tbuckley/cabot-search huggingface dataset:
Postischemic Acute Renal Failure Is Reduced by Short-Term Statin Treatment in a Rat Model
Authors: Faikah Gueler, Song Rong, Joon-Keun Park, Anette Fiebeler, Jan Menne, Marlies Elger, Dominik N. Mueller, Franziska Hampich, Ralf Dechend, Uta Kunter, Friedrich C. Luft, Hermann Haller
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Postischemic acute renal failure (ARF) is common and often fatal. Cellular mechanisms include cell adhesion, cell infiltration and generation of oxygen free radicals, and inflammatory cytokine production. Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors ("statins") directly influence inflammatory mechanisms. The hypothesis that ischemia-induced ARF could be ameliorated with statin treatment was investigated and possible molecular mechanisms were analyzed in a uninephrectomized rat model. Male Sprague-Dawley rats were pretreated with cerivastatin (0.5 mg/kg) or vehicle for 3 d. Ischemic ARF was induced by left renal artery clipping for 45 min, while the right kidney was being removed. After 24 h of ARF, serum creatinine levels were increased 7.5-fold in vehicle-treated control animals with ARF, compared with sham-operated animals (P < 0.005). Statin treatment reduced the creatinine level elevation by 40% (P < 0.005). Simultaneously, ischemia-induced severe decreases in GFR were significantly ameliorated by statin treatment (sham operation, 0.95 ± 0.09 ml/min, n = 13; ischemia without treatment, 0.06 ± 0.02 ml/min, n = 9; ischemia with statin pretreatment, 0.21 ± 0.03 ml/min, n = 11; P < 0.001). Furthermore, statin pretreatment prevented the occurrence of tubular necrosis, with marked loss of the brush border, tubular epithelial cell detachment, and tubular obstruction in the S3 segment of the outer medullary stripe. In addition, monocyte and macrophage infiltration was almost completely prevented, intercellular adhesion molecule-1 upregulation was greatly decreased, and inducible nitric oxide synthase expression was reduced. Fibronectin and collagen IV expression was reduced, approaching levels observed in sham-operated animals. In vehicle-treated rats with ARF, mitogen-activated protein kinase extracellular activated kinase-1/2 activity was increased and the transcription factors nuclear factor-κB and activator protein-1 were activated. Statin treatment reduced this activation toward levels observed in sham-operated rats. The data suggest that hydroxy-3-methylglutaryl coenzyme A reductase inhibition protects renal tissue from the effects of ischemia-reperfusion injury and thus reduces the severity of ARF. The chain of events may involve anti-inflammatory effects, with inhibition of mitogen-activated protein kinase activation and the redox-sensitive transcription factors nuclear factor-κB and activator protein-1.
Abatacept treatment reduces disease activity in early primary Sjögren's syndrome (open-label proof of concept ASAP study)
Authors: P M Meiners, A Vissink, F G M Kroese, F K L Spijkervet, N Sillevis Smitt-Kamminga, W H Abdulahad, J Bulthuis-Kuiper, E Brouwer, S Arends, H Bootsma
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objective</h3> To assess the efficacy and safety of abatacept in patients with early and active primary Sjögren9s syndrome (pSS). <h3>Methods</h3> All 15 patients (12 women, three men) included in the open-label Active Sjögren Abatacept Pilot study met the revised American-European Consensus Group criteria for pSS and were biological disease-modifying antirheumatic drug-naive. Patients were treated with eight intravenous abatacept infusions on days 1, 15 and 29 and every 4 weeks thereafter. Follow-up was conducted at 4, 12, 24 (on treatment), 36 and 48 weeks (off treatment). Disease activity was assessed with European League Against Rheumatism (EULAR) Sjögren9s Syndrome Disease Activity Index (ESSDAI) and EULAR Sjögren9s Syndrome Patient Reported Index (ESSPRI). Several other functional, laboratory and subjective variables were analysed. Generalised estimating equations were used to analyse parameters over time. <h3>Results</h3> ESSDAI, ESSPRI, rheumatoid factor and IgG levels decreased significantly during abatacept treatment and increased post-treatment. Salivary and lacrimal gland function did not change during treatment. Fatigue and health-related quality of life (HR-QoL) improved significantly during treatment. No serious side effects or infections were seen. <h3>Conclusions</h3> In this open-label study, abatacept treatment is effective, safe and well tolerated, and results in improved disease activity, laboratory parameters, fatigue and HR-QoL in patients with early and active pSS. <h3>Trial registration number</h3> 2009-015558-40.
The Lethal Phenotype of Cancer: The Molecular Basis of Death Due to Malignancy
Authors: R. D. Loberg, D. A. Bradley, S. A. Tomlins, A. M. Chinnaiyan, K. J. Pienta
Journal: CA A Cancer Journal for Clinicians (2007)

The last decade has seen an explosion in knowledge of the molecular basis and treatment of cancer. The molecular events that define the lethal phenotype of various cancers—the genetic and cellular alterations that lead to a cancer with a poor or incurable prognosis—are being defined. While these studies describe the cellular events of the lethal phenotype of cancer in detail, how these events result in the common clinical syndromes that kill the majority of cancer patients is not well understood. It is clear that the central step that makes most cancers incurable is metastasis. Understanding the traits that a cancer acquires to successfully grow and metastasize to distant sites gives insight into how tumors produce multiple factors that result in multiple different clinical syndromes that are lethal for the patient.
RIGHT- AND LEFT-HANDEDNESS IN PRIMITIVE MEN
Authors: G. E. Smith
Journal: BMJ (1925)

SBJO 1107 obtained in these five individuals were remarkably constantK and in some fifty tests rarely differed more than 10 per cent.from the average results given in Table IV.The results are expressed as percentages of the standard Batch Q. Charts 3 and 4 illustrate the manner in which the test were performed.
Laboratory testing for cobalamin deficiency in megaloblastic anemia
Authors: Matthew J. Oberley, David T. Yang
Journal: American Journal of Hematology (2013)

Cobalamin (vitamin B12) deficiency is a common cause of megaloblastic anemia in Western populations. Laboratory evaluation of megaloblastic anemia frequently includes the assessment of patient cobalamin and folate status. Current total serum cobalamin measurements are performed in the clinical laboratory with competitive binding luminescence assays, whose results may not always accurately reflect actual cobalamin stores. Surrogate markers of cobalamin deficiency such as methylmalonic acid and homocysteine have been utilized to improve diagnostic accuracy; however, the specificity of these tests by themselves is rather low. Measurement of the biologically active fraction of cobalamin, holotranscobalamin, has been proposed as a replacement for current total cobalamin assays. Although holotranscobalamin measurements appear to have slighter better sensitivity, the specificity of this assay remains to be determined. The relative merits and demerits of commonly available methods to assess cobalamin deficiency in patients with suspected megaloblastic anemia are discussed.
Pregnancies and terminations after 1995 warning about third-generation oral contraceptives
Authors: Susan S Jick, Catherine Vasilakis, Hershel Jick
Journal: The Lancet (1998)

On Oct 18, 1995, the Medicines Control Agency sent a warning letter based on in-press studies that reported that women who used third-generation oral contraceptives containing gestodene or desogestrel were at increased risk for venous thromboembolism compared with women using oral contraceptives containing levonorgestrel (“other” users). 1 Jick HJ Jick SS Gurewich V Myers MW Vasilakis C Risk of idiopathic cardiovascular death and nonfatal venous thromboembolism in women using oral contraceptives with differing progestagen components. Lancet. 1995; 346: 1589-1593 PubMed Scopus (727) Google Scholar , 2 World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone ContraceptionEffect of different progestagens in low oestrogen oral contraceptives on venous thromboembolic disease. Lancet. 1995; 346: 1582-1588 PubMed Scopus (617) Google Scholar The warning letter raised concerns that the number of pregnancies and terminations of pregnancy (TOP) would increase. 3 Ramsay S UK “pill scare” led to abortion increase. Lancet. 1996; 347: 1109 Abstract PubMed Google Scholar , 4 Child TJ Rees M MacKenzie IZ Pregnancy terminations after oral contraception scare. Lancet. 1996; 347: 1260 Abstract PubMed Scopus (14) Google Scholar With data from the General Practice Research Database, 2 World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone ContraceptionEffect of different progestagens in low oestrogen oral contraceptives on venous thromboembolic disease. Lancet. 1995; 346: 1582-1588 PubMed Scopus (617) Google Scholar , 5 Jick H Jick SS Derby LE Validation of information recorded on general practitioner based computerised data resource in the United Kingdom. BMJ. 1991; 302: 766-768 Crossref PubMed Scopus (739) Google Scholar we identified women who had received a third-generation or “other” oral contraceptive prescription in the months before October, 1994, and compared their subsequent use of oral contraceptives as well as the frequency of pregnancy and TOP in the subsequent 12 months with that of women who received oral contraceptives in the months prior to October, 1995, just before the Committee on Safety of Medicines warning.
Characteristics of marrow production and reticulocyte maturation in normal man in response to anemia
Authors: Robert S. Hillman
Journal: Journal of Clinical Investigation (1969)

Erythropoiesis in normal man was studied during periods of phlebotomy-induced anemia of varying severity. This study permitted a comparison of marrow production measurements over a wide range of marrow production levels. As long as the serum iron remained above 50 mug/100 ml, measurements of plasma iron turnover provided an excellent index of marrow production at all levels of red cell production. In contrast, the absolute reticulocyte count demonstrated a poor correlation with the other measurements. This was shown to be the result of a prolongation of the time required for circulating reticulocytes to lose their reticulum, which correlated with the severity of the anemia. For the clinical application of the reticulocyte count as a measurement of marrow production, an adjustment must be made for this alteration in the circulating reticulocyte maturation time.
Adenosine-sensitive ventricular tachycardia: evidence suggesting cyclic AMP-mediated triggered activity.
Authors: B B Lerman, L Belardinelli, G A West, R M Berne, J P DiMarco
Journal: Circulation (1986)

Catecholamine-induced triggered activity is thought to be caused by intracellular calcium overload mediated by elevation of intracellular cyclic AMP (cAMP). Although shown to occur in isolated preparations, evidence supporting its clinical existence has been lacking. Electrophysiologic studies were performed in four patients with structurally normal hearts who had exertionally related sustained ventricular tachycardia (VT). Programmed stimulation reproducibly initiated and terminated VT in all patients. Induction of tachycardia was also facilitated by infusion of isoproterenol. Adenosine, an endogenous nucleoside, whose only known electrophysiologic effect on ventricular myocardium and Purkinje fibers is antagonism of catecholamine-induced stimulation of intracellular cAMP production, reproducibly terminated all episodes of VT. The tachycardia was also terminated by intravenous verapamil and by the Valsalva maneuver and/or carotid sinus massage. Beta-Adrenergic receptor blockade with propranolol either terminated or prevented induction of VT during programmed stimulation or catecholamine challenge. Adenosine was also administered during VT to 14 patients whose arrhythmias fulfilled standard criteria for reentry, two of whom also had exercise-induced VT. Adenosine, at a dose (112.5 to 225 micrograms/kg iv) sufficient to cause either sinus slowing/arrest or ventriculoatrial block during ventricular pacing, failed to slow or terminate any episode of VT in these patients. Verapamil and autonomic modulation were also ineffective in this group of patients. Adenosine, verapamil, vagal maneuvers (acetylcholine), and beta-adrenergic receptor blockade are all known to decrease the slow-inward calcium current either directly by modulating calcium channels or indirectly by inhibiting production of cellular cAMP. Therefore the observation in this study that interventions that lower intracellular cAMP either terminate or prevent induction of VT in patients with structurally normal hearts and exercise-induced VT suggests that the mechanism of tachycardia may be cAMP-mediated triggered activity.
Atherogenesis in transgenic mice with human apolipoprotein B and lipoprotein (a).
Authors: M J Callow, J Verstuyft, R Tangirala, W Palinski, E M Rubin
Journal: Journal of Clinical Investigation (1995)

The engineering of mice that express a human apoB transgene has resulted in animals with high levels of human-like LDL particles and through crosses with human apo(a) transgenics, high levels of human-like lipoprotein (a) (Lp[a]) particles. In this study, these animals have been used to compare the atherogenic properties of apo(a), LDL, and Lp(a). The presence of the high expressing apoB (apoBH) transgene was associated with a 2.5-fold increase in VLDL-LDL cholesterol (primarily in the LDL fraction) and a 15-fold increase in proximal lesions compared with non-transgenic mice (P < or = 0.0001), while the presence of the low expressing human apoB (apoBL) transgene was not associated with major changes in lipoprotein profiles or increases in aortic lesion size. Examination of aortas of apoBH mice demonstrated lesions along the entire length of the aorta and immunochemical analysis of the lesions revealed features characteristically seen in human lesions including the presence of oxidized lipoproteins, macrophages, and immunoglobulins. Unlike animals with the apoBL transgene, animals with the apo(a) transgene had significant increases in proximal aortic fatty streak lesions compared to nontransgenic control animals (threefold; P < 0.02), while animals with both transgenes, the apo(a)/apo BL double transgenics, had lesions 2.5 times greater than animals expressing the apo(a) transgene alone and eightfold (P < 0.0006) greater than nontransgenic animals. These murine studies demonstrate that marked increases in apoB and LDL resulted in atherosclerotic lesions extending down the aorta which resemble human lesions immunochemically and suggest that apo(a) associated with apoB and lipid may result in a more pro-atherogenic state than when apo(a) is free in plasma.
Laparoscopic procedures for treatment of infertility related to polycystic ovarian syndrome
Authors: J Cohen
Journal: Human Reproduction Update (1996)

The use of laparoscopic techniques for the treatment of polycystic ovarian syndrome (PCOS) has included many different approaches in the 1980s and 90s. Broadly similar results have been obtained using biopsy, cauterization, multi-electrocoagulation and laser surgery; i.e. >50% ovulation and a mean pregnancy rate of 50%. Evaluation of the data is complicated by the lack of uniformity in these clinical studies and the variation in diagnostic criteria. None of the studies included a treatment-independent control group. Endocrine changes following laparoscopy have been identified in many studies, but the mode of action of these treatments remains a mystery. In conclusion, laparoscopic techniques have the advantage over surgical wedge resection of cost saving and a lower risk of post-operative adhesions. For clomiphene resistant patients, laparoscopic techniques have many advantages over gonadotrophin therapy including serial repetitive ovulation events, no increased risk of ovarian hyperstimulation or multiple pregnancies and a lower incidence of spontaneous abortion, but these procedures must not be considered as the first line treatment for the anovulatory patient with PCOS, for whom clomiphene citrate remains the first choice mode of therapy.
Control of microglial neurotoxicity by the fractalkine receptor
Authors: Astrid E Cardona, Erik P Pioro, Margaret E Sasse, Volodymyr Kostenko, Sandra M Cardona, Ineke M Dijkstra, DeRen Huang, Grahame Kidd, Stephen Dombrowski, RanJan Dutta, Jar-Chi Lee, Donald N Cook, Steffen Jung, Sergio A Lira, Dan R Littman, Richard M Ransohoff
Journal: Nature Neuroscience (2006)
The amino acid transporter SLC6A14 in cancer and its potential use in chemotherapy
Authors: Yangzom D. Bhutia, Ellappan Babu, Puttur D. Prasad, Vadivel Ganapathy
Journal: Asian Journal of Pharmaceutical Sciences (2014)

Tumor cells have an increased demand for glucose and amino acids to support their rapid growth, and also exhibit alterations in biochemical pathways that metabolize these nutrients. Transport across the plasma membrane is essential to feed glucose and amino acids into these tumor cell-selective metabolic pathways. Transfer of amino acids across biological membranes occurs via a multitude of transporters; tumor cells must upregulate one or more of these transporters to satisfy their increased demand for amino acids. Among the amino acid transporters, SLC6A14 stands out with specific functional features uniquely suited for the biological needs of the tumor cells. This transporter is indeed upregulated in tumors of epithelial origin, including colon cancer, cervical cancer, breast cancer, and pancreatic cancer. Since normal cells express this transporter only at low levels, blockade of this transporter should lead to amino acid starvation selectively in tumor cells, thus having little effect on normal cells. This offers a novel, yet logical, strategy for the treatment of cancers that are associated with upregulation of SLC6A14. In addition, a variety of amino acid-based prodrugs are recognized as substrates by SLC6A14, thus raising the possibility that anticancer drugs can be delivered into tumor cells selectively via this transporter in the form of amino acid prodrugs. This strategy allows exposure of SLC6A14-positive tumor cells to chemotherapy with minimal off-target effects. In conclusion, the amino acid transporter SLC6A14 holds great potential not only as a direct drug target for cancer therapy but also for tumor cell-selective delivery of anticancer drugs.
Integrins and Matrix in the Glomerulus
Authors: Jordan A. Kreidberg
Journal: Journal of the American Society of Nephrology (2008)

Objective. To determine the most efficient way to identify Attention-Deficit/Hyperactivity Disorder (ADHD) in a large, clinic-referred sample of youth with epilepsy. Background. Children with epilepsy are at increased risk for ADHD. Historically, this comorbidity has been under-identified and undertreated. Methods. Youth with epilepsy who were referred for comprehensive neuropsychological evaluation due to behavioral or learning problems comprised the sample. Data were obtained via archival record review. Youth with epilepsy were grouped according to ADHD diagnosis (no ADHD, ADHD - Combined Type, and ADHD - Predominantly Inattentive Type) and compared on a number of neurocognitive variables, seizure-related variables, and parent and teacher-completed behavior rating scales. Data were examined via generalized linear models with post hoc pairwise comparisons, employing Tukey procedure where appropriate. Results. Youth in this clinical case series (N=204) demonstrated a significantly higher rate of ADHD diagnosis (65[percnt]) as compared to the general pediatric population (5[percnt]-9[percnt]). ADHD-Combined Type was identified with slightly greater frequency than ADHD - Predominantly Inattentive Type. For all three groups (no ADHD, ADHD - Combined Type, and ADHD - Predominantly Inattentive Type), age of seizure onset, seizure classification, and seizure frequency did not differ significantly. The groups also did not differ on most neurocognitive variables examined (intellectual functioning, working memory, processing speed, and sustained attention). Significant group differences were found for parent and teacher-completed behavior rating scales assessing inattention, hyperactivity, and executive dysfunction. Specifically, the no ADHD group did not demonstrate clinically significant levels of inattention, hyperactivity, or executive dysfunction (BASC-2 and BRIEF T-scores&lt;65). In contrast, the ADHD groups demonstrated clinically elevated levels of inattention, hyperactivity, and executive dysfunction (BASC-2 and BRIEF T-scores&gt;65). Conclusion. Inclusion of behavior rating scales as part of routine care in neurology clinics may be the most efficient and cost effective way to identify ADHD in youth with epilepsy. <b>Disclosure:</b> Dr. Kral has nothing to disclose. Dr. Lally has nothing to disclose. Dr. Boan has nothing to disclose.
Collecting evidence for a stem cell hypothesis in HCC
Authors: A. Teufel, P. R. Galle
Journal: Gut (2010)

Ever since Ernest McCulloch and James E Till defined essential stem cell properties, the field of stem cell biology has attracted increasing interest.1 Manipulating embryonic stem cells has resulted in advanced genetic technologies such as knock-out and transgenic animals, providing valuable models to study genetic influence on a wide variety of diseases.2 The success in manipulating stem cells and the ability to differentiate them into diverse tissues brought with them countless concepts of utilising stem cells in medicine. The idea of perpetually dividing pluripotent cells, capable of differentiating into nearly every possible cell or tissue type, seems like an inexhaustible resource for regenerative medicine. At the same time it became increasingly clear that stem cells are not just beneficial since tumours of various origins also contain stem cells that help them to proliferate but also to escape conventional chemotherapy. Furthermore, even embryonic pluripotent stem cells have a tumourigenic potency, which is one of the major hurdles to their utilisation in therapeutic concepts. Thus, the existence of stem cells must be considered a double-edged sword.3

In general, adult stems cells may be found in multiple human tissues, among them the liver. These cells multiply by cell division and were described as replenishing dying cells and regenerating damaged tissues. Besides, these adult stem cells may also transdifferentiate into a whole spectrum of cell types of other tissues, the physiological relevance of which is still open to debate.4

The existence of stem cells in normal liver is widely accepted. They may be augmented by immunoselection for epithelial cell adhesion molecule-positive (EpCAM+) cells and are estimated to constitute ∼0.5–2.5% of the liver parenchymal cells. Furthermore these EpCAM+ liver cells were demonstrated to possess stem cell characteristics, as transplantation of …
A high school gym-induced disease
Authors: C S Seitz, E B Bröcker, A Trautmann
Journal: British Journal of Sports Medicine (2008)

Physical exercise may induce upper and lower airway symptoms such as rhinitis and asthma. Rhinitis symptoms are often neglected although runny nose and nasal congestion may interfere with performance of the affected individual. A detailed history regarding locality and time of symptoms is of most significance for taking the appropriate diagnostic measures and identifying, as in this case, an uncommon form of allergic rhinitis to airborne spores from moulds.
Folfirinox for Locally Advanced Pancreatic Adenocarcinoma. Results of an Ageo Multicenter Prospective Study
Authors: Lysiane Marthey, Antonio Sa-cunha, Jean Frederic Blanc, Melanie Gauthier, Adele Cueff, Eric François, Isabelle Trouilloud, David Malka, Jean Baptiste Bachet, Romain Coriat, Eric Terrebonne, Christellela De Fouchardière, Sylvain Manfredi, David Solub, Cedric Lecaille, Anne Thirot-Bidault, Franck Carbonnel, Julien Taïeb
Journal: Annals of Oncology (2013)