tbuckley/cabot-search huggingface dataset:
Alteration of H2 receptor sensitivity in duodenal ulcer patients after maintenance treatment with an H2 receptor antagonist.
Authors: D B Jones, C W Howden, D W Burget, C Silletti, R H Hunt
Journal: Gut (1988)

The effects of a specific H2 receptor agonist impromidine, on gastric acid secretion were measured in six patients with duodenal ulcer in clinical remission before and after three months treatment with ranitidine 150 mg nocte. After treatment basal acid output increased from 1.2 to 2.8 mmol/h and after maximal impromidine stimulation from 36.9 (4.7) to 44.2 (6.2) mmol/h (p less than 0.02). Intravenous ranitidine 50 mg was given at the end of the impromidine infusion on each study day; the antisecretory effect of intravenous ranitidine was accentuated after the treatment with ranitidine from a trough acid output of 8.5 (1.2) mmol/h before, to 3.8 (1.5) mmol/h (p less than 0.05) after, treatment. The increased response to the H2 agonist impromidine and the H2 antagonist ranitidine after treatment with ranitidine suggests an enhanced sensitivity of the H2 receptor. This might be explained on the basis of an increase in the number of H2 receptors (9up-regulation9).
Survival Rates Are Comparable After Radiofrequency Ablation or Surgery in Patients With Small Hepatocellular Carcinomas
Authors: Hung–Hsu Hung, Yi–You Chiou, Cheng–Yuan Hsia, Chien–Wei Su, Yi–Hong Chou, Jen–Huey Chiang, Wei–Yu Kao, Teh–Ia Huo, Yi–Hsiang Huang, Yu–Hui Su, Han–Chieh Lin, Shou–Dong Lee, Jaw–Ching Wu
Journal: Clinical Gastroenterology and Hepatology (2010)
Stationary Distributions of Microsatellite Loci Between Divergent Population Groups of the European Rabbit (Oryctolagus cuniculus)
Authors: G Queney, N Ferrand, S Weiss, F Mougel, M Monnerot
Journal: Molecular Biology and Evolution (2001)

Previous analysis of mitochondrial DNA polymorphism in the native range of the European rabbit (Oryctolagus cuniculus) demonstrated the occurrence of two highly divergent (2 Myr) maternal lineages with a well-defined geographical distribution. Analysis of both protein and immunoglobulin polymorphisms are highly concordant with this pattern of differentiation. However, the present analysis of nine polymorphic microsatellite loci (with a total of 169 alleles) in 24 wild populations reveals severe allele-size homoplasy which vastly underestimates divergence between the main groups of populations in Iberia. Nonetheless, when applied to more recent historical phenomena, this same data set not only confirms the occurrence of a strong bottleneck associated with the colonization of Mediterranean France but also suggests a two-step dispersal scenario that began with gene flow from northern Spain through the Pyrenean barrier and subsequent range expansion into northern France. The strength and appropriateness of applying microsatellites to more recent evolutionary questions is highlighted by the fact that both mtDNA and protein markers lacked the allelic diversity necessary to properly evaluate the colonization of France. The well-documented natural history of European rabbit populations provides an unusually comprehensive framework within which one can appraise the advantages and limitations of microsatellite markers in revealing patterns of genetic differentiation that have occurred across varying degrees of evolutionary time. The degree of size homoplasy presented in our data should serve as a warning to those drawing conclusions from microsatellite data sets which lack a set of complementary comparative markers, or involve long periods of evolutionary history, even within a single species.
Inhaled Fluticasone Reduces Sputum Inflammatory Indices in Severe Bronchiectasis
Authors: KENNETH W. T. TSANG, PAK-LEUNG HO, WAH-KIT LAM, MARY S. M. IP, KWOK-NING CHAN, CHU-SEK HO, CLARA C. G. OOI, KWOK Y. YUEN
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Although corticosteroid therapy might be clinically beneficial for bronchiectasis, very little is known of its effects on the inflammatory and infective markers in bronchiectasis. We have therefore performed a double-blind, placebo-controlled study to evaluate the effects of a 4-wk administration of inhaled fluticasone in bronchiectasis. Twenty-four patients (12 female; mean age 51 yr) were randomized into receiving either inhaled fluticasone (500 microgram twice daily) via the Accuhaler device (n = 12) or placebo. At each visit, spirometry, 24-h sputum volume, sputum leukocyte density, bacterial densities, and concentrations of interleukin (IL)-1beta, IL-8, tumor necrosis factor-alpha (TNF-alpha), and leukotriene B4 (LTB4) were determined. There was a significant (p < 0.05) decrease in sputum leukocyte density and IL-1beta, IL-8, and LTB4 after fluticasone treatment. The fluticasone group had one and the placebo group three episodes of exacerbation. There were no significant changes in spirometry (p > 0.05) or any reported adverse reactions in either group. The results of this study show that high-dose fluticasone is effective in reducing the sputum inflammatory indices in bronchiectasis. Large-scale and long-term studies are indicated to evaluate the effects of inhaled steroid therapy on the inflammatory components in bronchiectasis.
Dendritic Cells as Pharmacological Tools for Cancer Immunotherapy
Authors: Sébastien Anguille, Evelien L. Smits, Christian Bryant, Heleen H. Van Acker, Herman Goossens, Eva Lion, Phillip D. Fromm, Derek N. Hart, Viggo F. Van Tendeloo, Zwi N. Berneman
Journal: Pharmacological Reviews (2015)

Although the earliest—rudimentary—attempts at exploiting the immune system for cancer therapy can be traced back to the late 18th Century, it was not until the past decade that cancer immunotherapeutics have truly entered mainstream clinical practice. Given their potential to stimulate both adaptive and innate antitumor immune responses, dendritic cells (DCs) have come under intense scrutiny in recent years as pharmacological tools for cancer immunotherapy. Conceptually, the clinical effectiveness of this form of active immunotherapy relies on the completion of three critical steps: 1) the DCs used as immunotherapeutic vehicles must properly activate the antitumor immune effector cells of the host, 2) these immune effector cells must be receptive to stimulation by the DCs and be competent to mediate their antitumor effects, which 3) requires overcoming the various immune-inhibitory mechanisms used by the tumor cells. In this review, following a brief overview of the pivotal milestones in the history of cancer immunotherapy, we will introduce the reader to the basic immunobiological and pharmacological principles of active cancer immunotherapy using DCs. We will then discuss how current research is trying to define the optimal parameters for each of the above steps to realize the full clinical potential of DC therapeutics. Given its high suitability for immune interventions, acute myeloid leukemia was chosen here to showcase the latest research trends driving the field of DC-based cancer immunotherapy.
Phosphorylation Regulates Transcriptional Activity of PAX3/FKHR and Reveals Novel Therapeutic Possibilities
Authors: Ralf Amstutz, Marco Wachtel, Heinz Troxler, Peter Kleinert, Margret Ebauer, Torsten Haneke, Christoph Oehler-Jänne, Doriano Fabbro, Felix K. Niggli, Beat W. Schäfer
Journal: Cancer Research (2008)

Abstract Inhibition of constitutive active signaling pathways, which are a characteristic phenomenon for many tumors, can be an effective therapeutic strategy. In contrast, oncogenic transcription factors, often activated by mutational events, are in general less amenable to small-molecule inhibition despite their obvious importance as therapeutic targets. One example of this is alveolar rhabdomyosarcoma (aRMS), in which specific translocations lead to the formation of the chimeric transcription factor PAX3/FKHR. Here, we found unexpectedly that the transcriptional activity of PAX3/FKHR can be inhibited by the kinase inhibitor PKC412. This occurs via specific phosphorylation sites in the PAX3 domain, phosphorylation of which is required for efficient DNA-binding and subsequent transcriptional activity. Consequently, we show that PKC412 exerts a potent antitumorigenic potential for aRMS treatment both in vitro and in vivo. Our study suggests that posttranscriptional modifications of oncogenic transcription factors can be explored as a promising avenue for targeted cancer therapy. [Cancer Res 2008;68(10):3767–76]
Graphene may modulate the immune activation and survival of monocytes representative of the innate immunity
Authors: Jong Wook Shin, Jae Kook Nam, Young-Ae Baik, Jae Woo Jung, Jae Chol Choi, Jae Yeol Kim, In Won Park, Byoung Whui Choi, Kyung Soon Choi, Juhyun Park, Soo Young Kim
Journal: European Respiratory Journal (2012)

Background: The graphene which is an allotrope of carbon has the honeycombing structure of one-atom-thick planar sheets. It can be produced and chemically modified by chemical vaporization device. it is used in modern electronic, informative technologies including medical device. Graphene oxide (GO) has oxygen functional groups on the graphene plane. We performed this experiment to define the effect of GO on the innate immunologic function. Materials and Methods: GO was prepared by the modified Hummers method using 2g of graphite powder. After sequential procedure, GO in water was used for experiment. U-937 cells were cultivated in RPMI 1640 containing various concentration of GO particle solution. We checked the surviving and dying cells and cell size with the morphologic change with light microscopy. Results: The x-ray diffraction patterns observed for the graphite and GO. The pristine graphite has a peak centered at 2θ = 26.5 o (d = 0.33 nm). This peak was shifted to 2θ = 11.3o (d = 0.78 nm) after applying the Hummers method. This means that the graphite is exfoliated and the d-spacing increased, indicating that GO is formed. As the graphene concentration increased, the cell survival was diminished. U-937 cells were aggregated which might be associated with phagocytosis. Conclusion: GO in water diminishes the cell survival and activates phagocytosis and alters cell fate. as differentiation and molecules in the monocytes representative of the innate immunity.  Acknowledgement: This research was supported by Mid-career Research Program (2011-0028752) through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology.
EFFECT OF TEMOZOMIDE ON HUMAN DENDRITIC CELLS
Authors: A. Asai, R. Iwata, T. Ito, H. Oshige, K. Yoshimura, J.-i. Takeda
Journal: Neuro-Oncology (2014)

BACKGROUND: We are undertaking dendritic cell (DC) therapy against glioma stem-like cells (GSCs) with concomitant maintenance chemotherapy using temozolomide (TMZ). In general, anti-cancer agents are known to suppress immune response in patients. TMZ also suppresses immunity by inducing lymphopenia and myelosuppression in malignant glioma patients. However, there has been no study about the effect of TMZ on DC function. In this study, we evaluate whether concomitant TMZ affects DC function in vitro. METHODS: We isolated human blood plasmacytoid DCs (pDCs) and myelocytoid DCs (mDCs) from healthy volunteers by flow cytometry. These DC subsets were cultured in flat-bottomed 96-well plates at 5 × 104 cells in the final 200 µl of medium per well for 24 h. In the first set of experiment, we assessed cytotoxic activity of TMZ on DCs at clinically relevant concentration. After 24 h, viable cells were measured by a trypan-blue exclusion test. We next measured the Toll-like receptor ligand (TLRL) -induced cytokine production by DCs in the presence of TMZ. DC subsets were stained with FITC-labeled anti-CD83 and PE-labeled anti-CD86 antibody and then analyzed by FACS calibur. We also measured secreted IL-12p40 and IFN-alpha concentration in the supernatant of the cultures by ELISA. RESULTS: Analysis of trypan-blue exclusion of the dead cells showed that over 300 microM of TMZ started to kill both DC subsets and there was no cytocidal effect at 100 microM, a clinically relevant concentration. Therefore, we thereafter used 10 microM to 300 microM for the following assays. We found that TMZ did not affect IFN-alpha production by pDCs and IL-12 production by mDCs in response to various TLRLs. In addition, up to 100 microM of concentration, TMZ did not influence the CD83 and CD86 expression on both DC subsets. CONCLUSIONS: Temozolomide did not significantly affect on DC function, suggesting that DC therapy and concomitant chemotherapy using TMZ may be possible, although further assessment in the clinical setting is necessary. In the presentation, we also would like to present preliminary data on interaction between DCs and two types of GSCs (proneural and mesenchymal). SECONDARY CATEGORY: n/a.
Précis of <i>Breakdown of Will</i>
Authors: George Ainslie
Journal: Behavioral and Brain Sciences (2005)

Behavioral science has long been puzzled by the experience of temptation, the resulting impulsiveness, and the variably successful control of this impulsiveness. In conventional theories, a governing faculty like the ego evaluates future choices consistently over time, discounting their value for delay exponentially, that is, by a constant rate; impulses arise when this ego is confronted by a conditioned appetite. Breakdown of Will (Ainslie 2001) presents evidence that contradicts this model. Both people and nonhuman animals spontaneously discount the value of expected events in a curve where value is divided approximately by expected delay, a hyperbolic form that is more bowed than the rational, exponential curve. With hyperbolic discounting, options that pay off quickly will be temporarily preferred to richer but slower-paying alternatives, a phenomenon that, over periods from minutes to days, can account for impulsive behaviors, and over periods of fractional seconds can account for involuntary behaviors. Contradictory reward-getting processes can in effect bargain with each other, and stable preferences can be established by the perception of recurrent choices as test cases (precedents) in recurrent intertemporal prisoner's dilemmas. The resulting motivational pattern resembles traditional descriptions of the will, as well as of compulsive phenomena that can now be seen as side-effects of will: over-concern with precedent, intractable but circumscribed failures of self-control, a motivated (“dynamic”) unconscious, and an inability to exploit emotional rewards. Hyperbolic curves also suggest a means of reducing classical conditioning to motivated choice, the last necessary step for modeling many involuntary processes like emotion and appetite as reward-seeking behaviors; such modeling, in turn, provides a rationale for empathic reward and the “construction” of reality.
Doctors and Overpopulation
Authors: P. W. W. Gifford
Journal: BMJ (1972)

This letter is in response to a joint letter signed by 52 doctors on the problem of overpopulation in Britain.  The author agrees with the gravity of the problem and believes that the remedy lies in part with the medical profession.  Pediatric and adolescent medical services should be planned to cope with the boom.  The average family size of 2.4 will lead to a steadily growing population and infinitum the author declares and refers to a survey on womens attitudes toward their most recent birth in which 15% wished that it had not occurred.  A total liberalization of all family planning services is called for since it will free parents from unwanted children and will stabilize the the population in the long run.
Pharmacovigilance and reporting oversight in US FDA fast-track process: bisphosphonates and osteonecrosis of the jaw
Authors: Beatrice J Edwards, Mrinal Gounder, June M McKoy, Ian Boyd, Mathew Farrugia, Cesar Migliorati, Robert Marx, Salvatore Ruggiero, Meletios Dimopoulos, Dennis W Raisch, Seema Singhal, Ken Carson, Eniola Obadina, Steve Trifilio, Dennis West, Jayesh Mehta, Charles L Bennett
Journal: The Lancet Oncology (2008)
Triggering Receptor Expressed on Myeloid Cells-2 Protects against Polymicrobial Sepsis by Enhancing Bacterial Clearance
Authors: QiXing Chen, Kai Zhang, Yue Jin, Tao Zhu, BaoLi Cheng, Qiang Shu, XiangMing Fang
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Triggering receptor expressed on myeloid cells-2 (TREM-2) is a cell surface receptor primarily expressed on macrophages and monocyte-derived cells. TREM-2 not only functions as a regulator of inflammatory response, but also serves as a phagocytic receptor for bacteria. However, the role of TREM-2 in sepsis remains unknown.To investigate whether TREM-2 plays a role in sepsis.The manner of expression of TREM-2 was evaluated in patients with sepsis and in polymicrobial septic mouse model induced by the cecum ligation and puncture approach. Recombinant mouse TREM-2 was used to block the effect of TREM-2. Bone marrow-derived myeloid cells (BMMCs) that overexpress TREM-2 were administrated into septic mice at various times after cecum ligation and puncture.The expression levels of TREM-2 were up-regulated in patients with sepsis and septic mice. The kinetics of TREM-2 expression in polymicrobial sepsis was comparable with that of bacteria burden in peritoneal lavage fluid. Blocking the effect of TREM-2 resulted in markedly increased mortality and bacterial burden in polymicrobial sepsis. Administration of TREM-2-overexpressing BMMCs significantly reduced the mortality, even when it was administered 4 hours after the initiation of sepsis. However, injection of TREM-2-overexpressing BMMCs into LPS-challenged endotoxemia mice did not improve the survival rate. The protective effect of TREM-2 in polymicrobial sepsis was not associated with its antiinflammatory properties, but it enhanced bacterial clearance in vivo. Furthermore, administration of TREM-2-overexpressing BMMCs improved the organ injury.TREM-2 plays an important role in the host defense response to sepsis by enhancing bacterial clearance.
LRP1-Dependent Endocytic Mechanism Governs the Signaling Output of the Bmp System in Endothelial Cells and in Angiogenesis
Authors: Xinchun Pi, Christopher E. Schmitt, Liang Xie, Andrea L. Portbury, Yaxu Wu, Pamela Lockyer, Laura A. Dyer, Martin Moser, Guojun Bu, Edward J. Flynn, Suk-Won Jin, Cam Patterson
Journal: Circulation Research (2012)

Among the extracellular modulators of Bmp (bone morphogenetic protein) signaling, Bmper (Bmp endothelial cell precursor-derived regulator) both enhances and inhibits Bmp signaling. Recently we found that Bmper modulates Bmp4 activity via a concentration-dependent, endocytic trap-and-sink mechanism.To investigate the molecular mechanisms required for endocytosis of the Bmper/Bmp4 and signaling complex and determine the mechanism of Bmper's differential effects on Bmp4 signaling.Using an array of biochemical and cell biology techniques, we report that LRP1 (LDL receptor-related protein 1), a member of the LDL receptor family, acts as an endocytic receptor for Bmper and a coreceptor of Bmp4 to mediate the endocytosis of the Bmper/Bmp4 signaling complex. Furthermore, we demonstrate that LRP1-dependent Bmper/Bmp4 endocytosis is essential for Bmp4 signaling, as evidenced by the phenotype of lrp1-deficient zebrafish, which have abnormal cardiovascular development and decreased Smad1/5/8 activity in key vasculogenic structures.Together, these data reveal a novel role for LRP1 in the regulation of Bmp4 signaling by regulating receptor complex endocytosis. In addition, these data introduce LRP1 as a critical regulator of vascular development. These observations demonstrate Bmper's ability to fine-tune Bmp4 signaling at the single-cell level, unlike the spatial regulatory mechanisms applied by other Bmp modulators.
Diabetes Is Associated With Subclinical Functional Limitation in Nondisabled Older Individuals
Authors: Nathalie de Rekeneire, Helaine E. Resnick, Ann V. Schwartz, Ronald I. Shorr, Lewis H. Kuller, Eleanor M. Simonsick, Bruno Vellas, Tamara B. Harris
Journal: Diabetes Care (2003)

OBJECTIVE—The aim of this study was to examine the role of comorbid conditions and body composition in the association between diabetes and subclinical functional limitation, an indication of early functional decline, in well-functioning older individuals. RESEARCH DESIGN AND METHODS—This was a cross-sectional analysis of 3,075 well-functioning black and white men and women aged 70–79 years, enrolled in the Health, Aging, and Body Composition study. Diabetes was defined by self-report and/or hypoglycemic medication use or fasting glucose ≥126 mg/dl. Subclinical functional limitation was defined using self-report of capacity and objective performance measures. Comorbid conditions were identified by self-reported diagnoses, medication use, and clinical measures. Body composition measures included anthropometry and total fat (dual X-ray absorptiometry). RESULTS—Of 2,926 participants, 1,252 (42.8%) had subclinical functional limitation at baseline. Among 2,370 individuals without diabetes, 40% had subclinical functional limitation, whereas the prevalence was 53% among the 556 diabetic participants with an age/sex/race-adjusted odds ratio (OR) 1.70 (95% CI 1.40–2.06). This association remained significant when adjusted for body composition measures (OR 1.54 [1.26–1.88]), diabetes-related comorbidities, and other potential confounders (OR 1.40 [1.14–1.73]). In the fully adjusted model, consideration of HbA1c (&amp;lt; or ≥7%) and diabetes duration showed that poor glycemic control in diabetic individuals explained the association with subclinical functional limitation. CONCLUSIONS—In a well-functioning older population, diabetes is associated with early indicators of functional decline, even after accounting for body composition and diabetes-related comorbidities. Poor glycemic control contributes to this relationship. Whether improvement in glycemic control in older people with diabetes would change this association should be tested.
LIVER TRANSPLANTATION IN HEPATITIS DELTA VIRUS DISEASE
Authors: M Rizzetto, E Chiaberge, F Negro, C Di Giacomo, R Cortesini, M Doglia, S Macagno, G Verme, G Marinucci, D Alfani, F Milazzo, L.R Fassati, D Galmarini
Journal: The Lancet (1987)

Seven patients with hepatitis delta virus (HDV) cirrhosis underwent liver transplantation. In every case the HDV infection was florid but accompanied by an inactive hepatitis B virus (HBV) infection. The patients were given anti-HB surface antigen (HBsAg) serum globulins and HBV vaccine. Two patients cleared the HBsAg and the HDV, and are alive and well 14 and 15 months, respectively, after transplantation. HDV infection recurred in the other five patients: hepatitis developed in three, another died, and the fifth was re-transplanted for causes unrelated to viral hepatitis (reinfection was shown by the presence of HD antigen in the graft). Liver transplantation is feasible in patients with HDV disease but involves a high risk of HDV reinfection that cannot be predicted by the virological pattern of the native HBV infection or prevented by conventional HBV prophylaxis.