tbuckley/cabot-search huggingface dataset:
Upregulation of Na <sup>+</sup> /Ca <sup>2+</sup> Exchanger Expression and Function in an Arrhythmogenic Rabbit Model of Heart Failure
Authors: Steven M. Pogwizd, Ming Qi, Weilong Yuan, Allen M. Samarel, Donald M. Bers
Journal: Circulation Research (1999)

Abstract —Three-dimensional cardiac mapping in rabbits with nonischemic cardiomyopathy has shown that ventricular arrhythmias initiate by a nonreentrant mechanism that may be due to triggered activity from delayed afterdepolarizations. Delayed afterdepolarizations are thought to be due to spontaneous release of Ca 2+ from the sarcoplasmic reticulum (SR) and consequent activation of an inward Na + /Ca 2+ exchange (NaCaX) current. The goal of this study was to determine whether there is enhanced NaCaX gene expression and functional activity that may contribute to nonreentrant activation. Heart failure (HF) was induced in rabbits by combined aortic insufficiency and aortic constriction. HF rabbits had left ventricular enlargement (left ventricular end-diastolic dimension increased from 1.43±0.03 to 1.97±0.05 cm) and severely depressed function (fractional shortening reduced from 37% to 26%, P &lt;0.02). Heart-to-body weight was increased by 79% in HF. Western blots showed a 93% increase in NaCaX protein in HF ( P &lt;0.04). NaCaX mRNA (7-kb transcript) was increased by 104% relative to the 18S rRNA in HF. A 14-kb NaCaX transcript was also seen in the HF rabbits, raising total NaCaX mRNA to 2.7-fold compared with controls. The amplitude of caffeine-induced contractures, used to assess SR Ca 2+ load, was not significantly different in HF. Relaxation and [Ca 2+ ] i decline during caffeine-induced contractures is attributable to Ca 2+ transport by NaCaX and was 61% and 45% faster in HF ( P &lt;0.05), respectively. NaCaX current measured under controlled voltage clamp conditions was also 2-fold higher in HF cells. SR Ca 2+ -ATPase mRNA and protein levels and Ca 2+ current density were not significantly altered in HF. Twitch amplitudes from HF myocytes were 26% smaller compared with control ( P &lt;0.02), but twitch relaxation and [Ca 2+ ] i decline (due largely to SR Ca 2+ -ATPase) were not altered. Thus myocytes and myocardium from HF rabbits exhibit enhanced NaCaX expression and function. The enhanced NaCaX activity may contribute to depressed contractions, increased transient inward current (for a given SR Ca 2+ release), delayed afterdepolarizations, and nonreentrant initiation of ventricular tachycardia in this arrhythmogenic model of HF.
ERYTHEMA NODOSUM: AN ACUTE SPECIFIC FEVER
Authors: J. O. Symes
Journal: BMJ (1921)

I PROPOSE briefly to review the evidence tlhat can be adduced in favour of regarding erythema nodosum as an acute specific infectious fever comparable in every way to the zymotic fevers.The matter is one of very great importance f1om a national point of view on account of the varied theories that have been held with regard to the nature and causation of the disease.Briefly, these theories are:1.That erythema nodosum is a manifestation of acute rheumatism.2. That it is a cutaneous manifestation of a general intoxication due to several widely different causes.3. That it is tuberculous in origin, a septicaemia due to attenuated tubercle bacilli.4. That it is a manifestation of syphilis.Obviously, if erythema nodosum could be proved to be an early manifestation of tuberculosis or of acute rheum- atism, it would enable us to talke precautionary measures in the case of persons who have suffered from it, and possibly so to avert later attacks of phtliisis or carditis- two conditions which levy so heavy a toll upon the young adult life of the community.It is not my present purpose to criticize these theories, but it is necessary to make a few brief remarks in regard to them.The cases ef hea nodosum associated with syphilis have been reported chiefly in German and French journals, and these have been published with the view of slhowing that the disease is of syphilitic origin without considering the possibility of a symbiosis.Altogether the evidence is far from convincing.The rheumatic origin of erytbema nodosum is still taught in Englislh textbooks, but the evidence brought forward in its support is not very satisfactory.In the following table I briefly summarize the chief differences between erythema nodosum and acute rheumatic fever: Eryrthema Nodosum. Acute rbeumaticFever.Age incidence: Second and third decades 5-10 years.Seasonal incidence: Second and last quarters Some evidence of infectivity and epidemic occurrence Relapses and recurrei,ces rare Endocarditis rareNo relief of fever or arthritis from salicylates Phlyctenulae in about one-third of the cases Third quarter.Very little.Frequent.Frequent.
Transient development of anti-mitochondrial antibodies accompanies autoimmune hepatitis-sclerosing cholangitis overlap
Authors: M Bhat, M Guindi, E J Heathcote, G M Hirschfield
Journal: Gut (2008)

The biological basis of autoimmune liver diseases remains unclear, despite many suggestions.1–3 Not infrequently patients present in ways that demonstrate the artificial boundaries created by clinicians are simply that: classifications inadequately addressing underlying aetiopathogenesis.4

We describe a case that contributes further to our biological understanding. A 33-year-old man was initially diagnosed with primary sclerosing cholangitis (PSC) in 2003 at the time of an asymptomatic and anicteric cholestatic hepatitis: bilirubin 5 μmol/l (normal, <22), alanine aminotransferase (ALT) 221 U/l (normal, <40), aspartate transaminase (AST) 99 U/l (normal, <35), alkaline phosphatase (ALP) 487 U/l (normal, <110), and gamma-glutamyl transferase (GGT) 986 U/l (normal, <45). No other risk factors for liver disease were present either on history, examination or investigation, and pertinently the only immunological abnormality …
Level of Scientific Evidence Underlying Recommendations Arising From the National Comprehensive Cancer Network Clinical Practice Guidelines
Authors: Thejaswi K. Poonacha, Ronald S. Go
Journal: Journal of Clinical Oncology (2010)

Purpose The level of scientific evidence on which the National Comprehensive Cancer Network (NCCN) guidelines are based has not been systematically investigated. We describe the distribution of categories of evidence and consensus (EC) among the 10 most common cancers with regard to recommendations for staging, initial and salvage therapy, and surveillance. Methods NCCN uses a system of guideline development distinct from other major professional organizations. The NCCN definitions for EC are as follows: category I, high level of evidence with uniform consensus; category IIA, lower level of evidence with uniform consensus; category IIB, lower level of evidence without a uniform consensus but with no major disagreement; and category III, any level of evidence but with major disagreement. Results Of the 1,023 recommendations found in the 10 guidelines, the proportions of category I, IIA, IIB, and III EC were 6%, 83%, 10%, and 1%, respectively. Recommendations with category I EC were found in kidney (20%), breast (19%), lung (6%), pancreatic (6%), non-Hodgkin's lymphoma (6%), melanoma (6%), prostate (4%), and colorectal (1%) guidelines. Urinary bladder and uterine guidelines did not have any category I recommendations. Eight percent of all therapeutic recommendations were category I. Guidelines with the highest proportions of category I therapeutic recommendations were for breast (30%) and kidney (28%) cancers. No category I recommendations were found on screening or surveillance. Conclusion Recommendations issued in the NCCN guidelines are largely developed from lower levels of evidence but with uniform expert opinion. This underscores the urgent need and available opportunities to expand evidence base in oncology.
Double-tracer gas single breath washout - Variability and reproducibility compared with classical nitrogen washout tests
Authors: Kim Husemann, Nina Berg, Jennifer Engel, Johannes Port, Christoph Joppek, Ziran Tao, Holger Schulz, Martin Kohlhäufl
Journal: European Respiratory Journal (2013)

Background   Inert tracer gas washout tests are noninvasive tools to assess ventilation inhomogeneity in small airway diseases. Multiple breath washouts (MBW) are time consuming, single breath washouts (SBW) require a difficult breathing maneuver. We want to assess feasibility, variability and reproducibilitiy of a new fast and easy double tracer gas single breath washout (DTG-SBW) 1  and compare this test with conventional nitrogen (N 2 ) washouts.   Materials and methods   In 40 healthy nonsmokers (n = 20 ≤ 40, n = 20 > 40 years) we performed a triplet of N 2 -SBW, N 2 -MBW and tidal DTG-SBW. Follow up was after 1 week and 1 month. We measured the lung clearance index LCI (N 2 -MBW), slope of phase III dN 2  (N 2 -SBW) and DTG-slope III (DTG-SBW) calculated with a new automated algorhythm.   Results   Mean (SD) LCI at baseline was 6.93 (0.61), mean (SD) dN 2  0.99 (0.42) %N 2 /L and mean (SD) DTG-slope III -0.207 (0.106) g/mol*L. LCI showed a statistically significant difference between younger and older subjects (mean LCI (SD) 6.62 (0.37) ≤ 40 years vs. 7.25 (0.64) > 40 years, p  2  and 22.6 % for DTG-Slope-III. The mean difference between tests was small for all three washouts – considering short term (1st vs. 2nd) as well as long term reproducibility (1st vs 3rd test).   Conclusion   Variability of the DTG-SBW is acceptable, reproducibility is good and comparable with standard nitrogen washout tests. The fast and easy DTG-SBW with new automated analysis may be applicable for diagnosis and assessment of small airway diseases.   Reference    1  Singer F et al.  PLoS ONE  2011; 6: e17588.
A Randomized Trial of Exercise Training in Patients With Coronary Heart Disease
Authors: Victor Froelicher
Journal: JAMA (1984)

In order to determine whether or not regular exercise could alter myocardial perfusion or function, we randomized 146 male volunteers with stable coronary heart disease to either a supervised exercise program (n=72) or to a usual care program (n=74). Subjects underwent exercise tests initially and one year later. Significant differences between the two groups included improved aerobic capacity, thallium ischemia scores, and ventricular function in the exercise intervention group. It was not possible to classify the conditions of patients as to the likelihood of improvement or deterioration. This study demonstrated changes in myocardial perfusion and function in a select group of middle-aged men with coronary heart disease who underwent a medically appropriate exercise program lasting one year, but these changes were relatively modest. (<i>JAMA</i>1984;252:1291-1297)
Where do IgA plasma cells in the gut come from?
Authors: S J C Golby, J Spencer
Journal: Gut (2002)

The relationship between mucosal IgM and IgA has recently been addressed in murine systems to investigate how IgA secreting plasma cells localise in the intestine and to determine if switching from IgM to IgA occurs in the microenvironment of the gut mucosa

The gut is the major site of antibody production in humans. The most abundant isotype produced is IgA, but the importance of IgA has been questioned. On the one hand, in IgA deficient patients, IgM can compensate functionally1,2; on the other hand, it might be argued that such flexibility is an absolute requirement because the system is indispensable.3 The relationship between IgM and IgA in humans has been studied by analysis of the immunoglobulin genes used by plasma cells. Such studies can give information on the history of the B cells that generated them because they contain a unique fingerprint acquired during B cell development that enables the identification of related cells. Investigations of human mucosal plasma cells have shown that in humans, clonally related IgM+ and IgA+ plasma cells that probably secrete antibody with the same specificity can occupy the same mucosal microenvironment.4–7 In addition, immunoglobulin genes become mutated if the cell has been selected for the production of high affinity antibody. In the human gut, IgM is encoded by mutated genes4 and is therefore associated with secondary immune responses, alongside IgA and IgG, and it is perhaps not surprising that it can compensate functionally in IgA deficiency.

In mice the situation appears to be quite …
Screening for Diabetes and Prediabetes With Proposed A1C-Based Diagnostic Criteria
Authors: Darin E. Olson, Mary K. Rhee, Kirsten Herrick, David C. Ziemer, Jennifer G. Twombly, Lawrence S. Phillips
Journal: Diabetes Care (2010)

A1C screening can identify some patients with previously unrecognized diabetes and its complications (receiver operating characteristic area under the curve ∼0.80 in our study [1]), which is one objective of “diagnosis.” The ADA criterion (≥6.5%) provides good specificity because it is higher than levels where interindividual variation confounds the relationship between glucose and A1C.

However, it is also important to identify prediabetes. For this, A1C is inadequate (receiver operating characteristic area under the curve ∼0.70) because lower glucose levels are …
Bisphenol A Exposure and the Development of Wheeze and Lung Function in Children Through Age 5 Years
Authors: Adam J. Spanier, Robert S. Kahn, Allen R. Kunselman, Eric W. Schaefer, Richard Hornung, Yingying Xu, Antonia M. Calafat, Bruce P. Lanphear
Journal: JAMA Pediatrics (2014)

<h3>Importance</h3> Bisphenol A (BPA), a prevalent endocrine-disrupting chemical, has been associated with wheezing in children, but few studies have examined its effect on lung function or wheeze in older children. <h3>Objectives</h3> To test whether BPA exposure is associated with lung function, with wheeze, and with pattern of wheeze in children during their first 5 years. <h3>Design, Setting, and Participants</h3> A birth cohort study, enrolled during early pregnancy in the greater Cincinnati, Ohio, area among 398 mother-infant dyads. We collected maternal urine samples during pregnancy (at 16 and 26 weeks) and child urine samples annually to assess gestational and child BPA exposure. <h3>Main Outcomes and Measures</h3> We assessed parent-reported wheeze every 6 months for 5 years and measured child forced expiratory volume in the first second of expiration (FEV<sub>1</sub>) at age 4 and 5 years. We evaluated associations of BPA exposure with respiratory outcomes, including FEV<sub>1</sub>, child wheeze, and wheeze phenotype. <h3>Results</h3> Urinary BPA concentrations and FEV<sub>1</sub>data were available for 208 children and urinary BPA concentrations and parent-reported wheeze data were available for 360 children. The mean maternal urinary BPA concentration ranged from 0.53 to 293.55 µg/g of creatinine. In multivariable analysis, every 10-fold increase in the mean maternal urinary BPA concentration was associated with a 14.2% (95% CI, −24.5% to −3.9%) decrease in the percentage predicted FEV<sub>1</sub>at 4 years, but no association was found at 5 years. In multivariable analysis, every 10-fold increase in the mean maternal urinary BPA concentration was marginally associated with a 54.8% increase in the odds of wheezing (adjusted odds ratio, 1.55; 95% CI, 0.91-2.63). While the mean maternal urinary BPA concentration was not associated with wheeze phenotype, a 10-fold increase in the 16-week maternal urinary BPA concentration was associated with a 4.27-fold increase in the odds of persistent wheeze (adjusted odds ratio, 4.27; 95% CI, 1.37-13.30). Child urinary BPA concentrations were not associated with FEV<sub>1</sub>or wheeze. <h3>Conclusions and Relevance</h3> These results provide evidence suggesting that prenatal but not postnatal exposure to BPA is associated with diminished lung function and the development of persistent wheeze in children.
Prognostic Significance of Cytokeratin-20 Reverse Transcriptase Polymerase Chain Reaction in Lymph Nodes of Node-Negative Colorectal Cancer Patients
Authors: R. Rosenberg
Journal: Journal of Clinical Oncology (2002)

PURPOSE: Approximately 20% to 30% of patients with curatively resected, node-negative (pN0) colorectal cancer die of tumor recurrence, which can be caused by minimal residual disease. To identify patients with an increased risk of tumor recurrence and evaluate the prognostic value of cytokeratin-20 (CK-20), we detected CK-20–positive cells in histopathologically tumor-free lymph nodes (pN0) of patients with colorectal cancer. PATIENTS AND METHODS: Two peritumoral lymph nodes each from 85 patients with completely resected (R0) colorectal cancer without lymph node metastases (pN0) by routine examination were analyzed using a CK-20–specific reverse transcriptase polymerase chain reaction (RT-PCR) and compared with CK-20–specific immunohistochemistry (IHC). The results were correlated with histopathologic findings and with survival. RESULTS: CK-20 RT-PCR was positive in 44 patients (52%) and detected 83% of cancer-related death. Positive RT-PCR was significantly correlated with poorer overall survival (P < .009). Comparing RT-PCR with IHC, 13 patients with positive RT-PCR were identified, where the CK-20 expression was caused by tumor cell contamination located exclusively outside the lymph node capsule and had no prognostic impact. Defining these 13 patients as RT-PCR negative improved specificity of the RT-PCR assay from 57% to 75%. The 5-year overall survival of the 31 RT-PCR–positive patients was 71%, compared with 96% in the 54 negative patients (P < .001). Multivariate analysis showed expression of CK-20 mRNA to be an independent prognostic factor with a relative risk of cancer-related death of 6.1. CONCLUSION: CK-20 RT-PCR in peritumoral histopathologic tumor-free (pN0) lymph nodes of colorectal cancer is an independent prognostic factor for overall survival. Additional CK-20 IHC improves the specificity and prognostic value of RT-PCR for cancer-related death.
Regulation of Vascular Smooth Muscle Cell Proliferation
Authors: Felix B. Mehrhof, Ruth Schmidt-Ullrich, Rainer Dietz, Claus Scheidereit
Journal: Circulation Research (2005)

The transcription factor NF-κB regulates cell cycle progression and proliferation in a number of cell types. An important unresolved issue is the potential role of NF-κB in the proliferation of vascular smooth muscle cells (VSMCs) as a basis for the development of vascular disease. To investigate the contribution of NF-κB to mitogen-induced proliferation of VSMCs, a knock-in mouse model expressing the NF-κB superrepressor IκBαΔN ( c I κ B αΔ N ) was used. Comparing wild-type and IκBαΔN-expressing VSMCs, we found that proliferation rates did not differ after mitogenic stimulation by platelet-derived growth-factor-BB (PDGF-BB) or serum. In line with this, NF-κB activation was not observed in VSMCs derived from transgenic mice expressing an NF-κB–dependent lacZ reporter ( c (Igk)3conalacZ ). We further show, that classical mitogenic signaling pathways (namely mitogen-activated protein kinase [MAPK] and the phosphatidyl-inositol-3-OH-kinase [PI3K] pathways) control VSMC proliferation, but independently of NF-κB activation. In contrast to VSMCs, mouse embryonic fibroblasts (MEFs) derived from IκBαΔN-expressing mice showed significantly impaired proliferation rates after mitogenic stimulation. This was reflected by strongly impaired cyclin D1 expression in serum-stimulated MEFs derived from ( c I κ B αΔ N ) mice. These results implicate that essential pathogenetic functions of NF-κB in the development of atherosclerosis involve apoptotic and inflammatory signaling of VSMCs rather than proliferation. They further provide genetic evidence for a cell-type restricted requirement of NF-κB in the control of cellular proliferation.
Increased risk of lung cancer, non-Hodgkin's lymphoma, and leukemia following Hodgkin's disease.
Authors: F E van Leeuwen, R Somers, B G Taal, P van Heerde, B Coster, T Dozeman, S J Huisman, A A Hart
Journal: Journal of Clinical Oncology (1989)

The risk of second cancers (SCs) was assessed in 744 patients with Hodgkin's disease (HD) admitted to The Netherlands Cancer Institute from 1966 to 1983. Sixty-nine SCs were observed one month or more after start of first treatment. These included 14 cases of lung cancer, nine cases of non-Hodgkin's lymphoma (NHL), 16 cases of leukemia, and six cases of the myelodysplastic syndrome (MDS). The median interval between the diagnosis of HD and that of second lung cancer, NHL, and leukemia was 8.1, 13.3, and 5.7 years, respectively. The overall relative risks (RR) (observed/expected [O/E] ratios) of developing lung cancer, NHL, and leukemia were 4.9 (95% confidence limit [CL], 2.7 to 8.2), 31.0 (95% CL, 14.2 to 58.9) and 45.7 (95% CL, 26.1 to 74.2), respectively. At 15 years the cumulative risk of developing an SC amounted to 20.6% +/- 2.9%. The 15-year estimates of lung cancer, NHL, and leukemia were 6.2% +/- 1.9%, 5.9% +/- 2.1% and 6.3% +/- 1.7%, respectively. Increased lung cancer risk following HD has not frequently been clearly demonstrated before; that we were able to demonstrate such risk may be due to the completeness of follow-up over long periods that could be achieved in this study. Excess lung cancer risk was only noted in treatment regimens with radiotherapy (RT); also, all lung cancers arose in irradiation fields. Excess risk of leukemia was only found in treatment regimens involving chemotherapy (CT). For NHL, combined modality treatment was shown to be the most important risk factor. Risk of lung cancer and NHL increased with time since diagnosis. A time-dependent covariate analysis (Cox model) performed on leukemia and MDS showed an increasing risk with intensity of CT, age (greater than 40 years), and a splenectomy.
Similar prevalence of coeliac disease in children and middle-aged adults in a district of Sweden.
Authors: C Hallert, R Gotthard, G Jansson, K Norrby, A Walan
Journal: Gut (1983)

Coeliac disease in children and adults is considered to be a variety of the same disorder. This gains epidemiological support in the present study, which reports on the observed prevalence of coeliac disease in an area of Sweden (population, 140 500). On 1 July 1981, the prevalence rate was found to be 104/100 000 (1:960) among children, and the same figure, 106/00 000 (1:950), was found for coeliac disease unaccompanied by dermatitis herpetiformis in the middle-aged population. The figures were obtained in patients seeking medical are and thus represent minimum rates, and it is likely that the actual prevalence of coeliac disease in Sweden will prove still higher.
Granulopoietic differentiation in long‐term bone marrow cultures from children with congenital neutropenia
Authors: Laure Coulombel, Nada Morardet, Florence Veber, Christine Leroy, Francoise Mielot, Alain Fisher, Françoise Teillet‐Thiebaud, Gil Tchernia, Claude Griscelli, Claude Parmentier
Journal: American Journal of Hematology (1988)

Abstract The capacity of granulopoietic precursor cells (CFU‐GM) to differentiate in vitro was evaluated in five children with congenital neutropenia using short‐term colony assays and long‐term marrow cultures. In all five children, methylcellulose assays revealed normal numbers of CFU‐GM, which displayed an appropriate response to various sources of GM‐CSF and differentiated up to the polymorphonuclear leukocyte state (PMN). In contrast, neutrophil PMN were not observed in long‐term bone marrow cultures from three patients, despite a normal production of CFU‐GM, myeloblasts, and promyelocytes during the 5‐6‐week culture period. Thus, in these patients, the characteristic “block” in granulocytic maturation observed in vivo was reproduced in vitro in long‐term cultures. Granulocytic differentiation proceeded normally in long‐term cultures from the two other patients, thus indicating heterogeneity in the expression of the defect. These results might indicate abnormal interactions between stromal and hematopoietic cells in long‐term marrow cultures from some patients with congenital neutropenia. Furthermore, our results showed some correlation between the granulocytic defect in vitro and the clinical outcome in vivo.