tbuckley/cabot-search huggingface dataset:
A CASE OF PURPURA HEMORRHAGICA.
Authors: LOUIS A. LEVISON
Journal: JAMA (1906)

<h3>Patient.</h3> —A white woman, aged 55, was admitted to the Lucas County Hospital, Toledo, March 26, 1906, complaining of weakness and expectoration of blood. <h3>Family History.</h3> —The woman's parents died of "paralysis," aged 65 and 64, respectively. One sister died of typhoid fever. There was absolutely no tendency to bleeding in any member of the family, either immediate or collateral. The patient had five children, one of whom died in infancy. The other four children are alive, and with the exception of a low order of mentality in one son, show nothing of interest. <h3>Personal History.</h3> —The climacteric was passed at the age of 43, and neither then nor at her confinements was bleeding excessive. Her past life has been free from pathologic incidents, and with the exception of measles, "muscular rheumatism" and what she calls "eczema," there are no diseases to be recorded. The woman had once or twice
The role of longitudinal cohort studies in epigenetic epidemiology: challenges and opportunities
Authors: Jane WY Ng, Laura M Barrett, Andrew Wong, Diana Kuh, George Davey Smith, Caroline L Relton
Journal: Genome biology (2012)

Longitudinal cohort studies are ideal for investigating how epigenetic patterns change over time and relate to changing exposure patterns and the development of disease. We highlight the challenges and opportunities in this approach.
Obesity and the respiratory physician
Authors: F. Crummy, M. T Naughton, J S. Elborn
Journal: Thorax (2008)

Respiratory medicine has developed as a specialty in the wake of a number of public health milestones. The origins of many of the learned societies associated with respiratory medicine can be traced back to the epidemic of tuberculosis (TB) in the early 19th century.1 Effective public health and effective treatment regimes reduced the prevalence and mortality of TB. The seminal work linking the role of tobacco smoking and its detrimental effects on the lung2 was the second key finding which challenged our specialty. Public health measures and the development of new treatments are reducing the prevalence of smoking-related lung disease, although there is still much work to be done. Obesity has emerged in the opening years of this century as a major challenge to public health. The impact of obesity on the prevalence and mortality of many diseases is well documented, although there has been little attention paid to its impact on respiratory disease.

Obesity rates are rising at an alarming rate in developed and developing countries, in both sexes, in children and adults. The obesity epidemic in children is particularly concerning as …
HIV-1 sensitivity to zidovudine and clinical outcome
Authors: CharlesA.B. Boucher, JoepM.A. Lange, HorstG. Maxeiner, K.O. Habermehl, TH. Grünewald, B. Ruf, Gareth Tudor-Williams, MartyH. St Clair, RossE. Mckinney, Mary Maha, Emmanuel Walter, Shiela Santacroce, Mark Mintz, Karen O'Donnell, Tracy Rudoll, CindyL. Vavro, EdwardM. Connor, CatherineM. Wilfert
Journal: The Lancet (1992)
Hydrogen peroxide is an endothelium-derived hyperpolarizing factor in mice
Authors: Tetsuya Matoba, Hiroaki Shimokawa, Mikio Nakashima, Yoji Hirakawa, Yasushi Mukai, Katsuya Hirano, Hideo Kanaide, Akira Takeshita
Journal: Journal of Clinical Investigation (2000)

The endothelium plays an important role in maintaining vascular homeostasis by synthesizing and releasing several endothelium-derived relaxing factors, such as prostacyclin, nitric oxide (NO), and the previously unidentified endothelium-derived hyperpolarizing factor (EDHF). In this study, we examined our hypothesis that hydrogen peroxide (H2O2) derived from endothelial NO synthase (eNOS) is an EDHF. EDHF-mediated relaxation and hyperpolarization in response to acetylcholine (ACh) were markedly attenuated in small mesenteric arteries from eNOS knockout (eNOS-KO) mice. In the eNOS-KO mice, vasodilating and hyperpolarizing responses of vascular smooth muscle per se were fairly well preserved, as was the increase in intracellular calcium in endothelial cells in response to ACh. Antihypertensive treatment with hydralazine failed to improve the EDHF-mediated relaxation. Catalase, which dismutates H2O2 to form water and oxygen, inhibited EDHF-mediated relaxation and hyperpolarization, but it did not affect endothelium-independent relaxation following treatment with the K+ channel opener levcromakalim. Exogenous H2O2 elicited similar relaxation and hyperpolarization in endothelium-stripped arteries. Finally, laser confocal microscopic examination with peroxide-sensitive fluorescence dye demonstrated that the endothelium produced H2O2 upon stimulation by ACh and that the H2O2 production was markedly reduced in eNOS-KO mice. These results indicate that H2O2 is an EDHF in mouse small mesenteric arteries and that eNOS is a major source of the reactive oxygen species.
Acquired tolerance to experimental autoimmune encephalomyelitis by intrathymic injection of myelin basic protein or its major encephalitogenic peptide.
Authors: S J Khoury, M H Sayegh, W W Hancock, L Gallon, C B Carpenter, H L Weiner
Journal: The Journal of Experimental Medicine (1993)

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease of the central nervous system that can be induced in a number of species by immunization with myelin basic protein (MBP) in adjuvant, and serves as an experimental model for the study of multiple sclerosis. The role of the thymus in acquired tolerance in autoimmune models has not been thoroughly investigated. In this study, we examined the effects of intrathymic injection of MBP or its major encephalitogenic peptide on the course of EAE in Lewis rats. A single intrathymic injection of MBP 48 h pre- but not postimmunization protects animals from actively induced EAE. An intact MBP-primed thymus was required up to 10 d postimmunization, as thymectomy on days 1, 2, and 7 postimmunization abrogated the protective effect, whereas thymectomy on day 10 did not. The proliferative response of primed lymphocytes was significantly reduced in animals that were intrathymically injected with MBP. Protection against clinical EAE was induced by thymic injection of the major encephalitogenic region (residues 71-90) but not a nonencephalitogenic (21-40) MBP epitope. Immunohistologic examination of the brain from rats intrathymically injected with encephalitogenic peptide showed markedly reduced cellular infiltrate and virtual absence of activation and inflammatory cytokines as compared with rats intrathymically injected with the nonencephalitogenic peptide. These results indicate that the thymus may play an active role in acquired systemic immunologic tolerance in T cell-mediated experimental autoimmune diseases. This effect may be mediated by a process of clonal inactivation of autoreactive T cell clones circulating through the thymus.
Is Blood Superior to Crystalloid Cardioplegia?
Authors: Veena Guru, John Omura, Abdullah A. Alghamdi, Richard Weisel, Stephen E. Fremes
Journal: Circulation (2006)

Many small, randomized, controlled trials have evaluated the effectiveness of blood as compared with crystalloid cardioplegia for myocardial protection during cardiac surgery. Blood cardioplegia provides a closer approximation to normal physiology, which may translate into measurable clinical benefits. This meta-analysis describes the effectiveness of blood cardioplegia in lowering adverse postoperative outcomes.MEDLINE, EMBASE, and the Cochrane registry of controlled trials were searched for clinical trials. The search was restricted to peer-reviewed English language publications of randomized controlled trials that primarily compared blood and crystalloid cardioplegia in adult patients. Each trial was blindly assessed and abstracted by 2 reviewers. The primary outcomes were: low output syndrome (LOS), myocardial infarction (MI), and death. Surrogate outcomes included postoperative creatinine kinase MB (CKMB) increase. Random effects summary odds ratio (OR) for binary outcomes, and weighted mean difference for continuous outcomes were calculated. A total of 34 trials were included. The majority of trials were conducted in patients undergoing elective CABG surgery (n=18). The incidence of LOS was decreased significantly with blood cardioplegia (OR, 0.54; 95% confidence interval [CI], 0.34 to 0.84; P=0.006; 879 patients, 10 trials). The incidence of MI and death were similar between treatment groups (MI: OR, 0.78; 95% CI, 0.54 to 1.13; 4316 patients, 23 trials) (death: OR, 0.80; 95% CI, 0.46 to 1.40; 4022 patients, 17 trials). CKMB release after surgery at 24 hours was reduced with blood cardioplegia (5.9 U/L; 95% CI, 1.6 to 10.2; P=0.007; 821 patients, 7 trials).Blood cardioplegia provides superior myocardial protection as compared with crystalloid cardioplegia, including lower rates of LOS, and early CKMB increase, whereas the incidence of myocardial infarction and death are similar.
Oxidation, Type 2 Diabetes, and Coronary Heart Disease: A Complex Interaction
Authors: Saverio Stranges, Joan M. Dorn, Richard P. Donahue, Richard W. Browne, Jo L. Freudenheim, Kathleen M. Hovey, Maurizio Trevisan
Journal: Diabetes Care (2008)

OBJECTIVE—The purpose of this study was to analyze the interrelationship among oxidation, myocardial infarction (MI), and type 2 diabetes in a population-based case-control study of MI. RESEARCH DESIGN AND METHODS—Participants were 1,709 individuals from western New York: 257 women and men with incident MI and 1,452 healthy control subjects (aged 35–70 years). Lipid peroxidation was measured by plasma levels of thiobarbituric acid reactive substances (TBARS). History of type 2 diabetes was determined by self-reported history of medical diagnosis. RESULTS—In multivariate analyses, there was no significant difference in TBARS levels between case and control subjects in both sexes. In subgroup analyses by diabetes status, diabetic subjects, regardless of MI status, exhibited significantly higher TBARS values than nondiabetic subjects. For diabetic women, TBARS values were 1.84 and 1.83 nmol/ml for case and control subjects, respectively. Values for nondiabetic women were 1.29 and 1.31 nmol/ml, respectively. In diabetic men, values were 1.65 and 1.97 nmol/ml for case and control subjects, respectively. Values for nondiabetic men were 1.36 and 1.36 nmol/ml, respectively. CONCLUSIONS—Whereas type 2 diabetes may be an important correlate of lipid peroxidation, clinical coronary heart disease may not.
The Effect of Disodium Cromoglycate on <i>In Vitro</i> Mast Cell Degranulation in Human Jejunal Mucosa
Authors: B. H. Selbekk
Journal: Allergy (1979)

The in vitro effect of disodium cromoglycate (DSCG) on IgE antigen‐induced mast cell degranulation is described. Serum from an egg white allergic patient was used to sensitize jejunal mucosa from nine individuals. Egg white was used to challenge the IgE sensitized mast cells. DSCG in concentrations 3 × 10 −7 M to 3 × 10 −4 M was added to the mucosal specimens before antigen challenge. Mast cell degranulation in the sensitized specimens challenged with egg white was 38%. Mast cell degranulation in sensitized specimens treated with DSCG before and during antigen challenge was reduced to 2% at a concentration of 3 × 10 −5 M of DSCG ( P = 0.006) and to 28% at a concentration of 3 × 10 −6 M ( p =0.027). No significant reduction of mast cell degranulation was seen at concentrations of 3 × 10 −7 M and 3 × 10 −4 M. The results support a role for DSCG in the treatment of gastrointestinal allergy.
Environmental Tobacco Smoke and Lung Cancer in Nonsmoking Women
Authors: Elizabeth T. H. Fontham
Journal: JAMA (1994)

To determine the relative risk (RR) of lung cancer in lifetime never smokers associated with environmental tobacco smoke (ETS) exposure.Multicenter population-based case-control study.Five metropolitan areas in the United States: Atlanta, Ga, Houston, Tex, Los Angeles, Calif, New Orleans, La, and the San Francisco Bay Area, Calif.Female lifetime never smokers: 653 cases with histologically confirmed lung cancer and 1253 controls selected by random digit dialing and random sampling from the Health Care Financing Administration files for women aged 65 years and older.The RR of lung cancer, estimated by adjusted odds ratio (OR) with 95% confidence interval (CI), associated with ETS exposure.Tobacco use by spouse(s) was associated with a 30% excess risk of lung cancer: all types of primary lung carcinoma (adjusted OR = 1.29; P < .05), pulmonary adenocarcinoma (adjusted OR = 1.28; P < .05), and other primary carcinomas of the lung (adjusted OR = 1.37; P = .18). An increasing RR of lung cancer was observed with increasing pack-years of spousal ETS exposure (trend P = .03), such that an 80% excess risk of lung cancer was observed for subjects with 80 or more pack-years of exposure from a spouse (adjusted OR = 1.79; 95% CI = 0.99 to 3.25). The excess risk of lung cancer among women ever exposed to ETS during adult life in the household was 24%; in the workplace, 39%; and in social settings, 50%. When these sources were considered jointly, an increasing risk of lung cancer with increasing duration of exposure was observed (trend P = .001). At the highest level of exposure, there was a 75% increased risk. No significant association was found between exposure during childhood to household ETS exposure from mother, father, or other household members; however, women who were exposed during childhood had higher RRs associated with adult-life ETS exposures than women with no childhood exposure. At the highest level of adult smoke-years of exposure, the ORs for women with and without childhood exposures were 3.25 (95% CI, 2.42 to 7.46) and 1.77 (95% CI, 0.98 to 3.19), respectively.Exposure to ETS during adult life increases risk of lung cancer in lifetime nonsmokers.
The macrophage is an important and previously unrecognized source of macrophage migration inhibitory factor.
Authors: T Calandra, J Bernhagen, R A Mitchell, R Bucala
Journal: The Journal of Experimental Medicine (1994)

For over 25 years, the cytokine known as macrophage migration inhibitory factor (MIF) has been considered to be a product of activated T lymphocytes. We recently identified the murine homolog of human MIF as a protein secreted by the pituitary in response to endotoxin administration. In the course of these studies, we also detected MIF in acute sera obtained from endotoxin-treated, T cell-deficient (nude), and hypophysectomized mice, suggesting that still more cell types produce MIF. Here, we report that cells of the monocyte/macrophage lineage are an important source of MIF in vitro and in vivo. We observed high levels of both preformed MIF protein and MIF mRNA in resting, nonstimulated cells. In the murine macrophage cell line RAW 264.7, MIF secretion was induced by as little as 10 pg/ml of lipopolysaccharide (LPS), peaked at 1 ng/ml, and was undetectable at LPS concentrations &amp;gt; 1 microgram/ml. A similar stimulation profile was observed in LPS-treated peritoneal macrophages; however, higher LPS concentrations were necessary to induce peak MIF production unless cells had been preincubated with interferon gamma (IFN-gamma). In RAW 264.7 macrophages, MIF secretion also was induced by tumor necrosis factor alpha (TNF-alpha) and IFN-gamma, but not by interleukins 1 beta or 6. Of note, MIF-stimulated macrophages were observed to secrete bioactive TNF-alpha. Although previously overlooked, the macrophage is both an important source and an important target of MIF in vivo. The activation of both central (pituitary) and peripheral (macrophage) sources of MIF production by inflammatory stimuli provides further evidence for the critical role of this cytokine in the systemic response to tissue invasion.
Is thrombopenia in cord blood indicative of intra‐uterine sensitization?
Authors: C. G. M. Magnusson, A. L. De Weck
Journal: Allergy (1989)

The relation between platelet counts (PCT) and IgE was studied in cord blood from 136 European newborns. PCT was significantly lower ( P = 0.0014) when cord‐IgE was superior to 1.20 IU/ml ( n = 29; 245,000/μl) than when it was inferior to this value ( n = 107; 284,080/μl) which resulted in a significant negative Spearman rank correlation between PCT and cord‐IgE ( P = 0.002; r s =−0.25). A follow‐up by questionnaire in 97 of the newborns revealed that those newborns who had developed definite atopy within 18 months of age had significantly ( P = 0.002) lower PCT at birth ( n = 8; 196,000/μl) than those free of atopic symptoms ( n = 61; 286,000/μl). Further newborns to atopic mothers ( n = 23; 245,000/μl) had significantly ( P = 0.014) lower PCT than newborns to non‐atopic mothers ( n = 74; 286,000/μl). The lowest PCT was recorded when both the mother was atopic and the newborn had developed definite or probable atopy by the age of 18 months ( n = 7; 175,000/μl) as compared to atopy alone in mothers ( n = 16; 276,000/μl; P = 0.005), to atopy alone in infants ( n = 9; 281,000/μ1; P = 0.005) and to non‐atopic infants of non‐atopic mothers ( n = 65; 286,000/μl; P = 0.0007). Significantly ( P = 0.03) lower PCT amongst boys ( n = 49; 259,000/μl) compared with girls ( n = 48; 294,000/μl) was attributed to the higher incidence of elevated cord‐IgE and infant atopy among boys. These findings were limited to PCT, since the erythrocyte count, hematocrit and hemoglobin concentration in cord blood did not significantly ( P &gt; 0.10) differ in any of these groups. Paternal atopy and atopy in siblings did not influence PCT, neither did maternal smoking or drug intake (progesterone and β‐mimetics) during pregnancy. These data as a whole are compatible with a direct or indirect role for platelets and their mediators in immediate hypersensitivity reactions. We speculate that a low PCT in cord blood of newborns reflects an on‐going intra‐uterine sensitization and therefore it might be a complementary parameter to family history and cord‐IgE in predicting newborns at high risk of developing atopy.
KBF1 (p50 NF-kappa B homodimer) acts as a repressor of H-2Kb gene expression in metastatic tumor cells.
Authors: D Plaksin, P A Baeuerle, L Eisenbach
Journal: The Journal of Experimental Medicine (1993)

Downregulation of major histocompatibility complex class I expression is causally related to high malignancy and low immunogenicity of certain murine tumors. In this study, we have analyzed the roles of the nuclear factors KBF1/p50 and p65 in regulation of class I expression in high and low metastatic tumor cells. Low class I-expressing cells show at higher levels of KBF1/p50 and NF-kappa B (p50/p65) binding activity than high class I-expressing cells. However, an excess of KBF1 over NF-kappa B is observed in low expressing cells, while an excess of NF-kappa B over KBF1 is observed in high expressing cells. Stable transfection of a p65 expression vector into low class I-expressing cells activated H-2 transcription and cell surface expression, while stable transfection of p50 expression vector into high expressing cells suppressed H-2Kb transcription and cell surface expression. Our studies suggest that KBF1 has the potential of downregulating class I gene expression, whereas dimers containing the p65 subunit are activators of class I gene expression.
The role of omalizumab or rhuMAb‐E25 in the treatment of allergic rhinitis
Authors: D.K.C. Lee
Journal: European Respiratory Journal (2004)

The role of omalizumab or rhuMAb-E25 in the treatment of allergic rhinitisTo the Editor:I read with interest the recent article by HANF et al.[1], demonstrating the significant inhibition of both allergen challenge-induced nasal symptoms and the increase of human serum albumin in nasal lavage fluid after allergen challenge, in addition to the significant reduction in tumour necrosis factor-a levels in basal nasal lavage fluid, following administration of omalizumab.However, it is difficult to gauge from the study, the exact degree of disease severity in the study population, as no data were given with regards to the patients9 usual therapy for allergic rhinitis, be it topical or oral, and hence no assessment of correlation between treatment and symptoms can be made.In addition, the characterisation of the study population was inadequate, as to whether patients suffered from seasonal or perennial allergic rhinitis, as no detailed data with regards to each individual9s aeroallergen sensitisation were presented.Moreover, one has to be wary of the potential confounding effects of conducting the study during the pollen season, especially in patients who were sensitised to birch and grass pollen.Although the study did shed some light on the potential for the use of omalizumab in allergic rhinitis, the exact indications for its use remain unclear.It is a pity that patients were not better categorised or characterised, as one could have perhaps argued a case for the role of omalizumab as a second-or third-line agent following failure with conventional therapy, such as corticosteroids, histamine H 1 -receptor antagonists and leukotriene CysLT 1 -receptor antagonists.Furthermore, the fact that the mode of delivery of omalizumab is through subcutaneous administration must not be ignored, as this will disadvantage it against other established first-line topical or oral therapy for allergic rhinitis.
Chimeric Antigen Receptor Therapy for Cancer
Authors: David M. Barrett, Nathan Singh, David L. Porter, Stephan A. Grupp, Carl H. June
Journal: Annual Review of Medicine (2013)

Improved outcomes for patients with cancer hinge on the development of new targeted therapies with acceptable short-term and long-term toxicity. Progress in basic, preclinical, and clinical arenas spanning cellular immunology, synthetic biology, and cell-processing technologies has paved the way for clinical applications of chimeric antigen receptor-based therapies. This new form of targeted immunotherapy merges the exquisite targeting specificity of monoclonal antibodies with the potent cytotoxicity and long-term persistence provided by cytotoxic T cells. Although this field is still in its infancy, clinical trials have already shown clinically significant antitumor activity in neuroblastoma, chronic lymphocytic leukemia, and B cell lymphoma, and trials targeting a variety of other adult and pediatric malignancies are under way. Ongoing work is focused on identifying optimal tumor targets and on elucidating and manipulating both cell- and host-associated factors to support expansion and persistence of the genetically engineered cells in vivo. The potential to target essentially any tumor-associated cell-surface antigen for which a monoclonal antibody can be made opens up an entirely new arena for targeted therapy of cancer.