tbuckley/cabot-search huggingface dataset:
Abnormalities of B-cell activation and immunoregulation in patients with Crohn's disease.
Authors: G Sieber, F Herrmann, M Zeitz, H Teichmann, H Ruhl
Journal: Gut (1984)

We have studied B-lymphocyte function in 39 patients with Crohn9s disease and 35 normal individuals using a reverse haemolytic plaque assay as the effector system. Ten patients had active Crohn9s disease, the others being in an inactive state of the disease. Compared with normal individuals, the Crohn9s disease patients - especially those in the active state of the disease - had markedly raised numbers of spontaneous immunoglobulin secreting cells and severely decreased responses to the polyclonal activator pokeweed mitogen. The differences between the reactivity of patients with active disease and those with inactive disease were statistically significant. These findings indicate an in vivo polyclonal B-cell activation in Crohn9s disease patients, possibly due to antigen(s) or infectious agent(s). In vitro experiments were performed with separated lymphocytes in order to characterise the mechanism responsible for the altered immune reactivity in Crohn9s disease. These revealed an intrinsic B-cell defect as well as an impaired T-helper cell capacity in patients with Crohn9s disease. Findings supporting the hypothesis of an increased suppressor activity in Crohn9s disease patients could not be observed, and marker analyses revealed normal proportions with the exception of raised Leu 7 positive cells that mediate 9natural killer9 and 9killer9 cytolysis. We conclude that immune dysfunction in peripheral blood lymphocytes of Crohn9s disease patients involves B-cells as well as T-helper cells.
Central and Peripheral Circadian Clocks in Mammals
Authors: Jennifer A. Mohawk, Carla B. Green, Joseph S. Takahashi
Journal: Annual Review of Neuroscience (2012)

The circadian system of mammals is composed of a hierarchy of oscillators that function at the cellular, tissue, and systems levels. A common molecular mechanism underlies the cell-autonomous circadian oscillator throughout the body, yet this clock system is adapted to different functional contexts. In the central suprachiasmatic nucleus (SCN) of the hypothalamus, a coupled population of neuronal circadian oscillators acts as a master pacemaker for the organism to drive rhythms in activity and rest, feeding, body temperature, and hormones. Coupling within the SCN network confers robustness to the SCN pacemaker, which in turn provides stability to the overall temporal architecture of the organism. Throughout the majority of the cells in the body, cell-autonomous circadian clocks are intimately enmeshed within metabolic pathways. Thus, an emerging view for the adaptive significance of circadian clocks is their fundamental role in orchestrating metabolism.
Endocardial pacing site affects left ventricular end-diastolic volume and performance in the intact anesthetized dog.
Authors: M Grover, S A Glantz
Journal: Circulation Research (1983)

We investigated how pacing from different endocardial sites affects the left ventricular three-dimensional contraction pattern and performance in intact anesthetized dogs. We used data from the motion of radiopaque markers implanted in the left ventricular endocardium in an analysis based on the polar decomposition theorem to determine the left ventricle's three-dimensional principal directions and magnitudes of deformation, and its axis and angle of rotation during the cardiac cycle. This paper also derives a new procedure that permits statistical comparison of different left ventricular cavity deformation patterns. During normal sinus rhythm and pacing from the right atrium, left ventricular septum, left ventricular apex, and right ventricular apex, the principal directions of left ventricular deformation remained relatively fixed with respect to the left ventricle's anatomy, independent of heart rate and pacing site. These directions were oriented in septum-free wall, anterior-posterior, and apex-base directions. End-systolic pressure and volume did not vary significantly among pacing sites. End-diastolic volume varied significantly among pacing sites, with right ventricular apical pacing producing the smallest end-diastolic and stroke volume. These results reveal that beats produced by right ventricular apical pacing eject less blood compared with beats produced by right atrial, left ventricular septal, or left ventricular apical pacing.
PRODUCTION OF ULTRASTRUCTURAL MEMBRANE LESIONS BY THE FIFTH COMPONENT OF COMPLEMENT
Authors: Margaret J. Polley, Hans J. Müller-Eberhard, Joseph D. Feldman
Journal: The Journal of Experimental Medicine (1971)

A direct quantitative relationship has been demonstrated between the number of cell bound C4,2 complexes or C5 molecules and the number of ultrastructural lesions visualized on the cell membrane subsequent to immune hemolysis. When bound C4,2 complexes exceeded bound C5 molecules, the number of ultrastructural lesions seen corresponded to the number of C5 molecules. However, in the reverse situation, with bound C5 molecules in excess of bound C4,2 complexes, the latter determined the number of lesions. During the complement-reaction sequence, the lesions first became visible in the nonlytic intermediate complex EAC1,4,2,3,5 and their number was unaffected when lysis was induced by C6–C9. Since the lesions were also demonstrable on the intermediate complex EC5,6,7, it is concluded that the protein C5 is responsible for their production. Once formed, the physical presence of the C5 molecule is no longer required for the manifestation of the lesions as indicated by persistence of lesions after removal of C5 protein by trypsin. The C5-dependent ultra-structural phenomenon has therefore been interpreted to represent a true structural change of the membrane which, however, is not accompanied by a permeability defect.
NOTES for colorectal neoplasia—surgery through the looking glass
Authors: R Cahill, I Lindsey, C Cunningham
Journal: Gut (2009)

We read with great interest Dr Rosch’s piercing analysis of the current reality of natural orifice transluminal endoscopic surgery (NOTES) ( Gut 2008; 57 :1481–6) and agree that much regarding this experimental approach seems to belong more to the realm of Lewis Carroll fantasy than modern surgical science. All too often there are too few elements of real clinical applicability within many zealous technical reports and too much left in anticipation of “future technological innovation”.

We would, however, propose an extra facet to his critique in suggesting that NOTES may represent far more than minimally invasive access taken to an extreme conclusion if we choose to use it as a spur to reassess the actual operative blueprint. The “gold-standard” operation for colorectal malignancy has been unchanged now for decades. Even the advent and acceptance of laparoscopy only changed the access employed not the actual operative extent of the radical intra-abdominal procedure. Therefore, since subspecialisation, colorectal surgery has lagged …
CD44v6 is not a prognostic factor in primary breast cancer
Authors: R.H.L. Jansen, S.R. Joosten-Achjanie, J.W. Arends, A. Volovics, P.S.G.J. Hupperets, H.C. Schouten, H.F.P. Hillen
Journal: Annals of Oncology (1998)
Significance of early and late positive responses to insulin hypoglycaemia in patients with intact vagi
Authors: G. P. Burns, F. C. Y. Cheng, A. G. Cox, R. A. Payne, J. Spencer, R. B. Welbourn
Journal: Gut (1969)

Insulin tests were performed on 100 subjects with duodenal ulcer who had not undergone surgery. Thirty-seven per cent had `late9 positive responses to insulin. It was suggested that a late response to insulin after surgery was not necessarily an indication of `adequate9 vagotomy. The secretory responses to insulin before operation revealed no difference in peak acid concentrations or outputs between those with early and late responses. Basal acid concentrations were higher in those with late responses, though the difference was only significant when the division between early and late responses was made at 60 minutes. The distribution of the timing of the peak responses suggested that the division into `early9 and `late9 responders was artificial.
Tumor necrosis factor–alpha modulates CCAAT/enhancer binding proteins–DNA binding activities and promotes hepatocyte-specific gene expression during liver regeneration
Authors: Anna Mae Diehl, Shi Qi Yang, Ming Yin, Hui Zhi Lin, Steve Nelson, Greg Bagby
Journal: Hepatology (1995)

Injury-related cytokines, such as tumor necrosis factor-alpha (TNF), may preserve liver-specific gene expression during the subsequent regenerative response by modulating the activity of transcription factors, including CCAAT/enhancer binding proteins (C/EBPs), which regulate differentiated gene expression in hepato-cytes. To test this theory, rats were treated with neutralizing antibody to TNF or nonimmune immunoglobulin before partial hepatectomy (PH) and regenerative changes in the messenger RNAs (mRNAs), proteins, and DNA-binding activities of C/EBP isoforms and the expression of a C/EBP-regulated gene, phosphoenol pyruvate carboxykinase (PEPCK), were compared. Before PH, the expressions of C/EBP-α, C/EBP-β, and C/EBP-γ were similar in the two treatment groups. Dimers containing C/EBP-α and C/EBP-β accounted for virtually all of the C/EBP DNA binding activity and mRNA for PEPCK, the rate limiting hepatocyte enzyme for gluconeogenesis, was barely detected. After PH, in control rats, mRNA and nuclear protein concentrations of C/EBP-β and C/EBP-γ increased approximately fivefold by 3 hours after PH. This was accompanied by increased DNA binding activity of these C/EBP isoforms and decreased DNA binding activity of C/EBP-α. mRNA levels of PEPCK, a gene that is strongly transactivated by non-α C/EBP isoforms, increased fivefold. Pretreatment with anti-TNF antibodies prevented regenerative induction of C/EBP β and γ expression and DNA-binding activity. The nature of dimers binding to C/EBP cis-acting elements remained similar to that observed in liver before PH and increases in PEPCK mRNA were blunted. These results support the theory that TNF helps maintain liver-specific gene expression during liver regeneration by altering transcription factor complexes that regulate differentiated gene expression in hepatocytes. (Hepatology 1995; 22:252-261.)
Evolution of the atrial fibrillation substrate in experimental congestive heart failure: angiotensin-dependent and -independent pathways
Authors: S Cardin
Journal: Cardiovascular Research (2003)

Objective: Augmented atrial apoptosis, angiotensin II expression, and related signalling pathway activation have been shown in clinical atrial fibrillation (AF), but their significance is poorly understood. This study evaluated temporal relationships between changes in atrial histopathology, selected signalling mediators, and AF promotion, as well as effects of angiotensin-converting enzyme (ACE) inhibition, in a canine model of congestive heart failure (CHF). Methods: Dogs were subjected to ventricular tachypacing (VTP) for varying periods up to 5 weeks. Apoptosis was assessed by terminal dUTP nick-end labelling (TUNEL) and DNA fragmentation. Protein expression was determined by Western blot, angiotensin II concentration by ELISA (tissue) and radioimmunoassay (plasma), and caspase-3 activity by enzymatic assay. Histopathological analyses were used to quantify fibrosis, inflammation, and cell death. Results: Significant apoptosis developed 24 h after VTP onset and persisted for 1 week, returning to baseline thereafter. Apoptosis was preceded by increases in tissue (but not plasma) angiotensin II concentration; enhanced expression of phosphorylated mitogen-activated protein (MAP) kinases p38, JNK, and ERK; and augmented ratios of the proapoptotic protein Bax to the antiapoptotic protein Bcl-2. Increased cell death, leukocyte infiltration, and caspase-3 activity occurred at the time of peak apoptosis. Apoptosis was followed by interstitial fibrosis, which peaked at 5 weeks. ACE inhibition (enalapril) prevented increases in tissue angiotensin II concentration, phosphorylated ERK expression, Bax/Bcl-2 ratio, and cellular apoptosis, but did not affect total cell death, leukocyte infiltration, JNK or p38 activation, and reduced but did not eliminate tissue fibrosis. Conclusions: AF-promoting atrial structural remodeling in experimental CHF involves angiotensin II-dependent and angiotensin II-independent pathways. Significant apoptosis occurs, but prevention of apoptosis by ACE inhibition only partially prevents atrial structural remodeling.
Trends of Earlier and Later Responses of C-peptide to Oral Glucose Challenges With Progression to Type 1 Diabetes in Diabetes Prevention Trial–Type 1 Participants
Authors: Jay M. Sosenko, Jerry P. Palmer, Lisa E. Rafkin, Jeffrey P. Krischer, David Cuthbertson, Carla J. Greenbaum, George Eisenbarth, Jay S. Skyler
Journal: Diabetes Care (2009)

OBJECTIVE We studied the C-peptide response to oral glucose with progression to type 1 diabetes in Diabetes Prevention Trial-Type 1 (DPT-1) participants. RESEARCH DESIGN AND METHODS Among 504 DPT-1 participants <15 years of age, longitudinal analyses were performed in 36 progressors and 80 nonprogressors. Progressors had oral glucose tolerance tests (OGTTs) at baseline and every 6 months from 2.0 to 0.5 years before diagnosis; nonprogressors had OGTTs over similar intervals before their last visit. Sixty-six progressors and 192 nonprogressors were also studied proximal to and at diagnosis. RESULTS The 30-0 min C-peptide difference from OGTTs performed 2.0 years before diagnosis in progressors was lower than the 30-0 min C-peptide difference from OGTTs performed 2.0 years before the last visit in nonprogressors (P < 0.01) and remained lower over time. The 90-60 min C-peptide difference was positive at every OGTT before diagnosis in progressors, whereas it was negative at every OGTT before the last visit in nonprogressors (P < 0.01 at 2.0 years). The percentage whose peak C-peptide occurred at 120 min was higher in progressors at 2.0 years (P < 0.05); this persisted over time (P < 0.001 at 0.5 years). However, the peak C-peptide levels were only significantly lower at 0.5 years in progressors (P < 0.01). The timing of the peak C-peptide predicted type 1 diabetes (P < 0.001); peak C-peptide levels were less predictive (P < 0.05). CONCLUSIONS A decreased early C-peptide response to oral glucose and an increased later response occur at least 2 years before the diagnosis of type 1 diabetes.
Short-Term Heart Rate Variability Strongly Predicts Sudden Cardiac Death in Chronic Heart Failure Patients
Authors: Maria Teresa La Rovere, Gian Domenico Pinna, Roberto Maestri, Andrea Mortara, Soccorso Capomolla, Oreste Febo, Roberto Ferrari, Mariella Franchini, Marco Gnemmi, Cristina Opasich, Pier Giorgio Riccardi, Egidio Traversi, Franco Cobelli
Journal: Circulation (2003)

Background— The predictive value of heart rate variability (HRV) in chronic heart failure (CHF) has never been tested in a comprehensive multivariate model using short-term laboratory recordings designed to avoid the confounding effects of respiration and behavioral factors. Methods and Results— A multivariate survival model for the identification of sudden (presumably arrhythmic) death was developed with data from 202 consecutive patients referred between 1991 and 1995 with moderate to severe CHF (age 52±9 years, left ventricular ejection fraction 24±7%, New York Heart Association class 2.3±0.7; the derivation sample). Time- and frequency-domain HRV parameters obtained from an 8′ recording of ECG at baseline and during controlled breathing (12 to 15 breaths/min) were challenged against clinical and functional parameters. This model was then validated in 242 consecutive patients referred between 1996 and 2001 (validation sample). In the derivation sample, sudden death was independently predicted by a model that included low-frequency power (LFP) of HRV during controlled breathing ≤13 ms 2 and left ventricular end-diastolic diameter ≥77 mm (relative risk [RR] 3.7, 95% CI 1.5 to 9.3, and RR 2.6, 95% CI 1.0 to 6.3, respectively). The derivation model was also a significant predictor in the validation sample ( P =0.04). In the validation sample, LFP ≤11 ms 2 during controlled breathing and ≥83 ventricular premature contractions per hour on Holter monitoring were both independent predictors of sudden death (RR 3.0, 95% CI 1.2 to 7.6, and RR 3.7, 95% CI 1.5 to 9.0, respectively). Conclusions— Reduced short-term LFP during controlled breathing is a powerful predictor of sudden death in patients with CHF that is independent of many other variables. These results refine the identification of patients who may benefit from prophylactic implantation of a cardiac defibrillator.
Use of and Mortality After Bilateral Mastectomy Compared With Other Surgical Treatments for Breast Cancer in California, 1998-2011
Authors: Allison W. Kurian, Daphne Y. Lichtensztajn, Theresa H. M. Keegan, David O. Nelson, Christina A. Clarke, Scarlett L. Gomez
Journal: JAMA (2014)

Bilateral mastectomy is increasingly used to treat unilateral breast cancer. Because it may have medical and psychosocial complications, a better understanding of its use and outcomes is essential to optimizing cancer care.
Reye's syndrome
Authors: M Casteels-van Daele, E Eggermont
Journal: BMJ (1994)

fore repeated at a serum dilution of 1:20 after absorbing with double the quantity of anti-G antibodies, and unequivocal positive results for parvovirus B19 IgM were then obtained.It would be unfortunate if high concentrations of parvovirus Bi 9 IgG were to mask the laboratory confirmation of acute infection with less sensitive techniques when the diagnosis was suspected clinically.With regard to the management of an outbreak of parvovirus B19 infection, we have prepared a fact sheet for professionals and an explanatory leaflet for parents which we are happy to make available.
Advances in the Pathogenesis of Alzheimer’s Disease: Focusing on Tau-Mediated Neurodegeneration
Authors: Yale Duan, Suzhen Dong, Feng Gu, Yinghe Hu, Zheng Zhao
Journal: Translational Neurodegeneration (2012)

In addition to senile plaques and cerebral amyloid angiopathy, the hyperphosphorylation of tau protein and formation of intraneuronal neurofibrillary tangles (NFTs) represents another neuropathological hallmark in AD brain. Tau is a microtubule-associated protein and localizes predominantly in the axons of neurons with the primary function in maintaining microtubules stability. When the balance between tau phosphorylation and dephosphorylation is changed in favor of the former, tau is hyperphosphorylated and the level of the free tau fractions elevated. The hyperphosphorylation of tau protein and formation of NFTs represent a characteristic neuropathological feature in AD brain. We have discussed the role of Aβ in AD in our previous review, this review focused on the recent advances in tau-mediated AD pathology, mainly including tau hyperphosphorylation, propagation of tau pathology and the relationship between tau and Aβ.
Adenomatous Polyposis Families That Screen <i>APC</i> Mutation–Negative by Conventional Methods Are Genetically Heterogeneous
Authors: Elise T. Renkonen, Pekka Nieminen, Wael M. Abdel-Rahman, Anu-Liisa Moisio, Irma Järvelä, Sirpa Arte, Heikki J. Järvinen, Päivi Peltomäki
Journal: Journal of Clinical Oncology (2005)

Purpose One third of families with classical adenomatous polyposis (FAP), and a majority of those with attenuated FAP (AFAP), remain APC mutation–negative by conventional methods. Our purpose was to clarify the genetic basis of polyposis and genotype-phenotype correlations in such families. Patients and Methods We studied a cohort of 29 adenomatous polyposis families that had screened APC mutation–negative by the protein truncation test, heteroduplex analysis, and exon-specific sequencing. The APC gene was investigated for large genomic rearrangements by multiplex ligation-dependent probe amplification (MLPA), and for allelic mRNA expression by single nucleotide primer extension (SNuPE). The AXIN2 gene was screened for mutations by sequencing. Results Four families (14%) showed a constitutional deletion of the entire APC gene (three families) or a single exon (one family). Seven families (24%) revealed reduced or extinct mRNA expression from one APC allele in blood, accompanied by loss of heterozygosity in the APC region in six (75%) of eight tumors. In 15 families (52%), possible APC involvement could be neither confirmed nor excluded. Finally, as detailed elsewhere, three families (10%) had germline mutations in genes other than APC, AXIN2 in one family, and MYH in two families. Conclusion “APC mutation–negative” FAP is genetically heterogeneous, and a combination of MLPA and SNuPE is able to link a considerable proportion (38%) to APC. Significant differences were observed in clinical manifestations between subgroups, emphasizing the importance of accurate genetic and clinical characterization for the proper management of such families.
Effect of Endothelin-A Receptor Blockade With Atrasentan on Tumor Progression in Men With Hormone-Refractory Prostate Cancer: A Randomized, Phase II, Placebo-Controlled Trial
Authors: Michael A. Carducci, Robert J. Padley, Jurgen Breul, Nicholas J. Vogelzang, Bernard A. Zonnenberg, Danai D. Daliani, Claude C. Schulman, Azmi A. Nabulsi, Rod A. Humerickhouse, Mark A. Weinberg, Jennifer L. Schmitt, Joel B. Nelson
Journal: Journal of Clinical Oncology (2003)

To evaluate the efficacy and safety of atrasentan (ABT-627), an endothelin-A receptor antagonist, in the treatment of asymptomatic, hormone-refractory prostatic adenocarcinoma.A double-blind, randomized, placebo-controlled clinical trial of hormone-refractory prostate cancer (HRPCa) patients was conducted in the United States and Europe. Two hundred eighty-eight asymptomatic patients with HRPCa and evidence of metastatic disease were randomly assigned to one of three study groups receiving a once-daily oral dose of placebo, 2.5 mg atrasentan, or 10 mg atrasentan, respectively. Primary end point was time to progression; secondary end points included time to prostate-specific antigen (PSA) progression, bone scan changes, and changes in bone and tumor markers.The three treatment groups were similar in all baseline characteristics. Median time to progression in intent-to-treat (ITT) patients (n = 288) was longer in the 10-mg atrasentan group compared with the placebo group: 183 v 137 days, respectively; (P =.13). Median time to progression in evaluable patients (n = 244) was significantly prolonged, from 129 days (placebo group) to 196 days (10-mg atrasentan group; P =.021). For both ITT and evaluable populations in the 10-mg atrasentan group, median time to PSA progression was twice that of the placebo group (155 v 71 days; P =.002). Patients who received placebo continued to have significant increases from baseline in serum (lactate dehydrogenase [LDH]), a marker of disease burden; elevations in LDH were uniformly attenuated by atrasentan in the ITT population. Headache, peripheral edema, and rhinitis were primary side effects, typically of mild to moderate severity. Quality of life was not adversely affected by atrasentan.Atrasentan is an oral, targeted therapy with favorable tolerability and the potential to delay progression of HRPCa.