tbuckley/cabot-search huggingface dataset:
Leptin and Soluble Leptin Receptor in Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition Cohort
Authors: Krasimira Aleksandrova, Heiner Boeing, Mazda Jenab, H. Bas Bueno-de-Mesquita, Eugene Jansen, Fränzel J. B. van Duijnhoven, Sabina Rinaldi, Veronika Fedirko, Isabelle Romieu, Elio Riboli, Marc J. Gunter, Sabine Westphal, Kim Overvad, Anne Tjønneland, Jytte Halkjær, Antoine Racine, Marie-Christine Boutron-Ruault, Françoise Clavel-Chapelon, Rudolf Kaaks, Annekatrin Lukanova, Antonia Trichopoulou, Pagona Lagiou, Dimitrios Trichopoulos, Amalia Mattiello, Valeria Pala, Domenico Palli, Rosario Tumino, Paolo Vineis, Genevieve Buckland, María-José Sánchez, Pilar Amiano, José María Huerta, Aurelio Barricarte, Virginia Menéndez, Petra H. Peeters, Stefan Söderberg, Richard Palmqvist, Naomi E. Allen, Francesca L. Crowe, Kay-Tee Khaw, Nickolas Wareham, Tobias Pischon
Journal: Cancer Research (2012)

Abstract Leptin, a peptide hormone produced primarily by the adipocytes, is hypothesized to play a role in the pathogenesis of colorectal cancer (CRC). Soluble leptin receptor (sOB-R) may regulate leptin's physiologic functions; however its relation to CRC risk is unknown. This study explored the association of leptin and sOB-R with risk of CRC in a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 1,129 incident CRC cases (713 colon, 416 rectal) were matched within risk sets to 1,129 controls. Conditional logistic regression was used to calculate relative risks (RR) and 95% confidence intervals (CI). After multivariable adjustment including body mass index (BMI), waist circumference, and baseline leptin concentrations, sOB-R was strongly inversely associated with CRC (RR comparing the highest quintile vs. the lowest, 0.55; 95% CI, 0.40–0.76; Ptrend = 0.0004) and colon cancer (RR, 0.42; 95% CI, 0.28–0.63, Ptrend = 0.0001); whereas no association was seen for rectal cancer (RR adjusted for BMI and waist circumference, 0.83; 95% CI, 0.48–1.44, Ptrend = 0.38). In contrast, leptin was not associated with risk of CRC (RR adjusted for BMI and waist circumference, 0.85; 95% CI, 0.56–1.29, Ptrend = 0.23). Additional adjustments for circulating metabolic biomarkers did not attenuate these results. These novel findings suggest a strong inverse association between circulating sOB-R and CRC risk, independent of obesity measures, leptin concentrations, and other metabolic biomarkers. Further research is needed to confirm the potentially important role of sOB-R in CRC pathogenesis. Cancer Res; 72(20); 5328–37. ©2012 AACR.
Alpha interferon treatment of chronic hepatitis C in beta-thalassaemia.
Authors: V Di Marco, O Lo Iacono, M Capra, S Grutta, C Ciaccio, C Gerardi, A Maggio, D Renda, P Almasio, R Pisa
Journal: Gut (1993)

In this open, pilot study, interferon (IFN) alpha-2b seemed effective in the treatment of hepatitis C virus (HCV) infection in patients with beta-thalassaemia. In seven of nine patients who completed the study alanine aminotransferase activities returned to normal, and a completely stable response 24 months after treatment was seen in five. Liver biopsy specimen showed a clear reduction in portal, periportal, and lobular necroinflammation in all five cases. Three patients stopped treatment early because of side effects.
Recent Knowledge of the Incidence and Control of Cerebrospinal Fever
Authors: E. A. Underwood
Journal: BMJ (1940)

Many animals use visual motion cues for navigating within their surroundings. Both flies and vertebrates compute local motion by temporal correlation of neighboring photoreceptors, via so-called elementary motion detectors (EMDs). In the fly lobula plate and the vertebrate visual cortex the output from many EMDs is pooled in neurons sensitive to wide-field optic flow. Although the EMD has been the preferred model for more than 50 years, recent work has highlighted its limitations in describing some visual behaviors, such as responses to higher-order motion stimuli. Non-EMD motion processing may therefore serve an important function in vision. Here, we describe a novel neuron class in the fly lobula plate that clearly does not derive its input from classic EMDs. The centrifugal stationary inhibited flicker excited (cSIFE) neuron is strongly excited by flicker, up to very high temporal frequencies. The non-EMD driven flicker sensitivity leads to strong, nondirectional responses to high-speed, wide-field motion. Furthermore, cSIFE is strongly inhibited by stationary patterns, within a narrow wavelength band. cSIFE9s outputs overlap with the inputs of well described optic flow-sensitive lobula plate tangential cells (LPTCs). Driving cSIFE affects the active dendrites of LPTCs, and cSIFE may therefore play a large role in motion vision.
GM-CSF and IL-2 induce specific cellular immunity and provide protection against Epstein-Barr virus lymphoproliferative disorder
Authors: Robert A. Baiocchi, Jacqueline S. Ward, Lester Carrodeguas, Charles F. Eisenbeis, Ruoqi Peng, Sameek Roychowdhury, Srinivas Vourganti, Taryn Sekula, Maggie O’Brien, Melvin Moeschberger, Michael A. Caligiuri
Journal: Journal of Clinical Investigation (2001)

Epstein-Barr virus–associated lymphoproliferative disease (EBV-LPD) is a potentially life-threatening complication in immune-deficient patients. We have used the severe combined immune deficient (SCID) mouse engrafted with human leukocytes (hu-PBL-SCID) to evaluate the use of human cytokines in the prevention of EBV-LPD in vivo. Daily low-dose IL-2 therapy can prevent EBV-LPD in the hu-PBL-SCID mouse, but protection is lost if murine natural killer (NK) cells are depleted. Here we demonstrate that combined therapy with human GM-CSF and low-dose IL-2 is capable of preventing EBV-LPD in the hu-PBL-SCID mouse in the absence of murine NK cells. Lymphocyte depletion experiments showed that human NK cells, CD8+ T cells, and monocytes were each required for the protective effects of GM-CSF and IL-2 combination therapy. This treatment resulted in a marked expansion of human CD3+CD8+ lymphocytes in vivo. Using HLA tetramers complexed with EBV immunodominant peptides, a subset of these lymphocytes was found to be EBV-specific. These data establish that combined GM-CSF and low-dose IL-2 therapy can prevent the immune deficiencies that lead to fatal EBV-LPD in the hu-PBL-SCID mouse depleted of murine NK cells, and they point to a critical role for several human cellular subsets in mediating this protective effect.
CD40-CD40 ligand interactions are critical in T-B cooperation but not for other anti-viral CD4+ T cell functions.
Authors: A Oxenius, K A Campbell, C R Maliszewski, T Kishimoto, H Kikutani, H Hengartner, R M Zinkernagel, M F Bachmann
Journal: The Journal of Experimental Medicine (1996)

CD40-CD40 ligand (CD40L) interaction is required for the generation of antibody responses to T-dependent antigens as well as for the development of germinal centers and memory B cells. The role of the CD40-CD40L interaction in the induction of antigen-specific. Th cells and in mediating Th cell effector functions other than cognate help for B cells is less well understood. Using CD40- and CD40L-deficient mice together with lymphocytic choriomeningitis virus and vesicular stomatitis virus as viral model antigens, this study corroborates earlier findings that no lg isotype switching of virus-specific antibodies was measurable upon infection of CD40- or CD40L-deficient mice. In contrast, in vivo induction of virus-specific CD4+ T cells measured by proliferation and cytokine secretion of primed virus-specific Th cells in vitro was not crucially dependent on the CD40-CD40L interaction. In addition, virus-specific Th cells primed in a CD40-deficient environment, adoptively transferred into CD40-competent recipients, were able to mediate lg isotype switch. Th-mediated effector functions distinct from and in addition to T-B collaboration were analyzed in CD40- and CD40L-deficient and normal mice: (a) local inflammatory reactions upon LCMV infection mediated by LCMV-specific Th cells were not dependent on a functional CD40-CD40L interaction, (b) cytokine-mediated protection by CD4+ T cells primed by vesicular stomatitis virus against a challenge infection with recombinant vaccinia virus expressing the glycoprotein of vesicular stomatitis virus was found to be equivalent in CD40L-deficient and normal mice. Thus, CD40-CD40L interaction plays a crucial role in T-B interactions for Th-dependent activation of B cells but not, or to a much lesser extent, in T cell activation, antigen-specific Th cell responses in vitro, and for interleukin-mediated Th cell effector functions in vivo.
α–Fetoprotein in the Woodchuck Model of Hepadnavirus Infection and Disease: Immunochemical Analysis of Woodchuck α–Fetoprotein and Measurement in Serum by Quantitative Monoclonal Radioimmunoassay
Authors: Paul J. Cote, Christoph Pohl, Juanell Boyd, Bud C. Tennant, John L. Gerin
Journal: Hepatology (1990)

Woodchuck hepatitis virus infection of the eastern woodchuck represents a useful model for the study of hepatitis B virus infection and disease in humans, including hepatocellular carcinoma. In man, hepatocellular carcinoma is frequently detected and monitored using assays for serum alpha–fetoprotein. To study the relationship between α–fetoprotein and woodchuck hepatitis virus–induced hepatocellular carcinoma in the woodchuck model, we produced a monoclonal antibody to woodchuck α–fetoprotein and used biophysical and immunochemical methods to demonstrate its specificity and affinity (7 × 10 8 L/mol) for woodchuck α–fetoprotein. A competition radioimmunoassay was then developed and standardized for measuring serum α–fetoprotein concentrations. In the radioimmunoassay system, woodchuck α–fetoprotein was detected between 20 ng/ml (20% to 25% inhibition) and 8,500 ng/ml (97% to 98% inhibition). Elevated serum α–fetoprotein concentrations (450 to 452,000 ng/ml) were measured in 21 of 23 woodchucks in the advanced stages of woodchuck hepatitis virus–induced hepatocellular carcinoma. Serum α–fetoprotein was elevated above normal ( ≥ 450 ng/ml) as early as 3 to 11 mo before terminal hepatocellular carcinoma in 11 of 16 of the woodchuck hepatitis virus–carrier woodchucks. In a pilot study, serum α–fetoprotein became markedly elevated above normal in woodchuck hepatitis virus–carrier woodchucks that developed hepatocellular carcinoma but not in serologically recovered or uninifected woodchucks (i. e., without hepatocellular carcinoma). Thus, α–fetoprotein may provide a useful nonivasive marker in the woodchuck model for detecting and monitoring woodchuck hepatitis virus–induced hepatocellular carcinoma from earlier stages.(HEPATOLOGY 1990; 11:824–833.)
OBSERVATIONS ON THE GROWTH OF BACTERIA ON MEDIA CONTAINING VARIOUS ANILIN DYES
Authors: Charles Krumwiede, Josephine S. Pratt
Journal: The Journal of Experimental Medicine (1914)

Gentian violet and allied anilin dyes have a similar influence on bacterial growth, dividing bacteria into two groups corresponding in general to their reaction to the Gram stain. Among Gram-negative bacteria a strain is occasionally encountered which will not grow on violet agar, differentiating it from other members of the same species or variety. The reaction is quantitative, although the quantitative character is more marked with some species than with others. The streptococcus-pneumococcus group differ from other Gram-positive bacteria in their ability to grow in the presence of amounts of dye sufficient to inhibit the other species. The dysentery bacillus group shows marked variation in the presence of dyes. In the case of fuchsin the variation approaches closely a specific difference between the dysentery and paradysentery groups. The variations of the latter groups with other dyes show no correlation with the common differential characteristics. A closer study might reveal variations in other characteristics which would parallel the different reactions to dyes. Decolorization with sodium sulphite robs the dyes of some of their inhibitive powers.
An increased risk of community acquired pneumonia with gastric acid suppressive drug therapy
Authors: R Parker
Journal: Thorax (2005)

▴ Laheij RJF, Sturkenboom MCJM, Hassing RJ, et al . Risk of community-acquired pneumonia and use of gastric acid-suppressive drugs. JAMA2004;292:1955–60 [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] This study analysed 364 683 patients from an established Dutch primary care database comprising full electronic patient records. Patients were described as exposed (n = 19 459) if they were prescribed acid suppression (proton pump inhibitor (PPI) or H2 receptor antagonist (H2RA)) and were followed until the development of pneumonia or the end of the study … [1]: {openurl}?query=rft.jtitle%253DJAMA%26rft.stitle%253DJAMA%26rft.issn%253D0002-9955%26rft.aulast%253DLaheij%26rft.auinit1%253DR.%2BJ.%2BF.%26rft.volume%253D292%26rft.issue%253D16%26rft.spage%253D1955%26rft.epage%253D1960%26rft.atitle%253DRisk%2Bof%2BCommunity-Acquired%2BPneumonia%2Band%2BUse%2Bof%2BGastric%2BAcid-Suppressive%2BDrugs%26rft_id%253Dinfo%253Adoi%252F10.1001%252Fjama.292.16.1955%26rft_id%253Dinfo%253Apmid%252F15507580%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1001/jama.292.16.1955&link_type=DOI [3]: /lookup/external-ref?access_num=15507580&link_type=MED&atom=%2Fthoraxjnl%2F60%2F3%2F192.atom [4]: /lookup/external-ref?access_num=000224682900019&link_type=ISI
Comparison of Biosynthetic Human Insulin and Pork Insulin in the Gerritzen Test
Authors: Kurt Weinges, Manfred Ehrhardt, Franz Enzmann
Journal: Diabetes Care (1981)

Biosynthetic human insulin (BHI) produced by recombinant DNA technology has been proven to be identical to pancreatic human insulin. It differs from pork insulin in one carboxy-terminal amino acid of the B-chain, where alanine substitutes for threonine. This leads to a higher hydrophilicity and usually lowers the tendency of insulin molecules to aggregate. To study its biologic effect in man, the Gerritzen test was applied. BHI regular (10 IU) or purified pork insulin (PPI) (10 IU) was injected subcutaneously to evaluate the insulin action profile. The time course of plasma glucose levels under both BHI and PPI did not significantly. BHI seems to lower the blood glucose somewhat faster during the first 30 min and, during the late phase, somewhat less than pork insulin. In general, for both BHI and PPI, the onset of action occurs within 15 and 30 min; after 60 min, plasma glucose levels drop by 44.3% for BHI and by 40% for PPI. The plasma glucose minimum was reached about 2 h after injection; therefore, the slope of the plasma glucose fall after 60 min was only marginal. The minimum levels were steady over about 1.75 h. At 2.5 h postinjection plasma glucose rose gradually and reached starting levels after about 7 h. BHI was as well tolerated in the intradermal skin testing as were pork insulin and a placebo solution.
Economic Benefits of Intensive Insulin Therapy in Critically Ill Patients
Authors: Archana R. Sadhu, Alfonso C. Ang, Leslie A. Ingram-Drake, Dorothy S. Martinez, Willa A. Hsueh, Susan L. Ettner
Journal: Diabetes Care (2008)

The purpose of this study was to analyze the economic outcomes of a clinical program implemented to achieve strict glycemic control with intensive insulin therapy in patients admitted to the intensive care unit (ICU).A difference-in-differences (quasi-experimental) study design was used to examine the associations of an intensive insulin therapy intervention with changes in hospital length of stay (ICU and total), costs (ICU and total), and mortality. Hospital administrative data were obtained for 6,719 adult patients admitted between 2003 and 2005 to one of five intervention or four comparison ICUs in a large academic medical center. Linear regression models with log transformations and appropriate retransformations were used to estimate length of stay (LOS) and costs; logistic regressions were used to estimate mortality.After adjustment for observable patient characteristics and secular time trends, the intervention was consistently associated with lower average glucose levels and a trend toward shorter LOS, lower costs, and lower mortality. However, associations with resource use and outcomes were statistically significant in only ICU LOS, with an average reduction of 1.19 days of ICU care per admission. Other associations, although large in magnitude and in the hypothesized directions, were not estimated with sufficient precision to rule out other net effects. The associations with ICU days and costs were larger in magnitude than total days and costs.A clinical team focused on hyperglycemia management for ICU patients can be a valuable investment with significant economic benefits for hospitals.
Surgical Approaches to Epilepsy
Authors: H W Blume, D L Schomer
Journal: Annual Review of Medicine (1988)

Medically intractable epilepsy may be treated successfully with surgery in a high proportion of patients following appropriate clinical and diagnostic evaluation. Recent technical advances provide more precise diagnostic methods, especially for localizing the areas of seizure origin in the cerebral cortex. The excision of epileptogenic cortex remains the main surgical treatment for partial forms of epilepsy, while commissurotomies are appropriate for some patients with a secondary, generalized type of epilepsy. Limited experience with a variety of stereotaxic lesions and the modality of cerebellar stimulation has not yet provided definite evidence of efficacy of these techniques. Following surgical excisions, two thirds of the patients are significantly improved and over one third become seizure free, with morbidity-mortality rates of less than 0.5%.
Prolyl isomerase Pin1 is highly expressed in Her2-positive breast cancer and regulates erbB2 protein stability
Authors: Prudence B Lam, Laura N Burga, Bryan P Wu, Erin W Hofstatter, Kun Ping Lu, Gerburg M Wulf
Journal: Molecular Cancer (2008)

Abstract Overexpression of HER-2/Neu occurs in about 25–30% of breast cancer patients and is indicative of poor prognosis. While Her2/Neu overexpression is primarily a result of erbB2 amplification, it has recently been recognized that erbB2 levels are also regulated on the protein level. However, factors that regulate Her2/Neu protein stability are less well understood. The prolyl isomerase Pin1 catalyzes the isomerization of specific pSer/Thr-Pro motifs that have been phosphorylated in response to mitogenic signaling. We have previously reported that Pin1-catalyzed post-phosphorylational modification of signal transduction modulates the oncogenic pathways downstream from c-neu. The goal of this study was to examine the expression of prolyl isomerase Pin1 in human Her2+ breast cancer, and to study if Pin1 affects the expression of Her2/Neu itself. Methods Immunohistochemistry for Her2 and Pin1 were performed on two hundred twenty-three human breast cancers, with 59% of the specimen from primary cancers and 41% from metastatic sites. Pin1 inhibition was achieved using siRNA in Her2+ breast cancer cell lines, and its effects were studied using cell viability assays, immunoblotting and immunofluorescence. Results Sixty-four samples (28.7%) stained positive for Her2 (IHC 3+), and 54% (122/223) of all breast cancers stained positive for Pin1. Of the Her2-positive cancers 40 (62.5%) were also Pin1-positive, based on strong nuclear or nuclear and cytoplasmic staining. Inhibition of Pin1 via RNAi resulted in significant suppression of Her2-positive tumor cell growth in BT474, SKBR3 and AU565 cells. Pin1 inhibition greatly increased the sensitivity of Her2-positive breast cancer cells to the mTOR inhibitor Rapamycin, while it did not increase their sensitivity to Trastuzumab, suggesting that Pin1 might act on Her2 signaling. We found that Pin1 interacted with the protein complex that contains ubiquitinated erbB2 and that Pin1 inhibition accelerated erbB2 degradation, which could be prevented by treatments with the proteasome inhibitor ALLnL. Conclusion Pin1 is a novel regulator of erbB2 that modulates the ubiquitin-mediated degradation of erbB2. The overexpression of Pin1 in a majority of Her2-overexpressing breast cancer may contribute to maintain erbB2 levels. Pin1 inhibition alone and in conjunction with mTOR inhibition suppresses the growth of Her2+ breast cancer cells.
The Mechanical Consequences of Anomalous Atrioventricular Excitation (WPW Syndrome)
Authors: HAROLD W. MARCH, ARTHUR SELZER, HERBERT N. HULTGREN
Journal: Circulation (1961)

The mechanical consequences of anomalous atrioventricular excitation were studied in 12 patients by means of phonocardiograms, carotid pulse tracings, and in one instance, by data from cardiac catheterization. Three of these patients were also observed during normal conditions so that they supplied their own control data. In five instances mechanical anomalies were detectable as a consequence of the electrocardiographic abnormality. These anomalies were complex and consisted in one case of early onset and completion of ejection on both sides, and in another case of early completion on the left side. In three instances there was late activation on the contralateral side and possibly on the homolateral side as well. The remaining cases exhibited no such abnormalities by the methods studied, and in one subject this is illustrated with records made during both anomalous and normal conduction. The literature pertaining to this problem is critically reviewed, and an attempt is made to interpret both the previous and the present observations. The divergent nature of the observations suggests that the effect of anomalous excitation on the mechanics of the heart is the resultant of a number of variables, including the transmission time through the atrioventricular node and the site of entry of the anomalous focus. It is possible that the atrioventricular node does not function in some cases in which Wolff-Parkinson-White conduction is always present and it is not possible to induce normal beats with drugs, exercise, or respiratory maneuvers.
Bone mineral density in Crohn's disease Reply
Authors: F J COWAN, J W GREGORY, H R JENKINS, J JAHNSEN, J A FALCH, E AADLAND
Journal: Gut (1997)

Editor,—We were interested to read the recent article by Jahnsen et al ( Gut 1997; 40: 313–9). We have just published a similar study investigating the bone mineral content (BMC) of children with inflammatory bowel disease (IBD),1 and have also found that BMC was reduced in those with Crohn’s disease but not in those with ulcerative colitis. No relation could be found between BMC and disease duration, disease activity, …
Mouse Natural Cell-Mediated Cytotoxicity to Human Leukemia: Independence of Serum Source Used for Target-Cell Culturing and Cytotoxicity Assay 2
Authors: Otto Haller
Journal: JNCI Journal of the National Cancer Institute (1978)

Journal Article Mouse Natural Cell-Mediated Cytotoxicity to Human Leukemia: Independence of Serum Source Used for Target-Cell Culturing and Cytotoxicity Assay Get access Otto Haller, M.D. Otto Haller, M.D. 4 4Address reprint requests to Dr. Haller at his present address: Division of Experimental Microbiology, Institute for Medical Microbiology, University of Zürich, 8028 Zürich, Switzerland. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 60, Issue 6, June 1978, Pages 1433–1438, https://doi.org/10.1093/jnci/60.6.1433 Published: 01 June 1978 Article history Received: 14 September 1977 Accepted: 29 December 1977 Published: 01 June 1978