tbuckley/cabot-search huggingface dataset:
Antitumor Monoclonal Antibodies Enhance Cross-Presentation of Cellular Antigens and the Generation of Myeloma-specific Killer T Cells by Dendritic Cells
Authors: Kavita M. Dhodapkar, Joseph Krasovsky, Barbara Williamson, Madhav V. Dhodapkar
Journal: The Journal of Experimental Medicine (2002)

The mechanism of antitumor effect of monoclonal antibodies (mAbs) is not fully understood. Here we show that coating myeloma cells with anti–syndecan-1 antibody promotes cross-presentation of cellular antigens by dendritic cells (DCs) to autologous T cells from healthy donors. The tumor cells treated with anti–syndecan-1 or isotype-matched control antibody were fed to HLA-mismatched monocyte-derived immature DCs. Tumor cell–loaded mature DCs induced a strong CD8+ T cell response that was specific for the cancer-testis (C-T) antigens expressed in the tumor. The CD8+ T cells killed peptide-pulsed targets, as well as myeloma tumor cells. Importantly, mAbs-coated tumor-loaded DCs were consistently superior to DCs loaded with peptides or dying cells for eliciting tumor-specific killer T cells. This enhanced cross-presentation was not due to enhanced tumor cell uptake or to DC maturation. When mixtures of NY-Eso-1-positive and -negative myeloma cells were captured by DCs, the anti–syndecan-1 antibody had to be on the NY-Eso-1-positive cells to elicit NY-Eso-1–specific response. Cross-presentation was inhibited by pretreatment of DCs with Fcγ receptor blocking antibodies. Targeting of mAb-coated tumors to DCs may contribute to the efficacy of tumor-reactive mAb and offers a new strategy for immunotherapy.
Danazol relieves refractory pruritus associated with myeloproliferative disorders and other diseases
Authors: Luciano Kolodny, Lawrence L. Horstman, Bernd-Uwe Sevin, Harvey Brown, Yeon S. Ahn
Journal: American Journal of Hematology (1996)

Severe pruritus is frequently associated with myeloproliferative and other systemic illnesses, and often fails to respond to conventional measures. We used danazol (Danocrine), a synthetic attenuated androgen, in the treatment of severe pruritus refractory to conventional therapy. Eight patients had myeloproliferative disorders (MPD), seven had autoimmune disorders, and seven had skin diseases. Danazol at 400-800 mg/day was administered, and previous medications were tapered off. When itching was controlled with danazol alone, the dosage was reduced or discontinued, and resumed if itching recurred. Clinical responses were graded, and side effects were monitored. Overall, in 12 of 22 patients refractory to other measures, itching was controlled with danazol alone. In 10 patients itching returned when danazol was discontinued or dosage was continued for up to 5 years in responders. No serious side effects were observed. Our experience indicates that danazol is a good alternative for patients with severe pruritus associated with myeloproliferative and other systemic disorders.
The Respirator as an Oxygen Apparatus
Authors: H. L. Marriott
Journal: BMJ (1940)

tTHE BRITISH 519as regards tumour formation.Physiological stimulation, on the other hand, would appear to be free from such dangers.There is much evidence to show that compounds of the sulphydryl (-SH) group tend to stimulate growth by mitosis.Some clinical applications of sulphydryl therapy have been mentioned, and a plea is made for their wider trial at the present time.
Layers of Evolvability in a Bacteriophage Life History Trait
Authors: R. H. Heineman, J. J. Bull, I. J. Molineux
Journal: Molecular Biology and Evolution (2009)

Functional redundancy in genomes arises from genes with overlapping functions, allowing phenotypes to persist after gene knockouts. Evolutionary redundancy or evolvability of a genome is one step removed, in that functional redundancy is absent but the genome has the potential to evolve to restore a lost phenotype. Exploring the extent to which this recovery alters gene networks can illuminate how functional gene interactions change through time. Here, the evolvability of lysis was studied in bacteriophage T7, revealing hidden functional interactions. Lysis is the destruction of host cell wall and membranes that releases progeny and is therefore essential for phage propagation. In most phages, lysis is mediated by a two-component genetic module: a muralytic enzyme that degrades the bacterial cell wall (endolysin) and a holin that permeabilizes the inner membrane to allow the endolysin access to the cell wall. T7 carries one known holin, one endolysin, and a second muralytic enzyme that plays little role in lysis by wild-type phage. If the primary endolysin is deleted, the second muralytic enzyme evolves to restore normal lysis after selection for faster growth. Here, a second level of evolutionary redundancy was revealed. When the second muralytic enzyme was prevented from adapting in a genome lacking the primary endolysin, the phage reevolved lysis de novo in the absence of any known muralytic enzymes by changes in multiple genes outside the original lysis module. This second level of redundancy proved to be evolutionarily inferior to the first, and both result in a lower fitness and slower lysis than wild-type T7. Deletion of the holin gene delayed lysis time modestly; fitness was restored by compensatory substitutions in genes that lack known roles in lysis of the wild type.
An active school model to promote physical activity in elementary schools: Action schools! BC
Authors: P-J Naylor, H M Macdonald, D E R Warburton, K E Reed, H A McKay
Journal: British Journal of Sports Medicine (2008)

Objective: To assess the impact of an active school model on children’s physical activity (PA). Design: 16-month cluster randomised controlled trial. Setting: 10 elementary schools in Greater Vancouver, BC. Participants: 515 children aged 9–11 years. Intervention: Action Schools! BC (AS! BC) is an active school model that provided schools with training and resources to increase children’s PA. Schools implemented AS! BC with support from either external liaisons (liaison schools, LS; four schools) or internal champions (champion schools, CS; three schools). Outcomes were compared with usual practice (UP) schools (three schools). Main outcome measurements: PA was measured four times during the study using pedometers (step count, steps/day). Results: Boys in the LS group took 1175 more steps per day, on average, than boys in the UP group (95% CI: 97 to 2253). Boys in the CS group also tended to have a higher step count than boys in the UP group (+804 steps/day; 95% CI: −341 to 1949). There was no difference in girls’ step counts across groups. Conclusions: The positive effect of the AS! BC model on boys’ PA is important in light of the current global trend of decreased PA.
Pharmacokinetic Consequences of Aging
Authors: D P Richey, A D Bender
Journal: The Annual Review of Pharmacology and Toxicology (1977)

For the purpose of this review we have chosen a rather narrow definition of geriatric pharmacology. We deal with the influence of increasing age on the plasma concen­ tration of a drug and the factors that influence the peak concentration and the rate at which the drug leaves the body. We also discuss what changes in tissue sensitivity occur with age that would affect the overall response to a drug at a given blood level concentration. We do not discuss the extensive literature on the safety and utility of drugs in geriatric patients or the effect of increasing age on the incidence of adverse reactions and altered drug utility. Reviews on these have been published ( 1-5). Not considered as part of this review is one other aspect of geriatric phar­ macology, namely, the effect of drugs on the aging process. Information on this aspect of the subject can be found in other reviews (6,7). We would like to remark on the progress that has been made in our understanding of the effects of age on how a drug is handled by the body and the implications that these changes have on the utility of pharmacological agents in the treatment of diseases of old age. Until recently, most of the work has concerned the use of drugs in the elderly patient to determine their safety and their efficacy. There have been few comparisons with the response in younger populations. Even when such com­ parisons have been made, however, there have been few attempts to explain the reason for these differences and the basic biological rationale for them. In the last several years, however, greater attention has been focused on the effect of age on mechanisms responsible for drug disposition, and we are gradually laying the foun­ dation for understanding how drugs may be more effectively used in the treatment of diseases of the elderly patient (813). It is our hope that the review of this biological rationale, and more specifically the pharmacokinetic aspects of increasing age, will contribute to this understanding.
In vitro cancer cell–ECM interactions inform in vivo cancer treatment
Authors: Andrew W. Holle, Jennifer L. Young, Joachim P. Spatz
Journal: Advanced Drug Delivery Reviews (2015)

The general progression of cancer drug development involves in vitro testing followed by safety and efficacy evaluation in clinical trials. Due to the expense of bringing candidate drugs to trials, in vitro models of cancer cells and tumor biology are required to screen drugs. There are many examples of drugs exhibiting cytotoxic behavior in cancer cells in vitro but losing efficacy in vivo, and in many cases, this is the result of poorly understood chemoresistant effects conferred by the cancer microenvironment. To address this, improved methods for culturing cancer cells in biomimetic scaffolds have been developed; along the way, a great deal about the nature of cancer cell-extracellular matrix (ECM) interactions has been discovered. These discoveries will continue to be leveraged both in the development of novel drugs targeting these interactions and in the fabrication of biomimetic substrates for efficient cancer drug screening in vitro.
Diverse virological, histopathological and prognostic implications of seroconversion from hepatitis B e antigen to anti-HBe in chronic hepatitis B virus infection
Authors: Ih-Jen Su, Ming-Yang Lai, Hey-Chi Hsu, Ding-Shinn Chen, Pei-Ming Yang, Sou-Ming Chuang, Juei-Low Sung
Journal: Journal of Hepatology (1986)
Severe lung involvement in systemic scleromyxoedema: a highly unusual finding
Authors: P. Morales, M.Á. Martinez, F. Vera, G. Romero
Journal: European Respiratory Journal (2002)

Scleromyxoedema is a rare systemic disorder characterized by a lichenoid papular rash. Although scleromyxoedema can involve any organ, very few cases of pulmonary involvement have been reported. Moreover, there are no reports in the literature on treatment of this condition, especially with lung transplantation. The authors report a case of scleromyxoedema in a young man with neurological, skin and respiratory involvement, the latter being mainly characterized by pulmonary emphysema. Due to the serious respiratory compromise, and to the stability of the systemic lesions, a bilateral lung transplantation was performed with successful results at 4.5 yrs. In conclusion, lung transplantation may be required in patients with severe respiratory failure caused by scleromyxoedema.
Monocyte Chemotactic Protein-1 Mediates Prostate Cancer–Induced Bone Resorption
Authors: Yi Lu, Zhong Cai, Guozhi Xiao, Evan T. Keller, Atsushi Mizokami, Zhi Yao, G. David Roodman, Jian Zhang
Journal: Cancer Research (2007)

Prostate cancer preferentially metastasizes to bone, resulting in high mortality. Strategies to inhibit prostate cancer metastasis include targeting both tumor-induced osteoblastic lesions and underlying osteoclastic activities. We and others have previously shown that blocking receptor activator of nuclear factor-kappaB ligand (RANKL) partially blocks tumor establishment and progression in bone in murine models. However, levels of RANKL in the cell lines used in these studies were very low, suggesting that soluble factors other than RANKL may mediate the cancer-induced osteoclast activity. To identify these factors, a human cytokine antibody array was used to measure cytokine expression in conditioned medium collected from primary prostate epithelial cells (PrEC), prostate cancer LNCaP and its derivative C4-2B, and PC3 cells. All prostate cancer cells produced high amounts of monocyte chemotactic protein-1 (MCP-1) compared with PrEC cells. Furthermore, levels of interleukin (IL)-6, IL-8, GROalpha, ENA-78, and CXCL-16 were higher in PC3 than LNCaP. These results were confirmed by ELISA. Finally, human bone marrow mononuclear cells (HBMC) were cultured with PC3 conditioned medium. Although both recombinant human MCP-1 and IL-8 directly stimulated HBMC differentiation into osteoclast-like cells, IL-8, but not MCP-1, induced bone resorption on dentin slices with 21 days of culture in the absence of RANKL. However, the conditioned medium-induced bone resorption was inhibited by MCP-1 neutralizing antibody and was further synergistically inhibited with IL-8 antibody, indicating that MCP-1, in addition to IL-8, mediates tumor-induced osteoclastogenesis and bone resorption. MCP-1 may promote preosteoclast cell fusion, forming multinucleated tartrate-resistant acid phosphatase-positive osteoclast-like cells. This study may provide novel therapeutic targets for treatment of prostate cancer skeletal metastasis.
Interval cancers after negative colonoscopy: population-based case-control study
Authors: Hermann Brenner, Jenny Chang-Claude, Christoph M Seiler, Michael Hoffmeister
Journal: Gut (2011)

<h3>Objective</h3> The risk of colorectal cancer after a previous negative colonoscopy is very low. Nevertheless, interval cancers occur. We aimed to assess the characteristics and predictors of interval cancers after negative colonoscopy. <h3>Methods</h3> A population-based case-control study was conducted in Southern Germany in 2003–7. Sociodemographic and tumour characteristics were compared among 78 patients with interval cancers occurring 1–10 years after a negative colonoscopy and 433 colorectal cancers detected at screening. In addition, the indication for the preceding negative colonoscopy and its completeness were compared between patients with interval cancers and 515 controls with a preceding negative colonoscopy. <h3>Results</h3> 56.4% of interval cancers occurred among women compared with 33.7% of cases detected by screening (p=0.0001). After adjustment for covariates, female sex (OR 2.28, 95% CI 1.35 to 3.83) and location in the caecum or ascending colon (OR 1.98, 95% CI 1.17 to 3.35) were independently associated with occurrence of interval cancers. The preceding negative colonoscopy was more commonly conducted because of a positive faecal occult blood test (26.0% vs 12.9%, p=0.009) and was more often incomplete (caecum not reached: 18.1% vs 6.7%, p=0.001) among interval cancer cases than among controls. Characteristics of the preceding negative colonoscopy strongly and independently associated with occurrence of interval cancers were follow-up of a positive faecal occult blood test among men (OR 5.49, 95% CI 2.10 to 14.35) and incompleteness among women (OR 4.38, 95% CI 1.69 to 11.30). <h3>Conclusions</h3> The observed patterns suggest that a substantial proportion of interval cancers are due to neoplasms missed at colonoscopy and are potentially preventable by enhanced performance of colonoscopy.
Molecular Evolution of Seminal Proteins in Field Crickets
Authors: José A. Andrés, Luana S. Maroja, Steven M. Bogdanowicz, Willie J. Swanson, Richard G. Harrison
Journal: Molecular Biology and Evolution (2006)

In sexually reproducing organisms, male ejaculates are complex traits that are potentially subject to many different selection pressures. Recent experimental evidence supports the hypothesis that postmating sexual selection, and particularly sexual conflict, may play a key role in the evolution of the proteinaceous components of ejaculates. However, this evidence is based almost entirely on the study of Drosophila, a species with a mating system characterized by a high cost of mating for females. In this paper, we broaden our understanding of the role of selection on the evolution of seminal proteins by characterizing these proteins in field crickets, a group of insects in which females appear to benefit from mating multiply. We have used an experimental protocol that can be applied to other organisms for which complete genome sequences are not yet available. By combining an evolutionary expressed sequence tag screen of the male accessory gland in 2 focal species (Gryllus firmus and Gryllus pennsylvanicus) with a bioinformatics approach, we have been able to identify as many as 30 seminal proteins. Evolutionary analyses among 5 species of the genus Gryllus suggest that seminal protein genes evolve more rapidly than genes encoding proteins that are not involved with reproduction. The rates of synonymous substitution (dS) are similar in genes encoding seminal proteins and genes encoding "housekeeping" proteins. For the same comparison, the rate of fixation of nonsynonymous substitutions (dN) is 3 times higher in genes encoding seminal proteins, suggesting that the divergence of seminal proteins in field crickets has been accelerated by positive Darwinian selection. In spite of the contrasting characteristics of the Drosophila and Gryllus mating systems, the mean selection parameter omega and the proportion of loci estimated to be affected by positive selection are very similar.
Salt restriction inhibits renal growth and stabilizes injury in rats with established renal disease.
Authors: L D Dworkin, J A Benstein, E Tolbert, H D Feiner
Journal: Journal of the American Society of Nephrology (1996)

Salt restriction inhibits renal growth and stabilizes injury in rats with established renal disease. Male Munich-Wistar rats that underwent right nephrectomy and segmental infarction of two thirds of the left kidney were fed standard chow for 4 wk and then randomly assigned to ingest standard or low-salt chow for an additional 4 wk. Four wk after ablation, rats had systemic hypertension, proteinuria, and glomerular sclerosis. The prevalence of sclerosis, protein excretion rate, and glomerular volume increased between the fourth and eighth week in rats that were fed standard chow, however, in rats that were fed low-salt chow, the increase in glomerular volume and development of further glomerular sclerosis was prevented whereas the protein excretion rate actually declined. Micropuncture studies performed 8 wk after ablation revealed that the glomerular hydraulic pressure was elevated in remnant kidneys and was not affected by salt restriction. This study demonstrates that dietary salt restriction can prevent further glomerular injury and reduce proteinuria even when instituted in rats with established renal disease. These findings are also consistent with the hypothesis that glomerular hypertrophy promotes injury in this model of hypertension and progressive renal disease.
Natural antisense transcripts with coding capacity in Arabidopsis may have a regulatory role that is not linked to double-stranded RNA degradation.
Authors: Chih-Hung Jen, Ioannis Michalopoulos, David R Westhead, Peter Meyer
Journal: Genome biology (2005)

Overlapping transcripts in antisense orientation have the potential to form double-stranded RNA (dsRNA), a substrate for a number of different RNA-modification pathways. One prominent route for dsRNA is its breakdown by Dicer enzyme complexes into small RNAs, a pathway that is widely exploited by RNA interference technology to inactivate defined genes in transgenic lines. The significance of this pathway for endogenous gene regulation remains unclear.We have examined transcription data for overlapping gene pairs in Arabidopsis thaliana. On the basis of an analysis of transcripts with coding regions, we find the majority of overlapping gene pairs to be convergently overlapping pairs (COPs), with the potential for dsRNA formation. In all tissues, COP transcripts are present at a higher frequency compared to the overall gene pool. The probability that both the sense and antisense copy of a COP are co-transcribed matches the theoretical value for coexpression under the assumption that the expression of one partner does not affect the expression of the other. Among COPs, we observe an over-representation of spliced (intron-containing) genes (90%) and of genes with alternatively spliced transcripts. For loci where antisense transcripts overlap with sense transcript introns, we also find a significant bias in favor of alternative splicing and variation of polyadenylation.The results argue against a predominant RNA degradation effect induced by dsRNA formation. Instead, our data support alternative roles for dsRNAs. They suggest that at least for a subgroup of COPs, antisense expression may induce alternative splicing or polyadenylation.
Therapeutic angiogenesis with placental growth factor improves exercise tolerance of ischaemic rabbit hindlimbs
Authors: Petra Korpisalo, Tuomas T. Rissanen, Timo Bengtsson, Timo Liimatainen, Svetlana Laidinen, Henna Karvinen, Johanna E. Markkanen, Olli H. Gröhn, Seppo Ylä-Herttuala
Journal: Cardiovascular Research (2008)

We investigated the effects of angiogenic gene therapy with adenoviral placental growth factor131 (AdPlGF) on aerobic capacity and exercise tolerance in a rabbit hindlimb ischaemia model. We also assessed whether strong angiogenic changes such as capillary arterialization and formation of artery-venous shunts compromise oxygen transport to target tissues resulting in suboptimal therapeutic efficacy. Hindlimb ischaemia was surgically induced in New Zealand White rabbits (n = 20) that a day later received intramuscular (i.m.) AdPlGF or AdLacZ (3×1011vp) gene transfer (GT). Corresponding GTs were also done in healthy non-ischaemic rabbits (n = 10). Muscle energy metabolism and skeletal muscle perfusion were studied non-invasively before GT and at 6 and 28 days using 31P-magnetic resonance spectroscopy and contrast pulse sequence ultrasound, respectively. Oedema was quantified using modified Miles assay at sacrifice. AdPlGF increased perfusion 7.8-fold and improved aerobic capacity of ischaemic limbs 45% compared with AdLacZ controls (P < 0.05) at 6 days. In non-ischaemic limbs, strong angiogenic response to GT, including capillary arterialization and acute oedema, did not impair muscle energy metabolism. This study shows that proangiogenic gene therapy can significantly improve performance of ischaemic limbs and supports the concept of therapeutic angiogenesis for the treatment of patients with ischaemia.
DNA hypomethylation within specific transposable element families associates with tissue-specific enhancer landscape
Authors: Mingchao Xie, Chibo Hong, Bo Zhang, Rebecca F Lowdon, Xiaoyun Xing, Daofeng Li, Xin Zhou, Hyung Joo Lee, Cecile L Maire, Keith L Ligon, Philippe Gascard, Mahvash Sigaroudinia, Thea D Tlsty, Theresa Kadlecek, Arthur Weiss, Henriette O'Geen, Peggy J Farnham, Pamela A F Madden, Andrew J Mungall, Angela Tam, Baljit Kamoh, Stephanie Cho, Richard Moore, Martin Hirst, Marco A Marra, Joseph F Costello, Ting Wang
Journal: Nature Genetics (2013)