tbuckley/cabot-search huggingface dataset:
Epidemiological and clinical features of norovirus gastroenteritis in outbreaks: a population-based study
Authors: C. Arias, M.R. Sala, A. Domínguez, N. Torner, L. Ruíz, A. Martínez, R. Bartolomé, M. de Simón, J. Buesa
Journal: Clinical Microbiology and Infection (2009)
Neuroinflammation in Parkinson’s disease and its potential as therapeutic target
Authors: Qinqin Wang, Yingjun Liu, Jiawei Zhou
Journal: Translational Neurodegeneration (2015)

Parkinson's disease (PD), the second most common age-associated neurodegenerative disorder, is characterized by the loss of dopaminergic (DA) neurons and the presence of α-synuclein-containing aggregates in the substantia nigra pars compacta (SNpc). Chronic neuroinflammation is one of the hallmarks of PD pathophysiology. Post-mortem analyses of human PD patients and experimental animal studies indicate that activation of glial cells and increases in pro-inflammatory factor levels are common features of the PD brain. Chronic release of pro-inflammatory cytokines by activated astrocytes and microglia leads to the exacerbation of DA neuron degeneration in the SNpc. Besides, peripheral immune system is also implicated in the pathogenesis of PD. Infiltration and accumulation of immune cells from the periphery are detected in and around the affected brain regions of PD patients. Moreover, inflammatory processes have been suggested as promising interventional targets for PD and even other neurodegenerative diseases. A better understanding of the role of inflammation in PD will provide new insights into the pathological processes and help to establish effective therapeutic strategies. In this review, we will summarize recent progresses in the neuroimmune aspects of PD and highlight the potential therapeutic interventions targeting neuroinflammation.
CHEMO-IMMUNOLOGICAL STUDIES ON CONJUGATED CARBOHYDRATE-PROTEINS
Authors: Walther F. Goebel
Journal: The Journal of Experimental Medicine (1938)

1. Artificial antigens containing the azobenzyl glycosides of the disaccharide cellobiose and the aldobionic acid, cellobiuronic acid, give rise in rabbits to antibodies which are specific and characteristic of the saccharide constituent. The antiserum to cellobiuronic acid shows broader serological cross reactions than does that to cellobiose. 2. An antiserum to the cellobiuronic acid antigen precipitates the capsular polysaccharide of Type III Pneumococcus when the latter is combined with a heterologous protein. 3. The cellobiuronic acid test antigen precipitates vigorously in antipneumococcus sera Types II, III, and VIII. The mechanism of these reactions is discussed.
Test conditions greatly influence permeation of water soluble molecules through the intestinal mucosa: need for standardisation.
Authors: M Peeters, M Hiele, Y Ghoos, V Huysmans, K Geboes, G Vantrappen, P Rutgeerts
Journal: Gut (1994)

Permeability tests are widely used to investigate the pathogenesis of various gastrointestinal diseases including coeliac disease, infectious diarrhoea, and inflammatory bowel disease. In Crohn's disease they are used as activity parameters by some investigators. Lack of standardisation, however, makes it very difficult to compare data reported in different studies. The aim of this study was to gather permeation data in well controlled test conditions to standardise the methods. Nine healthy volunteers each received five consecutive permeability tests by mouth using polyethylene glycol-400 (PEG-400) and 51Cr-EDTA as probe molecules. The probes were dissolved in water, a glucose solution, a starch solution, a hyperosmolar lactulose-mannitol solution, and a liquid meal. A significantly decreased permeation for both probes was found when given with the hyperosmolar solution. The 51Cr-EDTA permeation was also decreased with water. The permeability index, 51Cr-EDTA/PEG-400, corrected for influencing factors, confirmed that the lactulose-mannitol solution and plain water yield lower values of macro-molecule permeation than starch, glucose or liquid meal. Hyperosmolarity was clearly accompanied by a decrease in permeability probably caused by reversed solvent drag. Interindividual variability of probe permeation and permeability index is very low with a standard liquid meal. It is proposed that for permeability studies a standard liquid meal is always used.
Involvement of the CD1d–Natural Killer T Cell Pathway in Neointima Formation After Vascular Injury
Authors: Åsa Ström, Maria Wigren, Anna Hultgårdh-Nilsson, Amit Saxena, Maria F. Gomez, Susanna Cardell, Gunilla Nordin Fredrikson, Jan Nilsson
Journal: Circulation Research (2007)

Recent studies have established that the immune system plays an important role in the development of atherosclerosis. However, its role in regulating the arterial response to mechanical injury is less well studied. Arterial injury is associated with local accumulation of antibodies, and mice lacking functional T and B cells exhibit increased neointima formation, indicating that adaptive immune responses to neoantigens in the damaged tissue modulate the vascular repair process. To study the role of lipid antigen presentation in the arterial response to injury, we analyzed neointima formation in mice deficient in the lipid antigen-presenting molecule CD1d using a carotid collar model. As compared with control mice, neointima formation was reduced by >60% (P<0.01) in CD1d-/- mice. Moreover, carotid injury of wild-type C57BL/6 mice was associated with expansion of CD1d-restricted natural killer T cells in the spleen and accumulation of natural killer T cells in the periadventitial space of injured arteries. The results suggest that presentation of lipid antigens through the CD1d-natural killer T cell pathway modulates vascular repair responses.
Why we need guidelines for clinical trials in vasculitis and systemic lupus erythematosus
Authors: C. Mukhtyar, D. Boumpas, C. Gordon, W. Gross, D. Jayne, R. Luqmani
Journal: Annals of the Rheumatic Diseases (2007)

See linked article, p 605

The systemic vasculitides and systemic lupus erythematosus (SLE) are uncommon systemic rheumatic diseases. They have attracted increasing clinical trial activity, for which there is a need for international consensus and guidelines on clinical research methodology. There have been a number of relatively small studies of these diseases. Unfortunately, these have had varying design, outcome and assessment measures, thus it is difficult to interpret the evidence or subject it to a meta-analysis, and this has resulted in considerable uncertainty—for example, in deciding the role and dosing of cyclophosphamide in vasculitis or SLE.1–4 Standardisation of the methodology for conducting clinical trials facilitates recruitment of patients into larger multicentre studies, which are likely to include non-expert centres, because of the low incidence and prevalence of cases. There is increasing involvement by the pharmaceutical industry in clinical trials of SLE and vasculitis. These companies will also need guidelines on which to base their trial protocols. Furthermore, standardisation allows for future inter-trial comparisons and meta-analysis of separately conducted studies. The purpose of this editorial is to highlight the existence of a new set of recommendations to improve the conduct of clinical trials in vasculitis and SLE.

The vasculitis and SLE working groups of the European League Against Rheumatism (EULAR) Standing Committee on …
Randomized Trial Comparing Six Versus Three Cycles of Epirubicin-Based Adjuvant Chemotherapy in Premenopausal, Node-Positive Breast Cancer Patients: 10-Year Follow-Up Results of the French Adjuvant Study Group 01 Trial
Authors: Pierre Fumoleau, Pierre Kerbrat, Pascale Romestaing, Pierre Fargeot, Alain Brémond, Moïse Namer, Simon Schraub, Marie-Jo Goudier, Jeanne Mihura, Alain Monnier, Pierre Clavère, Daniel Serin, Philippe Seffert, Christiane Pourny, Thomas Facchini, Jean-Philippe Jacquin, Jean-François Sztermer, Jean Datchary, René Ramos, Elisabeth Luporsi
Journal: Journal of Clinical Oncology (2003)

To evaluate the duration and dose intensity of epirubicin-based regimens in premenopausal patients with lymph node-positive breast cancer.Between 1986 and 1990, 621 patients with operable breast cancer were randomly assigned to receive fluorouracil (Roche SA, Basel, Switzerland) 500 mg/m2, epirubicin (Pharmacia SA, Milan, Italy) 50 mg/m2, and cyclophosphamide (Asta Medica AG, Frankfurt, Germany) 500 mg/m2 every 21 days (FEC 50) for six cycles (6 FEC 50); FEC 50 for three cycles (3 FEC 50); or the same regimen with epirubicin 75 mg/m2 (FEC 75) for three cycles (3 FEC 75). All patients in the three arms received chest wall irradiation at the end of the third cycle.After a 131-month median follow-up, the 10-year disease-free survival (DFS) was 53.4%, 42.5%, and 43.6% (P =.05) in the three arms, respectively. Pairwise comparisons demonstrate that 6 FEC 50 was superior both to 3 FEC 50 (P =.02) and to 3 FEC 75 (P =.05). The 10-year overall survival (OS) for the 6 FEC 50 arm was 64.3%, for the 3 FEC 50 arm it was 56.6%, and for the 3 FEC 75 arm, it was 59.7% (P =.25), respectively. Pairwise comparisons demonstrate that 6 FEC 50 was more effective than 3 FEC 50 (P =.10). Cox regression analysis demonstrates that OS was significantly better in the 6 FEC 50 than in the 3 FEC 50 arm (P =.046). No severe infections (grade 3 to 4), acute cardiac toxicity, or deaths from toxicity have been observed. Only five patients developed delayed cardiac dysfunctions, and three patients developed acute myeloblastic leukemia.After a long-term follow-up in an adjuvant setting, the benefit of six cycles of FEC 50 compared with three cycles, whatever the dose, is highly significant in terms of DFS. As regards OS, the group receiving six cycles of FEC 50 has significantly better results than the group receiving three cycles of FEC 50.
Regulation of transcriptome, translation, and proteome in response to environmental stress in fission yeast
Authors: Daniel H Lackner, Michael W Schmidt, Shuangding Wu, Dieter A Wolf, Jürg Bähler
Journal: Genome biology (2012)

Abstract Background Gene expression is controlled globally and at multiple levels in response to environmental stress, but the relationships among these dynamic regulatory changes are not clear. Here we analyzed global regulation during different stress conditions in fission yeast, Schizosaccharomyces pombe , combining dynamic genome-wide data on mRNA, translation, and protein profiles. Results We observed a strong overall concordance between changes in mRNAs and co-directional changes in translation, for both induced and repressed genes, in response to three conditions: oxidative stress, heat shock, and DNA damage. However, approximately 200 genes each under oxidative and heat stress conditions showed discordant regulation with respect to mRNA and translation profiles, with genes and patterns of regulation being stress-specific. For oxidative stress, we also measured dynamic profiles for 2,147 proteins, comprising 43% of the proteome. The mRNAs induced during oxidative stress strongly correlated with increased protein expression, while repressed mRNAs did not relate to the corresponding protein profiles. Overall changes in relative protein expression correlated better with changes in mRNA expression than with changes in translational efficiency. Conclusions These data highlight a global coordination and fine-tuning of gene regulation during stress that mostly acts in the same direction at the levels of transcription and translation. In the oxidative stress condition analyzed, transcription dominates translation to control protein abundance. The concordant regulation of transcription and translation leads to the expected adjustment in protein expression only for up-regulated mRNAs. These patterns of control might reflect the need to balance protein production for stress survival given a limited translational capacity.
Serum Zinc Level and Coronary Heart Disease Events in Patients With Type 2 Diabetes
Authors: Minna Soinio, Jukka Marniemi, Markku Laakso, Kalevi Pyörälä, Seppo Lehto, Tapani Rönnemaa
Journal: Diabetes Care (2007)

OBJECTIVE—Low serum zinc level may predispose nondiabetic subjects to cardiovascular diseases. Our aim was to investigate whether serum zinc level predicts coronary heart disease (CHD) events in subjects with type 2 diabetes RESEARCH DESIGN AND METHODS—The original study population consisted of 1,059 patients with type 2 diabetes, aged 45–64 years. Mean duration of diabetes was 8 years. Serum zinc values were available from 1,050 subjects. CHD mortality and the incidence of nonfatal myocardial infarction (MI) were assessed in a 7-year follow-up. RESULTS—During the follow-up, 156 patients died from CHD and 254 patients had a fatal or nonfatal MI. Patients with serum zinc concentration ≤14.1 μmol/l at baseline had a higher risk for death from CHD than patients with serum zinc level &amp;gt;14.1 μmol/l (20.8 and 12.8%, respectively; P = 0.001) The risks for fatal or nonfatal MI were 30.5 and 22.0%, respectively (P = 0.005). In Cox regression analyses, low serum zinc concentration was significantly associated with CHD mortality (relative risk [RR] 1.7, P = 0.002) and all CHD events (RR 1.37, P = 0.030), even after adjustment for confounding variables. CONCLUSIONS—In this large cohort of type 2 diabetic patients, low serum zinc level was an independent risk factor for CHD events.
Carbon monoxide diffusing capacity and the complexity of diagnosis in pulmonary arterial hypertension
Authors: Rogerio Souza, Caio J.C. Fernandes, Marius M. Hoeper
Journal: European Respiratory Journal (2014)

The increased interest in pulmonary arterial hypertension (PAH) witnessed during the last decades has dramatically changed our comprehension of the disease and its management, resulting in better functional capacity and haemodynamic profiles, and increased survival [1, 2]. The discovery of different pathophysiological pathways associated with PAH progression has allowed the development of targeted therapies that were responsible for such improvements [3].

Recently, more attention has been paid to the epidemiology and distinct phenotypes of PAH, not least by publication of several registries expanding our knowledge on the clinical and demographic characteristics of PAH patients [4–9] as well as on the burden that previously unrecognised forms of PAH might represent [10]. The pivotal study conducted by the US National Institutes of Health in the 1980s [11, 12] provided invaluable information about the natural course of PAH. The patients in that cohort were predominantly young females (mean age of 36 years) presenting with what was then called primary pulmonary hypertension, i.e. idiopathic, familial or appetite suppressant-associated PAH. The presence of comorbidities did not represent a significant issue at that time, …
Psychomotor Slowing as a Predictor of Fluoxetine Nonresponse in Depressed Outpatients
Authors: Bonnie P. Taylor, Gerard E. Bruder, Jonathan W. Stewart, Patrick J. McGrath, Jeffrey Halperin, Howard Ehrlichman, Frederic M. Quitkin
Journal: American Journal of Psychiatry (2006)

OBJECTIVE: This study examined the utility of baseline psychomotor speed, measured with neuropsychological tests, to predict fluoxetine response in moderately depressed outpatients. The authors hypothesized that since psychomotor slowing in depressed patients has been linked to reduced dopaminergic neurotransmission, patients with slowing would be unresponsive to fluoxetine, a selective serotonin reuptake inhibitor. METHOD: After baseline neuropsychological testing, patients were treated openly with fluoxetine for 12 weeks. Thirty-seven patients completed the trial. RESULTS: Compared to the 25 patients who responded, the 12 patients who did not respond to fluoxetine exhibited significantly poorer performance in verbal fluency on the Controlled Oral Word Association Test FAS and in color naming on the Stroop Color and Word Test. In addition, the nonresponders tended to perform worse than the responders on the Stroop Color and Word Test reading subtest and the WAIS-III digit symbol subtest. Differential treatment response was specific to psychomotor speed because responders and nonresponders did not perform differently on tasks of executive functioning, attention, visuospatial functioning, or verbal intelligence. CONCLUSIONS: Psychomotor slowing may identify a subgroup of depressed patients who have a dopaminergic deficit that is unresponsive to fluoxetine monotherapy and who should therefore receive an alternative treatment.
Depression of central respiratory drive by nitrazepam.
Authors: M Rudolf, D M Geddes, J A Turner, K B Saunders
Journal: Thorax (1978)

In a group of patients with chronic bronchitis, repeated night sedation with 10 mg nitrazepam produced a fall in central respiratory drive and a steady rise in arterial carbon dioxide tension. The changes produced over a five-day period were not clinically important, except in two patients who were already hypercapnic before receiving nitrazepam. The use of this drug in patients with carbon dioxide retention should be avoided.
MitoFish and MitoAnnotator: A Mitochondrial Genome Database of Fish with an Accurate and Automatic Annotation Pipeline
Authors: W. Iwasaki, T. Fukunaga, R. Isagozawa, K. Yamada, Y. Maeda, T. P. Satoh, T. Sado, K. Mabuchi, H. Takeshima, M. Miya, M. Nishida
Journal: Molecular Biology and Evolution (2013)

Mitofish is a database of fish mitochondrial genomes (mitogenomes) that includes powerful and precise de novo annotations for mitogenome sequences. Fish occupy an important position in the evolution of vertebrates and the ecology of the hydrosphere, and mitogenomic sequence data have served as a rich source of information for resolving fish phylogenies and identifying new fish species. The importance of a mitogenomic database continues to grow at a rapid pace as massive amounts of mitogenomic data are generated with the advent of new sequencing technologies. A severe bottleneck seems likely to occur with regard to mitogenome annotation because of the overwhelming pace of data accumulation and the intrinsic difficulties in annotating sequences with degenerating transfer RNA structures, divergent start/stop codons of the coding elements, and the overlapping of adjacent elements. To ease this data backlog, we developed an annotation pipeline named MitoAnnotator. MitoAnnotator automatically annotates a fish mitogenome with a high degree of accuracy in approximately 5 min; thus, it is readily applicable to data sets of dozens of sequences. MitoFish also contains re-annotations of previously sequenced fish mitogenomes, enabling researchers to refer to them when they find annotations that are likely to be erroneous or while conducting comparative mitogenomic analyses. For users who need more information on the taxonomy, habitats, phenotypes, or life cycles of fish, MitoFish provides links to related databases. MitoFish and MitoAnnotator are freely available at http://mitofish.aori.u-tokyo.ac.jp/ (last accessed August 28, 2013); all of the data can be batch downloaded, and the annotation pipeline can be used via a web interface.
Kappa/lambda immunoglobulin distribution in Graves' thyroid-stimulating antibodies. Simultaneous analysis of C lambda gene polymorphisms.
Authors: R C Williams, N J Marshall, K Kilpatrick, J Montano, P M Brickell, M Goodall, P A Ealey, B Shine, A P Weetman, R K Craig
Journal: Journal of Clinical Investigation (1988)

From patients with untreated Graves' disease 11 sera showing high cAMP release in the FRTL-5 cell assay were studied for relative proportions of kappa or lambda Ig molecules showing cAMP releasing activity. Immunoabsorption of gamma-globulins was performed using monoclonal murine anti-kappa or anti-lambda antibodies linked to cyanogen bromide-activated sepharose. Specific kappa- or lambda-adsorbed fractions were also eluted from immunoabsorbents using chaotrophic thiocyanate buffers and equilibrated with pH 7.4 low salt buffer by dialysis. Immunoabsorption and elution experiments showed that five Graves' sera contained predominant cAMP-releasing activity within lambda Ig fractions, whereas two Graves' sera showed predominant cAMP-releasing activity in kappa Ig fractions. Four sera showed cAMP release approximately equally divided between kappa and lambda Ig both after immunoabsorption and specific anti-kappa or anti-lambda eluates were studied. C lambda genotypes were examined by Southern blotting and restriction fragment length polymorphism analysis of Eco RI-digested genomic DNA from 158 patients with Graves' disease in parallel with 112 normal controls and 29 patients with autoimmune hypothyroidism. Notable shifts in proportions of 8/8 and 18/18 genotypes were present when Graves' patients were compared with normal controls. Allelic frequencies and ratios of genotype 8 to 18 were significantly different (P less than 0.05) when Graves' patients were compared either to normal controls or to patients with autoimmune hypothyroidism.
An Address ON THE PERIPHERAL CIRCULATION AND ITS TREATMENT: Delivered before the Annual Meeting of the British Balneological and Climatological Society, 1909
Authors: J. Barr
Journal: BMJ (1909)

THE arterioles and capillaries and venules pervade every tissue and organ of the body, and specialists in this line can never be accused of poaching on anotber man's preserves.The importance of -the capillaries has been aptly described by Leonard Hill, who says:The blood is brought into intimate relation with the tissues by diffusing through the endothelial wall of the capillaries, and this wall is of great tenuity; thereby takes place that change of material which maintains the combustion of the body and the fire of life.It is the resistance in -the arterioles and capillaries which maintains the mean or diastolic pressure in the aorta and large arteries, and any increase in this resistance has to be overcome 'by greater work on the part of the heart.The arterioles constitute the first line of defenace, and, as I said in my Toronto address,' it is exceedingly fortunate that there is this first line of defence created by the action of the vasomotor nerves in the sxiall arteries and arterioles, because if this were wanting, as at present constituted we would either have to go about on all fours or constantly run the risk of fatal -syncope.Moreover, the blood would gravitate into the most dependent parts, the cooling surface would be enormous, the capillary velocity would be diminished, the blood would become surcharged with 002, and we would become cold-blooded animals.When the vasomotor nerves of a rabbit are paralysed it appears all right until you suspend it by the ears, and then it imme- diately dies.The arteriolar resistance -saves us from such risks.When you get vasomotor paralysis the resistance is transferred to the capillaries, and you get a more gradual fall in the pressure gradient, the velocity of the brood in the capillaries is diminished, the pressure increased, and transudaition readily takes place.In severe cases of Addisonis disease in which the vasomotor nerves are deprived of their usual stimul as, the patient may not be able to assume the erect posture.The wonderful regulative mechanism !of the vasomotor system enables the blood to be driven from the high-pressure main, the aorta and its principal branches, to the organs or systems that immediately require it.Witness the great
Comparative Clinical Study of Oral Clonidine Versus Oral Pregabalin Premedication to Attenuate Pressor Response to Laryngoscopy and Tracheal Intubation in Patients Undergoing Laparoscopic Cholecystectomy: A Prospective, Randomized, Double-Blind Study
Authors: S. Parveen, D.S. Negi, N. Akhtar
Journal: Clinical Gastroenterology and Hepatology (2015)