tbuckley/cabot-search huggingface dataset:
THE IMMUNE RESPONSE OF RABBITS TOLERANT TO BOVINE SERUM ALBUMIN TO THE INJECTION OF OTHER HETEROLOGOUS SERUM ALBUMINS
Authors: William O. Weigle
Journal: The Journal of Experimental Medicine (1961)

Immunological tolerance produced in rabbits by neonatal injections of BSA can be terminated by a series of injections of certain heterologous serum albumins which cross-react with BSA. Injections of albumins distantly related to BSA were more effective in terminating the tolerant state than injections of albumins closely related to BSA. It was concluded from results obtained with several heterologous albumins that immunological tolerance to BSA is directed to both the over-all antigenic or physical-chemical composition of the protein and the individual determinant groups present on the protein. Several possible mechanisms were given to explain the ability of cross-reacting albumins to terminate the tolerant state of BSA-tolerant rabbits. A possible relationship between the termination of tolerance in BSA-tolerant rabbits injected with cross-reacting albumins and autoimmunily was discussed. It was also suggested that the relative ease with which tolerance could be established to heterologous serum proteins in comparison to bacterial antigens is the result of the close serological and physical-chemical relationship of the heterologous serum proteins to the serum proteins of the rabbit. Rabbits injected with 500 mg of BSA during the first 5 days of life failed to form antibody capable of either eliciting an immune elimination of an injection of I* BSA given 3 to 4 months later or complexing with the circulating I* BSA.
Standardizing double-blind, placebo-controlled oral food challenges: American Academy of Allergy, Asthma &amp; Immunology–European Academy of Allergy and Clinical Immunology PRACTALL consensus report
Authors: Hugh A. Sampson, Roy Gerth van Wijk, Carsten Bindslev-Jensen, Scott Sicherer, Suzanne S. Teuber, A. Wesley Burks, Anthony E.J. Dubois, Kirsten Beyer, Philippe A. Eigenmann, Jonathan M. Spergel, Thomas Werfel, Vernon M. Chinchilli
Journal: Journal of Allergy and Clinical Immunology (2012)
Exercise-induced SPARC prevents tumorigenesis of colon cancer
Authors: Yu-Peng Liu, Michael Hsiao
Journal: Gut (2012)

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in North America and Europe. Happily, the incidence and mortality of CRC have declined by 3.4% and 3.0%, respectively, from 2003 to 2007 in the USA.1 The decline in incidence is attributed to the public health emphasis on the importance of CRC screening and the reduction of behavioural risk factors. For the majority of people who do not use tobacco and alcohol, the most important determinants of CRC risk factors are weight control, dietary choice and level of physical activity. A number of investigations have demonstrated the benefit of exercise on CRC prevention, and guidelines released by governmental and non-governmental organisations also emphasise the importance of regular exercise for decreasing CRC incidence.

Although the correlation between exercise and CRC prevention is conclusive, the molecular mechanism for the protective effect of exercise remains largely unresolved. Epidemiological and experimental studies have proposed several possible biological mechanisms to explain the exercise–malignancy relationship, including regulation of metabolic activity, production of sex hormones, alterations of antioxidant enzymes and growth factors, body weight control, and alteration of immune system.2 Recent studies have shown interleukin-6 (IL-6), IL-8, IL-15, brain-derived neurotrophic factor and leukaemia inhibitory factor to be exercise-induced myokines that mediate several biological processes.3 However, none of these …
Pathophysiology of obstructive sleep apnoea
Authors: PC Deegan, WT McNicholas
Journal: European Respiratory Journal (1995)

The pathophysiology of obstructive sleep apnoea (OSA) is complex and incompletely understood. A narrowed upper airway is very common among OSA patients, and is usually in adults due to nonspecific factors such as fat deposition in the neck, or abnormal bony morphology of the upper airway. Functional impairment of the upper airway dilating muscles is particularly important in the development of OSA, and patients have a reduction both in tonic and phasic contraction of these muscles during sleep when compared to normals. A variety of defective respiratory control mechanisms are found in OSA, including impaired chemical drive, defective inspiratory load responses, and abnormal upper airway protective reflexes. These defects may play an important role in the abnormal upper airway muscle responses found among patients with OSA. Local upper airway reflexes mediated by surface receptors sensitive to intrapharyngeal pressure changes appear to be important in this respect. Arousal plays an important role in the termination of each apnoea, but may also contribute to the development of further apnoea, because of reduction in respiratory drive related to the hypocapnia which results from postapnoeic hyperventilation. A cyclical pattern of repetitive obstructive apnoeas may result. A better understanding of the integrated pathophysiology of OSA should help in the development of new therapeutic techniques.
New Option for the Initial Management of Metastatic Pancreatic Cancer?
Authors: James L. Abbruzzese, Kenneth R. Hess
Journal: Journal of Clinical Oncology (2014)

the results of a randomized clinical trial conducted in patients with metastatic pancreatic cancer that compared gemcitabine with a combination of gemcitabine and nab-paclitaxel. In this trial, 861 patients were randomly assigned: 431 to gemcitabine plus nab-paclitaxel and 430 to gemcitabine alone. The high-level results demonstrated a median overall survival of 8.5 months in the nab-paclitaxel group comparedwith6.7monthsinthegemcitabinegroup.Thehazardratiofor death was 0.72 (95% CI, 0.62 to 0.83; P .001). Other end points, including progression-free survival and response rate, were superior withthecombination.Grade3neutropeniaoccurredin38%ofthe patientstreatedwithgemcitabineplusnab-paclitaxel,with3%ofthese instances resulting in febrile neutropenia. Twenty-six percent of the patients received growth factors. Cumulative peripheral neuropathy occurredin17%ofthepatientstreatedwithnab-paclitaxel,anditwas managed with temporary discontinuation of nab-paclitaxel followed by a reduction in dose. Overall, however, 71% of the nab-paclitaxel doses were delivered at the intended starting dose. 1
Dynamic Changes in the Expression of Neutrophil Extracellular Traps in Acute Respiratory Infections
Authors: Tomoya Hirose, Shigeto Hamaguchi, Naoya Matsumoto, Taro Irisawa, Masafumi Seki, Osamu Tasaki, Hideo Hosotsubo, Kazunori Tomono, Takeshi Shimazu
Journal: American Journal of Respiratory and Critical Care Medicine (2012)
Sex Differences in Insulin Dose and Postprandial Glucose as BMI Increases in Patients With Type 2 Diabetes
Authors: Lois Jovanovič
Journal: Diabetes Care (2009)

In a recent review by Geer and Shen (1), using the PubMed database and the references cited in these reports, men were reported to have more lean mass and women to have higher adiposity. Men were also found to have more visceral and hepatic adipose tissue, whereas women had more peripheral or subcutaneous adipose tissue. The researchers concluded that these differences, as well as differences in sex hormones and adipokines, may contribute to a more insulin-sensitive environment in women than in men. When they normalized to kilograms of lean body mass, men and women had similar resting energy expenditure, but physical energy expenditure was more closely related to percent body fat in men than in women. Greater amounts of visceral and hepatic adipose tissue, in conjunction with the …
p53 immunohistochemistry can identify bronchial dysplastic lesions proceeding to lung cancer: a prospective study
Authors: A Ponticiello, E. Barra, U. Giani, M Bocchino, A Sanduzzi
Journal: European Respiratory Journal (2000)

Dysplasia is an important step in bronchial carcinogenesis and smokers present more dysplastic lesions than nonsmokers. These lesions not always lead to malignancy, so there is a need for additional, preferentially objective, diagnostic markers. To verify whether immunohistochemical overexpression of p53 protein in dysplastic areas could be a predictive marker of the development of lung cancer, we investigated p53 overexpression in 22 bronchial dysplastic lesions obtained by fibrebronchoscopy from heavy smokers who were not diagnosed as having lung cancer and were followed for a 4-yr period. Nine (41%) lesions showed p53-positivity. Seven lung cancers (78%), mostly squamous cell carcinomas, were detected within the follow-up in these patients and 3 in 13 (23%) patients with p53-negative lesions. Lung cancer occurred in all seven patients with dysplastic lesions showing >10% p53 positive nuclei. The positive predictive value of p53 immunostaining for lung cancer was 78%. The negative predictive value of p53 was 77%. p53 staining was not detected in squamous metaplasia lesions without atypia and in normal bronchial epithelium. Our findings provide evidence that p53-overexpression in bronchial dysplastic areas may be a clinically useful marker for identifying patients proceeding to, at least, squamous cell carcinoma and, in addition, may facilitate the detection of occult tumours.
Serial echocardiographic assessment of left ventricular dimensions and function after myocardial infarction in mice
Authors: X Gao
Journal: Cardiovascular Research (2000)

Objective: To test the usage of serial echocardiography in mice with induced myocardial infarct (MI) and to characterize the mouse model of MI. Methods: C57 mice underwent open-chest surgery to induce left coronary artery occlusion or sham-operation (SH). Echocardiography was performed before and at 1, 2.5, 6 and 9 weeks after surgery. Left ventricular end diastolic and end systolic dimensions (LVEDd, LVESd) and fractional shortening (FS) were measured. Haemodynamics was determined at week 9 by LV catheterization and hearts were examined morphologically. Results: Post-infarct mortality was 46% (10/22), of which, 70% died of acute heart failure or LV rupture within the first week. LV dimensions and FS remained stable in SH group (n=10) during the study period. In surviving MI mice (n=12), there was modest LV dilatation and fall in FS at week 1. Compared with week 0 values, there were progressive increase in LVEDd (+50∼+66%) and LVESd (+124∼+171%), and decline in FS (−53∼−73%) during the 2.5∼9 week period. Infarcted mice also had lower LV systolic pressure (LVSP), dP/dtmax and dP/dtmin (all P<0.01 vs. SH group). Infarct size, LVSP and dP/dt significantly correlated with FS and LV dimensions (r=0.61∼0.80, all P<0.01). Conclusions: LV remodeling and dysfunction in mice with MI are time-dependent processes and early remodeling seems associated with high risk of rupture and acute pump failure. Our findings provide a baseline description of this murine model and confirm echocardiography as a reliable means to serially assess changes of cardiac structure and function after MI.
Occupational exposure to crystalline silica and autoimmune disease.
Authors: C G Parks, K Conrad, G S Cooper
Journal: Environmental Health Perspectives (1999)

Occupational exposure to silica dust has been examined as a possible risk factor with respect to several systemic autoimmune diseases, including scleroderma, rheumatoid arthritis, systemic lupus erythematosus, and some of the small vessel vasculitidies with renal involvement (e.g., Wegener granulomatosis). Crystalline silica, or quartz, is an abundant mineral found in sand, rock, and soil. High-level exposure to respirable silica dust can cause chronic inflammation and fibrosis in the lung and other organs. Studies of specific occupational groups with high-level silica exposure (e.g., miners) have shown increased rates of autoimmune diseases compared to the expected rates in the general population. However, some clinic- and population-based studies have not demonstrated an association between silica exposure and risk of autoimmune diseases. This lack of effect may be due to the limited statistical power of these studies to examine this association or because the lower- or moderate-level exposures that may be more common in the general population were not considered. Experimental studies demonstrate that silica can act as an adjuvant to nonspecifically enhance the immune response. This is one mechanism by which silica might be involved in the development of autoimmune diseases. Given that several different autoimmune diseases may be associated with silica dust exposure, silica dust may act to promote or accelerate disease development, requiring some other factor to break immune tolerance or initiate autoimmunity. The specific manifestation of this effect may depend on underlying differences in genetic susceptibility or other environmental exposures.
Molecular Neurobiology of Drug Addiction
Authors: Jennifer Chao, Eric J. Nestler
Journal: Annual Review of Medicine (2004)

Addiction can be viewed as a form of drug-induced neural plasticity. One of the best-established molecular mechanisms of addiction is upregulation of the cAMP second messenger pathway, which occurs in many neuronal cell types in response to chronic administration of opiates or other drugs of abuse. This upregulation and the resulting activation of the transcription factor CREB appear to mediate aspects of tolerance and dependence. In contrast, induction of another transcription factor, termed DeltaFosB, exerts the opposite effect and may contribute to sensitized responses to drug exposure. Knowledge of these mechanisms could lead to more effective treatments for addictive disorders.
New Strategies in Personalized Medicine for Solid Tumors: Molecular Markers and Clinical Trial Designs
Authors: Juliane M. Jürgensmeier, Joseph P. Eder, Roy S. Herbst
Journal: Clinical Cancer Research (2014)

Abstract The delineation of signaling pathways to understand tumor biology combined with the rapid development of technologies that allow broad molecular profiling and data analysis has led to a new era of personalized medicine in oncology. Many academic institutions now routinely profile patients and discuss their cases in meetings of personalized medicine tumor boards before making treatment recommendations. Clinical trials initiated by pharmaceutical companies often require specific markers for enrollment or at least explore multiple options for future markers. In addition to the still small number of targeted agents that are approved for the therapy of patients with histological and molecularly defined tumors, a broad range of novel targeted agents in development are undergoing clinical studies with companion profiling to determine the best-responding patient population. Although the present focus of profiling lies in genetic analyses, additional tests of RNA, protein, and immune parameters are being developed and incorporated in clinical research, and these methods are likely to contribute significantly to future patient selection and treatment approaches. As the advances in tumor biology and human genetics have identified promising tumor targets, the ongoing clinical evaluation of novel agents will now need to show if the promise can be translated into benefit for patients. Clin Cancer Res; 20(17); 4425–35. ©2014 AACR.
Intervening Sequences in Paralogous Genes: A Comparative Genomic Approach to Study the Evolution of X Chromosome Introns
Authors: B. Cardazzo
Journal: Molecular Biology and Evolution (2003)

The enlargement of the genome size and the decrease in genome compactness with increase in the number and size of introns is a general pattern during the evolution of eukaryotes. Among the possible mechanisms for modifying intron size, it has been suggested that the insertion of transposable elements might have an important role in driving intron evolution. The analysis of large portions of the human genome demonstrated that a relatively recent (50 to 100 MYA) accumulation of transposable elements appears to be biased, favoring a preferential insertion of LINE1 transposons into sex chromosomes rather than into autosomes. In the present work, the effect of chromosomal location on the increase in size of introns was evaluated with a comparative analysis performed on pairs of human paralogous genes, one located on the X chromosome and the second on an autosome. A phylogenetic analysis was also performed on the X-encoded proteins and their paralogs to confirm orthology-paralogy and to approximately estimate the time of gene duplication. Statistical analysis of total intron length for each pair of paralogous genes provided no evidence for a larger size of introns in the gene copies located on the X chromosome. On the opposite, introns of autosomal genes were found to be significantly longer than introns of their X-linked paralogs. Likewise, LINE1 elements were not significantly more frequent in X-chromosome introns, whereas the frequency of SINE elements showed a marginally significant bias toward autosomal introns.
Regulation of Leukotrienes in the Management of Asthma: Biology and Clinical Therapy
Authors: Alan R. Leff
Journal: Annual Review of Medicine (2001)

▪ Abstract Leukotrienes (LTs) are the ultimate synthetic product resulting from the intracellular hydrolysis of membrane phospholipid at the nuclear envelope in inflammatory cells. Activated cytosolic phospholipase (cPLA 2 ) catalyzes the production of arachidonic acid, which is converted by cyclooxygenases into leukotriene A 4 (LTA 4 ) and subsequently into the chemotaxin LTB 4 , which has no direct bronchoconstrictor activity. In certain inflammatory cells, LTA 4 is converted into the cysteinyl leukotriene (cysLT) LTC 4 , which is converted into LTD 4 and finally to LTE 4 after extracellular transport. All cysLTs occupy the same receptors and are extremely potent bronchoconstricting agents that are pathogenetic in both asthma and allergy. With the identification of the structure of the cysLT receptor, antileukotriene therapies have been developed that either (a) inhibit synthesis of leukotriene (through 5-lipoxygenase inhibition) or (b) block the cysLT receptor. Preliminary investigations indicate that corticosteroids also may partially block the synthesis of cysLT and that cysLTs may be chemotactic for other inflammatory cells, e.g. eosinophils, by a mechanism that has not yet been defined. Currently, anti-LT therapies are approved by the US Food and Drug Administration (FDA) only for patients with asthma. These drugs generally are moderately efficacious agents, although they are highly efficacious in aspirin-induced asthma (AIA). In other forms of asthma, inhaled corticosteroid (ICS) therapy has been more effective than anti-LT therapy in improving air flow obstruction. However, anti-LT agents are additive to beta-adrenoceptor and ICS in their effects. Accordingly, anti-LT therapies are used frequently as supplemental treatments in asthmatic patients whose asthma is not optimally controlled by a combination of other drugs, including long-acting beta-adrenoceptor drugs and ICS agents. The growth of leukotriene receptor antagonists (LTRAs) has been extraordinary in the United States. The exceptional safety of these agents and their ease of administration as tablets taken once or twice daily has spurred this growth. In the past year, the high-affinity cysLT receptor has been cloned. This holds forth the promise of a second generation of LTRA agents of even greater efficacy and possibly greater duration of action.
PPAR-δ senses and orchestrates clearance of apoptotic cells to promote tolerance
Authors: Lata Mukundan, Justin I Odegaard, Christine R Morel, Jose E Heredia, Julia W Mwangi, Roberto R Ricardo-Gonzalez, Y P Sharon Goh, Alex Red Eagle, Shannon E Dunn, Jennifer U H Awakuni, Khoa D Nguyen, Lawrence Steinman, Sara A Michie, Ajay Chawla
Journal: Nature Medicine (2009)
Efficacy and safety of once-daily QVA149 compared with twice-daily salmeterol–fluticasone in patients with chronic obstructive pulmonary disease (ILLUMINATE): a randomised, double-blind, parallel group study
Authors: Claus F Vogelmeier, Eric D Bateman, John Pallante, Vijay KT Alagappan, Peter D'Andrea, Hungta Chen, Donald Banerji
Journal: The Lancet Respiratory Medicine (2012)
Quality of Care for Breast Cancer for Uninsured Women in California Under the Breast and Cervical Cancer Prevention Treatment Act
Authors: Jennifer L. Malin, Allison L. Diamant, Barbara Leake, Yihang Liu, Amardeep Thind, Katherine L. Kahn, Eric C. Schneider, Arnold M. Epstein, Rose C. Maly
Journal: Journal of Clinical Oncology (2010)

Purpose The objective of this study was to evaluate the quality of care provided to uninsured women with breast cancer who received treatment through the Breast and Cervical Cancer Prevention Treatment Program (BCCTP). Methods Participants included women with stage I to III breast cancer (n = 658) from a consecutive sample of women 18 years or older who received coverage through the California BCCTP between February 2003 and September 2005 who consented to a survey and medical record review (61% response rate). Quality of breast cancer care was evaluated using 29 evidence-based quality measures developed for the National Initiative for Cancer Care Quality (NICCQ). NICCQ, a largely insured cohort of women diagnosed with stage I to III breast cancer in 1998, was used to benchmark the results. Results Twenty-three percent of women presented with stage III disease compared with fewer than 10% nationally. Patients received 93% of recommended care (95% CI, 92% to 93%). Adherence to recommended care within domains ranged from 87% for post-treatment surveillance (95% CI, 84% to 90%) to 97% for diagnostic evaluation (95% CI, 96% to 97%). Compared to the NICCQ cohort, adherence to quality measures was as good or better for the BCCPT cohort in all domains except post-treatment surveillance. Conclusion The BCCTP has made important inroads in providing poor, uninsured women with access to high quality care when faced with the diagnosis of breast cancer; however, many present at an advanced stage, which is associated with worse outcomes.
An articulatory perspective on the locus equation
Authors: Björn Lindblom
Journal: Behavioral and Brain Sciences (1998)

Using an articulatory model we show that locus equations make special use of the phonetic space of possible locus patterns. There is nothing articulatorily inevitable about their linearity or slope- intercept characteristics. Nonetheless, articulatory factors do play an important role in the origin of simulated locus equations, but they cannot, by themselves, provide complete explanations for the observed facts. As in other domains, there is interaction between perceptual and motor factors.
Influence of the murine MHC (H-2) on Friend leukemia virus-induced immunosuppression.
Authors: R P Morrison, J Nishio, B Chesebro
Journal: The Journal of Experimental Medicine (1986)

Friend murine leukemia virus complex (FV)-induced immunosuppression was studied by assaying splenic anti-SRBC PFC responses and plasma antibody titers in mice at various times after FV inoculation. Genes located within the H-2 complex were found to influence resistance to FV-induced immunosuppression. Near normal responses were observed in mice having the H-2a/b or H-2b/b genotype, whereas mice having the H-2a/a genotype were suppressed. This H-2 effect was observed not only in mice having heterozygous C57BL/10 X A background genes, including Rfv-3r/s, but also was apparent in mice having homozygous A-strain background genes, including Rfv-3s/s. Therefore, the Rfv-3 gene did not appear to convey resistance to FV-induced immunosuppression. The suppression in susceptible H-2a/a mice was characterized by a partial suppression of the IgM response and a profound suppression of both the primary and secondary IgG responses. Neither splenomegaly nor viremia alone appeared to be sufficient for the induction or maintenance of the immunosuppression. The mechanism of suppression was unclear, but both B lymphocyte and T lymphocyte functions appeared to be altered.