tbuckley/cabot-search huggingface dataset:
Immune complexes, rheumatoid factors, and cellular immunological parameters in patients with giant cell arteritis.
Authors: B E Malmvall, B A Bengtsson, L A Nilsson, L M Bjursten
Journal: Annals of the Rheumatic Diseases (1981)

Circulating immune complexes were found in 2 of 15 patients with giant cell arteritis (GCA) by using a solid phase Clq enzyme linked immunoabsorbent assay (ELISA). The prevalence in controls was 5%. Rheumatoid factor could be demonstrated in 2 out of 27 patients and in 11% of the controls by using a similar ELISA technique. The prevalence of T cells in blood was similar in 25 patients with GCA and in controls. The blood lymphocyte blastogenic response to the mitogens, phytohaemagglutinin, concanavalin-A, and pokeweed mitogen did not differ in 25 untreated patients compared with controls. Stimulation of lymphocytes by arterial homogenates was tested in 8 patients. In no case could a significant simulation by obtained. We conclude that immune complexes and rheumatoid factors are present in the same low frequency in GCA patients as in the normal population, and that the studied parameters of cellular immunity appear to be normal.
Anti-HBV DNA vaccination does not prevent relapse after discontinuation of analogues in the treatment of chronic hepatitis B: a randomised trial—ANRS HB02 VAC-ADN
Authors: H Fontaine, S Kahi, C Chazallon, M Bourgine, A Varaut, C Buffet, O Godon, J F Meritet, Y Saïdi, M L Michel, D Scott-Algara, J P Aboulker, S Pol
Journal: Gut (2014)

<h3>Objective</h3> The antiviral efficacy of nucleos(t)ide analogues whose main limitation is relapse after discontinuation requires long-term therapy. To overcome the risk of relapse and virological breakthrough during long-term therapy, we performed a phase I/II, open, prospective, multicentre trial using a HBV envelope-expressing DNA vaccine. <h3>Design</h3> 70 patients treated effectively with nucleos(t)ide analogues for a median of 3 years (HBV DNA &lt;12 IU/mL for at least 12 months) were randomised into two groups: one received five intramuscular injections of vaccine (weeks 0, 8, 16, 40 and 44) and one did not receive the vaccine. Analogues were stopped after an additional 48 weeks of treatment in patients who maintained HBV DNA &lt;12 IU/mL with no clinical progression and monthly HBV DNA for 6 months. The primary endpoint was defined as viral reactivation at week 72 (HBV DNA &gt;120 IU/mL) or impossibility of stopping treatment at week 48. <h3>Results</h3> Reactivation occurred in 97% of each group after a median 28 days without liver failure but with an HBV DNA &lt;2000 IU/mL in 33%; 99% of adverse reactions were mild to moderate. Immune responses were evaluated by enzyme-linked immunosorbent spot and proliferation assays: there was no difference in the percentage of patients with interferon-γ secreting cells and a specific T-cell proliferation to HBcAg but not to HBsAg after reactivation in each group. <h3>Conclusions</h3> Although it is fairly well tolerated, the HBV DNA vaccine does not decrease the risk of relapse in HBV-treated patients or the rate of virological breakthrough, and does not restore the anti-HBV immune response despite effective viral suppression by analogues. <h3>Trial registration number</h3> NCT00536627.
Klotho Gene Deficiency Causes Salt-Sensitive Hypertension via Monocyte Chemotactic Protein-1/CC Chemokine Receptor 2–Mediated Inflammation
Authors: Xiaoli Zhou, Kai Chen, Han Lei, Zhongjie Sun
Journal: Journal of the American Society of Nephrology (2014)

Klotho (KL) is a newly discovered aging suppressor gene. In mice, the KL gene extends the lifespan when overexpressed and shortens the lifespan when disrupted. This study investigated if KL deficiency affects BP and salt sensitivity using KL mutant heterozygous (+/-) mice and wild-type (WT) mice (9 weeks of age, 16 mice per group). Notably, systolic BP in KL(+/-) mice began to increase at the age of 15 weeks, reached a peak level at the age of 17 weeks, and remained elevated thereafter, whereas systolic BP remained consistent in WT mice. High salt (HS) intake further increased BP in KL(+/-) mice but did not affect BP in WT mice. Blockade of CC chemokine receptor 2 (CCR2), involved in monocyte chemotaxis, by a specific CCR2 antagonist (INCB3284) abolished the HS-induced increase in BP in KL(+/-) mice. Furthermore, HS loading substantially increased the expression of monocyte chemotactic protein-1 and the infiltration of macrophages and T cells in kidneys in KL(+/-) mice, and treatment with INCB3284 abolished these effects. Treatment of KL(+/-) mice with INCB3284 also attenuated the increased renal expressions of serum glucocorticoid-regulated kinase 1, thiazide-sensitive NaCl cotransporter, and ATP synthase β along with the renal structural damage and functional impairment induced by HS loading. In conclusion, KL deficiency caused salt-sensitive hypertension and renal damage by CCR2-mediated inflammation.
Trefoil factor 1 is required for the commitment programme of mouse oxyntic epithelial progenitors
Authors: Sherif Mohamed Karam, Catherine Tomasetto, Marie-Christine Rio
Journal: Gut (2004)

Trefoil factor 1 (TFF1/pS2) is a major secretory product of the stomach and TFF1 knockout mice constantly develop adenomas and occasional carcinomas in the pyloric antrum.To analyse the role of TFF1 in the differentiation of gastric epithelial cell lineages using oxyntic mucosae from normal and TFF1 knockout mice.The various cell lineages were labelled using specific markers of pit, neck, parietal, and enteroendocrine cells. Patterns of TFF1, TFF2, and TFF3 expressions were defined using western blotting, immunohistochemistry, and/or immunogold electron microscopy.In normal mice, starting from postnatal day 1 (P1), TFF1 and TFF2 were produced by mucus secreting cells of the developing epithelium. At P7, TFF3 expression occurred in pit and parietal cells. When oxyntic glands were compartmentalised, at P21 and in older mice, TFF1 and TFF2 were expressed in pit and neck cells, respectively, and TFF3 was no longer in parietal cells but became a feature of zymogenic cells. In TFF1 deficient mice, alteration of oxyntic epithelial differentiation became obvious at P21, showing significant amplification of pit cells at the expense of parietal cells. At the molecular level, lack of TFF1 induced dramatic inhibition of TFF2 expression and more precocious TFF3 expression.In the oxyntic mucosa, all three TFFs are produced in a lineage specific manner and TFF1 is essential in maintaining the normal commitment programme of epithelial progenitors.
Adolescent Exposure to Cigarette Advertising in Magazines
Authors: Charles King III, Michael Siegel, Carolyn Celebucki, Gregory N. Connolly
Journal: JAMA (1998)

Context.-Understanding the relationship between cigarette advertising and youth smoking is essential to develop effective interventions.Magazine advertising accounts for nearly half of all cigarette advertising expenditures.Objective.-Toinvestigate whether cigarette brands popular among adolescent smokers are more likely than adult brands to advertise in magazines with high adolescent readerships.Design.-Cross-sectional analysis of 1994 data on (1) the presence of advertising by 12 cigarette brands in a sample of 39 popular US magazines; and (2) the youth (ages 12-17 years), young adult (ages 18-24 years), and total readership for each magazine.Main Outcome Measures.-Thepresence or absence of advertising in each of the 39 magazines in 1994 for each of the 12 cigarette brands.Results.-After controlling for total magazine readership, the percentage of young adult readers, advertising costs and expenditures, and magazine demographics, youth cigarette brands (those smoked by more than 2.5% of 10-to 15year-old smokers in 1993) were more likely than adult brands to advertise in magazines with a higher percentage of youth readers.Holding all other variables constant at their sample means, the estimated probability of an adult brand advertising in a magazine decreased over the observed range of youth readership from 0.73 (95% confidence interval [CI], 0.50-0.96)for magazines with 4% youth readers to 0.18 (95% CI, 0.00-0.47)for magazines with 34% youth readers.In contrast, the estimated probability of a youth brand advertising in a magazine increased from 0.32 (95% CI, 0.00-0.65)at 4% youth readership to 0.92 (95% CI, 0.67-1.00)at 34% youth readership.Conclusion.-Cigarette brands popular among young adolescents are more likely than adult brands to advertise in magazines with high youth readerships.
Transforming Acidic Coiled Coil 1 Promotes Transformation and Mammary Tumorigenesis
Authors: Megan Cully, Jessica Shiu, Roland P. Piekorz, William J. Muller, Susan J. Done, Tak W. Mak
Journal: Cancer Research (2005)

Abstract Transforming acidic coiled coil 1 (TACC1) is a putative oncogene located within a breast cancer amplicon found on human chromosome 8p11. Although TACC1 has been reported to transform fibroblasts, it is also down-regulated in a subset of mammary tumors treated with anthracyclin. Here, we show that ectopic TACC1 overexpression can cooperate with Ras to induce focus formation in murine fibroblast cultures and prevent death caused by overexpression of Pten or a dominant-negative form of protein kinase B (PKB)/Akt. In transgenic mice carrying TACC1 under the control of the mouse mammary tumor virus promoter, TACC1 expression reduced apoptosis during mammary gland involution, increased the penetrance of mammary tumors in a pten+/− background, and decreased the average age of mammary tumor onset in a mouse model based on a phosphatidylinositol 3′-kinase (PI3K)–decoupled mutant of polyoma middle T. Elevated levels of both phospho-PKB and phospho-extracellular signal-regulated kinase were found in mammary tissue containing the TACC1 transgene. Thus, TACC1 positively regulates the Ras and PI3K pathways, promotes Ras-mediated transformation, and prevents apoptosis induced by PI3K pathway inhibition. TACC1 also cooperates with tumorigenic mutations in the PI3K pathway and thereby plays an oncogenic role in tumor formation in the murine mammary gland.
Influence of mode of delivery on gut microbiota composition in seven year old children
Authors: S Salminen
Journal: Gut (2004)

Intestinal microbiota development begins immediately following birth.1 The composition of the infant’s evolving microbiota is initially defined by the mother, the source of the newborn’s first microbial inoculum. Colonising bacteria rapidly adapt to breast milk and epithelial mucins as sources of nutrients.

The prevalence of caesarean section delivery in Western countries is increasing. Caesarean born babies are deprived of contact with the maternal/vaginal microbiota and the first exposure is characterised by a lack of strict anaerobes and the presence of facultative anaerobes such as Clostridium species.2 Caesarean born infants have a more slowly diversifying microbiota, with differences reported from normally born infants, even after six months of age. Aberrancies in early microbiota acquisition can affect immunophysiological development with a heightened disease risk.2,3 This …
The Role of Oxygen Radicals as a Possible Mechanism of Tumor Promotion
Authors: W Troll, R Wiesner
Journal: The Annual Review of Pharmacology and Toxicology (1985)

Heme oxygenases (HO) catabolize free heme, that is, iron (Fe) protoporphyrin (IX), into equimolar amounts of Fe2+, carbon monoxide (CO), and biliverdin. The stress-responsive HO-1 isoenzyme affords protection against programmed cell death. The mechanism ...Read More
Pan-PIM Kinase Inhibition Provides a Novel Therapy for Treating Hematologic Cancers
Authors: Pablo D. Garcia, John L. Langowski, Yingyun Wang, Min Chen, Joseph Castillo, Christie Fanton, Marjorie Ison, Tatiana Zavorotinskaya, Yumin Dai, Jing Lu, Xiao-Hong Niu, Stephen Basham, Julie Chan, Jianjun Yu, Michael Doyle, Paul Feucht, Robert Warne, Jamie Narberes, Tiffany Tsang, Christine Fritsch, Audrey Kauffmann, Estelle Pfister, Peter Drueckes, Joerg Trappe, Christopher Wilson, Wooseok Han, Jiong Lan, Gisele Nishiguchi, Mika Lindvall, Cornelia Bellamacina, J. Alex Aycinena, Richard Zang, Jocelyn Holash, Matthew T. Burger
Journal: Clinical Cancer Research (2014)

Abstract Purpose: PIM kinases have been shown to act as oncogenes in mice, with each family member being able to drive progression of hematologic cancers. Consistent with this, we found that PIMs are highly expressed in human hematologic cancers and show that each isoform has a distinct expression pattern among disease subtypes. This suggests that inhibitors of all three PIMs would be effective in treating multiple hematologic malignancies. Experimental Design: Pan-PIM inhibitors have proven difficult to develop because PIM2 has a low Km for ATP and, thus, requires a very potent inhibitor to effectively block the kinase activity at the ATP levels in cells. We developed a potent and specific pan-PIM inhibitor, LGB321, which is active on PIM2 in the cellular context. Results: LGB321 is active on PIM2-dependent multiple myeloma cell lines, where it inhibits proliferation, mTOR-C1 signaling and phosphorylation of BAD. Broad cancer cell line profiling of LGB321 demonstrates limited activity in cell lines derived from solid tumors. In contrast, significant activity in cell lines derived from diverse hematological lineages was observed, including acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), multiple myeloma and non-Hodgkin lymphoma (NHL). Furthermore, we demonstrate LGB321 activity in the KG-1 AML xenograft model, in which modulation of pharmacodynamics markers is predictive of efficacy. Finally, we demonstrate that LGB321 synergizes with cytarabine in this model. Conclusions: We have developed a potent and selective pan-PIM inhibitor with single-agent antiproliferative activity and show that it synergizes with cytarabine in an AML xenograft model. Our results strongly support the development of Pan-PIM inhibitors to treat hematologic malignancies. Clin Cancer Res; 20(7); 1834–45. ©2014 AACR.
Pilot Study of Rapid Infusion of 2 L of 4°C Normal Saline for Induction of Mild Hypothermia in Hospitalized, Comatose Survivors of Out-of-Hospital Cardiac Arrest
Authors: Francis Kim, Michele Olsufka, David Carlbom, Steven Deem, W.T. Longstreth, Margret Hanrahan, Charles Maynard, Michael K. Copass, Leonard A. Cobb
Journal: Circulation (2005)

Recent clinical studies have demonstrated that mild hypothermia (32 degrees C to 34 degrees C) induced by surface cooling improves neurological outcome after resuscitation from out-of-hospital cardiac arrest. Results from animal models suggest that the effectiveness of mild hypothermia could be improved if initiated as soon as possible after return of spontaneous circulation. Infusion of cold, intravenous fluid has been proposed as a safe, effective, and inexpensive technique to induce mild hypothermia after cardiac arrest.In 17 hospitalized survivors of out-of-hospital cardiac arrest, we determined the effect on temperature and hemodynamics of infusing 2 L of 4 degrees C cold, normal saline during 20 to 30 minutes into a peripheral vein with a high-pressure bag. Data on vital signs, electrolytes, arterial blood gases, and coagulation were collected before and after fluid infusion. Cardiac function was assessed by transthoracic echocardiography before fluid administration and 1 hour after infusion. Passive (fans, leaving patient uncovered) or active (cooling blankets, neuromuscular blockade) cooling measures were used to maintain mild hypothermia for 24 hours. Infusion of 2 L of 4 degrees C cold, normal saline resulted in a mean temperature drop of 1.4 degrees C 30 minutes after the initiation of infusion. Rapid infusion of fluid was not associated with clinically important changes in vital signs, electrolytes, arterial blood gases, or coagulation parameters. The initial mean ejection fraction was 34%, and fluid infusion did not affect ejection fraction or increase central venous pressure, pulmonary pressures, or left atrial filling pressures as assessed by echocardiography. Passive measures were ineffective in maintaining hypothermia compared with active measures.Infusion of 2 L of 4 degrees C cold, normal saline is safe and effective in rapidly lowering body temperature in survivors of out-of-hospital cardiac arrest.
Notes of a Case of Inflammatory Bright's Disease: Fatal in Third Stage
Authors: T. G. Stewart
Journal: BMJ (1872)

favces.On examination, we found tllat the perinzeum hacl been com pletely ruptured, the rent extending througlh the external splhincter ani into the rectum.Owing to the urgent nature of the case, we had not noticed the rupture at the time when it occurred, and I can only account for it by supposing that, from the violence of the convulsive attack just at the momenit of delivery, one of the limbs of the child must lhave been forced through the perinxum.The patient was afterwards oper- ated upon very successfully by my colleague Mr. Coe.
Up-regulation of sarcoplasmic reticulum Ca2+ uptake leads to cardiac hypertrophy, contractile dysfunction and early mortality in mice deficient in CASQ2
Authors: Anuradha Kalyanasundaram, Véronique A. Lacombe, Andriy E. Belevych, Lucia Brunello, Cynthia A. Carnes, Paul M.L. Janssen, Bjørn C. Knollmann, Muthu Periasamy, Sandor Gyørke
Journal: Cardiovascular Research (2012)

Although aberrant Ca2+ release (i.e. Ca2+ 'leak') from the sarcoplasmic reticulum (SR) through cardiac ryanodine receptors (RyR2) is linked to heart failure (HF), it remains unknown whether and under what conditions SR-derived Ca2+ can actually cause HF. We tested the hypothesis that combining dysregulated RyR2 function with facilitated Ca2+ uptake into SR will exacerbate abnormal SR Ca2+ release and induce HF. We also examined the mechanisms for these alterations. We crossbred mice deficient in expression of cardiac calsequestrin (CASQ2) with mice overexpressing the skeletal muscle isoform of SR Ca2+ATPase (SERCA1a). The new double-mutant strains displayed early mortality, congestive HF with left ventricular dilated hypertrophy, and decreased ejection fraction. Intact right ventricular muscle preparations from double-mutant mice preserved normal systolic contractile force but were susceptible to spontaneous contractions. Double-mutant cardiomyocytes while preserving normal amplitude of systolic Ca2+ transients displayed marked disturbances in diastolic Ca2+ handling in the form of multiple, periodic Ca2+ waves and wavelets. Dysregulated myocyte Ca2+ handling and structural and functional cardiac pathology in double-mutant mice were associated with increased rate of apoptotic cell death. Qualitatively similar results were obtained in a hybrid strain created by crossing CASQ2 knockout mice with mice deficient in phospholamban. We demonstrate that enhanced SR Ca2+ uptake combined with dysregulated RyR2s results in sustained diastolic Ca2+ release causing apoptosis, dilated cardiomyopathy, and early mortality. Our data also suggest that up-regulation of SERCA activity must be advocated with caution as a therapy for HF in the context of abnormal RyR2 function.
Mr. Lucas on the Pathology of Rabies
Authors: P. B. Lucas
Journal: BMJ (1840)

in up.per.part of the left side; expectoration presents a deep uty tinge; muco-crepitating rile very dstinct be- ui.ath the left clavicle.Apply eight leeches.17.Feels better; leeches have made the cough easier; bas bad taste in the mouth; expectoration, frothy mucus; very little muco-crepitating rAle remaining; still slight 4dluess.A blister to the part.Gum emulsiin, six ounces; ipecacuanha wine, two drachms; syrup of poppies, two drachms; desert spoonful, according to circumstances.Give the powder twice a day.19.Is much improved; cough easy; little expectom- tion; mouth very sore; slight dulness still present.Onmit the powders; continue the other remedies.Another blster; to have beef tea and rice.25.The amendment has been progressing; he only corplains of debility, and a tenderness of the gums.I ordered him to wear flannel next his person, and to sponge the chest with following every morning, first taking the chill off it:-common vinegar, water, of each four ounces; spirit, two ounces.Nov. 3.I have to-day examined the patient Edwards, and be is in the enjoyment of excellent health; he has changed from the confined life of a tailor to a rural one.It may be well to add that phthisis prevails in the family.CAss II.-On the 20th of September I was called to visit Mrs. H., et.35, married, of a strumous habit and
Computed tomographic pulmonary angiography and prognostic significance in patients with acute pulmonary embolism
Authors: A Ghuysen
Journal: Thorax (2005)

<b>Background:</b> Patients with acute pulmonary embolism (APE) present with a broad spectrum of prognoses. Computed tomographic pulmonary angiography (CTPA) has progressively been established as a first line test in the APE diagnostic algorithm, but estimation of short term prognosis by this method remains to be explored. <b>Methods:</b> Eighty two patients admitted with APE were divided into three groups according to their clinical presentation: pulmonary infarction (n = 21), prominent dyspnoea (n = 29), and circulatory failure (n = 32). CTPA studies included assessment of both pulmonary obstruction index and right heart overload. Haemodynamic evaluation was based on systolic aortic blood pressure, heart rate, and systolic pulmonary arterial pressure obtained non-invasively by echocardiography at the time of diagnosis of pulmonary embolism. <b>Results:</b> The mortality rate was 0%, 13.8% and 25% in the three groups, respectively. Neither the pulmonary obstruction index nor the pulmonary artery pressure could predict patient outcome. In contrast, a significant correlation with mortality was found using the systolic blood pressure (p&lt;0.001) and heart rate (p&lt;0.05), as well as from imaging parameters including right to left ventricle minor axis ratio (p&lt;0.005), proximal superior vena cava diameter (p&lt;0.001), azygos vein diameter (p&lt;0.001), and presence of contrast regurgitation into the inferior vena cava (p = 0.001). Analysis from logistic regression aimed at testing for mortality prediction revealed true reclassification of 89% using radiological variables. <b>Conclusion:</b> These results suggest that CTPA quantification of right ventricular strain is an accurate predictor of in-hospital death related to pulmonary embolism.