tbuckley/cabot-search huggingface dataset:
Transfer of cow's milk beta-lactoglobulin to human serum after a milk load: a pilot study.
Authors: J A Lovegrove, D L Osman, J B Morgan, S M Hampton
Journal: Gut (1993)

A sensitive and specific enzyme linked immunosorbent assay (ELISA) was developed for the quantification of cow9s milk beta-lactoglobulin in human serum. The assay had a sensitivity of 80 pg/ml (2 standard deviations from zero) and did not cross react significantly with any other tested milk proteins. The absorption of cow9s milk beta-lactoglobulin and beta-lactoglobulin immunoglobulin G antibody levels after a milk load was investigated in eight healthy non-allergic individuals. There was a significant variation in the circulating beta-lactoglobulin antigen levels during the six hour period after feeding (p &lt; 0.01) for the combined data. A biphasic absorption pattern was seen in all subjects except one subject who had undetectable levels. No significant variation with time was observed for the beta-lactoglobulin IgG antibody levels and no correlation was found between the beta-lactoglobulin antigen levels and the beta-lactoglobulin IgG antibody levels. This pilot study offered information on the quantity of immunogenic cows9 milk protein transferred to the blood after a milk load in non-allergic healthy adults and confirmed a biphasic profile of antigen transfer. The sensitivity of the assay used has shown that transfer of food antigen does occur in the majority of healthy nonallergic subjects.
Neurosyphilis and Penicillin Levels in Cerebrospinal Fluid
Authors: John A. Mohr
Journal: JAMA (1976)

Because neurosyphilis may progress despite therapy with the recommended penicillin regimens, 15 subjects with positive tests for syphilis in the serum and cerebrospinal fluid (CSF) were studied. All of these patients had CSF pleocytosis. Two received penicillin G (5 and 10 million units per day intravenously, respectively) and 13 received benzathine penicillin G, 3.6 million units per week intramuscularly; treatment lasted four weeks. During intravenous and after intramuscular penicillin therapy, a spinal tap was performed on all subjects; later, assays were done. Of two patients who received intravenous penicillin G, one had 0.3 mug/ml and the other had 2.4 mug/ml penicillin in the CSF. Twelve of 13 patients who received benzathine penicillin G had no detectable penicillin in the CSF; one patient had 0.1 mug/ml penicillin in the CSF.
Studying Tumorigenesis through Network Evolution and Somatic Mutational Perturbations in the Cancer Interactome
Authors: Feixiong Cheng, Peilin Jia, Quan Wang, Chen-Ching Lin, Wen-Hsiung Li, Zhongming Zhao
Journal: Molecular Biology and Evolution (2014)

Cells govern biological functions through complex biological networks. Perturbations to networks may drive cells to new phenotypic states, for example, tumorigenesis. Identifying how genetic lesions perturb molecular networks is a fundamental challenge. This study used large-scale human interactome data to systematically explore the relationship among network topology, somatic mutation, evolutionary rate, and evolutionary origin of cancer genes. We found the unique network centrality of cancer proteins, which is largely independent of gene essentiality. Cancer genes likely have experienced a lower evolutionary rate and stronger purifying selection than those of noncancer, Mendelian disease, and orphan disease genes. Cancer proteins tend to have ancient histories, likely originated in early metazoan, although they are younger than proteins encoded by Mendelian disease genes, orphan disease genes, and essential genes. We found that the protein evolutionary origin (age) positively correlates with protein connectivity in the human interactome. Furthermore, we investigated the network-attacking perturbations due to somatic mutations identified from 3,268 tumors across 12 cancer types in The Cancer Genome Atlas. We observed a positive correlation between protein connectivity and the number of nonsynonymous somatic mutations, whereas a weaker or insignificant correlation between protein connectivity and the number of synonymous somatic mutations. These observations suggest that somatic mutational network-attacking perturbations to hub genes play an important role in tumor emergence and evolution. Collectively, this work has broad biomedical implications for both basic cancer biology and the development of personalized cancer therapy.
Kinetics of normal hematopoietic stem and progenitor cells in a Notch1-induced leukemia model
Authors: Xiaoxia Hu, Hongmei Shen, Chen Tian, Hui Yu, Guoguang Zheng, Richard XuFeng, Zhenyu Ju, Jing Xu, Jianmin Wang, Tao Cheng
Journal: Blood (2009)
Profilin as a severe food allergen in allergic patients overexposed to grass pollen
Authors: M. I. Alvarado, L. Jimeno, F. De La Torre, P. Boissy, B. Rivas, M. J. Lázaro, D. Barber
Journal: Allergy (2014)

Background Profilins are ubiquitous proteins that act as panallergens in sensitized patients, considered to be mild or incomplete food allergens. The aim of the study was to evaluate the role of profilins as severe food allergens in allergic patients overexposed to grass who were referred for severe food reactions and were sensitized to profilins. Methods After a careful in vitro screening, 26 patients were included, classified into two groups, mild (17) and severe reactors (9), based on clinical history and subsequently provoked orally with purified profilin in a double-blind placebo-controlled food challenge setup. Results A significant number of patients presented severe positive food challenge test reactions at low doses of the allergen profilin. Patients prone to suffer from severe reactions had lower IgG4/IgE ratio to major grass allergens than those who did not. Conclusion Profilins are complete food allergens in food-allergic patient populations that are exposed to high levels of grass pollen. This type of patient constitutes an optimal model to understand the link between respiratory and food allergies. The nature of the observed reactions and the low level of allergen eliciting the reactions suggest that intake through the oral mucosa might constitute a relevant route of exposure to food allergens.
Local Expression of C-Type Natriuretic Peptide Markedly Suppresses Neointimal Formation in Rat Injured Arteries Through an Autocrine/Paracrine Loop
Authors: Hikaru Ueno, Akihiro Haruno, Nobuhiro Morisaki, Mayumi Furuya, Kenji Kangawa, Akira Takeshita, Yasushi Saito
Journal: Circulation (1997)

In vivo gene transfer into injured arteries may provide a new means to facilitate molecular understanding of and to treat the intractable fibroproliferative arterial diseases. Selection of an optimal molecule to be transferred will be a key to successful gene therapy in the future. We tested the hypothesis that a secreted multifactorial molecule should act more efficiently through an autocrine/paracrine loop to suppress neointimal formation elicited in injured arteries than a simple growth-inhibiting molecule that might be expressed inside cells.We constructed an adenoviral vector (AdCACNP) expressing C-type natriuretic peptide (CNP), a secreted stimulator of membrane-bound guanyl cyclase. AdCACNP directs cells to secrete large quantities of biologically active CNP. Serum-stimulated DNA synthesis and cell proliferation were only moderately suppressed in arterial smooth muscle cells infected with AdCACNP in vitro. However, when AdCACNP was applied to balloon-injured rat carotid arteries in vivo, neointimal formation was markedly reduced (90% reduction) in an infection-site-specific manner without an increase in plasma CNP level.Our results showed that CNP, a secreted multifactorial molecule, was indeed effective in suppressing fibroproliferative response in injured arteries and suggest that the potent antiproliferation effect may not be the most critical factor for the effective suppression of neointimal formation. An adenovirus-mediated expression of CNP could be an effective and site-specific form of molecular intervention in proliferative arterial diseases.
Pre-eclampsia and eclampsia and change of paternity.
Authors: J S Scott, J G Feeney
Journal: BMJ (1980)

correction of known or suspected risk factors.There is clearly no magic formula, in my experience, which can be placed across the board and applied on a mass scale.There is, unfortunately, no alternative to the careful investigation of every patient on an individual level, correcting each risk factor presented, energetically, by the safest and most acceptable means for the patient.Clearly, the correction of hyperlipidaemia by all reasonable means must be included in any treatment programme for the prevention of atherosclerotic arterial disease.Unfortunately, all large multicentre trials that I have seen seem to fail in that they do not treat the whole patient, and for this reason grave doubt must be thrown on their validity in testing the concept of the primary prevention of arterial disease by studying one factor and seeking to match all other factors.The review article by Professor Lewis (19 July, p 177) gives a clear and positive approach to the problem without leaving the physician with no guidelines to offer the patient.
1022-81 Short door-to-balloon times with primary percutaneous coronary intervention for acute myocardial infarction improve late survival in patients with early, but not late presentation
Authors: Bruce R Brodie, Thomas D Stuckey, Charles J Hansen, Debra S VerSteeg, Denise B Muncy, Navin Gupta, William Downey
Journal: Journal of the American College of Cardiology (2004)
Mathematical Models of Isolation and Quarantine
Authors: C. Castillo-Chavez
Journal: JAMA (2003)

THE RECENT EMERGENCE OF SEVERE ACUTE RESPIRATORY syndrome (SARS) has drawn attention to the strategies of isolation and quarantine (I&Q) as a method of disease control. The fundamental dilemma associated with the implementation of I&Q is how to predict the populationlevel efficacy of individual quarantine: Which and how many individuals need to be quarantined to achieve effective control at the population level? Although some forms of I&Q have proven effective in SARS, 1,2 they are not appropriate for all infectious diseases. Diseases like varicella, for which costs of quarantine may be high (many work and school days are lost when noninfected contacts are kept at home) and the return minimal (a relatively mild disease is avoided), require a different approach. Furthermore, in some cases, I&Q may be not only costly but harmful. An I&Q policy for varicella, in the long run, may actually increase the average age (and therefore the severity) of first infection. Using I&Q to control rubella in China could actually lead to higher levels of disease because under the current system (of no control), about 97% of the population has rubella antibodies obtained from direct exposure to infectious individuals. 2 Such a level of natural immunity would be impossible to accomplish under the current effective US and Canadian vaccination policies. Mathematical modeling can help determine when I&Q arethebeststrategiesfordiseasecontrolaswellashowthey might affect short- and long-term disease dynamics. Mathematical modeling offers ways of integrating populationlevel knowledge based on previous epidemics with availableindividualandpopulationdatatopredicttheoutcomes of several alternative scenarios. This kind of mathematical epidemiologyisparticularlywellsuitedtoproblemsforwhich formal experimentation is impossible for logistical or ethical reasons. In these situations, mathematical models can play a role in planning and experimental design in epidemiology, ecology, and immunology. Mathematical disease modeling is an attempt to fit empirical data to abstract processes. Decisions must always be made about which variables to exclude from the model. Although inclusion of more variables (for example, the baselinehealthstatusofeveryindividual)wouldmakethemodel more accurate, such models would be impossibly complex. The balance between predictive power and its level of detail depends on the questions the model is intended to answer. Variables that can influence the outcome of I&Q policies include the number of contacts an infected person has per unit of time, the probability of infection per contact, and the proportion of the population that is vacci
Interim observations on benefit/risk of azathioprine versus D-penicillamine in the treatment of rheumatoid arthritis.
Authors: J R Ward, H J Williams
Journal: Annals of the Rheumatic Diseases (1982)

Azathioprine has been shown to be an effective drug for the treatment of rheumatoid arthritis.Levy et al124 MEASUREMENT OF DISEASE ACTIVITY For measurement of efficacy the following variables were measured at entry and every six weeks.(1) Functional assessment.(2) Duration of morning stiffness.
Reactive Oxygen Species Are Involved in Smoking-Induced Dysfunction of Nitric Oxide Biosynthesis and Upregulation of Endothelial Nitric Oxide Synthase
Authors: Rajat S. Barua, John A. Ambrose, Sudhesh Srivastava, Mary C. DeVoe, Lesley-Jane Eales-Reynolds
Journal: Circulation (2003)

Background— Our group has previously shown that human umbilical vein endothelial cells exposed to smokers’ serum decreased nitric oxide (NO) production and endothelial nitric oxide synthase (eNOS) activity in the presence of increased eNOS expression. In the present study, we examined whether these observations extended to human coronary artery endothelial cells (HCAECs). In addition, the role of reactive oxygen species in the observed alterations was examined. Methods and Results— HCAECs were incubated with serum from 10 nonsmokers and 15 smokers for 12 hours with or without the addition of either polyethylene glycol-superoxide dismutase (PEG-SOD, 300 U/mL), PEG-SOD+PEG-catalase (1000 U/mL), chelerythrine (3 μmol/L), or tetrahydrobiopterin (20 μmol/L). At the end of incubation, NO, eNOS protein, and eNOS activity were measured from the same culture. HCAECs incubated with smokers’ serum alone showed significantly lower NO production ( P &lt;0.05) and eNOS activity ( P &lt;0.005) but higher eNOS expression ( P &lt;0.005) compared with nonsmokers. In smokers, addition of PEG-SOD, PEG-SOD+PEG-catalase, or tetrahydrobiopterin significantly ( P &lt;0.05) improved NO levels and eNOS activity. Interestingly, in the same smokers, a significant decrease in eNOS expression was only seen with the addition of PEG-SOD+PEG-catalase ( P &lt;0.05) and treatment with PEG-SOD alone insignificantly increased eNOS expression. Conclusions— The present study indicates that in vitro, HCAECs show similar changes in NO biosynthesis as human umbilical vein endothelial cells when exposed to smokers’ serum and also confirms that oxidative stress plays a central role in smoking-mediated dysfunction of NO biosynthesis in endothelial cells. Furthermore, these data support other studies suggesting a role for hydrogen peroxide in the upregulation of eNOS.
Low Serum Pseudocholinesterase Levels Complicating Treatment with Phenelzine
Authors: P. O. Bodley, K. Halwax, L. Potts
Journal: BMJ (1969)

Four patients undergoing treatment with phenelzine developed low serum pseudocholinesterase levels. In one of the patients an apnoea of one hour followed modified electric convulsion therapy. In three cases investigations showed that the serum pseudocholinesterase levels returned to normal after withdrawal of phenelzine.
Harmful impact of EU clinical trials directive: …while paediatric oncology is being scuppered
Authors: Christopher D Mitchell
Journal: BMJ (2006)

EDITOR—The editorial by Hemminki and Kellokumpu-Lehtinen is a startling summary of the impact of the EU Clinical Trials Directive and the associated national legislation on the conduct of investigator led research.1 It is remarkable how little response or debate has emerged since the introduction of this directive: every investigator …
Ultrastructural patterns of Helicobacter pylori.
Authors: M Caselli, A Aleotti, P Boldrini, M Ruina, V Alvisi
Journal: Gut (1993)

Ultrastructural morphology of the bacterial bodies was studied in 40 Helicobacter pylori positive cases. Two bacterial patterns were identified, which were associated with different modes of contact with the epithelial cells and possibly with different stages of the natural history of the infection.
Why so many open windows?
Authors: Barrie Smith
Journal: BMJ (2008)

Vitamin D deficiency is widespread in Scotland I agree with Holick 1 and Sievenpiper et al 2 about the urgent need to highlight the neglected subject of vitamin D deficiency in the United Kingdom.We have found in our general practice in Edinburgh a (to us) surprisingly high prevalence of gross vitamin D deficiency.The deficiency affects not only our South Asian patients but also a considerable number of those with white skin colour.Between 2005 and 2007, blood samples were taken from 99 patients aged 15-85.We included patients suspected of having a possible vitamin D deficiency: patients of South Asian origin or other ethnic minorities, patients with vague musculoskeletal symptoms or overweight, patients taking antiepileptic drugs, patients using sunscreen or make up, housebound patients, and patients with little exposure to sunlight.The figure shows our as yet unpublished results.According to the definitions of most vitamin D researchers, insufficient vitamin D concentrations are those below 75 nmol/l.In our sample only 2% had a sufficient vitamin D concentration.Measurements below 25 nmol/l are defined as severe deficiency; in our sample, the proportion was 47%.We select the letters for these pages from the rapid responses posted on bmj.com favouring those received within five days of publication of the article to which they refer.Letters are thus an early selection of rapid responses on a particular topic.
Managing Depression in the Patient with Cancer
Authors: J. C. Holland
Journal: CA A Cancer Journal for Clinicians (1987)

Depression is the most common psychiatric problem encountered among patients with cancer. The acute stress response, which occurs at pivotal points during the course of illness, is normal. However, severe or protracted depressive symptoms should be evaluated and treated. The treatment of depression, which often involves a combined regimen of psychotherapy and psychopharmacologic intervention, can result in improved compliance with therapy, a greater tolerance for the disease and its outcome, and an improved quality of life.
Abstract 2622: SNP markers in the <i>FGF9</i> and <i>MAP3K1</i> region associate with testicular germ cell tumor susceptibility
Authors: Roelof Koster, Peter A. Kanetsky, Nandita Mitra, Saran Vardhanabhuti, Stephanie L. Ciosek, Richard Letrero, Kurt D'Andrea, David R. Doody, Chu Chen, David J. Vaughn, Stephen M. Schwartz, Katherine L. Nathanson
Journal: Cancer Research (2012)

Abstract Testicular germ cell tumors (TGCT) are the most common cancers in young men, and several lines of evidence point to their substantial genetic component. To date, genome-wide association (GWA) studies have uncovered six TGCT susceptibility loci. Together these loci account for 11-16% of TGCT disease risk to first degree relatives, arguing that additional genetic variation contributing to TGCT susceptibility must exist. Recently we and others indentified variation at DMRT1 associated with TGCT risk. DMRT1 is highly conserved across many species and plays a crucial role in male gonadal development and sex determination. Deletions in DMRT1 lead to male to female (XY) sex reversal. Therefore, we undertook a targeted pathway-based analysis of genes influencing XY sex reversal to identify associations with TGCT risk. Through review of the literature, we identified 27 additional genes in which mutations or deletions are associated with XY sex reversal. Using our existing GWA data in 349 cases and 919 controls, ∼570 risk markers in the 28 candidate loci were evaluated for replication based on a significance threshold of p &amp;lt; 2 x 10−5 for at least two SNP markers. Two markers that mapped near to MAP3K1 and FGF9 meet these criteria. We genotyped the most statistically significant SNP markers in the MAP3K1 (rs252906; p = 1.89 x 10Δ5) and FGF9 (rs628137; p = 1.66 x 10Δ5) region in two independent replication sample sets, consisting of 439 cases of TGCT and 960 controls and of 768 cases and 674 controls respectively. In combined analysis, TGCT cases had elevated odds of carriage of the rs252906 major T allele [per-allele odds ratio (OR) = 1.24, 95% confidence interval (CI) 1.16, 1.377; P = 5.87 × 10−5] and the rs628137 major G allele (per allele OR = 1.20, 95% CI 1.08, 1.34, P = 5.28 x 10−4 compared with controls. Similarly to KITLG, the susceptibility locus most strongly associated with TGCT risk, FGF9 is associated with proliferation, migration and survival of primordial germ cells, the progenitor cells for human TGCT. MAP3K1 and FGF9 play a crucial role in normal testes development. These finding strengthen the supposition that variation in genes influencing sex determination, and male germ cell development and differentiation play an important role in inherited TGCT susceptibility. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2622. doi:1538-7445.AM2012-2622
Cervical Incompetence and Preterm Delivery
Authors: Sabrina D. Craigo
Journal: New England Journal of Medicine (1996)

Premature delivery is one of the most troublesome problems in obstetrics. Occurring in 10 percent of all pregnancies, premature delivery is the second most important contributor to perinatal mortality, after fetal anomalies.1 Despite a great deal of research in this area, the rate of prematurity has not declined in the past 50 years.Many factors have contributed to the unsatisfactory progress in the management, as well as the prevention, of premature delivery. A limited understanding of the pathophysiology of premature labor, difficulty of making the diagnosis, the low predictive value of the known risk factors, and the lack of effective . . .
Officials warn of looming humanitarian crisis in Sudan
Authors: Peter Moszynski
Journal: BMJ (2004)

The recent escalation of fighting in western Sudan's Darfur province has led to a crisis in oneof the world's most inhospitable regions, with thousands of people fleeing into the desert. Agencies have been able to reach only 15% of people in need, with some three million people remaining beyond access.

The United Nations Office for Coordination of Humanitarian Affairs (OCHA) reports: “Half of Darfur's six million people are directly affected by the conflict. The number of people who have fled from Darfur to Chad has nearly doubled to 110,000 in the past three …