tbuckley/cabot-search huggingface dataset:
The Battered Child Syndrome
Authors: E. H. BENNIE, A. B. SCLARE
Journal: American Journal of Psychiatry (1969)

Ten cases of battered child syndrome are reviewed from the standpoint of the assailant as the patient. In certain persons with poor emotional control, aggression can be displaced and acted out upon a child. Definite significant experiences must have occurred in the patient's life before this form of release can take place. The authors discuss problems of early recognition and management.
Diagnostic Evaluation of HER-2 as a Molecular Target: An Assessment of Accuracy and Reproducibility of Laboratory Testing in Large, Prospective, Randomized Clinical Trials
Authors: Michael F. Press, Guido Sauter, Leslie Bernstein, Ivonne E. Villalobos, Martina Mirlacher, Jian-Yuan Zhou, Rooba Wardeh, Yong-Tian Li, Roberta Guzman, Yanling Ma, Jane Sullivan-Halley, Angela Santiago, Jinha M. Park, Alessandro Riva, Dennis J. Slamon
Journal: Clinical Cancer Research (2005)

To critically assess the accuracy and reproducibility of human epidermal growth factor receptor type 2 (HER-2) testing in outside/local community-based hospitals versus two centralized reference laboratories and its effect on selection of women for trastuzumab (Herceptin)-based clinical trials.Breast cancer specimens from 2,600 women were prospectively evaluated by fluorescence in situ hybridization (FISH) for entry into Breast Cancer International Research Group (BCIRG) clinical trials for HER-2-directed therapies.HER-2 gene amplification by FISH was observed in 657 of the 2,502 (26%) breast cancers successfully analyzed. Among 2,243 breast cancers with central laboratory immunohistochemistry (10H8-IHC) analysis, 504 (22.54%) showed overexpression (2+ or 3+). Outside/local laboratories assessed HER-2 status by immunohistochemistry in 1,536 of these cases and by FISH in 131 cases. Overall, the HER-2 alteration status determined by outside/local immunohistochemistry showed a 79% agreement rate [kappa statistic, 0.56; 95% confidence interval (95% CI), 0.52-0.60], with FISH done by the central laboratories. The agreement rate comparing BCIRG central laboratory 10H8-IHC and outside/local laboratory immunohistochemistry was 77.5% (kappa statistic, 0.51; 95% CI, 0.46-0.55). Finally, HER-2 status, determined by unspecified FISH assay methods at outside/local laboratories, showed a 92% agreement rate (kappa statistic, 0.83; 95% CI, 0.73-0.93), with FISH done at the BCIRG central laboratories.Compared with the HER-2 status determined at centralized BCIRG reference laboratories, these results indicate superiority of FISH to accurately and reproducibly assess tumors for the HER-2 alteration at outside/local laboratories for entry to clinical trials.
Nitric Oxide Increases Cardiac <i>I</i> <sub>K1</sub> by Nitrosylation of Cysteine 76 of Kir2.1 Channels
Authors: Ricardo Gómez, Ricardo Caballero, Adriana Barana, Irene Amorós, Enrique Calvo, Juan Antonio López, Helene Klein, Miguel Vaquero, Lourdes Osuna, Felipe Atienza, Jesús Almendral, Ángel Pinto, Juan Tamargo, Eva Delpón
Journal: Circulation Research (2009)

The cardiac inwardly rectifying K(+) current (I(K1)) plays a critical role in modulating excitability by setting the resting membrane potential and shaping phase 3 of the cardiac action potential.This study aims to analyze the effects of nitric oxide (NO) on human atrial I(K1) and on Kir2.1 channels, the major isoform of inwardly rectifying channels present in the human heart.Currents were recorded in enzymatically isolated myocytes and in transiently transfected CHO cells, respectively. NO at myocardial physiological concentrations (25 to 500 nmol/L) increased inward and outward I(K1) and I(Kir2.1). These effects were accompanied by hyperpolarization of the resting membrane potential and a shortening of the duration of phase 3 of the human atrial action potential. The I(Kir2.1) increase was attributable to an increase in the open probability of the channel. Site-directed mutagenesis analysis demonstrated that NO effects were mediated by the selective S-nitrosylation of Kir2.1 Cys76 residue. Single ion monitoring experiments performed by liquid chromatography/tandem mass spectrometry suggested that the primary sequence that surrounds Cys76 determines its selective S-nitrosylation. Chronic atrial fibrillation, which produces a decrease in NO bioavailability, decreased the S-nitrosylation of Kir2.1 channels in human atrial samples as demonstrated by a biotin-switch assay, followed by Western blot.The results demonstrated that, under physiological conditions, NO regulates human cardiac I(K1) through a redox-related process.
Oncological implications of RET gene mutations in Hirschsprung’s disease
Authors: R H Sijmons, R M W Hofstra, F A Wijburg, T P Links, R P Zwierstra, A Vermey, D C Aronson, G Tan-Sindhunata, G J Brouwers-Smalbraak, S M Maas, C H C M Buys
Journal: Gut (1998)

Background —Germline mutations of the RET proto-oncogene identical to those found in the tumour predisposition syndrome multiple endocrine neoplasia type 2A (MEN2A), were detected in 2.5–5% of sporadic and familial cases of Hirschsprung’s disease. Some patients with Hirschsprung’s disease may therefore be exposed to a highly increased risk of tumours. Aims —To define clinical use of RET gene testing in Hirschsprung’s disease and related patient management from an oncological point of view. Methods —Sixty patients with Hirschsprung’s disease were screened for RET mutations. In three, MEN2A type RET mutations were detected. Case reports for these three patients are presented. Results and conclusions —Only 22 families or sporadic patients with Hirschsprung’s disease and MEN2A type RET mutations have been reported. Therefore, it is difficult to predict tumour risk for patients with familial or sporadic Hirschsprung’s disease, and their relatives, who carry these mutations. For these mutation carriers, periodic screening for tumours as in MEN2A is advised, but prophylactic thyroidectomy is offered hesitantly. RET gene testing in familial or sporadic Hirschsprung’s disease is not recommended at present outside a complete clinical research setting. In combined MEN2A/Hirschsprung’s disease families RET gene testing, tumour screening, and prophylactic thyroidectomy are indicated as in MEN2A.
Tuberculosis complicating imatinib treatment for chronic myeloid leukaemia
Authors: J M A Daniels, A Vonk-Noordegraaf, J J W M Janssen, P E Postmus, R van Altena
Journal: European Respiratory Journal (2009)

Although imatinib is not considered a predisposing factor for tuberculosis (TB), the present case report describes three patients in whom imatinib treatment for chronic myeloid leukaemia was complicated by TB. This raises the question of whether imatinib increases susceptibility to TB. There are several reports suggesting that imatinib might impair the immune system, leading to a variety of infections, including varicella zoster and hepatitis B. Control of TB in healthy individuals is achieved through acquired immunity, in which antigen-specific T-cells and macrophages arrest growth of <i>Mycobacterium tuberculosis</i> bacilli and maintain control over persistent bacilli. In the chronic stage of the infection, CD8+ T-cells assist macrophages in controlling intracellular mycobacteria. The T-cell receptor orchestrates this process. The fact that tyrosine kinases play an important role in T-cell receptor signal transduction and that imatinib has been shown to affect T-cell receptor signal transduction, presents a mechanism by which imatinib might impair control of <i>Mycobacterium tuberculosis</i>; thereby leaving the host susceptible to reactivation of tuberculosis.
Increased degranulation of eosinophil and neutrophil granulocytes in cystic fibrosis.
Authors: D Y Koller, R Urbanek, M Götz
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Increased serum and sputum concentrations of eosinophil cationic protein (ECP) and of neutrophil myeloperoxidase (MPO) have been described in patients with cystic fibrosis. Because numbers of eosinophils are normal in both peripheral blood and in the lung of patients with cystic fibrosis, we investigated whether eosinophils presented with an increased propensity to release their granule proteins. We investigated 20 patients with cystic fibrosis, 19 individuals with bronchial asthma, and 21 healthy nonatopic subjects. Isolated granulocytes were stimulated with serum-opsonized Sephadex G15 particles and the released amounts of ECP and MPO were measured by using radioimmunoassays. Eosinophils of patients with cystic fibrosis released significantly higher amounts of ECP than control subjects (p < 0.0001) and individuals with bronchial asthma (p < 0.0001). The release of MPO from neutrophils was also higher (p < 0.0001 and p < 0.005, respectively). Furthermore, a significant relationship between clinical variables and secretory activity of eosinophils was found in cystic fibrosis. We conclude that eosinophils as well as neutrophils obtained from patients with cystic fibrosis have an increased propensity to release their granule proteins which may be due to priming mechanisms. These findings would support anti-inflammatory treatment modalities in cystic fibrosis.
Evolutionary Process of Amino Acid Biosynthesis in Corynebacterium at the Whole Genome Level
Authors: Yousuke Nishio, Yoji Nakamura, Yoshihiro Usuda, Shinichi Sugimoto, Kazuhiko Matsui, Yutaka Kawarabayasi, Hisashi Kikuchi, Takashi Gojobori, Kazuho Ikeo
Journal: Molecular Biology and Evolution (2004)

Corynebacterium glutamicum, which is the closest relative of Corynebacterium efficiens, is widely used for the large scale production of many kinds of amino acids, particularly glutamic acid and lysine, by fermentation. Corynebacterium diphtheriae, which is well known as a human pathogen, is also closely related to these two species of Corynebacteria, but it lacks such productivity of amino acids. It is an important and interesting question to ask how those closely related bacterial species have undergone such significant functional differentiation in amino acid biosynthesis. The main purpose of the present study is to clarify the evolutionary process of functional differentiation among the three species of Corynebacteria by conducting a comparative analysis of genome sequences. When Mycobacterium and Streptomyces were used as out groups, our comparative study suggested that the common ancestor of Corynebacteria already possessed almost all of the gene sets necessary for amino acid production. However, C. diphtheriae was found to have lost the genes responsible for amino acid production. Moreover, we found that the common ancestor of C. efficiens and C. glutamicum have acquired some of genes responsible for amino acid production by horizontal gene transfer. Thus, we conclude that the evolutionary events of gene loss and horizontal gene transfer must have been responsible for functional differentiation in amino acid biosynthesis of the three species of Corynebacteria.
Cardiac-specific overexpression of farnesyl pyrophosphate synthase induces cardiac hypertrophy and dysfunction in mice
Authors: Jian Yang, Yun Mou, Tao Wu, Yang Ye, Jun-Chang Jiang, Chen-Ze Zhao, Huan-Huan Zhu, Chang-Qing Du, Liang Zhou, Shen-Jiang Hu
Journal: Cardiovascular Research (2012)

Farnesyl pyrophosphate synthase (FPPS) is a key enzyme in the mevalonate pathway. In our previous study, we found that inhibition of FPPS attenuates cardiac hypertrophy in spontaneously hypertensive rats (SHRs) and prevents angiotensin (Ang) II-induced hypertrophy in cardiomyocytes. Here, we further investigate the role of FPPS in cardiac hypertrophy and heart failure (HF) using a transgenic (Tg) model, and its mechanisms. Tg mice with cardiac-specific expression of FPPS were studied as an experimental model. The results showed that Tg mice with overexpression of FPPS exhibited cardiac hypertrophy, fibrosis, and HF, as well as increased synthesis of farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate in heart tissue. These pathological changes were associated with the activation of RhoA and other known kinases in the hypertrophic signalling pathway, such as extracellular signal-related kinases 1/2 and p38. Adenoviral infection of FPPS in cultured neonatal cardiomyocytes induced a hypertrophic response characterized by an increased cell size and an increased extent of sarcomeric organization, as well as an increased activation profile of small GTPases and downstream protein kinases concordant with those seen in vivo. Further investigation showed a marked increase of FPPS protein levels in hypertrophic ventricles of patients with valvular heart disease. Taken together, these results suggest that FPPS may function as a potent regulator in myocardial remodelling. The FPPS-regulated signalling pathway is relevant to the pathological changes in cardiac hypertrophy and HF.
The Pharmacology of Memory: A Neurobiological Perspective
Authors: L R Squire, H P Davis
Journal: The Annual Review of Pharmacology and Toxicology (1981)

What is of interest in an area of scientific inquiry depends on one's perspec­ tive. If one looks primarily to find a drug that can improve memory in the healthy subject or retard the decline of memory in neurological disease, then any enhancing effect of a drug can hold promise. Further, a better memory test score occurring together with a wide spectrum of other drug actions might mean only that memory enhancement will inevitably be accompanied by side effects. Alternatively, if one wishes to know how the brain accom­ plishes memory storage, then drugs can be viewed as tools to dissect the neural machinery involved in memory and to reveal as much as possible about the neurotransmitter systems and biochemical steps involved. Drugs may also be viewed as tools to reveal structural principles of memory, such as how memory changes over time and how many processes are involved.
Not All Beta-Blockers Are Equal in the Management of Long QT Syndrome Types 1 and 2
Authors: Priya Chockalingam, Lia Crotti, Giulia Girardengo, Jonathan N. Johnson, Katy M. Harris, Jeroen F. van der Heijden, Richard N.W. Hauer, Britt M. Beckmann, Carla Spazzolini, Roberto Rordorf, Annika Rydberg, Sally-Ann B. Clur, Markus Fischer, Freek van den Heuvel, Stefan Kääb, Nico A. Blom, Michael J. Ackerman, Peter J. Schwartz, Arthur A.M. Wilde
Journal: Journal of the American College of Cardiology (2012)
<i>IDH1</i> and <i>IDH2</i> Mutations Are Frequent Genetic Alterations in Acute Myeloid Leukemia and Confer Adverse Prognosis in Cytogenetically Normal Acute Myeloid Leukemia With <i>NPM1</i> Mutation Without <i>FLT3</i> Internal Tandem Duplication
Authors: Peter Paschka, Richard F. Schlenk, Verena I. Gaidzik, Marianne Habdank, Jan Krönke, Lars Bullinger, Daniela Späth, Sabine Kayser, Manuela Zucknick, Katharina Götze, Heinz-A. Horst, Ulrich Germing, Hartmut Döhner, Konstanze Döhner
Journal: Journal of Clinical Oncology (2010)

Purpose To analyze the frequency and prognostic impact of isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) mutations in acute myeloid leukemia (AML). Patients and Methods We studied 805 adults (age range, 16 to 60 years) with AML enrolled on German-Austrian AML Study Group (AMLSG) treatment trials AML HD98A and APL HD95 for mutations in exon 4 of IDH1 and IDH2. Patients were also studied for NPM1, FLT3, MLL, and CEBPA mutations. The median follow-up for survival was 6.3 years. Results IDH mutations were found in 129 patients (16.0%) —IDH1 in 61 patients (7.6%), and IDH2 in 70 patients (8.7%). Two patients had both IDH1 and IDH2 mutations. All but one IDH1 mutation caused substitutions of residue R132; IDH2 mutations caused changes of R140 (n = 48) or R172 (n = 22). IDH mutations were associated with older age (P &lt; .001; effect conferred by IDH2 only); lower WBC (P = .04); higher platelets (P &lt; .001); cytogenetically normal (CN) –AML (P&lt; .001); and NPM1 mutations, in particular with the genotype of mutated NPM1 without FLT3 internal tandem duplication (ITD; P &lt; .001). In patients with CN-AML with the latter genotype, IDH mutations adversely impacted relapse-free survival (RFS; P = .02) and overall survival (P = .03), whereas outcome was not affected in patients with CN-AML who lacked this genotype. In CN-AML, multivariable analyses revealed a significant interaction between IDH mutation and the genotype of mutated NPM1 without FLT3-ITD (ie, the adverse impact of IDH mutation [RFS]; P = .046 was restricted to this patient subset). Conclusion IDH1 and IDH2 mutations are recurring genetic changes in AML. They constitute a poor prognostic factor in CN-AML with mutated NPM1 without FLT3-ITD, which allows refined risk stratification of this AML subset.
NATURE OF NON-PARALYTIC AND TRANSITORY PARALYTIC POLIOMYELITIS IN RHESUS MONKEYS INOCULATED WITH HUMAN VIRUS
Authors: Albert B. Sabin, Robert Ward
Journal: The Journal of Experimental Medicine (1941)

1. The occurrence of non-paralytic poliomyelitis in monkeys inoculated with human or first passage virus was proved by histological examination of the nervous system and by isolation of the virus. 2. The non-paralytic infection was almost invariably associated with the destruction of an appreciable number of nerve cells in the spinal cord, and failure of the process to progress seemed to depend upon an equilibrium between the host and the virus, in which the latter occasionally persisted in an active state since it could produce the typical paralytic disease on passage to other monkeys. 3. While there were no reliable clinical or laboratory criteria, the diagnosis of non-paralytic poliomyelitis was made when the following changes were found in the spinal cord: (a) outfall of neurons confirmed by the presence of the reaction of degeneration in the nerve roots, and (b) foci of glial infiltration and perivascular cuffing in the gray matter. 4. Anterior horn cells showing diffuse chromatolysis and acidophilic, intranuclear inclusions were present 2 days after disappearance of paralysis of short duration, and nerve cells with marginated Nissl substance and eccentric nuclei were found side by side with obviously older lesions in monkeys with non-paralytic poliomyelitis. These cytologic changes were not present in monkeys sacrificed in still later stages of the disease. 5. The transitory character of the paralysis in some monkeys may depend in part on the fact that apparently normal function can be carried on with less than the normal number of nerve cells and in part on the probable, but not proved, possibility that not all nerve cells attacked by poliomyelitis virus are irreversibly damaged.
Exogenous lipid pneumonia: a retrospective multicentre study of 44 cases in France
Authors: A. Gondouin, Ph. Manzoni, E. Ranfaing, J. Brun, J. Cadranel, D. Sadoun, J.F. Cordier, A. Depierre, J.C. Dalphin
Journal: European Respiratory Journal (1996)

A nationwide retrospective study of exogenous lipid pneumonia (ELP) was carried out to update the data on this disease, with emphasis on thoracic computed tomography (CT) scan and bronchoalveolar lavage (BAL) findings. The inclusion criteria were: 1) presence of abnormal imaging features compatible with the diagnosis of ELP; 2) presence of intrapulmonary lipids; and 3) exogenous origin of the lipid pneumonia. Forty four cases were included (20 males and 24 females; mean age 62 +/- 11 yrs), of which four were occupational (chronic inhalation of cutting mist or oily vapour in an industrial environment). Thirty of the 40 nonoccupational cases were related to aspiration of liquid paraffin used for the treatment of constipation. A condition possibly favouring oil aspiration or inhalation was present in 34 patients (77%), most commonly gastro-oesophageal reflux (n = 20) and neurological or psychiatric illness (n = 14). Fever (39%), weight loss (34%), cough (64%), dyspnoea (50%) and crepitations (45%) were the most frequent symptoms. BAL was performed in 39 cases: 23% had a lymphocytic alveolitis; 14% neutrophilic alveolitis; and 31% a mixed alveolitis (lymphocytic and neutrophilic). Alveolar consolidations (57%), ground glass opacities (39%), and alveolar nodules (23%) were the most common radiological abnormalities. The changes were bilateral (79%), predominant in the posterior and lower zones of the lobes concerned (74%), hypodense (71%), and spared the subpleural zones (52%). In 13 cases, hypodensity was retrospectively established on CT scan by the presence of a "positive angiogram". This sign may be of diagnostic value when the density measurement is either not possible or not reliable. In conclusion, this study provides an update of the clinical, biological and radiological profile of exogenous lipid pneumonia and, in particular, confirms the diagnostic benefit of computed tomography scan, which revealed bilateral and hypodense changes in a large majority of cases.
Permeability of human isolated airways increases after hydrogen peroxide and poly-L-arginine.
Authors: A R Hulsmann, H R Raatgeep, J C den Hollander, W H Bakker, P R Saxena, J C de Jongste
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

In asthma, the airway epithelium may be damaged by oxidants and cationic proteins produced by eosinophils. The degree of epithelial damage correlates with the level of bronchial hyperreactivity. An increase in airway permeability to bronchoactive agonists may be one of the factors responsible for airway hyperresponsiveness in asthma. We investigated the effects of the oxidant hydrogen peroxide and the major basic protein (MPB) analogue poly-L-arginine on the permeability and morphology of nonasthmatic human peripheral airways. In addition, we examined whether airway permeability depends on airway size. Human airway tubes (generation 7 to 12) mounted in an organ bath were luminally perfused with Krebs-Henseleit buffer containing the hydrophilic tracer 111In-diethyletriamine pentaacetic acid (111In-DTPA) or the lipophilic tracer 14C-antipyrine (14C-AP). Permeability of the airways was calculated from the fluxes of the tracer molecules across the airway wall. After experiments, light- and electromicroscopic examination of the airway epithelium was performed. Baseline permeability to 14C-AP was five times greater than to 111In-DTPA. Luminal exposure of the airways to 100 mmol/L H2O2 produced a significant, sixfold increase in permeability to 111In-DTPA but not to 14C-AP, indicating the opening of paracellular pathways. The H2O2-induced increase in permeability was partly reversible. Luminal exposure to polyarginine for 3 h and 16 h produced a significant 4.5- and 7-fold increase in permeability to 111In-DTPA, respectively. Histologic examination of epithelium exposed to H2O2 of poly-L-arginine showed focal loss of superficial cells with preservation of basal cells. Baseline airway permeability increased with decreasing airway size (rs = -0.75, p < 0.01). These results suggest that epithelial damage due to eosinophil products may increase airway permeability, and that this may at least partly explain the increased responsiveness to inhaled stimuli in asthma.