tbuckley/cabot-search huggingface dataset:
HEPATIC VITAMIN A IN THE RAT AS AFFECTED BY THE ADMINISTRATION OF DIBENZANTHRACENE
Authors: Jules C. Abels, Alice T. Gorham, Shirley L. Eberlin, Robert Halter, C. P. Rhoads
Journal: The Journal of Experimental Medicine (1942)

1. The decreased concentrations of vitamin A in the livers of rats given dibenzanthracene probably are due to a particular effect of the carcinogen on the ability of the liver to store the vitamin and not to the production of general hepatic dysfunction. 2. The administration of dibenzanthracene to normal rats does not (a) increase significantly their hepatic content of total fat nor decrease that of phospholipid; (b) impair the ability of their livers to fabricate serum albumin; (c) impair the capacity of their livers to esterify cholesterol or phenol; (d) interfere with the hepatic synthesis and conjugation of glucuronic acid; or (e) interfere with the hepatic storage of riboflavin. 3. The simultaneous ingestion of yeast by the dibenzanthracene-treated rats further depletes their hepatic stores of vitamin A. This depletion conceivably is due to the fact that yeast alone also might deplete the liver of its vitamin A and thus a summation of two similar effects is attained. 4. The results suggest a competition between vitamin A and dibenzanthracene for some substance, possibly a protein, to which vitamin A may be bound in the liver.
RNA-transfected dendritic cells in cancer immunotherapy
Authors: Duane A. Mitchell, Smita K. Nair
Journal: Journal of Clinical Investigation (2000)

The field of cancer immunotherapy has been recently invigorated by the discovery that vaccination with dendritic cells (DCs) pulsed with tumor antigens is a potent strategy to elicit protective immunity in tumor-bearing animals. The recognition that the cellular arm of the immune response is best equipped to recognize tumor cells as foreign and to lead to their eradication has shifted the emphasis in vaccine development. Vaccines that induce cellular responses, especially by the CD8+ cytotoxic T lymphocyte (CTL) arm of the immune system, are now favored over those that activate humoral immunity. At the same time, DCs have emerged as the most potent antigen-presenting cells (APCs) for eliciting antitumor CTLs. DCs can be generated from cancer patients by culturing adherent PBMCs from the patients for 5–7 days in the presence of cytokines (1).

The major research effort in many labs involves the choice of tumor antigen with which to load these DCs. The issues being addressed are, first, the composition of the antigen, whether a defined tumor antigen or an unfractionated mixture of tumor-derived antigens; and second, the form in which the antigen should be presented, whether as a polypeptide or a nucleic acid. Here, we focus on the use of RNA-transfected DCs in cancer immunotherapy, reviewing current data on the transfection of DCs with RNAs encoding either defined or unfractionated tumor antigens. We also consider the advantages and disadvantages of employing RNA transfection in loading DCs with tumor antigens and the merits of RNA transfection in situations where a low level of transiently expressed protein is sufficient to allow antigen presentation.
Insulin-Like Growth Factor-1 and PTEN Deletion Enhance Cardiac L-Type Ca <sup>2+</sup> Currents via Increased PI3Kα/PKB Signaling
Authors: Hui Sun, Benoit-Gilles Kerfant, Dongling Zhao, Maria G. Trivieri, Gavin Y. Oudit, Josef M. Penninger, Peter H. Backx
Journal: Circulation Research (2006)

Ca 2+ influx through the L-type Ca 2+ channel ( I Ca,L ) is a key determinant of cardiac contractility and is modulated by multiple signaling pathways. Because the regulation of I Ca,L by phosphoinositide-3-kinases (PI3Ks) and phosphoinositide-3-phosphatase (PTEN) is unknown, despite their involvement in the regulation of myocardial growth and contractility, I Ca,L was recorded in myocytes isolated from mice overexpressing a dominant-negative p110α mutant ( DN-p110α ) in the heart, lacking the PI3Kγ gene ( PI3Kγ −/− ) or with muscle-specific ablation of PTEN ( PTEN −/− ). Combinations of these genetically altered mice were also examined. Although there were no differences in the expression level of Ca V 1.2 proteins, basal I Ca,L densities were larger ( P &lt;0.01) in PTEN −/− myocytes compared with littermate controls, PI3Kγ −/− , or DN-p110α myocytes and showed negative shifts in voltage dependence of current activation. The I Ca,L differences seen in PTEN −/− mice were eliminated by pharmacological inhibition of either PI3Ks or protein kinase B (PKB) as well as in PTEN −/− / DN-p110α double mutant mice but not in PTEN −/− / PI3Kγ −/− mice. On the other hand, application of insulin-like growth factor-1 (IGF-1), an activator of PKB, increased I Ca,L in control and PI3Kγ −/− , while having no effects on I Ca,L in DN-p110α or PTEN −/− mice. The I Ca,L increases induced by IGF-1 were abolished by PKB inhibition. Our results demonstrate that IGF-1 treatment or inactivation of PTEN enhances I Ca,L via PI3Kα-dependent increase in PKB activation.
New frontier in liver cancer treatment: Oncolytic viral therapy
Authors: Sílvia Vilarinho, Tamar H. Taddei
Journal: Hepatology (2013)

Oncolytic viruses and active immunotherapeutics have complementary mechanisms of action (MOA) that are both self amplifying in tumors, yet the impact of dose on subject outcome is unclear. JX-594 (Pexa-Vec) is an oncolytic and immunotherapeutic vaccinia virus. To determine the optimal JX-594 dose in subjects with advanced hepatocellular carcinoma (HCC), we conducted a randomized phase 2 dose-finding trial (n = 30). Radiologists infused low- or high-dose JX-594 into liver tumors (days 1, 15 and 29); infusions resulted in acute detectable intravascular JX-594 genomes. Objective intrahepatic Modified Response Evaluation Criteria in Solid Tumors (mRECIST) (15%) and Choi (62%) response rates and intrahepatic disease control (50%) were equivalent in injected and distant noninjected tumors at both doses. JX-594 replication and granulocyte-macrophage colony-stimulating factor (GM-CSF) expression preceded the induction of anticancer immunity. In contrast to tumor response rate and immune endpoints, subject survival duration was significantly related to dose (median survival of 14.1 months compared to 6.7 months on the high and low dose, respectively; hazard ratio 0.39; P = 0.020). JX-594 demonstrated oncolytic and immunotherapy MOA, tumor responses and dose-related survival in individuals with HCC.
Toxic epidermal necrolysis caused by skin hypersensitivity to monosulfiram.
Authors: P. W. Copeman
Journal: BMJ (1968)

Neuman and Neuman (1957) have implied a process of ion exchange whereby calcium ions can enter the extracellular fluid only if the bone crystal takes up other cations-for example, Mg+ +-to maintain electroneutrality.In the presence of magnesium deficiency this exchange process may be inhibited.Correction of the deficiency would allow mobilization of calcium
Natural History and Prognosis of Atrial Septal Defect
Authors: ROBERT J. CRAIG, ARTHUR SELZER
Journal: Circulation (1968)

A series of 128 consecutive cases of atrial septal defect in adult patients was analyzed from the standpoint of the course and prognosis. The ages of the patients ranged from 18 to 67 years and the ratio of men to women was 1 to 2. Age distribution when compared with life expectancy tables indicated reduced life expectancy. Clinical analysis revealed that three quarters of the patients were symptomatic, but symptoms were mild to moderate and usually nonprogressive. Hemodynamic analysis revealed significant pulmonary hypertension in 22% of the series, of which 15% had high pulmonary vascular resistance, and significant arterial hypoxemia in 14%. The most serious risk factor in atrial septal defect is severe pulmonary hypertension. This complication, which develops in about 14% of patients with atrial septal defect when they are between 20 and 40 years of age, may be rapidly progressive, leading to shunt reversal, disability, and death. Once established, pulmonary hypertension may progress even when the defect is surgically closed. Heart failure occurs usually in older individuals and is associated mostly with chronic atrial arrhythmias rather than pulmonary hypertension.
Time-based gene expression programme following diaphragm injury in a rat model
Authors: S. N. Mehiri
Journal: European Respiratory Journal (2005)

It was hypothesised that diaphragm injury activates a time-based programme of gene expression in muscle repair. Gene expression of different substances, such as proteases (calpain 94 (p94)), transcription factors (myogenin and cFos), growth factors (both basic fibroblast growth factor (bFGF) and insulin-like growth factor (IGF)-II), and structural proteins (myosin heavy chain (MHC) and titin), was quantified by RT-PCR in rat diaphragms exposed to caffeine-induced injury. Injured and noninjured (control) rat hemidiaphragms were excised at different time points (1–240 h). In injured hemidiaphragms, in comparison with control muscles, p94 expression levels peaked at 1 h post-injury (PI), cFos mRNA levels began to rise, after an initial dip, and peaked at 96 h PI, while myogenin mRNA levels started to increase as early as 12 h PI, IGF-II mRNA levels initially decreased until 48 h PI and increased thereafter, peaking at 72 h PI, bFGF mRNA levels rose to a maximum at 96 h PI, and MHC and titin mRNA levels were significantly elevated at 72 h PI. Caffeine-induced diaphragm injury is followed by a time-based expression programme of different genes tailored to meet muscle repair needs.
Aplasia cutis congenita after exposure to methimazole: a causal relationship?
Authors: T. VOGT, W. STOLZ, M. LANDTHALER
Journal: British Journal of Dermatology (1995)

We report a child with scalp aplasia cutis congenita, whose mother was treated with methimazole during pregnancy. The relationship between antithyroid drug administration during pregnancy and the occurrence of scalp defects is discussed, and the pertinent literature is reviewed.
Circulating Androgen Levels and Self-reported Sexual Function in Women
Authors: Susan R. Davis
Journal: JAMA (2005)

ContextIt has been proposed that low sexual desire and sexual dysfunction are associated with low blood testosterone levels in women. However, evidence to support this is lacking.ObjectiveTo determine whether women with low self-reported sexual desire and sexual satisfaction are more likely to have low serum androgen levels than women without self-reported low sexual desire and sexual satisfaction.Design, Setting, and ParticipantsA community-based, cross-sectional study of 1423 women aged 18 to 75 years, who were randomly recruited via the electoral roll in Victoria, Australia, from April 2002 to August 2003. Women were excluded from the analysis if they took psychiatric medication, had abnormal thyroid function, documented polycystic ovarian syndrome, or were younger than 45 years and using oral contraception.Main Outcome MeasuresDomain scores of the Profile of Female Sexual Function (PFSF) and serum levels of total and free testosterone, androstenedione, and dehydroepiandrosterone sulfate.ResultsA total of 1021 individuals were included in the final analysis. No clinically significant relationships between having a low score for any PFSF domain and having a low serum total or free testosterone or androstenedione level was demonstrated. A low domain score for sexual responsiveness for women aged 45 years or older was associated with higher odds of having a serum dehydroepiandrosterone sulfate level below the 10th percentile for this age group (odds ratio [OR], 3.90; 95% confidence interval [CI], 1.54-9.81; P = .004). For women aged 18 to 44 years, having a low domain score for sexual desire (OR, 3.86; 95% CI, 1.27-11.67; P = .02), sexual arousal (OR, 6.39; 95% CI, 2.30-17.73; P&lt;.001), and sexual responsiveness (OR, 6.59; 95% CI, 2.37-18.34; P&lt;.001) was associated with having a dehydroepiandrosterone sulfate level below the 10th percentile.ConclusionsNo single androgen level is predictive of low female sexual function, and the majority of women with low dehydroepiandrosterone sulfate levels did not have low sexual function.
Estrogen Replacement Therapy and Endometrial Hyperplasia
Authors: M. T. R. Subbiah
Journal: JAMA (1996)

<h3>To the Editor.</h3> —The Writing Group for the Postmenopausal Estrogen/Progestin Intervention (PEPI) trial<sup>1</sup>recently reported on the development of endometrial hyperplasia as influenced by conjugated equine estrogens (CEE). Although estrogen replacement therapy is widely advocated as a means to combat symptoms of menopause and reduce the risk of osteoporosis and heart disease, increase in endometrial cancer continues to be a major concern. In many of the human studies, including the above-mentioned PEPI trial, CEE is the predominant form of estrogen used. One of the most ignored (but vital) facts that was left out of the discussion is that CEE represents a mixture of conjugated estrogens isolated from the urine of pregnant mares, which contains at least 7 major components.<sup>2,3</sup>Among these, estrone sulfate is the predominant estrogen (about 45%) with a significant amount of ring B unsaturated equine estrogens (predominantly 17α-dihydroequilin, equilin, equilenin amounting to nearly 51%), and
Statistical significance: A statistician's view
Authors: Helena Chmura Kraemer
Journal: Behavioral and Brain Sciences (1998)

From a statistician's viewpoint, the concepts discussed by Chow relating to “statistical” significance bear little resemblance to the concept developed in statistics. Whether or not “statistical significance” has a place in psychological research is a decision for psychologists, not statisticians, to make, but the decision should be based on a less flawed version of what is being considered.
Lack of usefulness of blood cultures to diagnose ventilator-associated pneumonia
Authors: J Rello, B Mirelis, C Alonso, G Prats
Journal: European Respiratory Journal (1991)

Since ventilator-associated pneumonia is a common complication in ventilated patients and is associated with very high mortality [1, 2], the precise identification of causative organisms and the accurate selection of antimicrobial treatment represent important clinical goals [3].However, the usefulness of blood cultures in ventilator-associated pneumonia is not yet well known.During a period of thirty months, we prospectively studied 129 episodes of ventilator-associated pneumonia in our intensive care unit.Ventilator-associated pneumonia was diagnosed when a patient developed new infiltrates on the chest radiograph, excluding those of noninfectious origin, after 48 h on mechanical ventilation, plus two of the following items: fever >38"C, leucocytosis >10 x 10 9 •[•1, purulent secretions from endotracheal tubes.Identification of the causative agent was possible in 92 (71%) episodes by means of highly specific techniques (telescoping plugged catheters (TPC), blood cultures, and/or necropsy).In only 10 (8%) of
Chemokine receptor CXCR4 and early-stage non-small cell lung cancer: pattern of expression and correlation with outcome
Authors: J.-P. Spano, F. Andre, L. Morat, L. Sabatier, B. Besse, C. Combadiere, P. Deterre, A. Martin, J. Azorin, D. Valeyre, D. Khayat, T. Le Chevalier, J.-C. Soria
Journal: Annals of Oncology (2004)
Putative mechanism of hypotensive action of platelet-activating factor in dogs.
Authors: S Yamanaka, K Miura, T Yukimura, M Okumura, K Yamamoto
Journal: Circulation Research (1992)

We examined the mechanism(s) of hypotensive action of platelet-activating factor (PAF) in anesthetized dogs. PAF (0.5 micrograms/kg i.v.) caused a biphasic hypotension; the first phase was transient and was accompanied by a decrease in systemic vascular resistance and an increase in cardiac output. Aspirin-DL-lysine, a cyclooxygenase inhibitor, had no effect on this phase. The second phase was characterized by a sustained hypotension caused by a reduction in cardiac output and was accompanied by an increase in systemic and pulmonary vascular resistance. The plasma concentrations of 6-ketoprostaglandin F1 alpha and thromboxane B2 also increased. These changes were markedly attenuated by aspirin. Both atrial pressures decreased during the second phase, thereby indicating that the PAF-induced reduction in cardiac output was related to a hindrance in venous return. The hematocrit increased, and aspirin did not affect this change. The extravasation of plasma probably plays a minor role, whereas venodilation would be the primary mechanism of the second-phase hypotension. S-1452, a prostaglandin H2/thromboxane A2 antagonist, abolished the PAF-induced pulmonary vasoconstriction but did not block the hypotensive action of PAF. OKY-046, a thromboxane A2 synthetase inhibitor, almost completely abolished the PAF-induced pulmonary vasoconstriction and the increase in plasma thromboxane B2 level, whereas it potentiated the hypotension and the increase in the plasma concentrations of prostaglandins; aspirin abolished this potentiation. These results suggest that PAF causes hypotension by two different mechanisms: 1) dilatation of resistance vessels independent of prostaglandins and 2) reduction of venous return due to venodilation, as mediated by prostaglandin(s).
Establishing the Role of Angiotensin-Converting Enzyme in Renal Function and Blood Pressure Control through the Analysis of Genetically Modified Mice
Authors: Kenneth E Bernstein, Hong D Xiao, Jon W Adams, Kristen Frenzel, Ping Li, Xiao Z Shen, Justin M Cole, Sebastien Fuchs
Journal: Journal of the American Society of Nephrology (2005)

Angiotensin II is a vasoconstrictor and a hypertensive peptide that binds to the AT1 receptor and, through both direct and indirect mechanisms, induces salt reabsorption. Also, angiotensin II is thought to be a profibrotic and proproliferative peptide; abundant evidence now suggests that angiotensin
Stevens-Johnson syndrome limited to multiple sites of radiation therapy in a patient receiving phenobarbital
Authors: Karynne O. Duncan, Robert E. Tigelaar, Jean L. Bolognia
Journal: Journal of the American Academy of Dermatology (1999)

Stevens-Johnson syndrome (SJS) is a severe cutaneous eruption that most often appears as an adverse reaction to a medication. There have been 21 reported cases of atypical erythema multiforme, toxic epidermal necrolysis, and SJS arising in patients receiving radiation therapy in addition to phenytoin, phenobarbital, or carbamazepine. We report the second case of SJS resulting from concomitant phenobarbital and radiation therapy, in which the eruption was limited to the sites of radiation, which were multiple.
Vitamin C Improves Endothelium-Dependent Vasodilation by Restoring Nitric Oxide Activity in Essential Hypertension
Authors: Stefano Taddei, Agostino Virdis, Lorenzo Ghiadoni, Armando Magagna, Antonio Salvetti
Journal: Circulation (1998)

Background —Essential hypertension is associated with impaired endothelium-dependent vasodilation. Inactivation of endothelium-derived nitric oxide by oxygen free radicals participates in endothelial dysfunction in experimental hypertension. To test this hypothesis in humans, we evaluated the effect of antioxidant vitamin C on endothelium-dependent responses in essential hypertensive patients. Methods and Results —In 14 healthy subjects (47.1±4.8 years; blood pressure, 120.6±4.5/80.9±3.5 mm Hg) and 14 essential hypertensive patients (47.3±5.1 years; blood pressure, 153.9±7.1/102.3±4.1 mm Hg), we studied forearm blood flow (strain-gauge plethysmography) modifications induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 μg · 100 mL −1 · min −1 ) or sodium nitroprusside (1, 2, and 4 μg/100 mL forearm tissue per minute), an endothelium-dependent and -independent vasodilator, respectively, in basal conditions and during infusion of intrabrachial vitamin C (2.4 mg/100 mL forearm tissue per minute). In hypertensive patients but not in control subjects, vitamin C increased ( P &lt;0.01) the impaired vasodilation to acetylcholine, whereas the response to sodium nitroprusside was unaffected. Moreover, in another 14 hypertensive patients (47.1±5.2 years; blood pressure, 155.2±6.9/103.7±4.5 mm Hg), the facilitating effect of vitamin C on vasodilation to acetylcholine was reversed by N G -monomethyl- l -arginine (100 μg/100 mL forearm tissue per minute), a nitric oxide synthase inhibitor, suggesting that in essential hypertension superoxide anions impair endothelium-dependent vasodilation by nitric oxide breakdown. Finally, because in adjunctive 7 hypertensive patients (47.8±6.1 years; blood pressure, 155.3±6.8/103.5±4.3 mm Hg), indomethacin (50 μg/100 mL forearm tissue per minute), a cyclooxygenase inhibitor, prevented the potentiating effect of vitamin C on vasodilation to acetylcholine, it is possible that in essential hypertension a main source of superoxide anions could be the cyclooxygenase pathway. Conclusions —In essential hypertensive patients, impaired endothelial vasodilation can be improved by the antioxidant vitamin C, an effect that can be reversed by the nitric oxide synthase inhibitor N G -monomethyl- l -arginine. These findings support the hypothesis that nitric oxide inactivation by oxygen free radicals contributes to endothelial dysfunction in essential hypertension.
Optimized conjugation ratios lead to allergen immunostimulatory oligodeoxynucleotide conjugates with retained immunogenicity and minimal anaphylactogenicity
Authors: Anthony A Horner, Kenji Takabayashi, Lucinda Beck, Bhavya Sharma, Jose Zubeldia, Stephen Baird, Stephan Tuck, Lev Libet, Hans L Spiegelberg, Fu-Tong Liu, Eyal Raz
Journal: Journal of Allergy and Clinical Immunology (2002)
Prepping Omics for the Clinic
Authors: R. S. Tuma
Journal: JNCI Journal of the National Cancer Institute (2012)

Evolution of Translational ' Omics: Lessons Learned and the Path Forward , released on March 23, focuses on how scientists can accurately develop omics-based tests for clinical use."We describe best practices for the discovery and confi rmation of a potential new test in a research lab, validation for the test in a clinical lab, and use of the test in clinical trialsand eventually in clinical practiceto assess its utility in guiding selection of patient therapies," said Gilbert Omenn, M.D., Ph.D., professor of internal medicine, human genetics, and public health, and director of the
Leptin—Much More Than a Satiety Signal
Authors: Ruth B. S. Harris
Journal: Annual Review of Nutrition (2000)

Much attention has focused on the effects of leptin as a central satiety agent. There is now a significant amount of evidence that leptin is active in the periphery. This review focuses on the ability of leptin to modify insulin sensitivity, tissue metabolism, stress responses, and reproductive function. Leptin's effect on several of these systems is mediated via the hypothalamic-pituitary axis. Therefore, although in vitro studies provide evidence for direct effects on specific tissues and metabolic pathways, it is essential to consider the interactions between leptin and other regulatory factors in vivo. Little is known about the regulation of peripheral receptor expression or the production of binding proteins. Both of these factors determine the bioactivity of circulating leptin and have the potential to induce a peripheral resistance to leptin, similar to the central "leptin resistance" observed in obese subjects. Future research will clarify which of the endocrine and metabolic actions of peripheral leptin are of physiological relevance and which should be considered a pharmacological manipulation.