tbuckley/cabot-search huggingface dataset:
Developmental Antecedents of Cardiovascular Disease
Authors: David J.P. Barker, Susan P. Bagby
Journal: Journal of the American Society of Nephrology (2005)

Knowledge of the fetal antecedents of cardiovascular disease has increased rapidly since the association between low birth weight and the disease was demonstrated 20 yr ago. It now is known that individuals who had low birth weight or who were thin or short at birth are at increased risk for both cardiovascular disease and type 2 diabetes. This has been shown in studies in different countries and cannot be explained by confounding variables. Through clinical and animal studies, the biologic processes that underlie the epidemiologic associations and how their effects are modified by postnatal growth and by living conditions in childhood and adult life are beginning to be understood. One such process is altered renal development, with reduced nephron numbers, which may initiate hypertension.
Hepatitis C viral infection is associated with fibrillary glomerulonephritis and immunotactoid glomerulopathy.
Authors: G S Markowitz, J T Cheng, R B Colvin, W M Trebbin, V D D'Agati
Journal: Journal of the American Society of Nephrology (1998)

The most common form of glomerular disease seen in association with hepatitis C virus (HCV) infection is membranoproliferative glomerulonephritis, with or without associated cryoglobulinemia. This study examines four cases of fibrillary glomerulonephritis and two cases of immunotactoid glomerulopathy in association with HCV infection. Findings at presentation included proteinuria, renal insufficiency, and hematuria. Renal biopsy revealed a membranoproliferative pattern of glomerular disease in five cases, and a membranous glomerulopathy with mesangial proliferative features in one. On immunofluorescence, all cases stained with IgG and C3. Electron microscopy revealed fibrils of the expected diameter, 16 to 28 nm in fibrillary glomerulonephritis and 33 to 45 nm in immunotactoid glomerulopathy. In only one case were cryoglobulins detected (at low titer and on only one of three assays). Antiviral therapy was not given in any of the six cases. Outcomes were mixed, with progression to renal failure occurring in two patients and persistent proteinuria with stable or improved renal function in three. Follow-up is not available on the sixth case. Both fibrillary glomerulonephritis and immunotactoid glomerulopathy have features that overlap with cryoglobulinemic glomerulonephritis. The relatedness of these three entities in a subset of patients with HCV infection suggests a common pathogenic mechanism of glomerular deposition of organized deposits.
Bevacizumab plus mFOLFOX-6 or FOLFOXIRI in patients with initially unresectable liver metastases from colorectal cancer: the OLIVIA multinational randomised phase II trial
Authors: T. Gruenberger, J. Bridgewater, I. Chau, P. García Alfonso, M. Rivoire, S. Mudan, S. Lasserre, F. Hermann, D. Waterkamp, R. Adam
Journal: Annals of Oncology (2014)
Experiences of non-UK-qualified doctors working within the UK regulatory framework: a qualitative study
Authors: A Slowther, GA Lewando Hundt, J Purkis, R Taylor
Journal: Journal of the Royal Society of Medicine (2012)

To explore the experience of non-UK-qualified doctors in working within the regulatory framework of the General Medical Council (GMC) document Good Medical Practice.Individual interviews and focus groups.United Kingdom.Non-UK-qualified doctors who had registered with the GMC between 1 April 2006 and 31 March 2008, doctors attending training/induction programmes for non-UK-qualified doctors, and key informants involved in training and support for non-UK-qualified doctors.Themes identified from analysis of interview and focus group transcripts.Information and support for non-UK qualified doctors who apply to register to work in the UK has little reference to the ethical and professional standards required of doctors working in the UK. Recognition of the ethical, legal and cultural context of UK healthcare occurs once doctors are working in practice. Non-UK qualified doctors reported clear differences in the ethical and legal framework for practising medicine between the UK and their country of qualification, particularly in the model of the doctor-patient relationship. The degree of support for non-UK-qualified doctors in dealing with ethical concerns is related to the type of post they work in. European doctors describe similar difficulties with working in an unfamiliar regulatory framework to their non-European colleagues.Non-UK-qualified doctors experience a number of difficulties related to practising within a different ethical and professional regulatory framework. Provision of information and educational resources before registration, together with in-practice support would help to develop a more effective understanding of GMP and its implications for practice in the UK.
Principles and Practice of Intensive Care Monitoring.
Authors: Martin J. Tobin
Journal: Thorax (1998)

A 35 year old HIV positive patient from Hong Kong presented with a fever, cough and a skin rash in association with a lung mass, all of which were due to disseminated Penicillium marneVei infection.He made a good response to antifungal therapy.The lung mass is a previously undescribed pulmonary manifestation of disseminated Penicillium marneVei infection.Infections with this fungus should be suspected in any patient with HIV and respiratory symptoms who has visited southeast Asia.
Insulin resistance but not hypertriglyceridemia per se is associated with endothelial dysfunction in chronic hypertriglyceridemia
Authors: I Jonkers
Journal: Cardiovascular Research (2002)

To infer the relative impact of elevated triglyceride levels and insulin resistance on endothelial dysfunction in patients with chronic hypertriglyceridemia (HTG).Endothelial function was studied in 11 HTG patients and 16 normolipidemic controls. Cumulative-dose infusions of 5-hydroxytryptamine (5HT) and sodium nitroprusside were infused locally into the brachial artery to study endothelium-dependent and endothelium-independent vasodilation, respectively. Data of the HTG patients were dichotomized around the median of insulin resistance, calculated as HOMA-index, forming HTG groups with mild (HTG-MIR) and severe insulin resistance (HTG-SIR).HTG patients had higher triglyceride levels and smaller LDL particle size than controls (both P< or =0.001), whereas these parameters did not differ between both HTG groups. Insulin resistance was higher in both HTG groups than in controls (11.1 (7.0-14.5) and 4.9 (4.0-6.7) vs. 2.4 (4.9-5.2), respectively, both P<0.001). Similarly, free fatty acid levels, another indicator of insulin resistance, were highest in the HTG-SIR group, followed by those in the HTG-MIR and control group (0.7 (0.6-0.8), 0.5 (0.4-0.6) and 0.4 (0.3-0.4) mmol/l, respectively, all P<0.05). Endothelial-dependent vasodilation was similar in HTG-MIR and controls. In contrast, the response to 5HT was attenuated in the HTG-SIR group compared to controls (low and high dose by, respectively, -60 and -44%, both P<0.01), and tended to be lower than in the HTG-MIR group (-43%, P=0.068 and -41%, P=0.100, respectively). Endothelium-independent vasodilation did not differ between the three groups.These findings indicate that chronic hypertriglyceridemia per se is not associated with endothelial dysfunction. In contrast, the presence of insulin resistance, characterized by hyperinsulinemia and FFA elevation, contributes to the induction of endothelial dysfunction in chronic HTG.
Retropositional parasitism of SINEs on LINEs: identification of SINEs and LINEs in elasmobranchs
Authors: I. Ogiwara, M. Miya, K. Ohshima, N. Okada
Journal: Molecular Biology and Evolution (1999)

Some previously unidentified short interspersed repetitive elements (SINEs) and long interspersed repetitive element (LINEs) were isolated from various higher elasmobranchs (sharks, skates, and rays) and characterized.These SINEs, members of the HE1 SINE family, were tRNA-derived and were widespread in higher elasmobranchs.The 3Ј-tail region of this SINE family was strongly conserved among elasmobranchs.The LINEs, members of the HER1 LINE family, encoded an amino acid sequence similar to that encoded by the chicken CR1 LINE family, and they contained a strongly conserved 3Ј-tail region in the 3Ј untranslated region.This tail region of the HER1 LINE family was almost identical to that of the HE1 SINE family.Thus, the HE1 SINE family and the HER1 LINE family provide a clear example of a pair of SINEs and LINEs that share the same tail region.Conservation of the secondary structures of the tail regions, as well as of the nucleotide sequences, between the HE1 SINE family and HER1 LINE family during evolution suggests that SINEs utilize the enzymatic machinery for retroposition of LINEs through the recognition of higher-order structures of the conserved 3Ј-tail region.A discussion is presented of the parasitism of SINEs on LINEs during the evolution of these retroposons.
Antiangiogenic Therapy Elicits Malignant Progression of Tumors to Increased Local Invasion and Distant Metastasis
Authors: Marta Pàez-Ribes, Elizabeth Allen, James Hudock, Takaaki Takeda, Hiroaki Okuyama, Francesc Viñals, Masahiro Inoue, Gabriele Bergers, Douglas Hanahan, Oriol Casanovas
Journal: Cancer Cell (2009)
Familial Risks, Early-Onset Breast Cancer, and BRCA1 and BRCA2 Germline Mutations
Authors: G. S. Dite, M. A. Jenkins, M. C. Southey, J. S. Hocking, G. G. Giles, M. R. E. McCredie, D. J. Venter, J. L. Hopper
Journal: JNCI Journal of the National Cancer Institute (2003)

Having a family history of breast cancer, particularly if it involves early-onset disease, is a risk factor for breast cancer, but little is known about specific causes of this association. Consequently, we studied mothers, sisters, and aunts of an age-stratified sample of 1567 unselected case patients diagnosed with breast cancer before age 60 years, recruited to a population-based, case-control-family study, in which case patients, control subjects, and their relatives were administered the same questionnaire.Extensive BRCA1 and BRCA2 mutation testing was carried out for 788 case patients diagnosed before age 40 years, including manual sequencing of DNA from 72 patients with two or more affected relatives. Standardized morbidity ratios, age-specific cumulative risks, and hazard ratios were calculated for groupings of relatives.Cumulative risks of breast cancer to age 50 years in the sisters, mothers, and aunts of the case patients, respectively, were 6, 3, and 2 times the population risk if the case patient was younger than age 40 years at diagnosis but were considerably lower if the case patient was older at diagnosis. When relatives of the case patients with a BRCA1 or BRCA2 mutation were excluded, these risks fell by, at most, 20%. Sisters and aunts, but not mothers, who had an additional first-degree relative with breast cancer were at increased risk, and the risk was greater when that relative was younger at diagnosis. Hazard ratios were 10.7 (95% confidence interval [CI] = 4.2 to 26.8) for sisters and 4.2 (95% CI = 2.2 to 8.1) for aunts, if the relative was aged 40 years at diagnosis. Fewer than one-third of the excess of breast cancers in relatives of case patients diagnosed before age 40 years that are attributed to familial factors are BRCA1- or BRCA2-related.Mutations in genes other than BRCA1 and BRCA2 may be associated with a high risk of breast cancer, especially in young women.
Abstract 3856: Progesterone generates breast cancer stem cells through nuclear receptor-independent mechanisms in irradiated human mammary cell lines
Authors: Guillaume Vares, Xing Cui, Bing Wang, Tetsuo Nakajima, Mitsuru Nenoi
Journal: Cancer Research (2014)

Abstract Epidemiological evidence has shown the existence of increased breast cancer risk following chest radiation exposure. There is strong evidence that steroid hormones influence radiosensitivity and breast cancer risk. Tumors may be initiated by a small subpopulation of cancer stem cells (CSCs). In order to evaluate whether the modulation of radiation-induced breast cancer risk by steroid hormones could involve CSCs, we measured the proportion of ALDH+ and CD44+/CD24- CSCs in irradiated breast cancer cell lines after progesterone and estrogen treatment. Progesterone stimulated the expansion of the CSC compartment both in progesterone receptor (PR)-positive breast cancer cells and in PR-negative normal cells. In MCF10A normal epithelial PR-negative cells, progesterone-treatment and irradiation triggered cancer and stemness-associated microRNA regulations (such as the down-regulation of miR-22 and miR-29c expression), which resulted in increased proportions of radiation-resistant tumor-initiating CSCs. Therefore progesterone might influence radiation-induced breast cancer risk by generating tumor-initiating breast CSCs through nuclear PR-independent mechanisms (such as membrane progesterone receptors - mPRs). Citation Format: Guillaume Vares, Xing Cui, Bing Wang, Tetsuo Nakajima, Mitsuru Nenoi. Progesterone generates breast cancer stem cells through nuclear receptor-independent mechanisms in irradiated human mammary cell lines. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3856. doi:10.1158/1538-7445.AM2014-3856
Lactic Acidosis Rates in Type 2 Diabetes
Authors: Jonathan B Brown, Kathryn Pedula, Joshua Barzilay, Michael K Herson, Peggy Latare
Journal: Diabetes Care (1998)

OBJECTIVE To provide a context for the interpretation of lactic acidosis risk among patients using metformin, we measured rates of lactic acidosis in patients with type 2 diabetes before metformin was approved for use in the U.S. RESEARCH DESIGN AND METHODS Using electronic databases of hospital discharge diagnoses and laboratory results maintained by a large, nonprofit health maintenance organization (HMO), we identified possible lactic acidosis events in three geographically and racially diverse populations with type 2 diabetes. We then reviewed hard-copy clinical records to confirm and describe each event and determine its likely cause(s). RESULTS From &amp;lt;41,000 person-years of experience, we found four confirmed, three possible, and three borderline cases of lactic acidosis. In each case, we identified at least one severe medical condition that could have caused the acidosis. The annual confirmed event rate is similar to published rates of metformin-associated lactic acidosis. CONCLUSIONS Lactic acidosis occurs regularly, although infrequently, among persons with type 2 diabetes, at rates similar to its occurrence among metformin users. The medical conditions with which both metformin-associated and naturally occurring lactic acidosis cooccur are also its potential causes. The observed association between metformin and lactic acidosis may be coincidental rather than causal. This possibility merits further study.
Identification of a 36,000-molecular weight, gag-related phosphoprotein in lymphoma cells transformed by radiation leukemia virus.
Authors: R G Bach, D Meruelo
Journal: The Journal of Experimental Medicine (1984)

Radiation leukemia virus (RadLV) causes thymic lymphoma in 90% of susceptible mice after a latent period of several months. The virally encoded polypeptides produced by RadLV-induced lymphoma cells were analyzed by immunoprecipitation and NaDodSO4/polyacrylamide gel electrophoresis. Along with the expected precursor and mature forms of gag and env gene products, a polypeptide of 36,000 molecular weight (p36) was precipitated by anti-gag antisera. It was not precipitable by normal sera or anti-env antibodies. Like the gag-associated fusion proteins of some acute leukemia viruses, p36 was found to be phosphorylated in vivo, although it lacked detectable ATP-specific protein kinase activity in vitro. By kinetics during pulse-chase labeling experiments and by comparison of two-dimensional tryptic peptide maps, this protein is not an intermediate in gag precursor processing. One lymphoma cell line is described that resembles a nonproducer RadLV-transformant, synthesizing relatively large amounts of p36 in the absence of Pr66gag or p30 production. Several RadLV-induced lymphoma cell lines also produce p36, while it was not detectable in the radiation-induced lines tested. In addition, p36 was not produced by mouse or mink fibroblasts or cultured thymocyte cell lines infected with virus passaged from the RadLV-induced lymphomas. We conclude that p36 may represent a previously unrecognized transformation-related protein induced directly or indirectly by infection with RadLV.
GATA3-Expressing ILC2 Are Selectively Enriched In Allergic Eosinophilic Nasal Polyposis
Authors: Hannah H. Walford, Andrew A. White, Christopher Bergeron, Jacob Husseman, Kelly Bethel, Rachel Baum, Sean Lund, Naseem Khorram, David R. Scott, David H. Broide, Taylor A. Doherty
Journal: Journal of Allergy and Clinical Immunology (2014)
Polymorphisms in A Disintegrin and Metalloprotease 33 (<i>ADAM33</i>) Predict Impaired Early-Life Lung Function
Authors: Angela Simpson, Nikolas Maniatis, Francine Jury, Julie A. Cakebread, Lesley A. Lowe, Stephen T. Holgate, Ashley Woodcock, William E. R. Ollier, Andrew Collins, Adnan Custovic, John W. Holloway, Sally L. John
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Rationale: Asthma commonly originates in early life in association with impaired lung function, which tracks to adulthood. Objectives: Within the context of a prospective birth cohort study, we investigated the association between single nucleotide polymorphisms (SNPs) in a disintegrin and metalloprotease 33 (ADAM33) gene and early-life lung function. Methods: Children were genotyped for 17 SNPs in ADAM33. Lung function at age 3 (n = 285) and 5 years (n = 470) was assessed using plethysmographic measurement of specific airway resistance (sRaw). At age 5, we also measured FEV1. SNPs were analyzed individually using logistic regression, followed by linkage disequilibrium mapping to identify the causal locus. Main Results: Carriers of the rare allele of F+1 SNP had reduced lung function at age 3 years (p = 0.003). When the recessive model was considered, four SNPs (F+1, S1, ST+5, V4) showed association with sRaw at age 5 years (p < 0.04). Using linkage disequilibrium mapping, we found evidence of a significant causal location between BC+1 and F1 SNPs, at the 5′ end of the gene. Four SNPs were associated with lower FEV1 (F+1, M+1, T1, and T2; p ⩽ 0.04). The risk of transient early wheezing more than doubled among children homozygous for the A allele of F+1 (odds ratio, 2.39; 95% confidence intervals, 1.18–4.86; p = 0.02), but there was no association between any SNP and allergic sensitization or physician-diagnosed asthma. Conclusions: Polymorphisms in ADAM33 predict impaired early-life lung function. The functionally relevant polymorphism is likely to be at the 5′ end of the gene.
Endothelin and heart transplantation
Authors: B Geny
Journal: Cardiovascular Research (1998)

Time for primary review 28 days. 

Endothelins are 21-amino-acid peptides that are produced ubiquitously by vascular endothelial and smooth muscle cells, but also by numerous other cells in many different organs. Endothelin-1 (ET-1) appears to be the predominantly produced isoform and to be responsible for most of the physiological and pathophysiological changes seen in humans. As suggested by its mitogenic properties, by its potent and long-lasting vasoconstrictor effects and by its origin in vasculature, ET-1 is thought to be mainly a cardiovascular hormone and/or paracrine factor that may play a key role in cardiovascular diseases such as systemic hypertension, atherogenesis, cardiac hypertrophy, heart and circulatory failures [1–5].

To date, although increased circulating ET-1 levels have been reported in heart-transplant recipients (Htx), suggesting a role for ET-1 in the cardiovascular and renal adaptation to human heart transplantation [6, 7], no attempt has been made to review the available literature concerning ET-1 after heart transplantation. We will thus discuss first the factors modulating ET-1 levels in Htx and will then investigate an eventual ET-1 pathophysiological role, addressing more particularly ET-1's participation in accelerated coronary artery disease, acute graft rejection, systemic hypertension and renal impairment after heart transplantation.

Although already increased in patients with heart failure, circulating ET-1 has generally been reported to be elevated after heart transplantation (Tables 1 and 2). Such an increase may result from decreased pulmonary or renal clearance and/or from enhanced ET-1 production.

View this table:

Table 2 
Mean values of endothelin-1 plasma levels in controls, in patients with heart failure and in heart transplant recipients early and late after transplantation



View this table:

Table 1 
Endothelin-1 plasma levels in normal subjects, in patients with heart failure and in heart transplant recipients early and late after transplantation



In the range of its plasma concentrations in Htx, pulmonary clearance is thought to contribute more than renal clearance … 

* Corresponding author. Tel: +33-3-8835-8768; Fax: +33-3-8824-3334; E-mail: francois.piquard@physio-ulp.u-strasbg.fr
Practice, efficacy and cost of staging suspected non-small cell lung cancer: a retrospective study in two Dutch hospitals
Authors: G J M Herder
Journal: Thorax (2002)

Background: A study was undertaken to investigate the clinical practice, yield, and costs of preoperative staging in patients with suspected NSCLC and to obtain baseline data for prospective studies on the cost effectiveness of <sup>18</sup>F-fluorodeoxyglucose positron emission tomography in the management of these patients. Methods: A retrospective study of the medical records of all patients with suspected NSCLC was performed during a 2 year interval (1993–4) in an academic and a large community hospital. Results: Three hundred and ninety five patients with suspected NSCLC were identified; 58 were deemed to be medically inoperable and 337 patients proceeded to the staging process. Staging required a mean (SD) of 5.1 (1.5) diagnostic tests per patient (excluding thoracotomy) carried out over a median period of 20 days (IQR 10–31). Many of the tests (including both invasive and non-invasive) were done because previous imaging tests had suggested metastases, and in most cases the results of initial tests proved to be false positives. After clinical staging, 168 patients were considered to be resectable (stage I/II) and 144 patients underwent surgery with curative intent. At surgery 33 patients (23% of those who underwent surgery) were found to have irresectable lesions and 19 (13%) had a benign lesion. Surgery was also considered to be futile in 22 patients (15%) who developed metastases or local recurrence within 12 months following radical surgery. Hospital admission was responsible for most of the costs. Conclusion: In many patients staging involved considerable effort in terms of the number of diagnostic tests, the duration of the staging period and the cost, with limited success in preventing futile surgery. Failures relate to the quality of diagnostic preparation at every level of the TNM staging system.