tbuckley/cabot-search huggingface dataset:
Inhibition of Renin Release in the Dog by Vasopressin and Vasotocin
Authors: ARTHUR J. VANDER
Journal: Circulation Research (1968)

In anesthetized dogs the intravenous infusion of arginine vasotocin, 25 mU/min, or vasopressin, 10 mU/min, inhibited renin secretion when control secretion rates were normal or when they were elevated by complete ureteral occlusion. Vasotocin, 5 mU/min, or vasopressin, 1 mU/min, was ineffective. Direct intraarterial infusion of vasotocin, 5 mU/min, into the right kidney inhibited renin secretion by the right kidney only. Glomerular filtration rate and renal plasma flow were not changed, and mean arterial pressure was either not changed or was decreased. Vasotocin caused no change in urine flow but did produce a significant natriuresis secondary to decreased tubular reabsorption. The physiological implications of these polypeptide-renal relationships are discussed.
Effect of Low-Fat Diet on Development of Prostate Cancer and Akt Phosphorylation in the Hi-Myc Transgenic Mouse Model
Authors: Naoko Kobayashi, R. James Barnard, Jonathan Said, Jenny Hong-Gonzalez, Dan M. Corman, Melvin Ku, Ngan Bao Doan, Dorina Gui, David Elashoff, Pinchas Cohen, William J. Aronson
Journal: Cancer Research (2008)

This study evaluated the effect of dietary fat on prostate cancer development by using the Hi-Myc mouse transgenic prostate cancer model. Hi-Myc mice develop murine prostatic intraepithelial neoplasia (mPIN) as early as 2 to 4 weeks and invasive adenocarcinoma between 6 and 9 months due to the overexpression of human c-Myc in the mouse prostate. Three-week-old male Hi-Myc mice were placed on high-fat (HF; 42% Kcal) or low-fat (LF; 12% Kcal) diets, and equal caloric intake was maintained until euthanasia at 7 months. The number of mice that developed invasive adenocarcinoma at 7 months was 27% less in the LF diet group (12/28) compared with the HF diet group (23/33, P < 0.05). Epithelial cells in mPIN lesions in the LF group had a significantly lower proliferative index compared with epithelial cells in the HF group (21.7% versus 28.9%, P < 0.05). During the mPIN phase of carcinogenesis (4 months), the LF group had higher serum insulin-like growth factor (IGF) binding protein-1 levels (21.0 +/- 8.9 ng/mL versus 3.2 +/- 0.8 ng/mL, P < 0.05) relative to the HF group. Akt (Ser(473)) phosphorylation, Akt kinase activity, and phosphorylation of downstream targets of Akt in prostates were significantly reduced in the LF diet group compared with the HF group. We conclude that dietary fat reduction delays transition from mPIN to invasive cancer in this Myc-driven transgenic mouse model, possibly through suppression of the IGF-Akt pathway and decreased proliferation of mPIN epithelial cells.
Initial heme uptake from albumin by short-term cultured rat hepatocytes is mediated by a transport mechanism differing from that of other organic anions
Authors: Charles M. Noyer, Stephan Immenschuh, Heng H. Liem, Ursula Muller-Eberhard, Allan W. Wolkoff
Journal: Hepatology (1998)

Although it is known that circulating heme accumulates in liver cells, the process by which heme enters hepatocytes is only partly understood. Hemopexin and a putative hemopexin receptor on hepatocyte membranes may mediate the uptake process. However, whether there are sufficient hemopexin receptors on rat hepatocytes to account for the bulk of heme entering cells is unknown. It is likely that heme may be transferred directly from albumin with the help of a plasma membrane heme transporter. To clarify the transport mechanism of heme into liver cells, we studied the uptake by short-term cultured rat hepatocytes of 55 Fe-heme incubated with rat serum albumin. In these cells, the initial uptake of 55 Fe-heme at 37°C was five- to eightfold higher than that at 4°C, linear for at least 5 minutes, and saturable. The K m of heme uptake was 0.95 ± 0.27 μmol/L, and the V max was 0.12 ± 0.01 pmol/min/mg protein (n = 3). Neither isosmotic substitution of sucrose for NaCl in the medium nor adenosine triphosphate (ATP) depletion, perturbations that are known to reduce uptake of bilirubin, sulfobromophthalein (BSP), and taurocholate, had any influence on 55 Fe-heme uptake. In addition, heme uptake was not reduced in the presence of a greater than 500-fold molar excess of BSP. These results indicate that hepatocytes take up heme by a process that is distinct from that of these other organic anions.
Spleens of myelofibrosis patients contain malignant hematopoietic stem cells
Authors: Xiaoli Wang, Sonam Prakash, Min Lu, Joseph Tripodi, Fei Ye, Vesna Najfeld, Yan Li, Myron Schwartz, Rona Weinberg, Paul Roda, Attilio Orazi, Ronald Hoffman
Journal: Journal of Clinical Investigation (2012)

Cancer stem cell behavior is thought to be largely determined by intrinsic properties and by regulatory signals provided by the microenvironment. Myelofibrosis (MF) is characterized by hematopoiesis occurring not only in the marrow but also in extramedullary sites such as the spleen. In order to study the effects of these different microenvironments on primitive malignant hematopoietic cells, we phenotypically and functionally characterized splenic and peripheral blood (PB) MF CD34+ cells from patients with MF. MF spleens contained greater numbers of malignant primitive HPCs than PB. Transplantation of PB MF CD34+ cells into immunodeficient (NOD/SCID/IL2Rγnull) mice resulted in a limited degree of donor cell chimerism and a differentiation program skewed toward myeloid lineages. By contrast, transplanted splenic MF CD34+ cells achieved a higher level of chimerism and generated both myeloid and lymphoid cells that contained molecular or cytogenetic abnormalities indicating their malignant nature. Only splenic MF CD34+ cells were able to sustain hematopoiesis for prolonged periods (9 months) and were able to engraft secondary recipients. These data document the existence of MF stem cells (MF-SCs) that reside in the spleens of MF patients and demonstrate that these MF-SCs retain a differentiation program identical to that of normal hematopoietic stem cells.
Modulation of melanocyte-stimulating hormone receptor expression on normal human melanocytes: evidence for a regulatory role of ultraviolet B, interleukin-1α, interleukin-1β, endothelin-1 and tumour necrosis factor-α
Authors: None Funasaka, None Chakraborty, None Hayashi, None Komoto, None Ohashi, None Nagahama, None Inoue, None Pawelek, None Ichihashi
Journal: British Journal of Dermatology (1998)

Melanocyte‐stimulating hormone (MSH) receptor binding activity and melanocortin‐1 receptor (MC1‐R) gene expression on normal human melanocytes have been studied as responses to the effects of ultraviolet B (UVB), interleukin‐1 (IL‐1), endothelin‐1 (ET‐1) and tumour necrosis factor‐α (TNF‐α), which are known as UV sensitive regulators of melanocytic function. MSH receptor (MSH‐R) binding activity was upregulated by UVB, IL‐1α, ‐1β and ET‐1, but was downregulated by TNF‐α. Northern blot analysis showed that MC1‐R mRNA expression was induced 24 h after UVB irradiation in a dose‐dependent manner, and that 24‐h treatment with ET‐1 also induced an expression of MC1‐R mRNA, whereas TNF‐α downregulated the expression. In addition, IL‐1α and ‐1β have a small but real inductive effect on MC1‐R mRNA expression. Taken together, our results suggest a model in which higher MC1‐R mRNA expression is accompanied by upregulation of MSH‐R binding activity, and enhanced by UVB or cytokines sensitive to UVB. Such a regulatory system would enable normal human melanocytes to respond to MSH more efficiently and induce an increase of melanization of the skin through the MSH/MSH‐R system after UVB radiation.
Lower Socioeconomic Status Is Associated with Worse Outcomes in Pulmonary Arterial Hypertension
Authors: Wen-Hui Wu, Lu Yang, Fu-Hua Peng, Jing Yao, Li-Ling Zou, Dong Liu, Xin Jiang, Jue Li, Lan Gao, Jie-Ming Qu, Steven M. Kawut, Zhi-Cheng Jing
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Lower socioeconomic status (SES) confers a heightened risk of common cardiovascular and pulmonary diseases and increased mortality. The association of SES with outcomes in patients with pulmonary arterial hypertension (PAH) is less clear.To determine the association between SES and outcomes in patients with PAH.We performed a prospective cohort study at a national referral center for patients with PAH in China. Two hundred sixty-two consecutive incident patients aged 18 to 65 years with a diagnosis of idiopathic PAH were recruited between January 2007 and June 2011 and followed up until November 2011. The primary endpoint was all-cause mortality. An SES score for each patient was derived from their educational level, annual household income, occupation, and medical reimbursement rate.Patients with a lower SES had higher unadjusted mortality rates, with 3-year survival estimates of 50.1, 70.8, and 86.0% in increasing tertiles of SES (P for trend < 0.001). After adjustment for clinical features, hemodynamics, and type of PAH treatment, the hazard ratios for death were 2.98 (95% confidence interval, 1.51-5.89) in the lowest tertile of SES and 1.80 (95% confidence interval, 0.89-3.63) in the middle tertile of SES compared with the upper tertile (P for trend = 0.006).A lower SES is strongly associated with a higher risk of death in idiopathic PAH. This association was independent of clinical characteristics, hemodynamics, and treatment. Addressing the health disparities associated with a lower SES may improve the outcomes of patients with PAH.
Does Managed Problem Solving Work and in What Setting?
Authors: Marijn de Bruin
Journal: JAMA Internal Medicine (2013)

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Phase I Trial of Recombinant Modified Vaccinia Ankara Encoding Epstein–Barr Viral Tumor Antigens in Nasopharyngeal Carcinoma Patients
Authors: Edwin P. Hui, Graham S. Taylor, Hui Jia, Brigette B.Y. Ma, Stephen L. Chan, Rosalie Ho, Wai-Lap Wong, Steven Wilson, Benjamin F. Johnson, Ceri Edwards, Deborah D. Stocken, Alan B. Rickinson, Neil M. Steven, Anthony T.C. Chan
Journal: Cancer Research (2013)

Epstein-Barr virus (EBV) is associated with several malignancies including nasopharyngeal carcinoma, a high incidence tumor in Chinese populations, in which tumor cells express the two EBV antigens EB nuclear antigen 1 (EBNA1) and latent membrane protein 2 (LMP2). Here, we report the phase I trial of a recombinant vaccinia virus, MVA-EL, which encodes an EBNA1/LMP2 fusion protein designed to boost T-cell immunity to these antigens. The vaccine was delivered to Hong Kong patients with nasopharyngeal carcinoma to determine a safe and immunogenic dose. The patients, all in remission more than 12 weeks after primary therapy, received three intradermal MVA-EL vaccinations at three weekly intervals, using five escalating dose levels between 5 × 10(7) and 5 × 10(8) plaque-forming unit (pfu). Blood samples were taken during prescreening, immediately before vaccination, one week afterward and at intervals up to one year later. Immunogenicity was tested by IFN-γ ELIspot assays using complete EBNA1 and LMP2 15-mer peptide mixes and known epitope peptides relevant to patient MHC type. Eighteen patients were treated, three per dose level one to four and six at the highest dose, without dose-limiting toxicity. T-cell responses to one or both vaccine antigens were increased in 15 of 18 patients and, in many cases, were mapped to known CD4 and CD8 epitopes in EBNA1 and/or LMP2. The range of these responses suggested a direct relationship with vaccine dose, with all six patients at the highest dose level giving strong EBNA1/LMP2 responses. We concluded that MVA-EL is both safe and immunogenic, allowing the highest dose to be forwarded to phase II studies examining clinical benefit.
Nocturnal oxygen desaturation and spirometric parameters in adults with cystic fibrosis.
Authors: M N Pond, S P Conway
Journal: Thorax (1995)

Correction of nocturnal hypoxaemia in patients with cystic fibrosis may delay the development of pulmonary hypertension. Descriptive statistics used for nocturnal arterial oxygen saturation (SpO2) lack uniformity. The relationship between SpO2 and spirometric parameters has not previously been explored in a large number of exacerbations in adult patients with cystic fibrosis.Over a 21 month period overnight SpO2, forced expiratory volume in one second (FEV1), and forced vital capacity (FVC) were recorded on admission and discharge in 120 treatments of pulmonary exacerbations in 47 patients with cystic fibrosis who did not receive supplemental oxygen during recording. Nocturnal SpO2 was related to spirometric parameters for the whole group and individually in 11 patients, each of whom had at least five treatments.There was a close linear relationship between the percentage of the recording spent with SpO2 < 90% and mean overnight SpO2. Mean SpO2 correlated moderately with percentage predicted FEV1(%FEV1), r = 0.6, and poorly with percentage predicted FVC (%FVC), r = 0.34. The relationship between mean SpO2 and % FEV1 was non-linear at mean SpO2 < 89%, but approximated to linearity above this value. After exclusion of treatments with mean SpO2 < 89% the regression relationship between mean SpO2 and %FEV1 was the same on admission and discharge. Individual correlation coefficients of mean SpO2 versus % FEV1 in the 11 patients with repeated treatments ranged from 0.57 to 0.77. The slopes of the regression lines did not differ, with a pooled slope of 0.116, but the intercepts varied widely.In patients with cystic fibrosis mean overnight SpO2 can be substituted for percentage of recording < 90%. The relationship between mean SpO2 and percentage predicted FEV1 is non-linear at low values of SpO2 and is not influenced by treatment of pulmonary exacerbations. Patients with cystic fibrosis desaturate at a uniform rate compared with percentage predicted FEV1, but the value of FEV1 at which desaturation first occurs varies between patients. The spirometric values do not accurately predict nocturnal desaturation in a cystic fibrosis population, but FEV1 is a useful guide in individual patients with moderate desaturation.
Dionysians and Apollonians
Authors: Michel Cabanac
Journal: Behavioral and Brain Sciences (2004)

There are two sorts of scientists: Dionysians, who rely on intuition, and Apollonians, who are more systematic. Self-experimentation is a Dionysian approach that is likely to open new lines of research. Unfortunately, the Dionysian approach does not allow one to predict the results of experiments. That is one reason why self-experimentation is not popular among granting agencies.
A phase I trial of a Bcl-2 antisense (G3139) and weekly docetaxel in patients with advanced breast cancer and other solid tumors
Authors: J. Marshall, H. Chen, D. Yang, M. Figueira, K.B. Bouker, Y. Ling, M. Lippman, S.R. Frankel, D.F. Hayes
Journal: Annals of Oncology (2004)
Differential influence of p38 mitogen activated protein kinase (MAPK) inhibition on acute phase protein synthesis in human hepatoma cell lines
Authors: J Westra
Journal: Annals of the Rheumatic Diseases (2005)

<b>Background:</b> Inhibition of intracellular signal transduction is considered to be an interesting target for treatment in inflammation. p38 MAPK inhibitors, especially, have been developed and are now in phase II clinical trials for rheumatoid arthritis (RA). <b>Objective:</b> To investigate the influence of p38 MAPK inhibition on acute phase protein (APP) production, which is dependent on both JAK/STAT and p38 MAPK pathways. <b>Methods:</b> The effects of p38 MAPK inhibition on APP production and mRNA expression in four human hepatoma cell lines was investigated, after stimulation with interleukin (IL)6 and/or IL1β or tumour necrosis factor α. <b>Results:</b> Two out of four cell lines produced C reactive protein (CRP), especially after combined IL6 and IL1β stimulation. CRP production was significantly inhibited by the p38 MAPK specific inhibitor RWJ 67657 at 1 μmol/l, which is pharmacologically relevant. Fibrinogen production was also inhibited at 1 μmol/l in all cell lines. Serum amyloid A (SAA) was produced in all four lines. In contrast with CRP, SAA production was not inhibited by RWJ 67657 at 1 μmol/l. <b>Conclusion:</b> Production and mRNA expression of CRP and fibrinogen, but not SAA production and mRNA expression, were significantly inhibited by p38 MAPK specific inhibitor in hepatoma cell lines. For p38 MAPK inhibitor treatment in RA SAA might be a better marker of disease activity than CRP and fibrinogen, because SAA is not directly affected by p38 MAPK inhibition.
Cognition and Depression: Current Status and Future Directions
Authors: Ian H. Gotlib, Jutta Joormann
Journal: Annual Review of Clinical Psychology (2010)

Cognitive theories of depression posit that people's thoughts, inferences, attitudes, and interpretations, and the way in which they attend to and recall information, can increase their risk for depression. Three mechanisms have been implicated in the relation between biased cognitive processing and the dysregulation of emotion in depression: inhibitory processes and deficits in working memory, ruminative responses to negative mood states and negative life events, and the inability to use positive and rewarding stimuli to regulate negative mood. In this review, we present a contemporary characterization of depressive cognition and discuss how different cognitive processes are related not only to each other, but also to emotion dysregulation, the hallmark feature of depression. We conclude that depression is characterized by increased elaboration of negative information, by difficulties disengaging from negative material, and by deficits in cognitive control when processing negative information. We discuss treatment implications of these conclusions and argue that the study of cognitive aspects of depression must be broadened by investigating neural and genetic factors that are related to cognitive dysfunction in this disorder. Such integrative investigations should help us gain a more comprehensive understanding of how cognitive and biological factors interact to affect the onset, maintenance, and course of depression.
Predictors of outcome in an AIEOP series of childhood ependymomas: a multifactorial analysis
Authors: Piergiorgio Modena, Francesca R. Buttarelli, Rosalba Miceli, Elena Piccinin, Caterina Baldi, Manila Antonelli, Isabella Morra, Libero Lauriola, Concezio Di Rocco, Maria Luisa Garrè, Iacopo Sardi, Lorenzo Genitori, Roberta Maestro, Lorenza Gandola, Federica Facchinetti, Paola Collini, Gabriella Sozzi, Felice Giangaspero, Maura Massimino
Journal: Neuro-Oncology (2012)

Several molecular biomarkers have been suggested as predictors of outcome for pediatric ependymomas but deserve further validation in independent case series. We analyzed intracranial ependymomas belonging to a series of 60 patients prospectively treated according to the protocol sponsored by the Italian Association of Pediatric Hematology-Oncology. We used a tissue microarray to analyze nucleolin (NCL), cyclin-dependent kinase inhibitor 2A (CDKN2A), tumor protein 53 (TP53), and epidermal growth factor receptor (EGFR) by immunohistochemistry and by 1q gain by fluorescent in situ hybridization. The mRNA expression levels of EGFR, human telomerase reverse-transcriptase (HTERT), and Prominin 1 (PROM 1)/CD133 were evaluated by quantitative real-time PCR from cases with fresh-frozen tumor material available. Univariate and multivariate analyses of updated clinical data confirmed the prognostic significance of surgery (P < .01) and tumor grading (P < .05) for both relapse-free survival (RFS) and overall survival (OS). Among biomolecular markers, HTERT mRNA expression emerged with the strongest association with OS at multivariate analysis (hazard ratio [HR] = 9.9; P = .011); the 5-year OS was 84% versus 48% in the subgroups with HTERT median value <6 versus ≥ 6, respectively (P = .005). Five-year RFS was 46% versus 20% in the subgroups with low versus high NCL protein expression, respectively (P = .004), while multivariate Cox analyses gave suggestively high HRs for high versus low NCL (HR = 1.9; P = .090). The other genes tested were not significant at multivariate analyses, and genetic alterations of CDKN2A, TP53, EGFR, and HTERT loci were rare. The PROM1/CD133 cancer stem cell marker was strongly expressed at both RNA and protein levels in a substantial fraction of cases and was suggestively associated with a more indolent form of the disease. We conclude that NCL and HTERT represent the strongest prognostic biomarkers of RFS and OS, respectively, in our ependymoma case series.
Direct Insulin and Leptin Action on Pro-opiomelanocortin Neurons Is Required for Normal Glucose Homeostasis and Fertility
Authors: Jennifer W. Hill, Carol F. Elias, Makoto Fukuda, Kevin W. Williams, Eric D. Berglund, William L. Holland, You Ree Cho, Jen Chieh Chuang, Yong Xu, Michelle Choi, Danielle Lauzon, Charlotte E. Lee, Roberto Coppari, James A. Richardson, Jeffrey M. Zigman, Streamson Chua, Philipp E. Scherer, Bradford B. Lowell, Jens C. Brüning, Joel K. Elmquist
Journal: Cell Metabolism (2010)
US guidelines say blood pressure of 120/80 mm Hg is not "normal"
Authors: J. Hopkins Tanne
Journal: BMJ (2003)

New US guidelines on hypertension take a stronger approach, reclassifying “high normal” blood pressure as “pre-hypertension” and calling for aggressive treatment, firstly by changing lifestyle and then with drugs.

The National Heart, Lung, and Blood Institute of the National Institutes of Health, 39 professional, public, and voluntary agencies, and seven federal agencies issued the seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7).

The report was presented at the American Society of Hypertension meeting in New York last week and is being published in the Journal of the American Medical Association …