tbuckley/cabot-search huggingface dataset:
MIXED MOLECULES OF HEMOCYANINS FROM TWO DIFFERENT SPECIES
Authors: Arne Tiselius, Frank L. Horsfall
Journal: The Journal of Experimental Medicine (1939)

By means of the improved electrophoretic technique it has been possible to study the association products which are formed when mixed and dissociated hemocyanins from two different species are reassociated. Both the dissociation and the reassociation of the hemocyanins have been produced simply by altering the pH of the solutions. Scale method electrophoretic diagrams have been used throughout this investigation. This method has adequately demonstrated its advantages and has permitted exact calculations of the mobility, concentration, and homogeneity of components which were either present in too small an amount or were too nearly similar electrochemically to have been defined by other methods. Evidence has been presented which indicates that a number of mixed hemocyanins have been produced. These mixed hemocyanin molecules contain fractions of the dissociated hemocyanins from two different species.
Cumulative association of 22 genetic variants with seropositive rheumatoid arthritis risk
Authors: Elizabeth W Karlson, Lori B Chibnik, Peter Kraft, Jing Cui, Brendan T Keenan, Bo Ding, Souyma Raychaudhuri, Lars Klareskog, Lars Alfredsson, Robert M Plenge
Journal: Annals of the Rheumatic Diseases (2010)

Background Recent discoveries of risk alleles have made it possible to define genetic risk profiles for patients with rheumatoid arthritis (RA). This study examined whether a cumulative score based on 22 validated genetic risk alleles for seropositive RA would identify high-risk, asymptomatic individuals who might benefit from preventive interventions. Methods Eight human leucocyte antigen (HLA) alleles and 14 single-nucleotide polymorphisms representing 13 validated RA risk loci were genotyped among 289 white seropositive cases and 481 controls from the US Nurses' Health Studies (NHS) and 629 white cyclic-citrullinated peptide antibody-positive cases and 623 controls from the Swedish Epidemiologic Investigation of Rheumatoid Arthritis (EIRA). A weighted genetic risk score (GRS) was created, in which the weight for each risk allele is the log of the published odds ratio (OR). Logistic regression was used to study associations with incident RA. Area under the curve (AUC) statistics were compared from a clinical-only model and clinical plus genetic model in each cohort. Results Patients with GRS &gt;1.25 SD of the mean had a significantly higher OR of seropositive RA in both NHS (OR=2.9, 95%CI 1.8 to 4.6) and EIRA (OR 3.4, 95% CI 2.3 to 5.0) referent to the population average. In NHS, the AUC for a clinical model was 0.57 and for a clinical plus genetic model was 0.66, and in EIRA was 0.63 and 0.75, respectively. Conclusion The combination of 22 risk alleles into a weighted GRS significantly stratifies individuals for RA risk beyond clinical risk factors alone. Given the low incidence of RA, the clinical utility of a weighted GRS is limited in the general population.
Aspirin Is Associated With Reduced Cardiovascular and All-Cause Mortality in Type 2 Diabetes in a Primary Prevention Setting
Authors: Greg Ong, Timothy M.E. Davis, Wendy A. Davis
Journal: Diabetes Care (2009)

OBJECTIVE To determine whether regular aspirin use (≥75 mg/day) is independently associated with cardiovascular disease (CVD) and all-cause mortality in community-based patients with type 2 diabetes and no history of CVD. RESEARCH DESIGN AND METHODS Of the type 2 diabetic patients recruited to the longitudinal observational Fremantle Diabetes Study, 651 (50.3%) with no prior CVD history at entry between 1993 and 1996 were followed until death or the end of June 2007, representing a total of 7,537 patient-years (mean ± SD 11.6 ± 2.9 years). Cox proportional hazards modeling was used to determine independent baseline predictors of CVD and all-cause mortality including regular aspirin use. RESULTS There were 160 deaths (24.6%) during follow-up, with 70 (43.8%) due to CVD. In Kaplan-Meier survival analysis, there was no difference in either CVD or all-cause mortality in aspirin users versus nonusers (P = 0.52 and 0.94, respectively, by log-rank test). After adjustment for significant variables in the most parsimonious Cox models, regular aspirin use at baseline independently predicted reduced CVD and all-cause mortality (hazard ratio [HR] 0.30 [95% CI 0.09–0.95] and 0.53 [0.28–0.98[, respectively; P ≤ 0.044). In subgroup analyses, aspirin use was independently associated with reduced all-cause mortality in those aged ≥65 years and men. CONCLUSIONS Regular low-dose aspirin may reduce all-cause and CVD mortality in a primary prevention setting in type 2 diabetes. All-cause mortality reductions are greatest in men and in those aged ≥65 years. The present observational data support recommendations that aspirin should be used in primary CVD prevention in all but the lowest risk patients.
Natural course of endothelium-dependent and -independent responses in autogenous femoral veins grafted into the arterial circulation of the dog.
Authors: T Ishii, K Okadome, K Komori, T Odashiro, K Sugimachi
Journal: Circulation Research (1993)

We examined the natural course of endothelium-dependent and -independent responses in reversed autogenous vein grafts during regeneration and tissue repair processes after vein grafting in dogs. Vein grafts implanted in the canine femoral artery were removed, cut into rings, and suspended in organ chambers for isometric tension recording at 3 days and 1, 2, 4, and 6 weeks after implantation. Endothelial cells were denuded from some rings. Control veins were taken from nonsurgically treated femoral veins. Acetylcholine caused endothelium-dependent relaxations in the control veins, whereas in the vein grafts there was no evidence of endothelium-dependent relaxations to acetylcholine 3 days after the operation. Acetylcholine caused endothelium-independent contractions throughout the study. The endothelium-dependent responses to ADP and calcium ionophore A23187 were constantly maintained. Three days after the operation, the amplitude of norepinephrine-induced contractions of the vein grafts was impaired, and at 1 week the amplitude was recovered, although it was significantly smaller than the amplitude of contractions of the control veins at any postoperative period. Endothelium-independent relaxations to sodium nitroprusside were maintained throughout the study. Thus, there was a selective loss of acetylcholine-mediated relaxation in vein grafts in the early postoperative stage, a time when the intima is not thickened. These altered responses in vein grafts in the early postoperative period may have a role in graft failure.
Small, Clonally Variant Antigens Expressed on the Surface of the <i>Plasmodium falciparum–</i>Infected Erythrocyte Are Encoded by the <i>rif</i> Gene Family and Are the Target of Human Immune Responses
Authors: Victor Fernandez, Marcel Hommel, Qijun Chen, Per Hagblom, Mats Wahlgren
Journal: The Journal of Experimental Medicine (1999)

Disease severity in Plasmodium falciparum infections is a direct consequence of the parasite's efficient evasion of the defense mechanisms of the human host. To date, one parasite-derived molecule, the antigenically variant adhesin P. falciparum erythrocyte membrane protein 1 (PfEMP1), is known to be transported to the infected erythrocyte (pRBC) surface, where it mediates binding to different host receptors. Here we report that multiple additional proteins are expressed by the parasite at the pRBC surface, including a large cluster of clonally variant antigens of 30–45 kD. We have found these antigens to be identical to the rifins, predicted polypeptides encoded by the rif multigene family. These parasite products, formerly called rosettins after their identification in rosetting parasites, are prominently expressed by fresh isolates of P. falciparum. Rifins are immunogenic in natural infections and strain-specifically recognized by human immune sera in immunoprecipitation of surface-labeled pRBC extracts. Furthermore, human immune sera agglutinate pRBCs digested with trypsin at conditions such that radioiodinated PfEMP1 polypeptides are not detected but rifins are detected, suggesting the presence of epitopes in rifins targeted by agglutinating antibodies. When analyzed by two-dimensional electrophoresis, the rifins resolved into several isoforms in the pI range of 5.5–6.5, indicating molecular microheterogeneity, an additional potential novel source of antigenic diversity in P. falciparum. Prominent polypeptides of 20, 22, 76–80, 140, and 170 kD were also detected on the surfaces of pRBCs bearing in vitro–propagated or field-isolated parasites. In this report, we describe the rifins, the second family of clonally variant antigens known to be displayed by P. falciparum on the surface of the infected erythrocyte.
Increased Incidence of Cervical and Vaginal Dysplasia in 3,980 Diethylstilbestrol-Exposed Young Women
Authors: Stanley J. Robboy, Kenneth L. Noller, Peter O'Brien, Raymond H. Kaufman, Duane Townsend, Ann B. Barnes, Jerome Gundersen, W. Dwayne Lawrence, Eric Bergstrahl, Susan McGorray, Barbara C. Tilley, John Anton, Geoffrey Chazen
Journal: JAMA (1984)

The incidence rates of dysplasia and carcinoma in situ (CIS) of the cervix and vagina were determined in 3,980 young women exposed prenatally to diethylstilbestrol. Strict criteria were developed to minimize selection bias among the subset of 744 pairs of matched exposed and unexposed (control) cohort participants, all of whom were identified through review of prenatal obstetrical records. A high degree of compliance was achieved throughout the seven-year study period since in each group about 90% of the women remained as active participants, kept 77% of the annual anniversary examinations, and had separate Papanicolaou smears of the cervix and vagina performed in 99% of the anniversary examinations. The incidence rate for dysplasia and CIS was significantly higher in the women exposed to diethylstilbestrol than in those not exposed in the matched cohort (15.7 v 7.9 cases per 1,000 person-years of follow-up). The rates were higher in the exposed women if squamous metaplasia extended to the outer half of the cervix or onto the vagina. In other respects, the matched cohorts were strikingly similar.
Advanced Breast Cancer Patients' Perceptions of Decision Making for Palliative Chemotherapy
Authors: Elizabeth A. Grunfeld, E. Jane Maher, Susannah Browne, Pippa Ward, Teresa Young, Bella Vivat, Gay Walker, Cathy Wilson, Henry W. Potts, Alex M. Westcombe, Michael A. Richards, Amanda J. Ramirez
Journal: Journal of Clinical Oncology (2006)

To examine advanced breast cancer patients' perceptions of the key decision-making consultation for palliative chemotherapy.One hundred two women with advanced breast cancer, who were offered palliative chemotherapy, participated in a study-specific semistructured interview examining perceptions of the information they had received and their involvement in the decision-making process. One hundred seventeen interviews included 70 in relation to first-line chemotherapy and 47 in relation to second-line chemotherapy (15 patients were interviewed in relation to both first- and second-line chemotherapy).Eighty-six percent of patient interviews (n = 101) reported patient satisfaction with the information they received, and 91% (n = 106) reported satisfaction with the decision-making process. Factors most influential in decisions to accept chemotherapy were the possibility of controlling the tumor (45%, n = 53 of patient interviews) and providing hope (33%, n = 28 of patient interviews; 19%, n = 13 being offered first-line chemotherapy v 43%, n = 20 being offered second-line chemotherapy; P = .006). Thirty-eight percent of patient interviews (n = 44) reported the patient as taking an active role in the decision-making process (33%, n = 23 at first-line chemotherapy v 43%, n = 20 at second-line chemotherapy; P = .06).Women offered second-line chemotherapy were more likely to undergo chemotherapy because of the hope it offers and were more likely to take an active role in that decision compared with women who were offered first-line chemotherapy. Compassionate and honest communication about prognosis and likelihood of benefit from treatment may help to close the gap between hope and expectation and enable patients to make fully informed decisions about palliative chemotherapy.
Functional outcomes following a non-operative treatment algorithm for anterior cruciate ligament injuries in skeletally immature children 12 years and younger. A prospective cohort with 2 years follow-up
Authors: Håvard Moksnes, Lars Engebretsen, Ingrid Eitzen, May Arna Risberg
Journal: British Journal of Sports Medicine (2013)

The methodological quality of studies on treatment of anterior cruciate ligament (ACL) injuries in skeletally immature children after ACL injury is low, and no prospective studies have evaluated the functional outcomes following a non-operative treatment algorithm.To report changes in knee function and activity level in skeletally immature children following a non-operative treatment algorithm for a minimum of 2 years after ACL injury.Prospective cohort.46 skeletally immature children aged 12 years and younger were evaluated at baseline and subsequent yearly follow-ups using patient-reported outcome measurements, isokinetic muscle strength measurements, single-legged hop tests and clinical examinations over a minimum period of 2 years. Participation in physical activities was monitored using a monthly online activity survey, and the main leisure-time sport activity was registered at the yearly follow-ups.36 (78%) of the children did not undergo an ACL reconstruction during the follow-up. Statistically significant changes with questionable clinical relevance were discovered with the patient-reported outcome measurements or hop tests. Leg symmetry indexes were consistently above 90% for muscle strength and single legged hop tests throughout the study, and the isokinetic muscle strength improved significantly in the injured limb. Ninety-one per cent maintained participation in pivoting sports and/or physical education in school, although 38% of the ACL deficient children changed their main activity from a level 1 to a level 2 activity.A non-operative treatment algorithm may be appropriate for ACL injured skeletally immature children, although a reduced participation in level 1 activities may be necessary for some children.
Occurrence and risk factors for falls in rheumatoid arthritis
Authors: C Armstrong
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objectives:</b> To determine the one year period prevalence of falls by age and sex in patients with rheumatoid arthritis and the influence of concurrent medical treatment and disability on the occurrence of falls in this group. <b>Methods:</b> A consecutive series of rheumatoid patients aged 35 years and over, attending hospital outpatient clinics at Hope hospital, Salford, were asked to complete an interview assisted questionnaire which asked about the occurrence and number of falls in the previous 12 months. Subjects who took part were asked about current treatment with antihypertensive agents, diuretics, sedatives or hypnotics, antidepressants, and a history of previous hip/knee surgery. They also completed the health assessment questionnaire (HAQ). Logistic regression was used to determine the association between these variables and falls in the previous 12 months. <b>Results:</b> 253 men and women, mean age 62 years, were studied, and 84 (33%) reported falling in the previous year (36% of women and 26% of men). Of these, 52% had fallen on more than one occasion. There was no important increase in the frequency of falls with age. After adjusting for age and sex, those who had fallen in the previous year were more likely to report taking antidepressant treatment (odds ratio (OR) = 2.09) and to have impairment in both walking (OR = 1.37) and rising (OR = 1.41). The HAQ score was higher in those who reported a fall than those who did not, though the difference was not statistically significant. <b>Conclusions:</b> In this hospital based survey, one in three patients with rheumatoid arthritis reported falling in the previous 12 months. Falls were associated with self reported impairment in lower limb function.
Interrogating the architecture of cancer genomes
Authors: Peter Campbell
Journal: Genome biology (2011)

Deep exome resequencing is a powerful approach for delineating patterns of protein-coding variation among genes, pathways, individuals and populations.We analyzed exome data from 2,440 individuals of European and African ancestry as part of the National Heart, Lung, and Blood Institute's Exome Project, the aim of which is to discover novel genes and mechanisms that contribute to heart, lung and blood disorders.Each exome was sequenced to a mean coverage of 116×, allowing detailed inferences about the population genomic patterns of both common variation and rare coding variation.We identifi ed more than 500,000 single nucleotide variations, the majority of which were novel and rare (76% of variants had a minor allele frequency of less than 0.1%), refl ecting the recent dramatic increase in the size of the human population.The unprecedented magnitude of this dataset allowed us to rigorously characterize the large variation in nucleotide diversity among genes (ranging from 0 to 1.32%), as well as the role of positive and purifying selection in shaping patterns of proteincoding variation and the diff erential signatures of population structure from rare and common variation.This dataset provides a framework for personal genomics and is an important resource that will allow inferences of broad importance to human evolution and health.
Effects of Acetylcholine on Automaticity and Conduction in the Proximal Portion of the His-Purkinje Specialized Conduction System of the Dog
Authors: JOHN C. BAILEY, KALMAN GREENSPAN, MARCELO V. ELIZARI, GARY J. ANDERSON, CHARLES FISCH
Journal: Circulation Research (1972)

Conventional intracellular recordings from the bundle of His and right bundle branch of the canine heart demonstrated that the slope of diastolic depolarization is markedly depressed by superfusion with relatively small concentrations (4-8 µg/ml) of acetylcholine. As the cells become less automatic, take-off potential increases, rise time of phase 0 is reduced, action potential amplitude increases, and conduction proceeds more rapidly.
Health Outcomes of Severely Obese Type 2 Diabetic Subjects 1 Year After Laparoscopic Adjustable Gastric Banding
Authors: John B. Dixon, Paul E. O’Brien
Journal: Diabetes Care (2002)

OBJECTIVE—To prospectively examine the effect of weight loss 1 year after laparoscopic adjustable gastric band surgery on a broad range of health outcomes in 50 diabetic subjects. RESEARCH DESIGN AND METHODS—A total of 50 (17 men, 33 women) of 51 patients with type 2 diabetes, from a total of 500 consecutive patients, were studied preoperatively and again 1 year after surgery. RESULTS—Preoperative weight and BMI (means ± SD) were 137 ± 30 kg and 48.2 ± 8 kg/m2, respectively; at 1 year, weight and BMI were 110 ± 24 kg and 38.7 ± 6 kg/m2, respectively. There was significant improvement in all measures of glucose metabolism. Remission of diabetes occurred in 32 patients (64%), and major improvement of glucose control occurred in 13 patients (26%); glucose metabolism was unchanged in 5 patients (10%). HbA1c was 7.8 ± 3.2% preoperatively and 6.2 ± 2.7% at 1 year (P &amp;lt; 0.001). Remission of diabetes was predicted by greater weight loss and a shorter history of diabetes (pseudo r2 = 0.44, P &amp;lt; 0.001). Improvement in diabetes was related to increased insulin sensitivity and β-cell function. Weight loss was associated with significant improvements in fasting triglyceride level, HDL cholesterol level, hypertension, sleep, depression, appearance evaluation, and health-related quality of life. Early complications occurred in 6% of patients (wound infections in 4%, respiratory support in 2%), and late complications occurred in 30% of patients (gastric prolapse in 20%, band erosion in 6%, and tubing leaks in 4%). All late complications were successfully revised surgically. CONCLUSIONS—Modern laparoscopic weight-loss surgery is effective in managing the broad range of health problems experienced by severely obese individuals with type 2 diabetes. Surgery should be considered as an early intervention.
96 weeks combination of adefovir dipivoxil plus emtricitabine vs. adefovir dipivoxil monotherapy in the treatment of chronic hepatitis B
Authors: Chee-Kin Hui, Hai-Ying Zhang, Scott Bowden, Stephen Locarnini, John M. Luk, Kar-Wai Leung, Yui-Hung Yueng, April Wong, Frank Rousseau, Kwok-Yung Yuen, Nikolai N. Naoumov, George K.K. Lau
Journal: Journal of Hepatology (2008)
Response to Comment on Inzucchi et al. Management of Hyperglycemia in Type 2 Diabetes, 2015: A Patient-Centered Approach. Update to a Position Statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2015;38:140–149
Authors: William H. Herman
Journal: Diabetes Care (2015)

The Professional Practice Committee of the American Diabetes Association would like to thank McCormack et al. (1) for their thoughtful letter regarding the American Diabetes Association’s Standards of Medical Care in Diabetes (2). While the committee agrees that shared decision making is a valuable aspect of diabetes care and that multivariate risk models can be developed using data from …
MicroRNA‐602 and MicroRNA‐608 Regulate Sonic Hedgehog Expression via Target Sites in the Coding Region in Human Chondrocytes
Authors: Nahid Akhtar, Mohammad S. Makki, Tariq M. Haqqi
Journal: Arthritis & Rheumatology (2014)

Hedgehog (HH) signaling has recently been associated with cartilage degradation in osteoarthritis (OA). Because interleukin-1β (IL-1β) has been implicated as a principal instigator of OA, we sought to determine whether IL-1β induces the expression of sonic HH (SHH) and its regulation by microRNAs (miRNAs) in human chondrocytes.Expression of SHH protein in human OA cartilage and in an animal model of OA was determined by immunohistochemical analysis and immunofluorescence analysis, respectively. Gene and protein expression in IL-1β- or SHH-stimulated OA chondrocytes was determined by TaqMan assays and Western blotting, respectively. The effect of overexpression of miRNA-602 (miR-602) and miR-608 or their antagomirs on SHH expression was evaluated by transient transfection of human chondrocytes and HEK 293 cells. The role of signaling pathways was evaluated using small molecule inhibitors. Binding of miRNAs with the putative seed sequence in SHH messenger RNA (mRNA) was validated using a luciferase reporter assay.Expression of SHH, patched 1, Gli-1, HH-interacting protein, matrix metalloproteinase 13 (MMP-13), and Colα1(X) was high in damaged OA cartilage. In damaged cartilage and in IL-1β-stimulated OA chondrocytes, expression of SHH was inversely correlated with expression of miR-608. Cotransfection of OA chondrocytes with miR-608 or miR-602 mimic inhibited reporter activity, and mutation of the miRNA seed sequences abolished the repression of reporter activity. Overexpression of miR-602 or miR-608 inhibited the expression of SHH mRNA and protein, and this was abrogated by antagomirs. Stimulation with recombinant human SHH protein up-regulated MMP-13 expression, and inhibition of HH signaling blocked MMP-13 expression in OA chondrocytes.MiR-602 and miR-608 are important posttranscription regulators of SHH expression in OA chondrocytes, and their suppression by IL-1β may contribute to the enhanced expression of SHH and MMP-13 in OA.