tbuckley/cabot-search huggingface dataset:
Rivastigmine for Dementia Associated with Parkinson's Disease
Authors: Murat Emre, Dag Aarsland, Alberto Albanese, E. Jane Byrne, Günther Deuschl, Peter P. De Deyn, Franck Durif, Jaime Kulisevsky, Teus van Laar, Andrew Lees, Werner Poewe, Alain Robillard, Mario M. Rosa, Erik Wolters, Peter Quarg, Sibel Tekin, Roger Lane
Journal: New England Journal of Medicine (2004)

Cholinergic deficits are prominent in patients who have dementia associated with Parkinson's disease. We investigated the effects of the dual cholinesterase inhibitor rivastigmine in such patients.
General and abdominal obesity and incident asthma in adults: the HUNT study
Authors: Ben Brumpton, Arnulf Langhammer, Pål Romundstad, Yue Chen, Xiao-Mei Mai
Journal: European Respiratory Journal (2012)

Measures of body mass index (BMI) and waist circumference define general obesity and abdominal obesity respectively. While high BMI has been established as a risk factor for asthma in adults, waist circumference has seldom been investigated. To determine the association between BMI, waist circumference and incident asthma in adults, we conducted a prospective study (n=23,245) in a population living in Nord-Trøndelag, Norway in 1995–2008. Baseline BMI and waist circumference were measured and categorised as general obesity (BMI ≥30.0 kg·m 2 ) and abdominal obesity (waist circumference ≥88 cm in females and ≥102 cm in males). Incident asthma was self-reported new-onset cases during an 11-yr follow-up period. Odds ratios for asthma associated with obesity were calculated using multivariable logistic regression. General obesity was a risk factor for asthma in females (OR 1.96, 95% CI 1.52–2.52) and males (OR 1.84, 95% CI 1.30–2.59). In females, after additional adjustment for BMI, abdominal obesity remained a risk factor for asthma development (OR 1.46, 95% CI 1.04–2.05). Abdominal obesity seems to increase the risk of incident asthma in females in addition to BMI, indicating that using both measures of BMI and waist circumference in females may be a superior clinical assessment for asthma risk than any measure alone.
KWASHIORKOR TYPE OF FATTY LIVER IN PRIMATES
Authors: George F. Wilgram, Colin C. Lucas, Charles H. Best
Journal: The Journal of Experimental Medicine (1958)

Fatty livers resembling those seen in the early stages of kwashiorkor have been produced in primates. Monkeys were fed, for about 1 year, purified diets free from choline and betaine and low in methionine. Supplementation with choline slightly improved food consumption and gain in weight. Choline prevented the appearance of any stainable lipide in the liver of the control animals. The extent to which the slightly greater intake of protein, including methionine, in the choline-supplemented animals contributed to the prevention of the periportal accumulation of fat in the liver is being determined.
The potassium channel Ether à go-go is a novel prognostic factor with functional relevance in acute myeloid leukemia
Authors: Jasmin R Agarwal, Frank Griesinger, Walter Stühmer, Luis A Pardo
Journal: Molecular Cancer (2010)

Abstract Background The voltage-gated potassium channel hEag1 (K V 10.1) has been related to cancer biology. The physiological expression of the human channel is restricted to the brain but it is frequently and abundantly expressed in many solid tumors, thereby making it a promising target for a specific diagnosis and therapy. Because chronic lymphatic leukemia has been described not to express hEag1, it has been assumed that the channel is not expressed in hematopoietic neoplasms in general. Results Here we show that this assumption is not correct, because the channel is up-regulated in myelodysplastic syndromes, chronic myeloid leukemia and almost half of the tested acute myeloid leukemias in a subtype-dependent fashion. Most interestingly, channel expression strongly correlated with increasing age, higher relapse rates and a significantly shorter overall survival. Multivariate Cox regression analysis revealed hEag1 expression levels in AML as an independent predictive factor for reduced disease-free and overall survival; such an association had not been reported before. As a functional correlate, specific hEag1 blockade inhibited the proliferation and migration of several AML cell lines and primary cultured AML cells in vitro . Conclusion Our observations implicate hEag1 as novel target for diagnostic, prognostic and/or therapeutic approaches in AML.
Olecranon stress fracture in a weight lifter: a case report
Authors: P S Rao, S K Rao, B C Navadgi
Journal: British Journal of Sports Medicine (2001)

Stress fractures have been reported in the upper limb of sportspeople involved in upper limb dominated events. Olecranon stress fractures have been cited in baseball pitchers, javelin throwers, and gymnasts. The unusual case of a stress fracture of the olecranon in a young weight lifter is reported here. The minimally displaced stress fracture was treated with tension band and two Kirschner wires. The fracture healed in four months and the patient returned to light sports activity after six months.
A Retroinhibition Approach Reveals a Tumor Cell–Autonomous Response to Rapamycin in Head and Neck Cancer
Authors: Panomwat Amornphimoltham, Vyomesh Patel, Kantima Leelahavanichkul, Robert T. Abraham, J. Silvio Gutkind
Journal: Cancer Research (2008)

Abstract Emerging evidence supporting the activation of the Akt-mammalian target of rapamycin (mTOR) signaling network in head and neck squamous cell carcinoma (HNSCC) progression has provided the rationale for exploring the therapeutic potential of inhibiting this pathway for HNSCC treatment. Indeed, rapamycin, a clinically relevant mTOR inhibitor, promotes the rapid regression of HNSCC-tumor xenografts in mice. However, rapamycin does not affect the growth of HNSCC cells in vitro, thus raising the possibility that, as for other cancer types, rapamycin may not target cancer cells directly but may instead act on a component of the tumor microenvironment, such as tumor-associated vasculature. Here, we used a retroinhibition approach to assess the contribution of cancer cell–autonomous actions of rapamycin to its antitumor activity in HNSCC. A rapamycin-resistant form of mTOR (mTOR-RR) was expressed in HNSCC cells while retaining the wild-type (rapamycin-sensitive) mTOR (mTOR-WT) alleles in host-derived endothelial and stromal cells. Expression of mTOR-RR prevented the decrease in phospho-S6 levels caused by rapamycin through mTOR in HNSCC cells but not in stromal cells, and rendered HNSCC xenografts completely resistant to the antitumoral activity of rapamycin. This reverse pharmacology strategy also enabled monitoring the direct consequences of inhibiting mTOR in cancer cells within the complex tumor microenvironment, which revealed that mTOR controls the accumulation of hypoxia-inducible factor-1α (HIF-1α) and the consequent expression of vascular endothelial growth factor and a glucose transporter, Glut-1, in HNSCC cells. These findings indicate that HNSCC cells are the primary target of rapamycin in vivo, and provide evidence that its antiangiogenic effects may represent a downstream consequence of mTOR inhibition in HNSCC cells. [Cancer Res 2008;68(4):1144–53]
Potential Role of Autoantibodies Belonging to the Immunoglobulin G-3 Subclass in Cardiac Dysfunction Among Patients With Dilated Cardiomyopathy
Authors: Alexander Staudt, Marko Böhm, Fabian Knebel, Yvonne Grosse, Claudia Bischoff, Astrid Hummel, Johannes B. Dahm, Adrian Borges, Nicoline Jochmann, Klaus D. Wernecke, Gerd Wallukat, Gert Baumann, Stephan B. Felix
Journal: Circulation (2002)

Immunoadsorption capable of removing circulating autoantibodies represents an additional therapeutic approach in dilated cardiomyopathy (DCM). The role played by autoantibodies belonging to the immunoglobulin (Ig) subclass G-3 in cardiac dysfunction remains to be elucidated.Patients with DCM (left ventricular ejection fraction <30%) participated in this case-control study. Nine patients underwent immunoadsorption with protein A (low affinity to IgG-3), and 9 patients were treated with anti-IgG, which removes all IgG subclasses. Immunoadsorption was performed in 4 courses at 1-month intervals until month 3. In the 2 groups, immunoadsorption induced comparable reduction of total IgG (>80%). IgG-3 was effectively eliminated only by anti-IgG adsorption (eg, during the first immunoadsorption course; protein A, -37+/-4%; anti-IgG, -89+/-3%; P<0.001 versus protein A). The beta1-receptor autoantibody was effectively reduced only by anti-IgG (P<0.01 versus protein A). Hemodynamics did not change in the protein A group. In the anti-IgG group during the first immunoadsorption course, cardiac index increased from 2.3+/-0.1 to 3.0+/-0.1 L x min(-1) x m(-2) (P<0.01 versus protein A). After 3 months, before the last immunoadsorption course, cardiac index was 2.2+/-0.1 L x min(-1) x m(-2) in the protein A group and 3.0+/-0.2 L x min(-1) x m(-2) in the anti-IgG group (P<0.01 versus protein A). Left ventricular ejection fraction increased only in the anti-IgG group (P<0.05 versus protein A).Autoantibodies belonging to IgG-3 may play an important role in cardiac dysfunction of DCM. The removal of antibodies of the IgG-3 subclass may represent an essential mechanism of immunoadsorption in DCM.
Donation Frequency, Iron Loss, and Risk of Cancer Among Blood Donors
Authors: Gustaf Edgren, Marie Reilly, Henrik Hjalgrim, Trung Nam Tran, Klaus Rostgaard, Johanna Adami, Kjell Titlestad, Agneta Shanwell, Mads Melbye, Olof Nyrén
Journal: JNCI Journal of the National Cancer Institute (2008)

Long-term deleterious effects of repeated blood donations may be masked by the donors' healthy lifestyle. To investigate possible effects of blood donation and iron loss through blood donation on cancer incidence while minimizing "healthy donor effects," we made dose-response comparisons within a cohort of Swedish and Danish blood donors.We used a nested case-control study design, in which case patients were defined as all donors who were diagnosed with a malignancy between their first recorded blood donation and study termination (n = 10866). Control subjects (n = 107140) were individually matched on sex, age, and county of residence. Using conditional logistic regression, we estimated relative risks of cancer according to number of blood donations made or estimated iron loss 3-12 years before a case patient was diagnosed with cancer. All statistical tests were two-sided.No clear association was observed between number of donations and risk of cancer overall. However, between the lowest (< or = median, < 0.75 g) and highest (> 90th percentile, > 2.7 g) categories of estimated iron loss, there was a trend (P(trend) < .001) of decreasing risk for cancers of the liver, lung, colon, stomach, and esophagus, which are thought to be promoted by iron overload (combined odds ratio [OR] = 0.70, 95% confidence interval [CI] = 0.58 to 0.84), but only among men and only with a latency of 3-7 years. The risk of non-Hodgkin lymphoma was higher among frequent plasma donors (> 25 vs 0 donations, OR = 2.14, 95% CI = 1.22 to 3.74).Repeated blood donation was not associated with increased or decreased risk of cancer overall. The lack of consistency across latency periods casts doubt on an apparent association between reduced cancer risk and iron loss in men. The positive association between frequent plasma donation and risk of non-Hodgkin lymphoma deserves further exploration.
Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study
Authors: Henry Krum, Markus Schlaich, Rob Whitbourn, Paul A Sobotka, Jerzy Sadowski, Krzysztof Bartus, Boguslaw Kapelak, Anthony Walton, Horst Sievert, Suku Thambar, William T Abraham, Murray Esler
Journal: The Lancet (2009)
The aging kidney
Authors: C Baylis, B Corman
Journal: Journal of the American Society of Nephrology (1998)

The rat provides a useful experimental model to study of the mechanisms of kidney aging. As in man, a wide diversity in the renal response to aging occurs in the rat, and because of this variability it is important to always specify experimental conditions, i.e., strain, gender, diet, and environment. Most aging rats display chronic progressive nephrosis, although the rate at which injury develops is highly variable. There are a number of known risk factors that potentiate injury, including male gender, genetic background, obesity, high protein/high calorie diet, and environmental exposure to pathogens. The causes of age-dependent glomerulopathy are multifactorial and include an imbalance between synthesis and degradation of extracellular matrix products, as well as hemodynamic alterations. Of importance, this damage is not inevitable and can be dissociated from normal kidney aging when optimal conditions for successful aging are provided. There is complex and sometimes contradictory information on vasoactive factors. It is, likely, however, that the activity of intrarenal AngII is somehow upregulated in the aging kidney of some, but not all, strains, and alpha 1-dependent renal nerve activity may also be enhanced. The endothelial vasodialtory prostaglandins and NO exert an increasingly important role in the maintenance of renal perfusion with advancing age, although their production may be diminished. In the future, we anticipate that comparison of rats with different genetic backgrounds will help to dissociate true aging from disease.
Etiological diagnostics of tuberculous pleurisy (PTB) in HIV-positive and HIV-negative patients
Authors: Viacheslav Zhuravlev, Kirill Vladimirov, Nataliay Kozlova, Aleksandr Ivanov
Journal: European Respiratory Journal (2012)

Purpose: verification of PTB by molecular-genetic methods (MG) in patients with and without HIV co-infection. Methods: pleural fluid (PF) of the patients was analyzed using MG. Isolation of DNA and amplification of nucleotide sequence IS6110 which is a marker of Mycobacterium TB (MTB) was carried out using real time PCR method (RT-PCR). Express evaluation of MBT drug resistance (DR) was performed using TB-BIOCHIP (TBCh) system. This method helps to identify IS6110 sequence in the sample and simultaneously identify mutations in rpoB gene associated with DR in rifampicin (R)-resistant strains, and in genes katG, inhA and ahpC-oxyR in isoniazid (H)-resistant strains. Results: group 1 included 72 HIV-infected patients with PTB. DNA of MBT was isolated in PF of 63.8%(n=46) cases. TBCh was made in 40 specimens. Mutations in rpoB gene were found in 29(72.5%) samples, among them 20(68.9%) were due to codon 531(Ser-Leu) replacement. Other common replacements were in codons 511(n=4), 512(n=4). DR to H was found in 30(75.0%) samples. KatG mutations were found in 26(86.6%) samples, mostly in the katG315–80.7%(n=21) and inhA mutations - in 26.9%(n=7) cases. Mutations confirming HR resistance were present in 24(60.0%) samples. 95 HIV-negative patients with PTB were group 2 among them DNA MBT was found in 21 tests (22.1%). DR to H was presented by gene katG mutations in codon 315(66.7%). DR to R was determined by gene rpoB mutations in codons 531(57.1%), 526(n=4), 516(n=2). Conclusion: Sensitivity of MG methods in detection of PTB was more promising in HIV(+) than in HIV(-) patients (p=0.001). Though total DR prevalence was high, the DR rates were similar in both groups.
Molecular heterogeneity of protein kinase C expression in human ventricle
Authors: H Shin
Journal: Cardiovascular Research (2000)

Objective: Although activation of protein kinase C (PKC) modulates the function of normal cardiac myocytes and likely plays a role in the pathogenesis of cardiomyopathic disease states, the molecular basis of PKC expression in human ventricle has not been examined in detail. Methods: We have performed Western analysis and immunohistochemistry on explanted human cardiac tissue from nondiseased and diseased specimens using isoform-specific antibodies directed against all known PKC isozymes. Results: In homogenates from left and right ventricle, all isoforms except PKC-γ and θ were detected by immunoblotting, with confirmation using a second antibody directed against a different epitope when possible. For PKC-βII, δ, and ε, data indicated that these isoforms were variably phosphorylated in vivo, resulting in multiple bands during immunoblotting. Because of potential antibody cross-reactivity, reverse transcriptase polymerase chain reaction (RT-PCR) was performed which confirmed expression of PKC-α, βI, and ζ. Immunohistochemistry demonstrated that all isoforms detected in ventricular homogenate by Western analysis could be localized to cardiac myocytes. From a methodologic standpoint, significant degradation of PKC isoforms could be demonstrated when samples were either frozen or allowed to remain at room temperature, compared to immediate subcellular fractionation. Conclusions: These findings indicate that the PKC expression in human ventricular myocytes is remarkably diverse, with multiple conventional, novel, and atypical isoforms present, and highlight the importance of sample preparation in comparative studies of PKC isoform expression.
<i>Salmonella</i> Promoters Preferentially Activated Inside Tumors
Authors: Nabil Arrach, Ming Zhao, Steffen Porwollik, Robert M. Hoffman, Michael McClelland
Journal: Cancer Research (2008)

Abstract Salmonella enterica and avirulent derivatives prefer solid tumors over normal tissue in animal models. The identification of endogenous Salmonella promoters that are preferentially activated in tumors could further our understanding of this phenomenon. Toward this goal, a random library of S. enterica typhimurium 14028 genomic DNA was cloned upstream of a promoterless gene encoding the green fluorescent protein (GFP) TurboGFP. A population of Salmonella containing this library was injected i.v. into tumor-free nude mice and into human PC3 prostate tumors growing subcutaneously in nude mice. After 2 days, fluorescence-activated cell sorting was used to enrich for bacterial clones expressing GFP from spleens or tumors. The resulting libraries were hybridized to an oligonucleotide tiling array of the Salmonella genome. Eighty-six intergenic regions were found to be enriched in tumor samples but not in spleen. Twenty of these candidate promoters were also detected in the sequences of 100 random clones from a library enriched for expression in bacteria growing in tumors. Three candidate promoter clones were individually tested in vivo, and enhanced GFP expression in bacteria growing in tumor relative to spleen was confirmed. Two of the three clones (pflE and ansB promoter regions) are known to be induced in hypoxic conditions that pertain to many tumors. For many of the other candidate promoters preferentially induced in bacteria growing in tumors, regulatory mechanisms may not be related to hypoxia. The expression of therapeutics in Salmonella under the regulation of one or more promoters that are activated preferentially in tumors has the potential to improve the targeting of drug delivery. [Cancer Res 2008;68(12):4827–32]
Mouse thymic virus (MTLV). A mammalian herpesvirus cytolytic for CD4+ (L3T4+) T lymphocytes.
Authors: S S Morse, J E Valinsky
Journal: The Journal of Experimental Medicine (1989)

Mouse thymic virus (MTLV; ICTV designation murid herpesvirus 3) infects developing T lymphocytes of neonatal mice, causing thymic necrosis and acute immunosuppression. Infected animals shed virus indefinitely. In the present report, two-color flow cytometric analysis of T lymphocyte subpopulations defined by the markers CD4 (L3T4) and CD8 (Lyt-2) was used to determine whether MTLV was lytic for a specific thymocyte population. At peak necrosis (8-11 d after infection), numbers of CD4+8+ cells in the thymus were reduced by 80% or more as compared with controls, and CD4+8- cells were reduced by greater than 98%. The major survivors were CD4-8+ and CD4-8- lymphocytes. These data indicate that the CD4 bearing lymphocyte is a primary target for cytolysis during MTLV infection. Possible parallels between MTLV and a newly described lymphotropic human herpesvirus, human herpesvirus 6 (HHV-6/HBLV), are also suggested.
Diabetes-Related Autoantibodies in Children With Acute Lymphoblastic Leukemia
Authors: Carla Bizzarri, Rita M. Pinto, Dario Pitocco, Elisa Astorri, Marco Cappa, Mohammed Hawa, Germana Giannone, Andrea Palermo, Ernesto Maddaloni, David R.G. Leslie, Paolo Pozzilli
Journal: Diabetes Care (2012)

Acute lymphoblastic leukemia (ALL) is the most common subtype of leukemia in children. Although ALL and type 1 diabetes appear to be biologically unrelated, there are common threads in both epidemiology and etiology. Rising incidence rates of both ALL (1) and type 1 diabetes (2) observed over recent decades in many Western countries seem to support common etiological factors (3).

In the current study, we report on diabetes-related autoantibodies (Abs) in a group of patients with ALL. Thirty-four consecutive children (19 males and 15 females, mean age 6.2 ± 4.6 years) were referred to our institution in 2004 for newly diagnosed ALL. Patients were tested for Abs to islet and thyroid antigens. After the initial investigation and treatment, 31/34 (91%) patients (3 died in the mean time) were followedup for 6 years to evaluate the evolution of the autoimmune markers and progression toward type 1 diabetes.

Glutamic acid decarboxylase (GAD) Abs by direct …
Variables associated with return to sport following anterior cruciate ligament reconstruction: a systematic review
Authors: Sylvia Czuppon, Brad A Racette, Sandra E Klein, Marcie Harris-Hayes
Journal: British Journal of Sports Medicine (2013)

Background As one of the purposes of anterior cruciate ligament reconstruction (ACLR) is to return athletes to their preinjury activity level, it is critical to understand variables influencing return to sport. Associations between return to sport and variables representing knee impairment, function and psychological status have not been well studied in athletes following ACLR. Purpose The purpose of this review was to summarise the literature reporting on variables proposed to be associated with return to sport following ACLR. Study design Systematic review. Methods Medline, EMBASE, CINAHL and Cochrane databases were searched for articles published before November 2012. Articles included in this review met these criteria: (1) included patients with primary ACLR, (2) reported at least one knee impairment, function or psychological measure, (3) reported a return to sport measure and (4) analysed the relationship between the measure and return to sport. Results Weak evidence existed in 16 articles suggesting variables associated with return to sport included higher quadriceps strength, less effusion, less pain, greater tibial rotation, higher Marx Activity score, higher athletic confidence, higher preoperative knee self-efficacy, lower kinesiophobia and higher preoperative self-motivation. Conclusions Weak evidence supports an association between knee impairment, functional and psychological variables and return to sport. Current return to sport guidelines should be updated to reflect all variables associated with return to sport. Utilising evidence-based return to sport guidelines following ACLR may ensure that athletes are physically and psychologically capable of sports participation, which may reduce reinjury rates and the need for subsequent surgery.