tbuckley/cabot-search huggingface dataset:
Stiff-man syndrome. Two patients treated with diazepam
Authors: L. Cohen
Journal: JAMA (1966)

MEDICAL histories of two patients with stiff-man syndrome are compared with other cases in the literature, demonstrating the similarity of backgrounds and mismanagement of this disease. One of the purposes of this report alludes to the fact that frequently in medicine, when we are confronted with a new set of symptoms that we cannot explain, we readily label these as hysterical or functional. <h3>Report of Cases</h3><h3>Case 1.—</h3> A 36-year-old white woman clerical worker, three years prior to her first hospitalization, noted that minor emotional stimulation, such as being teased by her fellow workers, caused her leg muscles to contract and her legs to become stiff, so that it was necessary for her to walk stiff-legged. At this time she consulted her physician because of extreme emotional instability and difficulty in walking. Her physician was confident that this was a hysterical manifestation, and he strongly advised her to have psychiatric
FcγRIIB Mediates C-Reactive Protein Inhibition of Endothelial NO Synthase
Authors: Chieko Mineo, Andrew K. Gormley, Ivan S. Yuhanna, Sherri Osborne-Lawrence, Linda L. Gibson, Lisa Hahner, Ralph V. Shohet, Steven Black, Jane E. Salmon, David Samols, David R. Karp, Gail D. Thomas, Philip W. Shaul
Journal: Circulation Research (2005)

C-reactive protein (CRP) is an acute-phase reactant that is positively correlated with cardiovascular disease risk and endothelial dysfunction. Whether CRP has direct actions on endothelium and the mechanisms underlying such actions are unknown. Here we show in cultured endothelium that CRP prevents endothelial NO synthase (eNOS) activation by diverse agonists, resulting in the promotion of monocyte adhesion. CRP antagonism of eNOS occurs nongenomically and is attributable to blunted eNOS phosphorylation at Ser1179. Okadaic acid or knockdown of PP2A by short-interference RNA reverses CRP antagonism of eNOS, indicating a key role for the phosphatase. Aggregated IgG, the known ligand for Fcγ receptors, causes parallel okadaic acid–sensitive loss of eNOS function, FcγRIIB expression is demonstrable in endothelium, and heterologous expression studies reveal that CRP antagonism of eNOS requires FcγRIIB. In FcγRIIB +/+ mice, CRP blunts acetylcholine-induced increases in carotid artery vascular conductance; in contrast, CRP enhances acetylcholine responses in FcγRIIB −/− mice. Thus FcγRIIB mediates CRP inhibition of eNOS via PP2A, providing a mechanistic link between CRP and endothelial dysfunction.
Effect of a novel PACAP-27 analogue on muscarinic airway responsiveness in guinea-pigs in vivo
Authors: A Okazawa, ZH Cui, J Lotvall, S Yoshihara, BE Skoogh, K Kashimoto, A Linden
Journal: European Respiratory Journal (1998)

A recent study showed that the novel pituitary adenylate cyclase-activating peptide (PACAP)-27 analogue [Arg15,20,21,Leu17]-PACAP-27-Gly-Lys-Arg-NH2 causes sustained airway smooth muscle relaxation in vitro. This study examined whether this analogue also has bronchoprotective effects, by inhibiting muscarinic airway responsiveness in vivo. Total lung resistance was measured in anaesthetized, tracheostomized and ventilated guinea-pigs. Increasing doses of acetylcholine were given i.v. once before and thereafter repeatedly each hour after intratracheal instillation of either the PACAP-27 analogue or the clinical beta2-agonist bronchodilator salbutamol. Mean arterial blood pressure (MAP) was monitored to detect cardiovascular side-effects. Both the PACAP-27 analogue and salbutamol significantly attenuated the airway responsiveness to acetylcholine. The total inhibitory effect of the PACAP-27 analogue (350 nmol) corresponded to that of salbutamol (35 nmol). The inhibitory effect of salbutamol (35 nmol) peaked during the second hour and disappeared prior to 5 h after administration. In contrast, the corresponding effect of the analogue (350 nmol) gradually increased and peaked during the fifth hour after administration, whereas it did not fade during the observation period. Both the PACAP-27 analogue (350 nmol) and salbutamol (35 nmol) produced a transient decrease in MAP within 6 min after administration. In conclusion, the novel pituitary adenylate cyclase-activating peptide-27 analogue has bronchoprotective properties, by decreasing muscarinic airway responsiveness in guinea pigs in vivo. The time course of its effect is compatible with a more sustained duration of action compared with salbutamol.
Association football injuries to the brain. A preliminary report.
Authors: A. Tysvaer, O. Storli
Journal: British Journal of Sports Medicine (1981)

In 1975 the authors sent a questionnaire to all players in the Norwegian First Division League Clubs to record the incidence of head injuries due to heading. The conclusion of the questionnaire is that there seems to be a low percentage of serious head injuries. None of the players had been operated on for epi- or subdural hematoma or other brain damage and only a few have had concussion due to heading. In sixty per cent of the players a full neurological examination and EEG recording was undertaken. The result of these studies will be published in a subsequent article.
Performance of four current risk algorithms in predicting cardiovascular events in patients with early rheumatoid arthritis
Authors: E E A Arts, C Popa, A A Den Broeder, A G Semb, T Toms, G D Kitas, P L van Riel, J Fransen
Journal: Annals of the Rheumatic Diseases (2014)

This study was undertaken to assess the predictive ability of 4 established cardiovascular (CV) risk models for the 10-year risk of fatal and non-fatal CV diseases in European patients with rheumatoid arthritis.Prospectively collected data from the Nijmegen early rheumatoid arthritis (RA) inception cohort was used. Discriminatory ability for CV risk prediction was estimated by the area under the receiver operating characteristic curve. Calibration was assessed by comparing the observed versus expected number of events using Hosmer-Lemeshov tests and calibration plots. Sensitivity and specificity were calculated for the cut-off values of 10% and 20% predicted risk.Areas under the receiver operating characteristic curve were 0.78-0.80, indicating moderate to good discrimination between patients with and without a CV event. The CV risk models Systematic Coronary Risk Evaluation (SCORE), Framingham risk score (FRS) and Reynolds risk score (RRS) primarily underestimated CV risk at low and middle observed risk levels, and mostly overestimated CV risk at higher observed risk levels. The QRisk II primarily overestimated observed CV risk. For the 10% and 20% cut-off values used as indicators for CV preventive treatment, sensitivity ranged from 68-87% and 40-65%, respectively and specificity ranged from 55-76% and 77-88%, respectively. Depending on the model, up to 32% of observed CV events occurred in patients with RA who were classified as low risk (<10%) for CV disease.Established risk models generally underestimate (Systematic Coronary Risk Evaluation score, Framingham Risk Score, Reynolds risk score) or overestimate (QRisk II) CV risk in patients with RA.
Regulation Of Expression Of Pendrin Protein In CRS With Nasal Polyps and In Airway Epithelial Cells
Authors: Sudarshan Seshadri, Xiang Lu, Matthew Purkey, Tetsuya Homma, Andrew Choi, Roderick Carter, James Norton, Lydia Suh, Atsushi Kato, Pedro C. Avila, Anju T. Peters, David Conley, Rakesh Chandra, Bruce K. Tan, Leslie C. Grammer, Robert C. Kern, Robert P. Schleimer
Journal: Journal of Allergy and Clinical Immunology (2014)
The Cycle of Classification: <scp>DSM-I</scp> Through <scp>DSM-5</scp>
Authors: Roger K. Blashfield, Jared W. Keeley, Elizabeth H. Flanagan, Shannon R. Miles
Journal: Annual Review of Clinical Psychology (2014)

The Diagnostic and Statistical Manual of Mental Disorders (DSM) was created in 1952 by the American Psychiatric Association so that mental health professionals in the United States would have a common language to use when diagnosing individuals with mental disorders. Since the initial publication of the DSM, there have been five subsequent editions of this manual published (including the DSM-III-R). This review discusses the structural changes in the six editions and the research that influenced those changes. Research is classified into three domains: (a) issues related to the DSMs as measurement systems, (b) studies of clinicians and how clinicians form diagnoses, and (c) taxonomic issues involving the philosophy of science and metatheoretical ideas about how classification systems function. The review ends with recommendations about future efforts to revise the DSMs.
Accelerated re-epithelialization in β3-integrin-deficient- mice is associated with enhanced TGF-β1 signaling
Authors: L E Reynolds, F J Conti, M Lucas, R Grose, S Robinson, M Stone, G Saunders, C Dickson, R O Hynes, A Lacy-Hulbert, K Hodivala-Dilke
Journal: Nature Medicine (2005)
Clonal strains of Pseudomonas aeruginosa in paediatric and adult cystic fibrosis units
Authors: M.R. O'Carroll, M.W. Syrmis, C.E. Wainwright, R.M. Greer, P. Mitchell, C. Coulter, T.P. Sloots, M.D. Nissen, S.C. Bell
Journal: European Respiratory Journal (2004)

Despite recent reports of clonal strains of Pseudomonas aeruginosa in cystic fibrosis (CF) units, the need for routine microbiological surveillance remains contentious. Sputum was collected prospectively from productive patients attending the regional paediatric and adult CF units in Brisbane, Australia. All P. aeruginosa isolates were typed using pulsed-field gel electrophoresis. Spirometry, anthropometrics, hospitalisations and antibiotic sensitivity data were recorded. The first 100 sputum samples (first 50 patients at each clinic) harboured 163 isolates of P. aeruginosa . A total of 39 patients shared a common strain (pulsotype 2), 20 patients shared a strain with at least one other patient and 41 patients harboured unique strains. Eight patients shared a strain identical to a previously reported Australian transmissible strain (pulsotype 1). Compared with the unique strain group, patients harbouring pulsotype 2 were younger and had poorer lung function. Treatment requirements were similar in these two groups, as were the rates of multiresistance. In conclusion, 59% of patients harboured a clonal strain, supporting the need for routine microbiological surveillance. In contrast to previously described clonal strains, the dominant pulsotype was indistinguishable from nonclonal strains with respect to both colonial morphology and multiresistance. The clinical significance of clonal strains remains uncertain and requires longitudinal study.
Decrypting the structure of major histocompatibility complex class I-restricted cytotoxic T lymphocyte epitopes with complex peptide libraries.
Authors: K Udaka, K H Wiesmüller, S Kienle, G Jung, P Walden
Journal: The Journal of Experimental Medicine (1995)

Complex synthetic peptide libraries with defined amino acids in one or more positions of the H-2Kb-restricted cytotoxic T lymphocyte (CTL) epitopes SIINFEKL and RGYVYQGL and mixtures of 19 amino acids in the remaining positions were used to analyze the structural requirements of peptide binding to MHC class I molecules and antigen recognition by CTLs. This approach provides means to assess semiquantitatively the contribution of every amino acid to the binding of peptides to major histocompatibility complex (MHC) molecules without biases introduced by naturally processed peptides. Primary and secondary anchor residues were defined for their major contribution to the binding efficiency of the peptides. In contrast to primary anchors, secondary anchor amino acids vary greatly in their side chains and position in the sequences. All amino acids in the octapeptide sequences were found to exhibit positive or negative influences on binding to the MHC molecules and on recognition of the resulting complexes by CTLs. Strong interdependence of the effects of the individual residues in the epitope sequences was demonstrated. CTL responses to peptide libraries were suppressed when residues were introduced; however, they were augmented when the critical residues for T cell recognition were fixed, suggesting a potential use of the peptide libraries for defining epitope sequences in general.
Suppressed monocyte recruitment drives macrophage removal from atherosclerotic plaques of Apoe–/– mice during disease regression
Authors: Stephane Potteaux, Emmanuel L. Gautier, Susan B. Hutchison, Nico van Rooijen, Daniel J. Rader, Michael J. Thomas, Mary G. Sorci-Thomas, Gwendalyn J. Randolph
Journal: Journal of Clinical Investigation (2011)

Experimental models of atherosclerosis suggest that recruitment of monocytes into plaques drives the progression of this chronic inflammatory condition. Cholesterol-lowering therapy leads to plaque stabilization or regression in human atherosclerosis, characterized by reduced macrophage content, but the mechanisms that underlie this reduction are incompletely understood. Mice lacking the gene Apoe (Apoe–/– mice) have high levels of cholesterol and spontaneously develop atherosclerotic lesions. Here, we treated Apoe–/– mice with apoE-encoding adenoviral vectors that induce plaque regression, and investigated whether macrophage removal from plaques during this regression resulted from quantitative alterations in the ability of monocytes to either enter or exit plaques. Within 2 days after apoE complementation, plasma cholesterol was normalized to wild-type levels, and HDL levels were increased 4-fold. Oil red O staining and quantitative mass spectroscopy revealed that esterified cholesterol content was markedly reduced. Plaque macrophage content decreased gradually and was 72% lower than baseline 4 weeks after apoE complementation. Importantly, this reduction in macrophages did not involve migratory egress from plaques or CCR7, a mediator of leukocyte emigration. Instead, marked suppression of monocyte recruitment coupled with a stable rate of apoptosis accounted for loss of plaque macrophages. These data suggest that therapies to inhibit monocyte recruitment to plaques may constitute a more viable strategy to reduce plaque macrophage burden than attempts to promote migratory egress.
Biologic significance of angiopoietin-2 expression in human hepatocellular carcinoma
Authors: Shinji Tanaka, Masaki Mori, Yoshihiro Sakamoto, Masatoshi Makuuchi, Keizo Sugimachi, Jack R. Wands
Journal: Journal of Clinical Investigation (1999)

Human hepatocellular carcinoma (HCC) is generally a highly vascular tumor, but the mechanisms of neovascularization that permit rapid growth have not been defined. Angiopoietins (Ang) recently have been identified as ligands for vascular endothelial-specific Tie2 receptor tyrosine kinase and may be important growth factors in the generation of new blood vessels. We investigated Ang expression in 23 samples of HCC and paired adjacent uninvolved liver samples to determine if these genes have a potential role in the growth and spread of this disease. The full coding sequence of a variant angiopoietin-2 (Ang2) cDNA was obtained from HCC specimens, and the biologic consequences of overexpression on tumor formation and hemorrhage were determined in an animal model system. Angiopoietin-1 (Ang1) was equally expressed in HCC and adjacent noncarcinomatous liver tissue. Surprisingly, Ang2 was found to be highly expressed only in tumor tissue. In addition, Ang2 was expressed in 10 of 12 hypervascular HCC, but only in 2 of 11 hypovascular HCC. Ectopic expression of Ang2 in nonexpressing HCC cells promotes the rapid development of human hepatomas and produces hemorrhage within tumors in nude mice. These results suggest a role for Ang2 in the neovascularization of HCC. This enhanced gene expression may contribute to the clinical hypervascular phenotype, as well as tumor formation and progression.
Pathological complete response after neoadjuvant chemotherapy with trastuzumab-containing regimen in gastric cancer: a case report
Authors: Jun Wang, George W Saukel, Carlos A Garberoglio, Wichit Srikureja, Chung-Tsen Hsueh
Journal: Journal of Hematology & Oncology (2010)

Abstract We report a 49-year-old Chinese male with locally advanced gastric adenocarcinoma achieving pathological complete response after neoadjuvant chemotherapy with trastuzumab-containing regimen. He underwent esophagogastroduodenoscopy in September 2009, which revealed a 2-cm gastric ulcer on the lesser curvature proximal to angularis. Biopsy of gastric ulcer showed moderately differentiated adenocarcinoma with overexpression of human epidermal growth factor receptor 2 (HER2) by immunohistochemistry and fluorescence in situ hybridization. Further workups with endoscopic ultrasound, computed tomography and positron emission tomography staged his cancer as T3N1M0. He received 3 cycles of neoadjuvant chemotherapy consisting of trastuzumab, oxaliplatin, docetaxel and capecitabine without severe toxicities except grade 2 diarrhea near the completion of cycle 3 requiring discontinuation of capecitabine. Afterwards, he received total gastrectomy with extended D2 lymph node dissections showing pathological complete response. He went on to receive 3 more cycles of chemotherapy postoperatively. The role of trastuzumab as a part of perioperative therapy in gastric cancer overexpressing HER2 is worth further investigation.
Secreted PLA2 induces proliferation in astrocytoma through the EGF receptor: another inflammation-cancer link
Authors: M. Hernandez, R. Martin, M. D. Garcia-Cubillas, P. Maeso-Hernandez, M. L. Nieto
Journal: Neuro-Oncology (2010)

We have investigated mechanisms that contribute to reinforce the relationship between inflammation and cancer. Secreted phospholipase A2 group IIA (sPLA2-IIA) is a molecule relevant in inflammatory events and has been proposed as a marker for some of these. Previously, we reported the mitogenic properties of this sPLA2 in the human astrocytoma cell line 1321N1. Here, we go deeper into the mechanisms that link this inflammatory protein with proliferation in one of the most aggressive types of tumors. We found that phosphorylation of the extracellular regulated kinase (ERK) was preceded by the activation of the small GTPase Ras, and both failed to be activated by inhibiting protein kinase C (PKC). Fractionation and immunofluorescence studies revealed translocation of PKC alpha, delta, and epsilon to the membrane fraction upon stimulation with sPLA2-IIA. Immunoprecipitation analysis showed that sPLA2-IIA induces phosphorylation of the epidermal growth factor receptor (EGFR) through a PKC-dependent pathway. We found that phosphorylation of this receptor contributed to Ras and ERK activation and that inhibition of ERK, PKC, and EGFR blocked the mitogenic response induced by sPLA2-IIA. This study showed that sPLA2-IIA is able to bring into play EGFR to trigger its signaling and that PKC leads the distribution of resources. Interestingly, we found that this is not a cell-specific response, because sPLA2-IIA was also able to transactivate EGFR in MCF7 human breast cancer cells. Therefore, this mechanism could contribute to worsen the prognosis of a tumor in an inflammatory microenvironment. We also present more links of the tumor chain possibly susceptible to targeting.
Inducing Indigestion: Companies Embrace Autophagy Inhibitors
Authors: K. Garber
Journal: JNCI Journal of the National Cancer Institute (2011)

Autophagy, the process of “selfeating” within cells, has been controversial in cancer since it was first linked to the disease in 1999. Because autophagy can either suppress or promote tumors, depending on the context, the field has been marked by both confusion and unwillingness by drug companies to get involved in therapies.
ABCA1 and ABCG1 Protect Against Oxidative Stress–Induced Macrophage Apoptosis During Efferocytosis
Authors: Laurent Yvan-Charvet, Tamara A. Pagler, Tracie A. Seimon, Edward Thorp, Carrie L. Welch, Joseph L. Witztum, Ira Tabas, Alan R. Tall
Journal: Circulation Research (2010)

Rationale : Antiatherogenic effects of plasma high-density lipoprotein (HDL) include the ability to inhibit apoptosis of macrophage foam cells. The ATP-binding cassette transporters ABCA1 and ABCG1 have a major role in promoting cholesterol efflux from macrophages to apolipoprotein A-1 and HDL and are upregulated during the phagocytosis of apoptotic cells (efferocytosis). Objective : The goal of this study was to determine the roles of ABCA1 and ABCG1 in preserving the viability of macrophages during efferocytosis. Methods and Results : We show that despite similar clearance of apoptotic cells, peritoneal macrophages from Abca1 −/− Abcg1 −/− , Abcg1 −/− , and, to a lesser extent, Abca1 −/− mice are much more prone to apoptosis during efferocytosis compared to wild-type cells. Similar findings were observed following incubations with oxidized phospholipids, and the ability of HDL to protect against oxidized phospholipid-induced apoptosis was markedly reduced in Abca1 −/− Abcg1 −/− and Abcg1 −/− cells. These effects were independent of any role of ABCA1 and ABCG1 in mediating oxidized phospholipid efflux but were reversed by cyclodextrin-mediated cholesterol efflux. The apoptotic response observed in Abca1 −/− Abcg1 −/− macrophages after oxidized phospholipid exposure or engulfment of apoptotic cells was dependent on an excessive oxidative burst secondary to enhanced assembly of NADPH oxidase (NOX)2 complexes, leading to sustained Jnk activation which turned on the apoptotic cell death program. Increased NOX2 assembly required Toll-like receptors 2/4 and MyD88 signaling, which are known to be enhanced in transporter deficient cells in a lipid raft–dependent fashion. Conclusions : We identified a new beneficial role of ABCA1, ABCG1 and HDL in dampening the oxidative burst and preserving viability of macrophages following exposure to oxidized phospholipids and/or apoptotic cells.
Origin and Evolution of B Chromosomes in the Cichlid Fish Astatotilapia latifasciata Based on Integrated Genomic Analyses
Authors: Guilherme T. Valente, Matthew A. Conte, Bruno E.A. Fantinatti, Diogo C. Cabral-de-Mello, Robson F. Carvalho, Marcelo R. Vicari, Thomas D. Kocher, Cesar Martins
Journal: Molecular Biology and Evolution (2014)

Approximately 15% of eukaryotes contain supernumerary B chromosomes. When present, B chromosomes frequently represent as much as 5% of the genome. Despite thousands of reports describing the distribution of supernumeraries in various taxa, a comprehensive theory for the origin, maintenance, and evolution of B chromosomes has not emerged. Here, we sequence the complete genomes of individual cichlid fish (Astatotilapia latifasciata) with and without B chromosomes, as well as microdissected B chromosomes, to identify DNA sequences on the B. B sequences were further analyzed through quantitative polymerase chain reaction and in situ hybridization. We find that the B chromosome contains thousands of sequences duplicated from essentially every chromosome in the ancestral karyotype. Although most genes on the B chromosome are fragmented, a few are largely intact, and we detect evidence that at least three of them are transcriptionally active. We propose a model in which the B chromosome originated early in the evolutionary history of Lake Victoria cichlids from a small fragment of one autosome. DNA sequences originating from several autosomes, including protein-coding genes and transposable elements, subsequently inserted into this proto-B. We propose that intact B chromosome genes involved with microtubule organization, kinetochore structure, recombination and progression through the cell cycle may play a role in driving the transmission of the B chromosome. Furthermore, our work suggests that karyotyping is an essential step prior to genome sequencing to avoid problems in genome assembly and analytical biases created by the presence of high copy number sequences on the B chromosome.