tbuckley/cabot-search huggingface dataset:
Direct Stenting for Stable Angina Pectoris Is Associated With Reduced Periprocedural Microcirculatory Injury Compared With Stenting After Pre-Dilation
Authors: Thomas Cuisset, Michalis Hamilos, Narbeh Melikian, Eric Wyffels, Jaydeep Sarma, Giovanna Sarno, Emanuele Barbato, Jozef Bartunek, William Wijns, Bernard De Bruyne
Journal: Journal of the American College of Cardiology (2008)
Medical Genetics
Authors: Victor A. McKusick
Journal: JAMA (1993)

WITHIN the last year, medical genetics has been fully recognized as a bona fide clinical specialty. The American Board of Medical Genetics, established in 1979 under the wing of the American Society of Human Genetics (with first examinations in 1981), was accepted into the family of specialty-certifying boards as the 24th member of the American Board of Medical Specialties. In 1992, the American College of Medical Genetics was established in parallel to the colleges of other specialties. The development of this clinical specialty has taken place during the last 40 years, and many involved in that development are still active to tell the story.<sup>1</sup> The American Board of Medical Genetics is unusual among specialty boards in the fact that PhD geneticists are certified for working in clinical genetics, and the board has specialized certification in clinical genetics, biochemical genetics, and molecular genetics on the basis of separate examinations. (The
Prognosis of patients with HIV-1 infection starting antiretroviral therapy in sub-Saharan Africa: a collaborative analysis of scale-up programmes
Authors: Margaret May, Andrew Boulle, Sam Phiri, Eugene Messou, Landon Myer, Robin Wood, Olivia Keiser, Jonathan AC Sterne, Francois Dabis, Matthias Egger
Journal: The Lancet (2010)
Non-glycosylated BMP-2 can induce ectopic bone formation at lower concentrations compared to glycosylated BMP-2
Authors: F.C.J. van de Watering, J.J.J.P. van den Beucken, S.P. van der Woning, A. Briest, A. Eek, H. Qureshi, L. Winnubst, O.C. Boerman, J.A. Jansen
Journal: Journal of Controlled Release (2012)
Pre-apoptotic response to therapeutic DNA damage involves protein modulation of Mcl-1, Hdm2 and Flt3 in acute myeloid leukemia cells
Authors: Line Wergeland, Gry Sjøholt, Ingvild Haaland, Randi Hovland, Øystein Bruserud, Bjørn Tore Gjertsen
Journal: Molecular Cancer (2007)

Abstract Background Acute myeloid leukemia (AML) cells are characterized by non-mutated TP53 , high levels of Hdm2, and frequent mutation of the Flt3 receptor tyrosine kinase. The juxtamembrane mutation of FLT3 is the strongest independent marker for disease relapse and is associated with elevated Bcl-2 protein and p53 hyper-phosphorylation in AML. DNA damage forms the basic mechanism of cancer cell eradication in current therapy of AML. Hdm2 and pro-apoptotic Bcl-2 members are among the most intensely induced genes immediately after chemotherapy and Hdm2 is proposed a role in receptor tyrosine kinase regulation. Thus we examined the DNA damage related modulation of these proteins in relation to FLT3 mutational status and induction of apoptosis. Results Within one hour after exposure to ionizing radiation (IR), the AML cells (NB4, MV4-11, HL-60, primary AML cells) showed an increase in Flt3 protein independent of mRNA levels, while the Hdm2 protein decreased. The FLT3 mutant MV4-11 cells were resistant to IR accompanied by presence of both Mcl-1 and Hdm2 protein three hours after IR. In contrast, the FLT3 wild type NB4 cells responded to IR with apoptosis and pre-apoptotic Mcl-1 down regulation. Daunorubicin (DNR) induced continuing down regulation of Hdm2 and Mcl-1 in both cell lines followed by apoptosis. Conclusion Both IR and DNR treatment resulted in concerted protein modulations of Mcl-1, Hdm2 and Flt3. Cell death induction was associated with persistent attenuation of Mcl-1 and Hdm2. These observations suggest that defining the pathway(s) modulating Flt3, Hdm2 and Mcl-1 may propose new strategies to optimize therapy for the relapse prone FLT3 mutated AML patients.
Children's PTSD reactions one year after a sniper attack at their school
Authors: K Nader, R Pynoos, L Fairbanks, C Frederick
Journal: American Journal of Psychiatry (1990)

Fourteen months after a sniper attack at an elementary school, level of exposure to that event remained the primary predictor of ongoing posttraumatic stress reactions in 100 schoolchildren who were followed up. Guilt feelings and knowing the child who was killed were associated with a greater number of symptoms. Grief reactions occurred independent of degree of exposure to the event. The authors discuss the public health implications of these longitudinal findings.
Ethnic and social disparity in glycaemic control in type 2 diabetes; cohort study in general practice 2004–9
Authors: Gareth D James, Peter Baker, Ellena Badrick, Rohini Mathur, Sally Hull, John Robson
Journal: Journal of the Royal Society of Medicine (2012)

Objective To determine whether ethnic group differences in glycated haemoglobin (HbA1c) changed over a 5-year period in people on medication for type 2 diabetes. Design Open cohort in 2004–9. Setting Electronic records of 100 of the 101 general practices in two inner London boroughs. Participants People aged 35 to 74 years on medication for type 2 diabetes. Main outcome measures Mean HbA1c and proportion with HbA1c controlled to ≤7.5%. Results In this cohort of 24,111 people, 22% were White, 58% South Asian and 17% Black African/Caribbean. From 2004 to 2009 mean HbA1c improved from 8.2% to 7.8% for White, from 8.5% to 8.0% for Black African/Caribbean and from 8.5% to 8.0% for South Asian people. The proportion with HbA1c controlled to 7.5% or less, increased from 44% to 56% in White, 38% to 53% in Black African/Caribbean and 34% to 48% in South Asian people. Ethnic group and social deprivation were independently associated with HbA1c. South Asian and Black African/Caribbean people were treated more intensively than White people. Conclusion HbA1c control improved for all ethnic groups between 2004–9. However, South Asian and Black African/Caribbean people had persistently worse control despite more intensive treatment and significantly more improvement than White people. Higher social deprivation was independently associated with worse control.
Endothelin-1 in the lungs of patients with pulmonary hypertension
Authors: Patrice Cacoub, Richard Dorent, Patrick Nataf, Alain Carayon, Marc Riquet, Eric Noe, Jean Charles Piette, Pierre Godeau, Iradj Gandjbakhch
Journal: Cardiovascular Research (1997)

Background: Pulmonary hypertension (PH) is characterized by an increase in vascular tone and an abnormal proliferation of muscle cells in the walls of pulmonary arteries. Recent studies have found high plasma endothelin-1 (ET-1) concentrations in patients with PH. This study was conducted to assess whether elevated circulating ET-1 levels in PH really reflect excessive local pulmonary production. Methods: We prospectively studied ET-1 concentration in lung specimens from 6 control subjects and 13 patients with severe PH referred for lung or heart-lung transplantation (6 patients had primary PH and 7 PH secondary to congenital heart defect). Endothelin-like immunoreactivity (ET-LI) was measured in plasma and lung tissue, using a radioimmunoassay, after ET-1 extraction. Reverse-phase high-performance liquid chromatography was also performed. Results: Peripheral venous plasma ET-LI concentrations in patients with PH, whatever the cause, were greater than those in controls (10.7 ± 0.8 vs 5.3 ± 0.7 pg/ml; P < 0.0005). Pulmonary ET-LI was significantly higher in patients with PH, irrespective of its cause, than in controls (25.2 ± 5.1 vs 8.1 ± 1.1 pg/mg, P < 0.03). ET-LI pulmonary concentrations were slightly higher in Eisenmenger than in primary PH, but this was not significant (27.1 ± 8.6 vs 22.8 ± 5.4 pg/mg). Linear regression analysis indicated a small but significant correlation between ET-LI pulmonary concentrations and pulmonary vascular resistance in the patients with PH (r = 0.38; P = 0.047). In each case, HPLC separation of ET indicated that most of the immuno-reactivity was detected in the same fraction as ET-1. Conclusions: The striking increase in ET-1 pulmonary concentration provides new evidence that excessive local pulmonary ET-1 production may contribute to the vascular abnormalities of pulmonary hypertension.
Parathyroid hormone related peptide gene expression in human fetal and adult heart
Authors: T D Bui, A Shallal, A N Malik, S Al-Mahdawi, G Moscoso, M E S Bailey, P B J Burton, C Moniz
Journal: Cardiovascular Research (1993)

The aim was to investigate the expression of parathyroid hormone related peptide (PTHrP) gene in the human fetal and adult heart.Molecular biological techniques were employed as well as immunocytochemistry and western blot analysis using rabbit polyclonal anti-PTHrP(1-34) and anti-PTHrP (56-86) on normal human fetal and adult heart tissues. Northern blot analysis of both normal human fetal and adult heart total RNA, using a human full length cDNA probe, and polymerase chain reaction analysis of normal human fetal and adult heart cDNAs with exon specific oligonucleotides were carried out.Positive staining was detected with both anti-PTHrP(1-34) and anti-PTHrP(56-86) in fetal heart at 12 weeks of gestation. In both fetal and adult hearts, multiple putative PTHrP proteins were observed with apparent molecular mass of 14-125 kDa. Multiple hybridising PTHrP mRNA isoforms (1.4, 2.1, 3.2, and 4.5 kb) were detected in both fetal and adult heart total RNAs. The fetal and adult heart cDNAs amplified from the cDNA libraries showed the presence of the 5' non-coding exon II and coding exons III-IV but not the 5' non-coding exon Ic.PTHrP is expressed in normal human fetal and adult hearts suggesting that it has a function as an endogenous modulator of the cardiovascular system.
Acute Asthma in Children
Authors: Andrew C. Martin, Ingrid A. Laing, Siew-Kim Khoo, Guicheng Zhang, Kristina Rueter, Laurel Teoh, Shahir Taheri, Catherine M. Hayden, Gary C. Geelhoed, Jack Goldblatt, Peter N. LeSouëf
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

The majority of previous studies investigating asthma genetics have focused on cohorts with stable disease and have not defined mechanisms important during acute asthma. CD14 and CC16 each play a key role in biologically important inflammatory pathways and the gene of each has a functional promoter-region polymorphism.This study was designed to determine the influence of these polymorphisms on plasma levels of their products and clinical disease during acute asthma. We hypothesized that genotype-related differences in CD14 and CC16 production would be more marked during acute asthma and related to disease severity.We studied 148 children on presentation with acute asthma and again in convalescence. CD14 C-159T and CC16 A38G genotypes were determined, and plasma levels of soluble CD14 (sCD14) and CC16 were measured at both times.During acute asthma, plasma sCD14 levels were higher for the whole group (p = 0.003), but increases were only in subjects with CD14 -159TT (p = 0.003) and -159CT (p = 0.004), and not in those with -159CC. Plasma CC16 levels were also elevated acutely for the whole group (p = 0.013), but only in those with CC16 38GG (p = 0.043) and 38AG (p = 0.014), and not in those with CC16 38AA. Subjects with CD14 -159CC and CC16 38AA were more likely to have moderate or severe acute asthma.Plasma levels of sCD14 and CC16 were higher during acute asthma in the subjects. Those with CD14 -159CC and CC16 38AA had no change in sCD14 and CC16 levels and more severe asthma.
Targeting of melanoma brain metastases using engineered neural stem/progenitor cells1
Authors: Karen S. Aboody, Joseph Najbauer, Nils Ole Schmidt, Wendy Yang, Julian K. Wu, Yuzheng Zhuge, Wojciech Przylecki, Rona Carroll, Peter M. Black, George Perides
Journal: Neuro-Oncology (2006)

Brain metastases are an increasingly frequent and serious clinical problem for cancer patients, especially those with advanced melanoma. Given the extensive tropism of neural stem/progenitor cells (NSPCs) for pathological areas in the central nervous system, we expanded investigations to determine whether NSPCs could also target multiple sites of brain metastases in a syngeneic experimental melanoma model. Using cytosine deaminase-expressing NSPCs (CD-NSPCs) and systemic 5-fluorocytosine (5-FC) pro-drug administration, we explored their potential as a cell-based targeted drug delivery system to disseminated brain metastases. Our results indicate a strong tropism of NSPCs for intracerebral melanoma metastases. Furthermore, in our therapeutic paradigm, animals with established melanoma brain metastasis received intracranial implantation of CD-NSPCs followed by systemic 5-FC treatment, resulting in a significant (71%) reduction in tumor burden. These data provide proof of principle for the use of NSPCs for targeted delivery of therapeutic gene products to melanoma brain metastases.
Lysis of antibody-coated cells by platelets.
Authors: W D Soper, S P Bartlett, H J Winn
Journal: The Journal of Experimental Medicine (1982)

Antibody-coated erythrocytes are lysed by murine C5- whole blood but not by plasma separated from such blood. The lytic activity has been shown to derive from platelets that attach to sensitized cells probably through membrane receptors for C3b. Whole blood or platelet-rich plasma (prp) obtained from mice that have been treated with purified cobra venom factor has little or no activity unless it is fortified with fresh C5- plasma. Lysis is observed only if the reactants are incubated at 37 degrees C and mechanical shaking is practiced, at least intermittently, throughout the period of incubation. Adherence of platelets and subsequent lysis are mediated by antibodies of a variety of immunoglobulin classes, including those that fail to mediate complement-dependent lysis. Platelet-mediated lysis is limited to cells to which the platelets adhere; 51Cr labeled, unsensitized cells that are mixed with prp and sensitized, unlabeled cells do not release 51Cr. Normal murine lymphoid cells and ascites tumor cells of mice, rats, and guinea pigs were apparently unaffected by sensitization and incubation with prp. However, because adherence of platelets to these sensitized cells was not observed, it is not clear whether the cells are resistant to the lytic action of platelets or whether the conditions of incubation were unfavorable for the attachment of platelets to the surfaces of nucleated cells. The significance of the lytic reaction described here is not known but may lie in antibody mediated release of microbicidal substances from platelets.
Origins of magic: review of genetic and epigenetic effects
Authors: Sreeram V Ramagopalan, Marian Knight, George C Ebers, Julian C Knight
Journal: BMJ (2007)

<b>Objective</b> To assess the evidence for a genetic basis to magic. <b>Design</b> Literature review. <b>Setting</b> Harry Potter novels of J K Rowling. <b>Participants</b> Muggles, witches, wizards, and squibs. <b>Interventions</b> Limited. <b>Main outcome measures</b> Family and twin studies, magical ability, and specific magical skills. <b>Results</b> Magic shows strong evidence of heritability, with familial aggregation and concordance in twins. Evidence suggests magical ability to be a quantitative trait. Specific magical skills, notably being able to speak to snakes, predict the future, and change hair colour, all seem heritable. <b>Conclusions</b> A multilocus model with a dominant gene for magic might exist, controlled epistatically by one or more loci, possibly recessive in nature. Magical enhancers regulating gene expressionmay be involved, combined with mutations at specific genes implicated in speech and hair colour such as FOXP2 and MCR1.
Regional differences in Finland in the prevalence of rheumatoid factor in the presence and absence of arthritis
Authors: T Korpilahde
Journal: Annals of the Rheumatic Diseases (2003)

To look for possible regional differences in the prevalence of rheumatoid factor (RF) in the presence and absence of arthritis.The study covered a representative sample of the Finnish population aged 30 years or over, primarily comprising 8000 people, of whom 7217 participated in the field survey carried out in 1978-80. RF from serum samples from 7116 subjects was determined by the Waaler-Rose (sensitised sheep cell agglutination) test. Titres >or=32 were regarded as positive and titres >or=128 as strongly positive. Arthritis was diagnosed by a thorough clinical examination.In the absence of arthritis the prevalence of positive and strongly positive RF reactions was 2.1% and 1.0%, respectively. The lowest prevalence of strongly "false positive" RF occurred in south western Finland. After adjustment for age, sex, smoking, and coffee consumption the odds ratio of having a strongly "false positive" RF reaction in eastern Finland was 3.16 (95% confidence interval 1.29 to 7.72) and in northern Finland 2.94 (1.13 to 7.64) compared with south western Finland. The corresponding odds ratio of strongly RF positive arthritis in eastern Finland was 5.08 (1.41 to 18.27).Regional differences are found in the prevalence of a strongly positive RF reaction in the Finnish population. The findings are in accordance with recent results from another study concerning regional differences in the incidence of rheumatoid arthritis in Finland.
`Gastroenterology revision' illustrated case histories and MCQs
Authors: I. A D Bouchier
Journal: Gut (1985)

<h3>Abstract</h3> Individual differences in brain anatomy can be used to predict variability in cognitive function. Most studies to date have focused on broad population-level trends, but the extent to which the observed predictive features are shared across sexes and age groups remains to be established. While it is standard practice to account for intracranial volume (ICV) using proportion correction in both regional and whole-brain morphometric analyses, in the context of brain-behavior predictions the possible differential impact of ICV correction on anatomical features and subgroups within the population has yet to be systematically investigated. In this work, we evaluate the effect of proportional ICV correction on sex-independent and sex-specific predictive models of individual cognitive abilities across multiple anatomical properties (surface area, gray matter volume, and cortical thickness) in healthy young adults (Human Connectome Project; n=1013, 548 females) and typically developing children (Adolescent Brain Cognitive Development study; n=1823, 979 females). We demonstrate that ICV correction generally reduces predictive accuracies derived from surface area and gray matter volume, while increasing predictive accuracies based on cortical thickness in both adults and children. Furthermore, the extent to which predictive models generalize across sexes and age groups depends on ICV correction: models based on surface area and gray matter volume are more generalizable without ICV correction, while models based on cortical thickness are more generalizable with ICV correction. Finally, the observed neuroanatomical features predictive of cognitive abilities are unique across age groups regardless of ICV correction, but whether they are shared or unique across sexes (within age groups) depends on ICV correction. These findings highlight the importance of considering individual differences in ICV, and show that proportional ICV correction does not remove the effects of cranium volumes from anatomical measurements and can introduce ICV bias where previously there was none. ICV correction choices affect not just the strength of the relationships captured, but also the conclusions drawn regarding the neuroanatomical features that underlie those relationships.
A Stepped Care Strategy Using Buprenorphine and Methadone Versus Conventional Methadone Maintenance in Heroin Dependence: A Randomized Controlled Trial
Authors: Johan Kakko, Leif Grönbladh, Kerstin Dybrandt Svanborg, Joachim von Wachenfeldt, Christian Rück, Bob Rawlings, Lars-Håkan Nilsson, Markus Heilig
Journal: American Journal of Psychiatry (2007)

Objective: Both methadone and buprenorphine are effective therapy for heroin dependence. Efficacy is best documented for methadone maintenance therapy, but safety concerns limit its use. Buprenorphine offers lower overdose risk and improved access, but efficacy may be lower. The authors compared adaptive, buprenorphine-based stepped care to optimal methadone maintenance treatment. Method: This randomized controlled trial was undertaken 2004–2006. It consisted of a 24-day uniform double-blind induction phase followed by single-blind flexible dosing based on structured clinical criteria, for a total of 6 months. Ninety-six self-referred subjects with heroin dependence were randomly assigned to methadone or to stepped treatment initiated with buprenorphine/naloxone and escalated to methadone if needed. All subjects received intensive behavioral treatment. Primary outcome was retention in treatment. Secondary outcomes were completer analyses of problem severity (Addiction Severity Index) and proportion of urine samples free of illicit drugs. Results: Overall, 6-month retention was 78%. Stepped treatment and methadone maintenance therapy outcomes were virtually identical. Among completers of stepped therapy, 46% remained on buprenorphine/naloxone. Proportion of urine samples free of illicit opiates increased over time and ultimately reached approximately 80% in both arms. Problem severity decreased significantly and uniformly in both arms. Conclusions: A stepped treatment of heroin dependence as described here appears equally efficacious compared to optimally delivered methadone maintenance therapy. Together with prior data on the advantageous safety of buprenorphine, this suggests that broad implementation of strategies using buprenorphine as first-line treatment should be considered.
P-24: a human leukemia-associated and lymphohemopoietic progenitor cell surface structure identified with monoclonal antibody.
Authors: J H Kersey, T W LeBien, C S Abramson, R Newman, R Sutherland, M Greaves
Journal: The Journal of Experimental Medicine (1981)

This study was directed at surface structures that are found on human lymphohemopoietic progenitor cells in normal and leukemic bone marrow. A monoclonal antibody was produced against an acute lymphoblastic leukemia (ALL) cell line of the pre-B phenotype; this antibody (BA-2) was used to demonstrate a cell surface polypeptide of approximately 24,000 mol wt that migrates similarly in both reduced and nonreduced form. This polypeptide, p24/BA-2, was shown by immune precipitation and gel electrophoresis and cell distribution studies to be different from HLA-DR and gp 100/cALLa. p24/BA-2 was present on the surface of 77% (54/70) of cases of non-T, non-B ALL; BA-2 staining was less bright or nondetectable in surface Ig+ (SIg+) chronic lymphocytic leukemia (CLL) and T ALL and nondetectable on peripheral T and B lymphocytes. Approximately 3% of bone marrow mononuclear cells were p24/BA-2+, and these cells were E rosette-, surface (SIg-), and nonphagocytic. Marrow TdT+ progenitor cells were frequently p 24/BA-2+. Results suggest that p24/BA-2 represents a surface structure present on lymphohemopoietic bone marrow progenitor cells and that most common types of ALL bear the p25/BA-2 structure.