tbuckley/cabot-search huggingface dataset:
Measurement of very low density and low density lipoprotein apolipoprotein (Apo) B-100 and high density lipoprotein Apo A-I production in human subjects using deuterated leucine. Effect of fasting and feeding.
Authors: J S Cohn, D A Wagner, S D Cohn, J S Millar, E J Schaefer
Journal: Journal of Clinical Investigation (1990)

Six normolipidemic male subjects, after an 8-h overnight fast, were given a bolus injection and then a 15-h constant intravenous infusion of [D3]L-leucine. Subjects were studied in the fasted state and on a second occasion in the fed state (small, physiological meals were given every hour for 15 h). Apolipoproteins were isolated by preparative gradient gel electrophoresis from plasma lipoproteins separated by sequential ultracentrifugation. Incorporation of [D3]L-leucine into apolipoproteins was monitored by negative ionization, gas chromatography-mass spectrometry. Production rates were determined by multiplying plasma apolipoprotein pool sizes by fractional production rates (calculated as the rate of isotopic enrichment [IE] of each protein as a fraction of IE achieved by VLDL (d less than 1.006 g/ml) apo B-100 at plateau. VLDL apo B-100 production was greater, and LDL (1.019 less than d less than 1.063 g/ml) apo B-100 production was less in the fed compared with the fasted state (9.9 +/- 1.7 vs. 6.4 +/- 1.7 mg/kg per d, P less than 0.01, and 8.9 +/- 1.2 vs. 13.1 +/- 1.2 mg/kg per d, P less than 0.05, respectively). No mean change was observed in high density lipoprotein apo A-I production. We conclude that: (a) this stable isotope, endogenous-labeling technique, for the first time allows for the in vivo measurement of apolipoprotein production in the fasted and fed state; and (b) since LDL apo B-100 production was greater than VLDL apo B-100 production in the fasted state, this study provides in vivo evidence that LDL apo B-100 can be produced independently of VLDL apo B-100 in normolipidemic subjects.
A ZEB1-HDAC pathway enters the epithelial to mesenchymal transition world in pancreatic cancer: Figure 1
Authors: Günter Schneider, Oliver H Krämer, Dieter Saur
Journal: Gut (2011)

<h3>Abstract</h3> Cellular diversity supports the computational capacity and flexibility of cortical circuits. Accordingly, principal neurons at the CA1 output node of the hippocampus are increasingly recognized as a heterogeneous population. Their genes, molecular content, intrinsic morpho-physiology, connectivity, and function seem to segregate along the main anatomical axes of the hippocampus. Since these axes reflect the temporal order of principal cell neurogenesis, we directly examined the relationship between birthdate and CA1 pyramidal neuron diversity, focusing on the ventral hippocampus. We used a genetic fate-mapping approach that allowed tagging three groups of agematched principal neurons: pioneer, early- and late-born. Using a combination of neuroanatomy, slice physiology, connectivity tracing and cFos staining, we show that birthdate is a strong predictor of CA1 principal cell diversity. We unravel a subpopulation of pioneer neurons recruited in familiar environments with remarkable positioning, morpho-physiological features, and connectivity. Therefore, despite the expected plasticity of hippocampal circuits, given their role in learning and memory, the diversity of their main components is significantly predetermined at the earliest steps of development.
ALLEGATIONS OF TORTURE IN TURKEY
Authors: Yavuz Renda, Kalbiye Yalaz, Haluk Topaloglu, Meral Topcu, Kivilcim Gucuyener, A.Yuksel Bozer, Atalay Sahin, Mehmet Tuncel, Zeki Soypaçaci, Sabit Sahin, Taner Tatli, SüleymanSs Gökalp, Hasan Yilmaz, Ilhan Demiryilmaz, Fatma Uzun, Elizabeth Gordon, Stuart Turner, Tom Landau, Jill Hinshelwood, Helen Bamber
Journal: The Lancet (1989)
Chlamydial pelvic inflammatory disease
Authors: J Paavonen, M Lehtinen
Journal: Human Reproduction Update (1996)

Pelvic inflammatory disease (PID) is the most important complication present in the female lower genital tract, causing major medical, social and economic problems. Although PID can be caused by multiple micro-organisms, it results most frequently from the ascent of sexually transmitted Chlamydia.trachomatis or Neisseria gonorrhoeae infections from the cervix to the upper genital tract. The importance of cervical chlamydial infection in the pathogenesis of PID is well recognized. Recent data from many developed countries have shown a striking decrease in the incidence of gonococcal infections, while the rates of chlamydial infections remain high in most countries. Complications of PID are common and usually irreversible. Emerging evidence suggests that universal or selected screening of defined populations for cervical chlamydial infection leads to a dramatic reduction in the incidence of PID. Recent technological advances should further enhance efforts to prevent chlamydial infection and PID. Gene amplification-based diagnostic tests, screening by testing first-void urine, and single dose antimicrobial therapy greatly facilitate chlamydia control programmes. Thus, screening for chlamydia is the key approach in the secondary prevention of PID. The obvious challenge is to make screening for chlamydia the standard for health care for young, sexually active individuals. Since PID is the most important consequence of sexually transmitted bacterial infections, it is also imperative to develop better treatments to prevent the long-term sequelae of this disease. The development and implementation of new and effective intervention programmes for prevention and control of PID is one of the major challenges for the year 2000 and beyond.
Clinical and Pharmacologic Reappraisal of Dichloromethotrexate
Authors: A. Hantel, E. K. Rowinsky, D. A. Noe, W. P. McGuire, L. B. Grochow, B. L. Vito, D. S. Ettinger, R. C. Donehower
Journal: JNCI Journal of the National Cancer Institute (1988)

Dichloromethotrexate (DCMTX) has been the subject of sporadic clinical development for the last 30 years. Although DCMTX was developed in hopes of discovering a more potent antifolate, the potential pharmacologic and toxicologic advantages of the analog have become of greater interest. This phase I and pharmacokinetic trial of DCMTX given on days 1, 8, and 15 every 28 days was undertaken to test these potential advantages. The maximally tolerated dose on this schedule was 980 mg/m2. Hepatic toxicity was dose limiting. Malaise, myelosuppression, and mucositis were also major toxic effects. The recommended dose for subsequent phase II studies of DCMTX administered on this schedule is 785 mg/m2 with a reduction to 625 mg/m2 for patients with a poor performance status or extensive prior therapy. Plasma disappearance curves for most patients were biphasic or triphasic, although several demonstrated more complex kinetic patterns that suggested significant enterohepatic circulation. The magnitude of the area under the plasma disappearance curve was related to the severity of DCMTX-induced hepatotoxicity. The elimination kinetics were linear, with a mean plasma clearance of 294 mL/min (range, 128-715). The pharmacokinetic behavior of DCMTX does not support its use over methotrexate in regional perfusion. DCMTX's primarily nonrenal elimination suggests that it may have an advantage over methotrexate when combined with nephrotoxic drugs such as cisplatin. However, there is little reason to commit major resources to further evaluation of DCMTX unless significant advantages in antineoplastic activity are identified.
S100 proteins: A missing piece in the puzzle of heart failure?
Authors: S PLEGER, P MOST, H KATUS
Journal: Cardiovascular Research (2007)

See article by Schneider et al.  [13]  (pages 40–50) in this issue. 

Heart failure (HF) represents the common endpoint of many different kinds of cardiopulmonary diseases. Essentially, loss of myocardium triggers a sequence of molecular, cellular and physiological responses leading to ventricular remodelling and the inability of the ventricle to maintain an output sufficient for the metabolic requirements of the tissues of the body [1]. Although these responses may be viewed as compensatory in nature, many of them are or become counterregulatory and lead to long-term adverse effects [1]. Thus, novel insight into the regulatory mechanisms that contribute to the compensation and subsequent decompensation is urgently needed to broaden our knowledge about HF and to develop therapeutic strategies that can prevent the progressive deterioration of cardiac function and ultimately avoid this disease.

S100 proteins constitute the largest subfamily of EF-hand Ca2+-binding proteins. Several biological activities, such as the regulation of myocardial and skeletal muscle contractility, hypertrophy, apoptosis, the regulation of metabolic enzymes, proliferation, migration, and cell differentiation, are affected by S100 proteins [2–4]. Members of the S100 protein family display a tissue- and cell type-specific expression pattern and exhibit distinct functional properties [2–4]. Interestingly, several in vitro and in vivo … 

* Corresponding author. hugo_katus{at}med.uni-heidelberg.de
The Consequences of Overdiagnosis and Overtreatment of Lyme Disease: An Observational Study
Authors: M. Carrington Reid
Journal: Annals of Internal Medicine (1998)

Background: The adverse consequences associated with overdiagnosis and overtreatment of Lyme disease, although previously recognized, have received inadequate attention. Objective: To determine the use of health services and occurrence of treatment-related illness, disability, and distress among patients in whom Lyme disease is inappropriately diagnosed or treated. Design: Observational cohort study. Setting: University-based Lyme disease clinic. Participants: 209 patients with a presumptive diagnosis of Lyme disease previously assigned by referring physicians, the patients themselves, or both. Measurements: Self-reported data, review of medical records, and standardized instruments were used to determine 1) use of health services in terms of number of outpatient visits, number of physicians seen, types of serologic tests, and days of antibiotic treatment; 2) occurrence of antibiotic-related adverse events; and 3) levels of disability, depression, and stress. Results: Of the 209 patients, 44 (21%) met criteria for active Lyme disease, 40 (19%) had previous but not active Lyme disease, and 125 (60%) had no evidence of current or previous infection. In general, patients with active Lyme disease (who were not the focus of this study) had good outcomes. Patients with previous Lyme disease and patients with no evidence of Lyme disease used considerable health resources (median number of office visits, 11 and 7; median number of serologic tests, 4 and 4; and median days of antibiotic treatment, 75 and 42), had frequent minor adverse drug events (53% and 55%), reported significant disability (proportion of symptomatic days during which normal activities could not be performed, 16% and 18%), and had high rates of depression (38% and 42%) and stress (52% and 45%). Conclusions: Overdiagnosis and overtreatment of Lyme disease are associated with inappropriate use of health services, avoidable treatment-related illness, and substantial disability and distress.
Breast Cancer Following Ovarian Cancer in<i>BRCA</i>Mutation Carriers
Authors: Alexandra Gangi, Ilana Cass, Daniel Paik, Galinos Barmparas, Beth Karlan, Catherine Dang, Andrew Li, Christine Walsh, Bobbie J. Rimel, Farin F. Amersi
Journal: JAMA Surgery (2014)

BRCA mutation carriers are at increased risk of developing breast cancer. However, the incidence of breast cancer after a diagnosis of epithelial ovarian cancer (EOC), one of the tubal/peritoneal cancers collectively referred to as pelvic serous carcinomas, is not well known. Optimal breast cancer surveillance and detection for these patients have also not been well characterized.To determine the incidence of breast cancer after a diagnosis of EOC and to evaluate the need for breast cancer surveillance for these patients.A retrospective database review of 364 patients who underwent BRCA mutation testing for EOC (stages I-IV) between 1998 and 2012 at an academic medical center with gynecologic and breast cancer centers.Incidence of breast cancer and methods of surveillance.Of 364 patients, 135 (37.1%) were found to carry a germline BRCA1 or BRCA2 mutation. The mean age of patients at diagnosis of EOC was 49.5 years (range, 28-89 years). Of the 135 patients, 12 (8.9%) developed breast cancer. The median time from diagnosis of EOC to diagnosis of breast cancer was 50.5 months. Annual mammography was performed for 80 patients (59.3%), with annual magnetic resonance imaging of the breasts performed for 60 patients (44.4%). Thirteen patients (9.6%) underwent a bilateral prophylactic mastectomy at a median of 23 months following EOC diagnosis. Breast cancer was most commonly diagnosed by mammography for 7 of the 12 patients (58.3%), 3 (25.0%) of whom had a palpable mass and 2 (16.7%) of whom had incidental breast cancer detected during a prophylactic mastectomy. Seven patients with breast cancer (58.3%) underwent a bilateral mastectomy. All patients had early-stage breast cancer (stages 0-II). Four patients (33.3%) received adjuvant chemotherapy. At a median follow-up of 6.3 years, 4 of the 12 patients (33.3%) died of recurrent EOC after a diagnosis of breast cancer. The overall 10-year survival rate for the entire cohort of 135 patients was 17.0%.The risk of metachronous breast cancer is low in patients with known BRCA mutations and EOC. A majority of these cases of breast cancer at an early stage are detected by use of mammography. Despite the small number of patients in our study, these results suggest that optimal breast cancer surveillance for patients with BRCA-associated EOC needs to be reevaluated given the low incidence of breast cancer among these high-risk patients. Confirmation of our findings from larger studies seems to be indicated.
High- and low-level pressure support during walking in people with severe kyphoscoliosis
Authors: C. Menadue, J.A. Alison, A.J. Piper, K.K. Wong, C. Hollier, E.R. Ellis
Journal: European Respiratory Journal (2010)

To determine whether the level of pressure support (PS) provided during exercise influences endurance time in people with severe kyphoscoliosis, a double-blind randomised crossover study was performed. We hypothesised that high-level PS would be required to enhance endurance time in this population with high impedance to inflation. 13 participants with severe kyphoscoliosis performed four endurance treadmill tests in random order: unassisted; with sham PS; low-level PS of 10 cmH 2 O (PS 10); and high-level PS of 20 cmH 2 O (PS 20). Participants and assessors were blinded to the level of PS delivered during exercise. Endurance time was greater with PS 20 (median (interquartile range) 217 (168–424) s) compared with unassisted exercise (139 (111–189) s), sham PS (103 (88–155) s) and PS 10 (159 (131–206) s). In addition, isotime respiratory rate was decreased by 8 breaths·min −1 (95% CI -11– -5 breaths·min −1 ) and isotime oxygen saturation increased by 4% (95% CI 1–7%) with PS 20 compared with unassisted exercise. People with severe kyphoscoliosis require high-level PS during walking to improve exercise performance. Investigation of high-level PS as an adjunct to exercise training or to assist in the performance of daily activities is warranted.
Role of Cyclic Guanosine Monophosphate in Late Preconditioning in Conscious Rabbits
Authors: Eitaro Kodani, Yu-Ting Xuan, Hitoshi Takano, Ken Shinmura, Xian-Liang Tang, Roberto Bolli
Journal: Circulation (2002)

Background — Although NO has been shown to serve both as the trigger and the mediator of the late phase of ischemic preconditioning (PC), it is unknown whether NO acts via activation of soluble guanylate cyclase (sGC). The objective of this study was to investigate the role of sGC in late PC in conscious rabbits using the selective sGC inhibitor 1 H -[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). Methods and Results — A total of 172 conscious rabbits were used. When nonpreconditioned rabbits were subjected to a sequence of 4-minute coronary occlusion/4-minute reperfusion cycles, myocardial cyclic guanosine monophosphate (cGMP) levels increased significantly at the end of the third and sixth occlusions. In rabbits preconditioned 24 hours earlier (on day 1) with six occlusion/reperfusion cycles, myocardial cGMP levels on day 2 were significantly higher than in nonpreconditioned rabbits even before ischemia but did not increase further during a second sequence of 4-minute occlusion/reperfusion cycles. Administration of ODQ before the six occlusion/reperfusion cycles on day 1 did not prevent the development of late PC against either stunning or infarction on day 2. In contrast, administration of ODQ on day 2 completely ablated the late PC effect against both stunning and infarction. Conclusions — These results indicate that enhanced synthesis of cGMP by sGC is not necessary for ischemia to trigger a late PC effect but is required for the protection to become manifest 24 hours later. This implies that NO participates in late PC via two distinct mechanisms; ie, it triggers late PC on day 1 via a cGMP-independent mechanism and it mediates late PC on day 2 via a cGMP-dependent mechanism.
Role of Purkinje conducting system in triggering of idiopathic ventricular fibrillation
Authors: Michel Haïssaguerre, Dipen C Shah, Pierre Jaïs, Morio Shoda, Josef Kautzner, Thomas Arentz, Dietrich Kalushe, Alan Kadish, Mike Griffith, Fiorenzo Gaïta, Teiichi Yamane, Stephane Garrigue, Meleze Hocini, Jacques Clémenty
Journal: The Lancet (2002)
Non-A, Non-B Hepatitis and Antibody to Hepatitis C Virus
Authors: J W Mosley, R D Aach, F B Hollinger, C E Stevens, L H Barbosa, G J Nemo, P V Holland, W H Bancroft, H J Zimmerman, G Kuo
Journal: JAMA (1990)

Stored serum samples from the Transfusion-transmitted Viruses Study in the 1970s were tested for the presence of antibody to hepatitis C virus (anti-HCV). Single specimens from five control subjects who did not receive transfusions tested negative for anti-HCV. Of four control subjects who did not receive transfusions and who developed non-A, non-B (NANB) hepatitis after hospitalization, three remained anti-HCV negative; the fourth person with postoperative NANB hepatitis tested anti-HCV positive before the operation. Five transfusion recipients with posttransfusion hepatitis B virus infection remained seronegative; a sixth with NANB hepatitis as well as hepatitis B virus infection had seroconversion for anti-HCV. Five of nine transfusion recipients with NANB hepatitis had anti-HCV seroconversion. These results show that present anti-HCV testing demonstrates an etiologic basis for approximately half of the cases of transfusion-associated NANB hepatitis, particularly those that develop chronicity. Although cases of NANB hepatitis without seroconversion may be explained otherwise, they may be caused by another, presently unidentified, virus.
Infant feeding practices and ulcerative colitis in childhood.
Authors: S Koletzko, A Griffiths, M Corey, C Smith, P Sherman
Journal: BMJ (1991)

TABLE A2 -Independent variables signtficantly associated with still-birth or neonatal death excludedfrom model because of covariance Height of mother Number of previous premature births Haemoglobin concentration Duration of first stage of labour Miaternal age Fetal distress (cord/prolapse/ meconium/fetal heart) Social and economic status Fever/tonsillitis/laryngitis Urinary tract infection Type of resuscitation Prescription of drugs to baby Lobelline Streptomycin included in the model that optimally estimates the log odds of stillbirth or neonatal death in the whole British perinatal mortality survey ( 1958) cohort.This list of variables includes the names of categorical variables together with the design variables that are generated (for example, "parity" is a categorical variable with four categories and hence three design variables labelled as "1", "2", "3"), as well as their coefficients.Categorical variables with two categories have been listed in table A2 as having only a single entry in the model.No interactions were included in the model owing to the computational problems that these would have generated for little improvement of the model.
Prediction of Postprandial Glycemic Exposure
Authors: Ohad Cohen, Rita Basu, Gerlies Bock, Chiara Dalla Man, Marco Campioni, Ananda Basu, Gianna Toffolo, Claudio Cobelli, Robert A. Rizza
Journal: Diabetes Care (2006)

To determine the best predictors of total postprandial glycemic exposure and peak glucose concentrations in nondiabetic humans.Data from 203 nondiabetic volunteers who ingested a carbohydrate-containing mixed meal were analyzed.Fasting glucose and insulin concentrations were poor predictors of postprandial glucose area above basal (R2 = approximately 0.07, P < 0.001). The correlation was stronger for 2-h glucose concentration (R2 = 0.55, P < 0.001) and improved slightly but significantly (P < 0.001) with the addition of fasting glucose, insulin, age, sex, and body weight to the model (r2 = 0.58). The 2-h glucose concentration also predicted the peak glucose concentration (R2 = 0.37, P < 0.001) with strength of the prediction increasing (P < 0.001) modestly with the addition of fasting glucose, insulin, age, sex, and body weight to the model (R2 = 0.48, P < 0.001). On the other hand, addition of measures of body function and composition did not improve prediction of total glycemic exposure or peak glucose concentration.Isolated measures of fasting or 2-h glucose concentrations alone or in combination with more complex measures of body composition and function are poor predictors of postprandial glycemic exposure or peak glucose concentration. This may explain, at least in part, the weak and at times inconsistent relationship between these parameters and cardiovascular risk.