tbuckley/cabot-search huggingface dataset:
THE IMMUNOLOGICAL SIGNIFICANCE OF COLOSTRUM
Authors: Theobald Smith, Ralph B. Little
Journal: The Journal of Experimental Medicine (1930)

Under certain safeguards, such as isolation, calves from a large dairy herd have been raised by feeding normal and immune cow serum in place of colostrum. The losses were about one out of ten in the later experiments. This outcome may probably be improved by the subcutaneous injection of serum during the first day. This loss may be no greater than that under ordinary conditions, since sporadic deaths among calves are not infrequent. However, no satisfactory statistics are available for comparison with results as given above.
The Glycoprotein Ib-IX-V Complex Is a Platelet Counterreceptor for P-Selectin
Authors: Gabriel M. Romo, Jing-Fei Dong, Alicia J. Schade, Elizabeth E. Gardiner, Geoffrey S. Kansas, Chester Q. Li, Larry V. McIntire, Michael C. Berndt, José A. López
Journal: The Journal of Experimental Medicine (1999)

We have identified platelet glycoprotein (GP) Ibα as a counterreceptor for P-selectin. GP Ibα is a component of the GP Ib-IX-V complex, which mediates platelet adhesion to subendothelium at sites of injury. Cells expressing P-selectin adhered to immobilized GP Ibα, and GP Ibα–expressing cells adhered to and rolled on P-selectin and on histamine-stimulated endothelium in a P-selectin–dependent manner. In like manner, platelets rolled on activated endothelium, a phenomenon inhibited by antibodies to both P-selectin and GP Ibα. Unlike the P-selectin interaction with its leukocyte ligand, PSGL-1 (P-selectin glycoprotein ligand 1), the interaction with GP Ibα required neither calcium nor carbohydrate core-2 branching or α(1,3)-fucosylation. The interaction was inhibited by sulfated proteoglycans and by antibodies against GP Ibα, including one directed at a tyrosine-sulfated region of the polypeptide. Thus, the GP Ib-IX-V complex mediates platelet attachment to both subendothelium and activated endothelium.
Asymmetrical directional mutation pressure in the mitochondrial genome of mammals
Authors: A. Reyes, C. Gissi, G. Pesole, C. Saccone
Journal: Molecular Biology and Evolution (1998)

The base composition of 25 complete mammalian mitochondrial (mt) genomes has been analyzed taking into account all three codon positions (P1230 and fourfold degenerate sites (P4FD) of H-strand genes. In the nontranscribed L strand, G is the less represented base and A is the most represented one in all cases, while C and T differ among species. H-strand protein-coding genes show an asymmetric distribution of the four bases between the two strands. The asymmetry indexes AT and GC skews on P4FD are much higher than those on P123, suggesting the existence of asymmetrical directional mutation pressure. Relationships between the compositional features and transcription of replication processes have been investigated in order to find a possible mechanism that could explain the origin of this asymmetry. AT and GC skews, the base composition in fourfold degenerate sites, and the number of variable sites for each gene are significantly correlated with the duration of single-stranded state of the H-stranded genes during replication. We tested different replication-related hypotheses, such as the existence of biased dNTP pools, gamma DNA polymerase mispairing, and the asymmetric replication itself. Most of them failed to explain the observed results, hydrolytic deaminations being the only one in agreement with our data. Thus, we hypothesize that one of the crucial processes for the origin of asymmetric and biased base composition of mammalian mitochondrial genomes is the spontaneous deamination of C and A in the H strand during replication.
Contribution of kinins to the cardiovascular actions of angiotensin-converting enzyme inhibitors.
Authors: W Linz, G Wiemer, P Gohlke, T Unger, B A Schölkens
Journal: Pharmacological Reviews (1995)

From pharmacological investigations and clinical studies, it is known that ACE inhibitors exhibit additional local actions that are not related to hemodynamic changes and that cannot be explained only by interference with the renin-angiotensin system by means of an inhibition of ANG II formation. Because ACE is identical to kininase II, which inactivates the nonapeptide BK and related kinins, potentiation of kinins might be responsible for these additional effects of ACE inhibitors. ACE inhibition, concentration, and time dependently increased the formation of NO and PGI2 in cultured endothelial cells of different origin and from different species, including humans. The specific B2 kinin receptor antagonist, icatibant, suppressed the ACE inhibitor-induced increase in endothelial cyclic GMP accumulation index for NO-formation and, in parallel, attenuated the increase in PGI2 release. In renovascular models of hypertension associated with a stimulated renin-angiotensin system (two-kidney, one-clip), blood pressure reduction by ACE inhibitors was attenuated by icatibant, whereas in rats with genetic hypertension with normal to low plasma renin, blood pressure reduction through ACE inhibitors was not affected. In experimental atherosclerosis in rabbits, ACE inhibitors were able to preserve endothelial function and vascular reactivity and to reduce surface involvement. In the balloon denudation model of carotid arteries in rats, it was found that ACE inhibition markedly reduced neointima formation. However, when the ACE inhibitor was given together with icatibant, its effect was significantly blunted. Perfusion with ACE inhibitors induced a reduction of the incidence, as well as of the duration, of ventricular fibrillation and improved cardiodynamics and myocardial metabolism. BK perfusion induced comparable cardioprotective effects. In addition, perfusion with ACE inhibitors markedly increased the outflow of BK and related kinins from isolated rat hearts. The antiischemic effect of ACE inhibitors and BK were abolished by the addition of L-NNA (1 x 10(-6) mol/l) or icatibant (1 x 10(-9) mol/l). Similar results were found in dogs and rabbits with myocardial infarction. BK and related kinins also seem to be involved in preconditioning and remodeling. The effect of ACE inhibition in LVH was investigated in rats made hypertensive by aortic banding. ACE inhibition with ramipril, in the antihypertensive dose of 1 mg/kg/day for 6 weeks, prevented the increase in blood pressure and the development of LVH. A lower, nonantihypertensive dose of the ACE inhibitor (10 micrograms/kg/day for 6 weeks) had no effect on the increase in blood pressure or on plasma ACE activity, but also prevented LVH after aortic banding.4+ off
A host type I interferon response is induced by cytosolic sensing of the bacterial second messenger cyclic-di-GMP
Authors: Sarah M. McWhirter, Roman Barbalat, Kathryn M. Monroe, Mary F. Fontana, Mamoru Hyodo, Nathalie T. Joncker, Ken J. Ishii, Shizuo Akira, Marco Colonna, Zhijian J. Chen, Katherine A. Fitzgerald, Yoshihiro Hayakawa, Russell E. Vance
Journal: The Journal of Experimental Medicine (2009)

The innate immune system responds to unique molecular signatures that are widely conserved among microbes but that are not normally present in host cells. Compounds that stimulate innate immune pathways may be valuable in the design of novel adjuvants, vaccines, and other immunotherapeutics. The cyclic dinucleotide cyclic-di–guanosine monophosphate (c-di-GMP) is a recently appreciated second messenger that plays critical regulatory roles in many species of bacteria but is not produced by eukaryotic cells. In vivo and in vitro studies have previously suggested that c-di-GMP is a potent immunostimulatory compound recognized by mouse and human cells. We provide evidence that c-di-GMP is sensed in the cytosol of mammalian cells via a novel immunosurveillance pathway. The potency of cytosolic signaling induced by c-di-GMP is comparable to that induced by cytosolic delivery of DNA, and both nucleic acids induce a similar transcriptional profile, including triggering of type I interferons and coregulated genes via induction of TBK1, IRF3, nuclear factor κB, and MAP kinases. However, the cytosolic pathway that senses c-di-GMP appears to be distinct from all known nucleic acid–sensing pathways. Our results suggest a novel mechanism by which host cells can induce an inflammatory response to a widely produced bacterial ligand.
Comparative Evaluation of Capsular Polysaccharide-Specific IgM and IgG Antibodies and F(ab′)2 and Fab Fragments as Delivery Vehicles for Radioimmunotherapy of Fungal Infection
Authors: Ekaterina Dadachova, Ruth A. Bryan, Xianchun Huang, Geraldina Ortiz, Tiffany Moadel, Arturo Casadevall
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The applicability of radioimmunotherapy with organism-specific monoclonal antibodies to treatment of infectious disease in experimental models has been recently shown for fungal, bacterial, and viral infections. To identify the best delivery vehicle for radioimmunotherapy of human pathogenic fungus Cryptococcus neoformans (CN), we have done comparative evaluation of capsular polysaccharide-specific antibodies with IgG1 and IgM isotypes and F(ab′)2 and Fab fragments. Experimental Design: 18B7 IgG1 and 13F1 IgM and their isotype-matching controls were radiolabeled with 188Re, and their binding to 24067 and H99 CN strains was evaluated by doing Scatchard and kinetics analyses. The doses delivered during in vitro radioimmunotherapy were estimated using a cellular dosimetry algorithm. The biodistribution of 188Re-labeled 18B7 and 13F1 and of 111In-labeled 18B7 and its F(ab′)2 and Fab fragments was done in A/JCr mice systemically infected with 24067 CN strain. Results: 18B7 IgG1 showed superior to 13F1 IgM binding to 24067 CN (Ka = 1.7 × 109 mol/L−1 and 5.4 × 107 mol/L−1, respectively). Substantial killing of 24067 and H99 CN cells was achieved with 1 μCi 188Re-18B7 (55 cGy dose), whereas no killing was observed for 1 μCi 188Re-13F1 (2 cGy dose). In vivo 188Re-18B7 localized specifically in the lungs of CN-infected mice, whereas uptake of 188Re-13F1 was nonspecific. 111In-F(ab′)2 fragments showed higher uptake in the lungs and lower in the liver at the 48-h time point in comparison with intact 111In-18B7. Conclusions: Comparative evaluation of IgG and IgM and of F(ab′)2 and Fab fragments as potential delivery vehicles for radioimmunotherapy of cryptococcal infection strongly suggests that affinity for the target antigen is an important prerequisite for successful targeting of infection in vivo and that in vitro affinity measurements may predict the in vivo efficacy of candidate monoclonal antibodies.
Response assessment by combined PET–CT scan versus CT scan alone using RECIST in patients with locally advanced head and neck cancer treated with chemoradiotherapy
Authors: V.A. Passero, B.F. Branstetter, Y. Shuai, D.E. Heron, M.K. Gibson, S.Y. Lai, S.W. Kim, J.R. Grandis, R.L. Ferris, J.T. Johnson, A. Argiris
Journal: Annals of Oncology (2010)
Plasma levels of pentosidine in diabetic patients
Authors: S Sugiyama, T Miyata, Y Ueda, H Tanaka, K Maeda, S Kawashima, C Van Ypersele de Strihou, K Kurokawa
Journal: Journal of the American Society of Nephrology (1998)

Nonenzymatic reactions between glucose and proteins yield advanced glycation end products (AGE) such as pentosidine. AGE accumulate in diabetic patients, alter the structure and function of tissue proteins, stimulate cellular response, and have thus been implicated in diabetic tissue damage. The present study was undertaken to assess the factors determining plasma total pentosidine level in diabetic patients and the possible relation between plasma pentosidine level and diabetic complications. In diabetic patients, including patients with renal failure, plasma pentosidine levels, assessed by HPLC assay, were correlated with serum creatinine (P < 0.0001). In patients with normal renal function, pentosidine levels were correlated with blood glucose control (hemoglobin Alc: P = 0.0028; fructoselysine: P = 0.0133), serum creatinine (P = 0.029), patient age (P = 0.0416), duration of diabetes (P = 0.0431), and total cholesterol (P = 0.0056) and LDL-cholesterol (P = 0.0208). Multiple regression analysis revealed an independent influence of hemoglobin Alc and serum creatinine on pentosidine levels (r2 = 0.216, P = 0.0026). Pentosidine levels were higher in patients with than in those without hypertension (P = 0.043) or ischemic heart diseases (P = 0.0061). No such differences were observed between patients with and without albuminuria or retinopathy. Multiple regression analysis revealed an independent influence of plasma pentosidine on the presence of hypertension (r2 = 0.129, P = 0.0382) and of plasma pentosidine and HDL-cholesterol on the presence of ischemic heart disease (r2 = 0.326, P = 0.0012). The present study demonstrated that plasma pentosidine level was significantly influenced by the quality of glycemic control and renal function. Pentosidine level was also correlated with hypertension and ischemic heart disease, and might be taken as a biomarker of diabetic cardiovascular risk.
Genome-wide prioritization of disease genes and identification of disease-disease associations from an integrated human functional linkage network
Authors: Bolan Linghu, Evan S Snitkin, Zhenjun Hu, Yu Xia, Charles DeLisi
Journal: Genome biology (2009)

We integrate 16 genomic features to construct an evidence-weighted functional-linkage network comprising 21,657 human genes. The functional-linkage network is used to prioritize candidate genes for 110 diseases, and to reliably disclose hidden associations between disease pairs having dissimilar phenotypes, such as hypercholesterolemia and Alzheimer's disease. Many of these disease-disease associations are supported by epidemiology, but with no previous genetic basis. Such associations can drive novel hypotheses on molecular mechanisms of diseases and therapies.
Reciprocal activation between ATPase inhibitory factor 1 and NF-κB drives hepatocellular carcinoma angiogenesis and metastasis
Authors: Ruipeng Song, Huiwen Song, Yingjian Liang, Dalong Yin, Heng Zhang, Tongsen Zheng, Jiabei Wang, Zhaoyang Lu, Xuan Song, Tiemin Pei, Youyou Qin, Yuejin Li, Changming Xie, Boshi Sun, Huawen Shi, Shuai Li, Xianzhi Meng, Guangchao Yang, Shangha Pan, Jiyuan Zhu, Shuyi Qi, Hongchi Jiang, Zhiyong Zhang, Lianxin Liu
Journal: Hepatology (2014)

Hepatocellular carcinoma (HCC) is a highly vascularized tumor with frequent extrahepatic metastasis. Active angiogenesis and metastasis are responsible for rapid recurrence and poor survival of HCC. However, the mechanisms that contribute to tumor metastasis remain unclear. Here we evaluate the effects of ATPase inhibitory factor 1 (IF1), an inhibitor of the mitochondrial H(+)-adenosine triphosphate (ATP) synthase, on HCC angiogenesis and metastasis. We found that increased expression of IF1 in human HCC predicts poor survival and disease recurrence after surgery. Patients with HCC who have large tumors, with vascular invasion and metastasis, expressed high levels of IF1. Invasive tumors overexpressing IF1 were featured by active epithelial-mesenchymal transition (EMT) and increased angiogenesis, whereas silencing IF1 expression attenuated EMT and invasion of HCC cells. Mechanistically, IF1 promoted Snai1 and vascular endothelial growth factor (VEGF) expression by way of activating nuclear factor kappa B (NF-κB) signaling, which depended on the binding of tumor necrosis factor (TNF) receptor-associated factor 1 (TRAF1) to NF-κB-inducing kinase (NIK) and the disruption of NIK association with the TRAF2-cIAP2 complex. Suppression of the NF-κB pathway interfered with IF1-mediated EMT and invasion. Chromatin immunoprecipitation assay showed that NF-κB can bind to the Snai1 promoter and trigger its transcription. IF1 was directly transcribed by NF-κB, thus forming a positive feedback signaling loop. There was a significant correlation between IF1 expression and pp65 levels in a cohort of HCC biopsies, and the combination of these two parameters was a more powerful predictor of poor prognosis. Conclusion : IF1 promotes HCC angiogenesis and metastasis by up-regulation of Snai1 and VEGF transcription, thereby providing new insight into HCC progression and IF1 function. (Hepatology 2014;60:1659–1673)
Rates and Patterns of Molecular Evolution in Inbred and Outbred Arabidopsis
Authors: Stephen I. Wright, Beatrice Lauga, Deborah Charlesworth
Journal: Molecular Biology and Evolution (2002)

The evolution of self-fertilization is associated with a large reduction in the effective rate of recombination and a corresponding decline in effective population size. If many spontaneous mutations are slightly deleterious, this shift in the breeding system is expected to lead to a reduced efficacy of natural selection and genome-wide changes in the rates of molecular evolution. Here, we investigate the effects of the breeding system on molecular evolution in the highly self-fertilizing plant Arabidopsis thaliana by comparing its coding and noncoding genomic regions with those of its close outcrossing relative, the self-incompatible A. lyrata. More distantly related species in the Brassicaceae are used as outgroups to polarize the substitutions along each lineage. In contrast to expectations, no significant difference in the rates of protein evolution is observed between selfing and outcrossing Arabidopsis species. Similarly, no consistent overall difference in codon bias is observed between the species, although for low-biased genes A. lyrata shows significantly higher major codon usage. There is also evidence of intron size evolution in A. thaliana, which has consistently smaller introns than its outcrossing congener, potentially reflecting directional selection on intron size. The results are discussed in the context of heterogeneity in selection coefficients across loci and the effects of life history and population structure on rates of molecular evolution. Using estimates of substitution rates in coding regions and approximate estimates of divergence and generation times, the genomic deleterious mutation rate (U) for amino acid substitutions in Arabidopsis is estimated to be approximately 0.2–0.6 per generation.
Gastroesophageal Reflux Therapy Is Associated with Longer Survival in Patients with Idiopathic Pulmonary Fibrosis
Authors: Joyce S. Lee, Jay H. Ryu, Brett M. Elicker, Carmen P. Lydell, Kirk D. Jones, Paul J. Wolters, Talmadge E. King, Harold R. Collard
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Rationale: Gastroesophageal reflux (GER) is highly prevalent in patients with idiopathic pulmonary fibrosis (IPF). Chronic microaspiration secondary to GER may play a role in the pathogenesis and natural history of IPF.Objectives: To investigate the relationship between GER-related variables and survival time in patients with IPF.Methods: Regression analysis was used to investigate the relationship between GER-related variables and survival time in a retrospectively identified cohort of patients with well-characterized IPF from two academic medical centers.Measurements and Main Results: Two hundred four patients were identified for inclusion. GER-related variables were common in this cohort: reported symptoms of GER (34%), a history of GER disease (45%), reported use of GER medications (47%), and Nissen fundoplication (5%). These GER-related variables were significantly associated with longer survival time on unadjusted analysis. After adjustment, the use of GER medications was an independent predictor of longer survival time. In addition, the use of gastroesophageal reflux medications was associated with a lower radiologic fibrosis score. These findings were present regardless of center.Conclusions: The reported use of GER medications is associated with decreased radiologic fibrosis and is an independent predictor of longer survival time in patients with IPF. These findings further support the hypothesis that GER and chronic microaspiration may play important roles in the pathobiology of IPF.
Multifocal aplasia cutis congenita, distal limb hemimelia, and cutis marmorata telangiectatica in a patient with Adams–Oliver syndrome
Authors: K. BORK, J. JFEIFLE
Journal: British Journal of Dermatology (1992)

Journal Article Multifocal aplasia cutis congenita, distal limb hemimelia, and cutis marmorata telangiectatica in a patient with Adams–Oliver syndrome Get access K. BORK, K. BORK Department of Dermatology, University of Mainz, Germany Professor Dr Konrad Bork, Department of Dermatology, University of Mainz, Langenbeckstraße 1, 6500 Mainz, Germany. Search for other works by this author on: Oxford Academic Google Scholar J. JFEIFLE J. JFEIFLE Department of Dermatology, University of Mainz, Germany Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 127, Issue 2, 1 August 1992, Pages 160–163, https://doi.org/10.1111/j.1365-2133.1992.tb08049.x Published: 01 August 1992
Carboplatin, etoposide, and ifosfamide as intensive chemotherapy for small-cell lung cancer.
Authors: I E Smith, T J Perren, S A Ashley, J Woodiwiss, G V Forgeson, J R Yarnold, H T Ford
Journal: Journal of Clinical Oncology (1990)

Thirty-two previously untreated, fit patients with small-cell lung carcinoma (SCLC) were treated with an intensive combination chemotherapy regimen, with the aim of prolonging survival, as follows: carboplatin 400 mg/m2 intravenously (IV) day 1, ifosfamide 5 g/m2 IV day 1 in a 24-hour infusion with mesna, and etoposide 100 mg/m2 IV days 1 to 3, repeating at 28-day intervals for six courses. Limited-disease (LD) patients were given concurrent hyperfractionated radiotherapy for the first two courses, and all patients achieving a complete remission (CR) were offered prophylactic cranial irradiation (PCI). For 18 LD patients, the overall response was 94% with 72% CRs. For 14 extensive-disease (ED) patients the overall response was 100% with 29% CRs. Median response duration for LD patients was 11.5 months and for ED patients 7.5 months. Median survival for LD patients was 19 months with a predicted 24% 2-year survival and for ED patients 9.5 months with a predicted 14% 2-year survival. Hematologic toxicity was severe with 100% developing World Health Organization (WHO) grade 3-4 neutropenia and 94% WHO grade 3-4 thrombocytopenia during treatment. Seventy-two percent of patients required a dose reduction at some stage during treatment because of neutropenic infection or thrombocytopenia requiring platelet transfusions. Despite very high response rates, this intensive regimen achieves survival results only modestly better, if at all, than those reported for less toxic conventional regimens.