tbuckley/cabot-search huggingface dataset:
Direct Surgery for Coronary Artery Disease
Authors: W. Sterling Edwards
Journal: JAMA (1970)

Direct anastomosis of the end of the internal mammary artery to the side of the distal left anterior descending coronary artery with microsurgical technique produces an immediate increase in myocardial perfusion rather than a delayed increase as after mammary artery implantation. The distal left coronary artery is usually soft and widely patent even in patients with diffuse disease of this vessel. Seven consecutive patients have undergone this procedure; five had a simultaneous aorto-right coronary artery bypass with the saphenous vein. All but one survived and were markedly improved.
The Spectrum of Primary Immunodeficiency Diseases in A Saudi Tertiary Care Hospital Over Two Years
Authors: Bandar Al-Saud, S. Al-Muhsen, A. Al-Ghonaium, S. Al Gazlan, H. Al-Dhekri, R. Arnaout, A. Al-Seraihy, N. Elsayed, M. Shoukri, J. Afzal, H. Al-Mousa
Journal: Journal of Allergy and Clinical Immunology (2013)
Mesenchymal stem cells engineered to express selectin ligands and IL-10 exert enhanced therapeutic efficacy in murine experimental autoimmune encephalomyelitis
Authors: Wenbin Liao, Victor Pham, Linan Liu, Milad Riazifar, Egest J. Pone, Shirley Xian Zhang, Fengxia Ma, Mengrou Lu, Craig M. Walsh, Weian Zhao
Journal: Biomaterials (2015)
Genistein supplementation stimulates the oxytocin system in the aorta of ovariectomized rats
Authors: D Wang
Journal: Cardiovascular Research (2002)

Objective: In the present study, we localized oxytocin (OT) and its receptor (OTR) in the rat aorta, and investigated whether genistein, an isoflavonic phytoestrogen, influences their expression in ovariectomized (OVX) rats deficient in estrogen. Methods and results: OVX Sprague–Dawley rats were randomized to the following groups: genistein (from 0.02 to 5 μg/g/day, s.c. for 10 days), estradiol (E2, 0.1 μg/g/day, s.c. for 10 days) or their respective vehicles. OT and OTR immunostaining was concentrated in the aortic tunica intima, suggesting their paracrine/autocrine action within endothelial cells. Reverse transcription-polymerase chain reaction analysis showed that 1 and 5 μg/g but not 0.1 μg/g genistein elevated OT mRNA (2-fold P<0.05), OTR mRNA (2.5-fold, P<0.05) and endothelial nitric oxide synthase (eNOS) mRNA (2-fold, P<0.05) in the aorta of OVX rats. In addition, genistein treatment increased estrogen receptor α (ERα) (2- to 3-fold, P<0.05) but resulted in a 50% decrease of ERβ (P<0.05). These genistein effects were neutralized by treatment of OVX rats with the ER antagonist ICI 182,780 (1.5 μg/g/day, s.c. for 10 days). Similarly, Western blot analysis revealed an increase of 67-kDa OTR, 140-kDa eNOS, 62-kDa ERα and a decrease of 55-kDa ERβ (P<0.05) in the aorta of OVX rats treated with genistein. In contrast, the treatment of OVX rats with E2 elevated ERβ mRNA (1.5 fold, P<0.05) but similarly to genistein increased OT, OTR, eNOS and ERα mRNA. Conclusion: These results provide the first evidence of OT and OTR co-localization in endothelial cells. The response to genistein via ER activation can be regarded as a recovery from endothelial dysfunction induced by ovariectomy.
Surgical treatment of bronchial obstruction in primary tuberculosis in children: report of seven cases.
Authors: A J Nakvi, H C Nohl-Oser
Journal: Thorax (1979)

Seven children, aged 4 months to 10 years, with bronchial compression due to tuberculous hilar lymphadenitis have been treated surgically since 1974. The indications for surgical treatment were lack of response to chemotherapy and in particular the development of respiratory distress. Excision or curettage of the affected nodes was found to be a safe and sure method of relieving the acute symptoms and preventing permanent damage to the lung.
Suppression of time-dependent outward current in guinea pig ventricular myocytes. Actions of quinidine and amiodarone.
Authors: J R Balser, P B Bennett, L M Hondeghem, D M Roden
Journal: Circulation Research (1991)

Prolongation of cardiac action potentials may mediate some of the arrhythmia-suppressing and arrhythmia-aggravating actions of antiarrhythmic agents. In this study, suppression of time-dependent outward current by quinidine and amiodarone was assessed in guinea pig ventricular myocytes. The net time-dependent outward current contained at least two components: a slowly activating, La(3+)-resistant delayed rectifier current (IK) and a rapidly activating, La(3+)-sensitive current. Quinidine block of total time-dependent outward current during clamp steps to positive potentials was relieved as a function of time, whereas that induced by amiodarone was enhanced. In contrast, at negative potentials, suppression of current, whereas amiodarone reduced IK but not the La(3+)-sensitive current, suggesting that differential block of the two components of time-dependent current underlies the distinct effects of the two agents. In contrast to these disparate effects on total time-dependent outward current, steady-state reduction of IK by both drugs increased at positive voltages and saturated at approximately +40 mV; the voltage dependence of block by quinidine (17% per decade, +10 to +30 mV) was steeper than that by amiodarone (5% per decade, +10 to +20 mV). Block by quinidine was time dependent at negative potentials: on stepping from +50 to -30 mV, block initially increased very rapidly, and subsequent deactivation of IK was slowed. This effect was not seen with amiodarone. At -80 mV, quinidine block was relieved with a time constant of 40 +/- 15 msec (n = 4, twin-pulse protocol). The effects of quinidine on IK were compatible with neither a purely voltage-dependent model of quinidine binding nor a model incorporating both voltage- and state-dependent binding of quinidine to delayed rectifier channels having only one open state. The voltage- and time-dependent features of quinidine block were well described by a model in which quinidine has greater affinity for one of two open states of the channel. We conclude that the effects of quinidine and amiodarone on time-dependent outward current reflects block of multiple channels. Quinidine block of IK was far more voltage dependent than that produced by amiodarone, suggesting the drugs act by different mechanisms.
Cytotoxic T cells clear virus but augment lung pathology in mice infected with respiratory syncytial virus.
Authors: M J Cannon, P J Openshaw, B A Askonas
Journal: The Journal of Experimental Medicine (1988)

We have examined the function of class I MHC-restricted cytotoxic T cells in experimental respiratory syncytial virus (RSV) infection of BALB/c mice by transfer of T cell line MJC-A2 and CTL clone E8a into RSV-infected mice. The T cell line cleared pulmonary RSV infection within 5 d in persistently infected gamma-irradiated mice, but caused acute respiratory disease. This was only seen in infected mice and was often lethal after transfer of greater than 3 x 10(6) CTL. Lower numbers of CTL produced less severe disease but still cleared lung RSV, albeit over a longer time course (up to 10 d). Clearance of lung RSV in immunocompetent mice by the T cell line and CTL clone was again accompanied by acute and sometimes lethal respiratory disease. Bronchoalveolar lavage showed severe lung hemorrhage and frequent neutrophil efflux in mice with CTL-augmented disease.
New Clinical Implications of Molecular Genetics
Authors: David M. Kurnit
Journal: JAMA (1979)

The article by Dozy et al (p 1610) reflects the advent of a new era in medicine and medical genetics—the application of techniques from molecular biology to the solution of clinical problems. This important development has resulted from recent major advances in isolating and deciphering specific human gene sequences. Dozy et al as well as Orkin and colleagues<sup>1</sup>were able to diagnose certain hemoglobinopathies antenatally by the detection of an abnormal pattern of DNA fragments in fetal cells. Antenatal detection of hemoglobinopathies from globin gene deletion is now made possible by analysis of cells recovered by the relatively simple and safe method of early second trimester amniocentesis. Clinically important deletion syndromes include α-thalassemia and δ-β-thalassemia.<sup>2</sup>A more difficult and less reliable method for detection of hemoglobin abnormalities, which requires fetal blood sampling by placental puncture or under direct vision, carries a substantial risk (up to 10%) of fetal
10-Year Follow-up of Intensive Glucose Control in Type 2 Diabetes
Authors: Rury R. Holman, Sanjoy K. Paul, M. Angelyn Bethel, David R. Matthews, H. Andrew W. Neil
Journal: New England Journal of Medicine (2008)

During the United Kingdom Prospective Diabetes Study (UKPDS), patients with type 2 diabetes mellitus who received intensive glucose therapy had a lower risk of microvascular complications than did those receiving conventional dietary therapy. We conducted post-trial monitoring to determine whether this improved glucose control persisted and whether such therapy had a long-term effect on macrovascular outcomes.Of 5102 patients with newly diagnosed type 2 diabetes, 4209 were randomly assigned to receive either conventional therapy (dietary restriction) or intensive therapy (either sulfonylurea or insulin or, in overweight patients, metformin) for glucose control. In post-trial monitoring, 3277 patients were asked to attend annual UKPDS clinics for 5 years, but no attempts were made to maintain their previously assigned therapies. Annual questionnaires were used to follow patients who were unable to attend the clinics, and all patients in years 6 to 10 were assessed through questionnaires. We examined seven prespecified aggregate clinical outcomes from the UKPDS on an intention-to-treat basis, according to previous randomization categories.Between-group differences in glycated hemoglobin levels were lost after the first year. In the sulfonylurea-insulin group, relative reductions in risk persisted at 10 years for any diabetes-related end point (9%, P=0.04) and microvascular disease (24%, P=0.001), and risk reductions for myocardial infarction (15%, P=0.01) and death from any cause (13%, P=0.007) emerged over time, as more events occurred. In the metformin group, significant risk reductions persisted for any diabetes-related end point (21%, P=0.01), myocardial infarction (33%, P=0.005), and death from any cause (27%, P=0.002).Despite an early loss of glycemic differences, a continued reduction in microvascular risk and emergent risk reductions for myocardial infarction and death from any cause were observed during 10 years of post-trial follow-up. A continued benefit after metformin therapy was evident among overweight patients. (UKPDS 80; Current Controlled Trials number, ISRCTN75451837.)
The Effective Population Sizes of the Anthropoid Ancestors of the Human-Chimpanzee Lineage Provide Insights on the Historical Biogeography of the Great Apes
Authors: C. G. Schrago
Journal: Molecular Biology and Evolution (2013)

The recent development of methods that apply coalescent theory to phylogenetic problems has enabled the study of the population-level phenomena that drove the diversification of anthropoid primates. Effective population size, Ne, is one of the main parameters that constitute the theoretical underpinning of these new analytical approaches. For this reason, the ancestral Ne of selected primate lineages has been thoroughly investigated. However, for some of these lineages, the estimates of ancestral Ne reported in several studies present significant variation. This is the case for the common ancestor of humans and chimpanzees. Moreover, several ancestral anthropoid lineages have been ignored in the studies conducted so far. Because Ne is fundamental to understand historic species demography, it is a crucial component of a complete description of the historical scenario of primate evolution. It also provides information that is helpful for differentiating between competing biogeographical hypotheses. In this study, the effective population sizes of the anthropoid ancestors of the human–chimp lineage are inferred using data sets of coding and noncoding sequences. A general pattern of a serial decline of population sizes is found between the ancestral lineage of Anthropoidea and that of Homo and Pan. When the theoretical distribution of gene trees was derived from the parametric estimates obtained, it closely corresponded to the empirical frequency of inferred gene trees along the genome. The most abrupt decrease of Ne was found between the ancestors of all great apes and those of the African great apes alone. This suggests the occurrence of a genetic bottleneck during the evolution of Homininae, which corroborates the origin of African apes from a Eurasian ancestor.
Cervical spine involvement is rare in early arthritis
Authors: I C van Eijk
Journal: Annals of the Rheumatic Diseases (2005)

Chronic inflammatory arthritis may cause subluxation of the cervical spine.1,2 Risk factors for this complication include the presence of rheumatoid factor and severe peripheral joint disease.3–7

The reported prevalence of cervical involvement in patients with rheumatoid arthritis (RA) varies widely from 17% to 88%.7–9 In early RA5,6,10 cervical involvement is much less common, and a recent trial suggested that it might be further reduced with the use of early aggressive treatment for RA.5 The present cross sectional study assesses the prevalence and clinical significance of cervical spine involvement as encountered in our early arthritis clinic, which includes patients with peripheral arthritis …
Medical treatment on holiday abroad.
Authors: R. N. Smith
Journal: BMJ (1969)

Personal experience of medical problems associated with holi day abroad has prompted inquiries into aspects which may concern British doctors. Most doctors travelling on holiday abroad meet compatriots who are ill, and in these circumstances many practitioners offer medical advice. Such consultations with people who are not seriously ill usually arise from casual encounters, and the advantages for the patient determine the decision to give advice. For instance, the ease of communica tion in describing symptoms to a fellow countryman certainly allays much anxiety and may avoid confusion and an uncertain diagnosis. On the other hand, the patients' holiday arrange ments might be disrupted if they sought advice from a local doctor or hospital, and, furthermore, they would have to pay in local currency for the consultation.
Genomic degradation of a young Y chromosome in Drosophila miranda
Authors: Doris Bachtrog, Emily Hom, Karen M Wong, Xulio Maside, Pieter de Jong
Journal: Genome biology (2008)

Abstract Background Y chromosomes are derived from ordinary autosomes and degenerate because of a lack of recombination. Well-studied Y chromosomes only have few of their original genes left and contain little information about their evolutionary origin. Here, we take advantage of the recently formed neo-Y chromosome of Drosophila miranda to study the processes involved in Y degeneration on a genomic scale. Results We obtained sequence information from 14 homologous bacterial artificial chromosome (BAC) clones from the neo-X and neo-Y chromosome of D. miranda , encompassing over 2.5 Mb of neo-sex-linked DNA. A large fraction of neo-Y DNA is composed of repetitive and transposable-element-derived DNA (20% of total DNA) relative to their homologous neo-X linked regions (1%). The overlapping regions of the neo-sex linked BAC clones contain 118 gene pairs, half of which are pseudogenized on the neo-Y. Pseudogenes evolve significantly faster on the neo-Y than functional genes, and both functional and non-functional genes show higher rates of protein evolution on the neo-Y relative to their neo-X homologs. No heterogeneity in levels of degeneration was detected among the regions investigated. Functional genes on the neo-Y are under stronger evolutionary constraint on the neo-X, but genes were found to degenerate randomly on the neo-Y with regards to their function or sex-biased expression patterns. Conclusion Patterns of genome evolution in D. miranda demonstrate that degeneration of a recently formed Y chromosome can proceed very rapidly, by both an accumulation of repetitive DNA and degeneration of protein-coding genes. Our data support a random model of Y inactivation, with little heterogeneity in degeneration among genomic regions, or between functional classes of genes or genes with sex-biased expression patterns.
Treatment of Chronic Lymphocytic Leukemia with a Hypomethylating Agent Induces Expression of NXF2, an Immunogenic Cancer Testis Antigen
Authors: Jason A. Dubovsky, Douglas G. McNeel, John J. Powers, John Gordon, Eduardo M. Sotomayor, Javier A. Pinilla-Ibarz
Journal: Clinical Cancer Research (2009)

Critical to the success of active immunotherapy against cancer is the identification of immunologically recognized cancer-specific proteins with low tolerogenic potential. Cancer testis antigens (CTA), in particular, fulfill this requirement as a result of their aberrant expression restricted to cancer cells and lack of expression in normal tissues bypassing tolerogenic mechanisms against self. Although CTAs have been extensively studied in solid malignancies, little is known regarding their expression in chronic lymphocytic leukemia (CLL).Using a two-pronged approach we evaluated the immunogenicity of 29 CTAs in 22 patients with CLL and correlated these results to reverse transcriptase PCR data from CLL cell lines and patient cells.We identified IgG-specific antibodies for one antigen, NXF2, and confirmed this response by ELISA and Western blot. We found that treatment of CLL with 5-aza-2'-deoxycytidine can induce expression of NXF2 that lasted for several weeks after treatment. Treatment also increased levels of MHC and costimulatory molecules (CD80, CD86, and CD40) necessary for antigen presentation. In addition, we identified other promising antigens that may have potential immunotherapeutic application.Our findings suggest that NXF2 could be further pursued as an immunotherapeutic target in CLL, and that treatment with demethylating agents could be exploited to specifically modulate CTA expression and effective antigen presentation in malignant B cells.
Classification of vasculitis: EMA classification using CHCC 2012 definitions
Authors: Rita Abdulkader, Suzanne E Lane, David G I Scott, Richard A Watts
Journal: Annals of the Rheumatic Diseases (2013)

The classification of the antineutrophil cytoplasmic antibody (ANCA) associated vasculitides (granulomatosis with polyangiitis (Wegener's) (GPA), eosinophilic granulomatosis with polyangiitis (Churg Strauss) (EGPA), and microscopic polyangiitis (MPA)) and polyarteritis nodosa (PAN) remains contentious.1 The American College of Rheumatology (ACR) 1990 classification criteria do not include MPA or use ANCA, while the Chapel Hill Consensus Conference (CHCC) definitions (1994) did not include ANCA and although not intended to be used in classification, are widely used for that purpose.2 In order to harmonise the use of the two systems for epidemiological studies, a consensus algorithm for the classification of ANCA vasculitis and PAN was …
Altered trans-Regulatory Control of Gene Expression in Multiple Anthocyanin Genes Contributes to Adaptive Flower Color Evolution in Mimulus aurantiacus
Authors: Matthew A. Streisfeld, Mark D. Rausher
Journal: Molecular Biology and Evolution (2008)

A fundamental goal in evolutionary biology is to identify the molecular changes responsible for adaptive evolution. In this study, we describe a genetic analysis to determine whether the molecular changes contributing to adaptive flower color divergence in Mimulus aurantiacus affect gene expression or enzymatic activity. High performance liquid chromatography analysis confirms that flower color differences are caused by the presence versus absence of anthocyanin pigments. Cosegregation analysis and in vitro enzymatic assays rule out mutations that affect enzymatic function in the anthocyanin pathway genes. By contrast, cosegregation of gene expression with flower color suggests that tissue-specific differences in pigment production are caused by the coordinated regulatory control of three anthocyanin pathway genes. We provide evidence indicating that these expression differences are caused by a locus that acts in trans- and explains 45% of the phenotypic variance in flower color. A second locus with sequence similarity to the R2R3 MYB family of transcription factors explains 9% of the variation but does so in a complex fashion. These results demonstrate one of only two examples where we have clear evidence of both the adaptive nature of a flower color transition and evidence for its genetic basis. In both cases, mutations appear to affect expression of the anthocyanin structural genes. Future studies will allow us to determine whether these differences represent a real bias in favor of mutations that affect gene expression.
Infliximab for Induction and Maintenance Therapy for Ulcerative Colitis
Authors: Paul Rutgeerts, William J. Sandborn, Brian G. Feagan, Walter Reinisch, Allan Olson, Jewel Johanns, Suzanne Travers, Daniel Rachmilewitz, Stephen B. Hanauer, Gary R. Lichtenstein, Willem J.S. de Villiers, Daniel Present, Bruce E. Sands, Jean Frédéric Colombel
Journal: New England Journal of Medicine (2005)

Infliximab, a chimeric monoclonal antibody directed against tumor necrosis factor alpha, is an established treatment for Crohn's disease but not ulcerative colitis.Two randomized, double-blind, placebo-controlled studies--the Active Ulcerative Colitis Trials 1 and 2 (ACT 1 and ACT 2, respectively)--evaluated the efficacy of infliximab for induction and maintenance therapy in adults with ulcerative colitis. In each study, 364 patients with moderate-to-severe active ulcerative colitis despite treatment with concurrent medications received placebo or infliximab (5 mg or 10 mg per kilogram of body weight) intravenously at weeks 0, 2, and 6 and then every eight weeks through week 46 (in ACT 1) or week 22 (in ACT 2). Patients were followed for 54 weeks in ACT 1 and 30 weeks in ACT 2.In ACT 1, 69 percent of patients who received 5 mg of infliximab and 61 percent of those who received 10 mg had a clinical response at week 8, as compared with 37 percent of those who received placebo (P<0.001 for both comparisons with placebo). A response was defined as a decrease in the Mayo score of at least 3 points and at least 30 percent, with an accompanying decrease in the subscore for rectal bleeding of at least 1 point or an absolute rectal-bleeding subscore of 0 or 1. In ACT 2, 64 percent of patients who received 5 mg of infliximab and 69 percent of those who received 10 mg had a clinical response at week 8, as compared with 29 percent of those who received placebo (P<0.001 for both comparisons with placebo). In both studies, patients who received infliximab were more likely to have a clinical response at week 30 (P< or =0.002 for all comparisons). In ACT 1, more patients who received 5 mg or 10 mg of infliximab had a clinical response at week 54 (45 percent and 44 percent, respectively) than did those who received placebo (20 percent, P<0.001 for both comparisons).Patients with moderate-to-severe active ulcerative colitis treated with infliximab at weeks 0, 2, and 6 and every eight weeks thereafter were more likely to have a clinical response at weeks 8, 30, and 54 than were those receiving placebo. (ClinicalTrials.gov numbers, NCT00036439 and NCT00096655.)