tbuckley/cabot-search huggingface dataset:
An Account of some Researches into the Nature and Action of Snake Venom
Authors: R. H. Elliot
Journal: BMJ (1900)

4 MWICLC JOU NAj among whom plague was at the time prevailing.The belief was expressed that the animals had died from plague, but no positive proof of this is adduced.56Experimental evidence of the susceptibility of squirrels to plague is apparently lacking.These animals are extremely common in India, and the rarity of recorded instances of their contractiDg the disease must be taken to indicate that they are not highly susceptible to the virus.The part they take in its spread must be an extremely small one.Plague in Guinea-pigs.In the laboratory these animals are very-susceptible to the virus of plague, and they are among the most convenient for experimental purposes.I am aware of no published evidence that these animals have contracted the disease in a natural state.Plague in Porcupines.The single reference that I have seen to the occurrence of plague in these animals is the following brief statement pub- lished last autumn: "It is reported at Mysore that several porcupines have died in the Zoological Gardens from bubonic plague."57 In view of the great susceptibility of other rodents to plague, there is no a priori reason why porcupines should not be liable to it.Detailed observations upon the manner in which animals with so impenetrable an epidermic covering contracted the disease should prove interesting. Plague in Marmots.In the Transbaikal province in Eastern Siberia, a marmot known as the Tarbagan (Arctomys bobac) suffers at times from a disease believed to be plague, and this disease is occasion- ally transmitted to human beings.In an endemic plague centre in Eastern Mongolia there is also some evidence that these animals contract the disease.I have elsewhere58 discussed in detail what is known of these two centres of disease and the part taken-by the marmot in its spread.Rabbits.These animals, though susceptible to the disease in the laboratory, do not appear to have ever contracted it under natural conditions.Should plague, which has now for the first time in history reached Australia, spread at all widely there, it will be of great interest to observe whether these animals, which abound so in Australia, suffer at all from the disease.NoTES AND REFNRENCES.lThe presTnt discussion of the subject will be confined to recent evi- dence. 2 Thirtieth Annual Report of the Sanitary Commissioner with the Government of the North-West Provinces.Ibid.4Indian Medieal Gazette, March, I899.Plague in Monkeys and Squirrels.By Alice Corthorn
Improving the health of the unemployed: a job for health authorities and health workers.
Authors: R Smith
Journal: BMJ (1986)

Health authorities and health workers have been slow to wake up to the considerable health implications of mass unemployment. It was 15 years ago that British unemployment first hovered around a million and more than 10 years ago that the rapid increase began, reaching a record total of 3 407 729 (14*4% of the workforce) on the day that I write.1 ' Even 15 years ago there was ample evidence? much of it from work done in the 1930s?that unemployment was associated with ill health and an increased workload for hospitals and general practitioners. Since then, despite much of the necessary research not having been done, the evidence that unemployment harms health and brings people to their doctors has grown much stronger. Yet still no health authority has published a comprehensive strategy for tackling health problems caused by unemployment, and few have understood that they could themselves?as large em? ployers?offer work opportunities to the unemployed, either on their own initiative or through the Manpower Services Commission. The departments of health have only recently and grudgingly accepted the importance of unemployment in harming health. None of the royal colleges has published a report on the problem, the Health Education Council has paid it only scant attention, and, although the British Medical Association now has a working party looking at inequalities and health, it has not addressed itself to unemployment.
Prevalence, Determinants, and Effect on Quality of Life of Freezing of Gait in Parkinson Disease
Authors: Santiago Perez-Lloret, Laurence Negre-Pages, Philippe Damier, Arnaud Delval, Pascal Derkinderen, Alain Destée, Wassilios G. Meissner, Ludwig Schelosky, Francois Tison, Olivier Rascol
Journal: JAMA Neurology (2014)

Freezing of gait (FOG) is a common axial symptom of Parkinson disease (PD).To determine the prevalence of FOG in a large group of PD patients, assess its relationship with quality of life and clinical and pharmacological factors, and explore its changes from the off to on conditions in patients with motor fluctuations.Cross-sectional survey of 683 patients with idiopathic PD. Scores for FOG were missing in 11 patients who were not included in the analysis. Patients were recruited from referral centers and general neurology clinics in public or private institutions in France.Patients with FOG were identified as those with a score of 1 or greater on item 14 of the Unified Parkinson's Disease Rating Scale (UPDRS) in the on condition. Item 14 scores for FOG in the off condition were also collected in patients with fluctuating motor symptoms.Quality of life (measured by the 39-item Parkinson's Disease Questionnaire and 36-Item Short Form Health Survey), anxiety and depression (Hospital Anxiety and Depression Scale), clinical features (UPDRS), and drug consumption.Of 672 PD patients, 257 reported FOG during the onstate (38.2%), which was significantly related to lower quality of life scores (P < .01). Freezing of gait was also correlated with longer PD duration (odds ratio, 1.92 [95% CI, 1.28-2.86]), higher UPDRS parts II and III scores (4.67 [3.21-6.78]), the presence of apathy (UPDRS item 4) (1.94 [1.33-2.82]), a higher levodopa equivalent daily dose (1.63 [1.09-2.43]), and more frequent exposure to antimuscarinics (3.07 [1.35-6.97]) (logistic regression). The FOG score improved from the off to on states in 148 of 174 patients with motor fluctuations (85.1%) and showed no change in 13.8%. The FOG score improved by more than 50% in 43.7% of patients. Greater improvement in the on state was observed in younger patients (r = -0.25; P < .01) with lower UPDRS II and III scores (r = -0.50; P < .01) and no antimuscarinic use (r = -0.21; P < .01).Freezing of gait in PD patients correlates with poor quality of life, disease severity, apathy, and exposure to antimuscarinics. Dopaminergic therapy improved FOG in most patients with motor fluctuations, especially younger ones with less severe disease and no antimuscarinic use. This finding suggests that quality of life is impaired in PD patients with FOG and that optimizing dopaminergic therapy and avoiding antimuscarinics should be considered.
Distribution of pyruvate dehydrogenase dihydrolipoamide acetyltransferase (PDC-E2) and another mitochondrial marker in salivary gland and biliary epithelium from patients with primary biliary cirrhosis
Authors: Ruth E. Joplin, Gerald D. Johnson, John B. Matthews, John Hamburger, Gordon J. Lindsay, Stefan G. Hubscher, Alastair J. Strain, James M. Neuberger
Journal: Hepatology (1994)

Previous studies in which quantitative immunofluorescence was used have shown that certain biliary epithelial cells in liver with primary biliary cirrhosis show increased levels of pyruvate dehydrogenase dihydrolipoamide acetyltransferase compared with controls. This study was designed to determine whether the increase in intensity of pyruvate dehydrogenase dihydrolipoamide acetyltransferase in biliary epithelial cells is accounted for by an increase in the number of mitochondria in the same cells. A double-antibody staining technique was used with antibodies specific for pyruvate dehydrogenase dihydrolipoamide acetyltransferase and another mitochondrial inner membrane marker, recognized by the mouse monoclonal antibody MCA151A. Distribution of the antigens was studied in sections of liver and salivary gland, an additional site that is frequently involved in primary biliary cirrhosis. Confocal microscopy was used to quantify the intensity of fluorescence resulting from binding of fluorochrome-labeled antibody. In both liver and salivary glands MCA151A binding was similar in normal and sections with primary biliary cirrhosis and corresponded to the predicted distribution of mitochondria in these tissues. In the liver staining was less intense in biliary epithelial cells than in hepatocytes. In salivary gland binding of both antibodies was predominantly localized to duct cells, with those forming striated ducts, known to be rich in mitochondria, being most intensely stained. There was high coincidence of the two antigens in salivary glands (p < 0.01) and in biliary epithelial cells from normal liver (p = 0.01). However, in liver with primary biliary cirrhosis, despite high coincidence between the antigens on hepatocytes, biliary epithelial cells showed high intensity of pyruvate dehydrogenase dihydrolipoamide acetyltransferase but not MCA151A.(ABSTRACT TRUNCATED AT 250 WORDS)
FRS2α-Mediated FGF Signals Suppress Premature Differentiation of Cardiac Stem Cells Through Regulating Autophagy Activity
Authors: Jue Zhang, Junchen Liu, Yanqing Huang, Julia Y.F. Chang, Leyuan Liu, Wallace L. McKeehan, James F. Martin, Fen Wang
Journal: Circulation Research (2011)

Although the fibroblast growth factor (FGF) signaling axis plays important roles in heart development, the molecular mechanism by which the FGF regulates cardiogenesis is not fully understood.To investigate the mechanism by which FGF signaling regulates cardiac progenitor cell differentiation.Using mice with tissue-specific ablation of FGF receptors and FGF receptor substrate 2α (Frs2α) in heart progenitor cells, we demonstrate that disruption of FGF signaling leads to premature differentiation of cardiac progenitor cells in mice. Using embryoid body cultures of mouse embryonic stem cells, we reveal that FGF signaling promotes mesoderm differentiation in embryonic stem cells but inhibits cardiomyocyte differentiation of the mesoderm cells at later stages. Furthermore, we also report that inhibiting FRS2α-mediated signals increases autophagy and that activating autophagy promotes myocardial differentiation and vice versa.The results indicate that the FGF/FRS2α-mediated signals prevent premature differentiation of heart progenitor cells through suppressing autophagy. The findings provide the first evidence that autophagy plays a role in heart progenitor differentiation.
Effects of Cardiac Resynchronization on Disease Progression in Patients With Left Ventricular Systolic Dysfunction, an Indication for an Implantable Cardioverter-Defibrillator, and Mildly Symptomatic Chronic Heart Failure
Authors: William T. Abraham, James B. Young, Angel R. León, Stuart Adler, Alan J. Bank, Shelley A. Hall, Randy Lieberman, L. Bing Liem, John B. O’Connell, John S. Schroeder, Kevin R. Wheelan
Journal: Circulation (2004)

The effects of cardiac resynchronization therapy (CRT) in patients with mildly symptomatic heart failure have not been fully elucidated.The Multicenter InSync ICD Randomized Clinical Evaluation II (MIRACLE ICD II) was a randomized, double-blind, parallel-controlled clinical trial of CRT in NYHA class II heart failure patients on optimal medical therapy with a left ventricular (LV) ejection fraction < or =35%, a QRS > or =130 ms, and a class I indication for an ICD. One hundred eighty-six patients were randomized: 101 to the control group (ICD activated, CRT off) and 85 to the CRT group (ICD activated, CRT on). End points included peak VO2, VE/CO2, NYHA class, quality of life, 6-minute walk distance, LV volumes and ejection fraction, and composite clinical response. Compared with the control group at 6 months, no significant improvement was noted in peak VO2, yet there were significant improvements in ventricular remodeling indexes, specifically LV diastolic and systolic volumes (P=0.04 and P=0.01, respectively), and LV ejection fraction (P=0.02). CRT patients showed statistically significant improvement in VE/CO2 (P=0.01), NYHA class (P=0.05), and clinical composite response (P=0.01). No significant differences were noted in 6-minute walk distance or quality of life scores.In patients with mild heart failure symptoms on optimal medical therapy with a wide QRS complex and an ICD indication, CRT did not alter exercise capacity but did result in significant improvement in cardiac structure and function and composite clinical response over 6 months.
Regulating the regulators: SOCS3 joins the dance
Authors: M. Drennan, D. Elewaut
Journal: Annals of the Rheumatic Diseases (2011)

Invariant natural killer T (iNKT) cells belong to a prototypical regulatory T cell lineage that functions at the interface of innate immunity and adaptive immunity. Unlike peptide-restricted T cells, iNKT cells recognise and respond to various glycolipid antigens presented in the context of the major histocompatibility complex class I-like molecule CD1d.1 iNKT cells possess a number of unique effector functions, including the ability to rapidly secrete large quantities of Th1, Th2 and Th17 cytokines, and, as such, have had a number of regulatory functions assigned to them. Consequently, iNKT cells are able to regulate a large number of bystander cells that form part of the innate and adaptive immune systems, and iNKT cell biology has subsequently been linked to a broad range of diseases, including cancer, certain infections (eg, Lyme disease) and various autoimmune disorders (eg, rheumatoid arthritis, systemic lupus erythematosus). However, many studies have shown that several mechanisms of iNKT cell activation exist. These differential mechanisms control the mode of activation, the nature of the stimulating glycolipid, genetic background or even the timing of iNKT cell activation. As such, the outcome of experimental models of autoimmunity has been shown to range from protection to disease aggravation, the findings of which have led to a matter of debate as to the precise role of these cells in autoimmune diseases (for reviews, see Coppieters et al 2 and Drennan et al 3). In …
'Chondroprotection' by non-steroidal anti-inflammatory drugs.
Authors: M Doherty
Journal: Annals of the Rheumatic Diseases (1989)

Non steroidal anti-inflammatory drugs may influence the osteoarthritis process osteoarthritis is a dynamic, metabolically active remodelling process with potential to compensate for a variety of triggering insults. NSAIDs may variably influence several aspects of cartilage metabolism
Insulin Resistance, Metabolic Syndrome, and Subclinical Atherosclerosis
Authors: Alain G. Bertoni, Nathan D. Wong, Steven Shea, Shuangge Ma, Kiang Liu, Srikanthan Preethi, David R. Jacobs, Colin Wu, Mohammed F. Saad, Moyses Szklo
Journal: Diabetes Care (2007)

To investigate the association of insulin resistance and clinically defined metabolic syndrome (MetS) with subclinical atherosclerosis and examine whether these relationships vary by race/ethnicity or sex.Subclinical atherosclerosis was assessed by coronary artery calcium (CAC) and carotid intima-medial thickness (IMT) in 5,810 participants without diabetes in the Multi-Ethnic Study of Atherosclerosis, a cohort of adults aged 45-84 years without prior cardiovascular disease (CVD). Fasting insulin and glucose were utilized to estimate insulin resistance by the homeostasis model assessment of insulin resistance (HOMA-IR) index, and the revised National Cholesterol Education Program definition of MetS was utilized. Multivariable linear or relative risk regression was used to analyze the association between HOMA-IR and subclinical atherosclerosis and assess its independence from MetS components.HOMA-IR was associated with increased IMT after adjustment for demographics (age, site, and education), smoking, education, and LDL cholesterol in each ethnic group, except Hispanic subjects, and in both men and women. After further adjusting for nonglucose MetS components, HOMA-IR was not associated with increased IMT. Subjects in the highest quintile of HOMA-IR had an elevated prevalence of CAC in each ethnic group and both sexes, after adjustment for demographics, smoking, and LDL but not after further adjustment for nonglucose MetS components. Among those with detectable CAC, there was no significant relationship between HOMA-IR and the amount of CAC.Although HOMA-IR was associated with increased subclinical atherosclerosis, the association was not independent of the risk factors that comprise MetS. Determination of HOMA-IR is unlikely to contribute to improved determination of risk of subclinical CVD.
Uptake of Radiolabeled 2′-Fluoro-2′-Deoxy-5-Iodo-1-β- <scp>d</scp> -Arabinofuranosyluracil in Cardiac Cells After Adenoviral Transfer of the Herpesvirus Thymidine Kinase Gene
Authors: Frank M. Bengel, Martina Anton, Norbert Avril, Thomas Brill, Ngoc Nguyen, Roland Haubner, Elisabeth Gleiter, Bernd Gansbacher, Markus Schwaiger
Journal: Circulation (2000)

Gene therapy is a promising approach for the treatment of cardiac diseases. Coexpression of therapeutic genes with a suitable marker gene would allow for the noninvasive imaging of successful gene transfer and expression via radiolabeled marker substrates. In the present study, such an approach was first applied to cardiac tissue.The combination of the herpesvirus thymidine kinase reporter gene (HSV1-tk) and radiolabeled 2'-fluoro-2'-deoxy-5-iodo-1-beta-D-arabinofuranosyluracil (FIAU) was evaluated. H9c2 rat cardiomyoblasts were infected in vitro with a replication-defective HSV1-tk-containing adenovirus and a negative control virus. The intracellular uptake of [(14)C]FIAU increased with increasing multiplicity of infection and with time after infection. Uptake in negative controls remained <15% of positive controls. Additionally, vectors were applied intramyocardially in Wistar rats. The marker substrate [(125)I]FIAU was injected intravenously 3 days later, and animals were killed after 24 hours. Autoradiographically, regional transgene expression was clearly identified in animals receiving the adenovirus containing HSV1-tk (3. 4+/-2.2-fold increase of radioactivity at vector administration site compared with remote myocardium), whereas nonspecific uptake in negative controls was low (<10% of positive controls).Using an adenoviral vector, HSV1-tk can be successfully expressed in cardiac cells in vitro and in vivo, yielding high uptake of radiolabeled FIAU. The results suggest that imaging transgene expression in the heart is feasible and may be used to monitor gene therapy noninvasively.
ABCB1 Genotype of the Donor but Not of the Recipient Is a Major Risk Factor for Cyclosporine-Related Nephrotoxicity after Renal Transplantation
Authors: Ingeborg A. Hauser, Elke Schaeffeler, Stefan Gauer, Ernst H. Scheuermann, Binytha Wegner, Jan Gossmann, Hanns Ackermann, Christian Seidl, Berthold Hocher, Ulrich M. Zanger, Helmut Geiger, Michel Eichelbaum, Matthias Schwab
Journal: Journal of the American Society of Nephrology (2005)

Cyclosporine (CsA) nephrotoxicity is a severe complication in organ transplantation because it leads to impaired renal function and chronic allograft nephropathy, which is a major predictor of graft loss. Animal models and in vivo studies indicate that the transmembrane efflux pump P-glycoprotein contributes substantially to CsA nephrotoxicity. It was hypothesized that the TT genotype at the ABCB1 3435C-->T polymorphism, which is associated with decreased expression of P-glycoprotein in renal tissue, is a risk factor for developing CsA nephrotoxicity. In a case-control study, 18 of 97 patients developed CsA nephrotoxicity and showed complete recovery of renal function in all cases when switched to a calcineurin inhibitor-free regimen. Both recipients and donors were genotyped for ABCB1 polymorphisms at the positions 3435C-->T and 2677G-->T/A. For controlling for population stratification, two additional polymorphisms, CYP2D6*4 and CYP3A5*3, with intermediate allelic frequencies were studied. The P-glycoprotein low expressor genotype 3435TT only of renal organ donors but not of the recipients was overrepresented in patients with CsA nephrotoxicity as compared with patients without toxicity (chi2 = 10.5; P = 0.005). CsA dosage, trough levels, and the concentration per dose ratio were not different between the patient groups. In a multivariate model that included several other nongenetic covariates, only the donor's ABCB1 3435TT genotype was strongly associated with CsA nephrotoxicity (odds ratio, 13.4; 95% confidence interval, 1.2 to 148; P = 0.034). A dominant role of the donor's ABCB1 genotype was identified for development of CsA nephrotoxicity. This suggests that P-glycoprotein is an important factor in CsA nephrotoxicity.
Effects of vagal stimulation on cesium-induced early afterdepolarizations and ventricular arrhythmias in rabbits.
Authors: N Takahashi, M Ito, S Ishida, T Fujino, T Saikawa, M Arita
Journal: Circulation (1992)

Previous evidence has shown that increased sympathetic tone enhances the cesium chloride (Cs)-induced early afterdepolarizations (EADs) and ventricular tachycardias (VTs).We assessed the effects of vagal stimulation on Cs-induced EADs and ventricular arrhythmias in the rabbit heart. Monophasic action potentials (MAPs) of the left ventricular endocardium were recorded simultaneously with surface ECG. Two protocols were used: 1) While in their intrinsic sinus rhythm, 11 rabbits were given three intravenous Cs injections (1 mM/kg) 20 minutes apart, and the effects of vagal stimulation on the ventricular arrhythmias thus induced were examined. 2) Under constant atrial pacing (cycle length, 250 msec), EAD amplitude was measured after Cs injection (1 mM/kg) without (five rabbits, control group) or with (four rabbits, vagal stimulation group) vagal stimulation. We observed the following. 1) Cs produced EADs and VTs of polymorphic (PVT) and monomorphic (MVT) types. During PVT, the take-off potential of repetitive premature action potentials in MAP recordings was about the same as the peak level of EADs, and during MVT, the take-off potential was the level of full repolarization. Vagal stimulation suppressed PVT but not MVT. Vagal stimulation after spontaneous termination of MVT restarted MVT of the same morphology at a rate much slower than the preceding sinus rate. 2) EAD amplitude was significantly smaller in the vagal stimulation group than in the control group.The results suggest that PVT originated from triggering by EADs, whereas MVT was of different origin, and that vagal stimulation suppressed PVT by decreasing the amplitude of EADs.