the following factors to be significantly more motivating reasons to exercise; ‘I want to be physically fit’ (p=0.002); ‘I exercise because a health professional advised me to’ (p=0.029); ‘I want to stay in shape’ (p=0.019) and ‘exercising gives me energy’ (p=0.0210). Conversely the non-exercisers had significantly higher mean barrier score (p=0.003) and rated the following as significantly greater barriers; ‘Shortness of breath’ (p=0.013); ‘lack of energy’ (p=0.011); ‘having a limited health/physical condition’ (p=0.028); ‘painful joints’ (p=0.002); ‘not knowing what you are capable of, or should be doing’ (p=0.030); fear of, injury (p=0.032), falling (p=0.036) and safety (p=0.021). None of these factors changed over time since completing PR. <h3>Conclusion</h3> This study quantified 21 motivating factors to exercise and 14 barriers that prevent exercise in the post-PR population. Some factors were rated significantly differently between exercisers and non-exercisers and did not significantly vary over time since completion of PR. Further research is required to establish if targeting specific factors could guide/assist maintenance strategies.
Endothelial Alpha-Parvin Controls Integrity of Developing Vasculature and Is Required for Maintenance of Cell–Cell Junctions
Authors: Alessia Fraccaroli, Bettina Pitter, Abdallah Abu Taha, Jochen Seebach, Stephan Huveneers, Julian Kirsch, Ricardo P. Casaroli-Marano, Stefan Zahler, Ulrich Pohl, Holger Gerhardt, Hans-J. Schnittler, Eloi Montanez
Journal: Circulation Research (2015)

Angiogenesis and vessel integrity depend on the adhesion of endothelial cells (ECs) to the extracellular matrix and to adjacent ECs. The focal adhesion protein α-parvin (α-pv) is essential for vascular development. However, the role of α-pv in ECs in vivo is not known.To determine the function of α-pv in ECs during vascular development in vivo and the underlying mechanisms.We deleted the α-pv gene specifically in ECs of mice to study its role in angiogenesis and vascular development. Here, we show that endothelial-specific deletion of α-pv in mice results in late embryonic lethality associated with hemorrhages and reduced vascular density. Postnatal-induced EC-specific deletion of α-pv leads to retinal hypovascularization because of reduced vessel sprouting and excessive vessel regression. In the absence of α-pv, blood vessels display impaired VE-cadherin junction morphology. In vitro, α-pv-deficient ECs show reduced stable adherens junctions, decreased monolayer formation, and impaired motility, associated with reduced formation of integrin-mediated cell-extracellular matrix adhesion structures and an altered actin cytoskeleton.Endothelial α-pv is essential for vessel sprouting and for vessel stability.
RANKL Increases Vascular Smooth Muscle Cell Calcification Through a RANK-BMP4–Dependent Pathway
Authors: Sara Panizo, Anna Cardus, Mario Encinas, Eva Parisi, Petya Valcheva, Susana López-Ongil, Blai Coll, Elvira Fernandez, Jose M. Valdivielso
Journal: Circulation Research (2009)

Vascular calcification commonly associated with several pathologies and it has been suggested to be similar to bone mineralization. The axis RANKL-OPG (receptor activator of nuclear factor κB ligand–osteoprotegerin) finely controls bone turnover. RANKL has been suggested to increase vascular calcification, but direct evidence is missing. Thus, in the present work, we assess the effect of RANKL in vascular smooth muscle cell (VSMC) calcification. VSMCs incubated with RANKL showed a dose-dependent increase in calcification, which was abolished by coincubation with OPG. To test whether the effect was mediated by signaling to its receptor, knockdown of RANK was accomplished by short hairpin (sh)RNA. Indeed, cells lacking RANK showed no increases in vascular calcification when incubated with RANKL. To further elucidate the mechanism by which RANK activation increases calcification, we blocked both nuclear factor (NF)-κB activation pathways. Only IKKα inactivation inhibited calcification, pointing to an involvement of the alternative NF-κB activation pathway. Furthermore, RANKL addition increased bone morphogenetic protein (BMP)4 expression in VSMCs, and that increase disappeared in cells lacking RANK or IKKα. The increase in calcification was also blunted by Noggin, pointing to a mediation of BMP4 in the calcification induced by RANKL. Furthermore, in an in vivo model, the increase in vascular calcium content was parallel to an increase in RANKL and BMP4 expression, which was localized in calcified areas. However, blood levels of the ratio RANKL/OPG did not change. We conclude that RANKL increases vascular smooth muscle cell calcification by binding to RANK and increasing BMP4 production through activation of the alternative NF-κB pathway.
Evaluation of the Perceived Association Between Resident Turnover and the Outcomes of Patients Who Undergo Emergency General Surgery
Authors: Adil A. Shah, Cheryl K. Zogg, Stephanie L. Nitzschke, Navin R. Changoor, Joaquim M. Havens, Ali Salim, Zara Cooper, Adil H. Haider
Journal: JAMA Surgery (2015)

The influx of new surgical residents and interns at the beginning of the academic year is assumed to be associated with poor outcomes. Referred to as the July phenomenon, this occurrence has been anecdotally associated with increases in the frequency of medical errors due to intern inexperience. Studies in various surgical specialties provide conflicting results.To determine whether an association between the July phenomenon and outcomes exists among a nationally representative sample of patients who underwent emergency general surgery (EGS).Retrospective analysis of data from the 2007-2011 Nationwide Inpatient Sample. Data on adult patients (≥16 years of age) presenting to teaching hospitals with a principal diagnosis of an EGS condition, as defined by the American Association for the Surgery of Trauma, were retrospectively analyzed. The patients who were included in our study were dichotomized into early (July-August) vs late (September-June) management. The original analyses were conducted in March 2015.Risk-adjusted multivariable regression based on calculated propensity scores was assessed for associations with differences in in-hospital mortality, complications, length of stay, and total hospital cost.A total of 1,433,528 patients who underwent EGS were included, weighted to represent 7,095,045 patients from 581 teaching hospitals nationwide; 17.6% were managed early. Relative to patients managed later, early patients had marginally lower risk-adjusted odds of mortality (odds ratio [OR], 0.96 [95% CI, 0.92-0.99]), complications (OR, 0.98 [95% CI, 0.96-0.99]), and developing a secondary EGS condition (OR, 0.97 [95% CI, 0.97-0.98]). Length of stay and total hospital cost were comparable between the 2 groups (P > .05).Contrary to expectations, the EGS patients who were managed early fared equally well, if not better, than the EGS patients who were managed later. Potentially attributable to increased manpower and/or hypervigilance on the part of supervising senior residents or attending physicians, the results suggest that concerns among EGS patients related to the July phenomenon are unfounded.
Survival after Surgery in Stage IA and IB Non–Small Cell Lung Cancer
Authors: David Ost, Judith Goldberg, Linda Rolnitzky, William N. Rom
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Whether histologic subtype of non-small cell lung cancer (NSCLC) has an important effect on prognosis after surgery is unknown.We hypothesized that we could predict mortality more effectively by integrating precise tumor size and histology rather than relying on conventional staging.We used the SEER (Surveillance, Epidemiology, and End Results) registry. Inclusion criteria were as follows: (1) primary squamous cell or adenocarcinoma; (2) potentially curative surgery, defined as a lobectomy or bilobectomy; (3) lymph node dissection performed; and (4) pathologic stage IA or IB.From 1988 to 2000, 7,965 patients were included. For both all-cause and lung cancer-associated mortality, tumor size demonstrated the strongest association (log-rank P < 0.0001 for each). When tumors were small (</=2 cm), lung cancer-associated mortality was similar for adenocarcinoma when compared with squamous cell carcinoma. When tumors were 3 cm or larger in size, lung cancer-associated mortality was higher for adenocarcinoma. The increased risk of lung cancer-associated mortality with adenocarcinoma was more pronounced in those younger than 65 years. Survival prediction using precise size and histology had much better discriminatory power than conventional TNM (tumor-node-metastasis) staging (P = 0.005).Staging that takes into account size, histology, late recurrence risk, and patient age is more accurate than the current TNM system and is clinically relevant because improved prediction can facilitate better decisions on the use of adjuvant chemotherapy.
Regulation of Human Lipolysis IN VIVO OBSERVATIONS ON THE ROLE OF ADRENERGIC RECEPTORS
Authors: Thomas W. Burns, James M. Mohs, Paul E. Langley, Roy Yawn, Gerald R. Chase
Journal: Journal of Clinical Investigation (1974)

Changes in the plasma free fatty acids of a pancreatectomized subject and in free fatty acids and insulin in 10 normal subjects in response to the in vivo infusion of epinephrine alone, epinephrine plus phentolamine, and epinephrine plus propranolol indicate that both alpha and beta adrenergic receptors are present in human adipose tissue. Under the experimental conditions used, adipose tissue appeared to be more responsive to epinephrine than did the cardiovascular system.
New Strategies in Diffuse Large B-cell Lymphoma: Translating Findings from Gene Expression Analyses into Clinical Practice
Authors: Jonathan W. Friedberg
Journal: Clinical Cancer Research (2011)

Abstract Gene expression profiling has had a major impact on our understanding of the biology and heterogeneity of diffuse large B-cell lymphoma (DLBCL). Using this technology, investigators can identify biologic subgroups of DLBCL that provide unique targets for rational therapeutic intervention. This review summarizes these potential targets and updates the progress of clinical development of exciting novel agents for the treatment of DLBCL. Results of ongoing studies suggest that in the near future, we will be able to use gene expression profiling, or an accurate surrogate, to define the best therapeutic approach for individual patients with DLBCL. Clin Cancer Res; 17(19); 6112–7. ©2011 AACR.