tbuckley/cabot-search huggingface dataset:
<i>In vitro</i> and <i>In vivo</i> Antitumor Activity of the Novel Derivatized Polyvinyl Alcohol-Based Polymer P10(4)
Authors: Lizzie Raffaghello, Guendalina Zuccari, Roberta Carosio, Isabella Orienti, Paolo G. Montaldo
Journal: Clinical Cancer Research (2006)

Abstract Purpose: The major limitation to successful chemotherapy of neuroblastoma is the toxicity of traditional antitumor drugs. Hence, less toxic and more effective drugs are to be found, and novel formulations of conventional compounds allowing a more favorable biodistribution should be sought for. In an attempt to pursue this task, we recently synthesized an amphiphilic polymer based on a polyvinyl alcohol backbone [P10(4)]. Experimental Design: The cytotoxic activity of P10(4) was evaluated both in vitro on neuroblastoma and melanoma cell lines and in vivo in pseudometastatic neuroblastoma models. Apoptosis was assessed by morphology, cytofluorimetric analysis of DNA content, and DNA fragmentation assay. Caspases activation was investigated by kits specific for caspase-1, caspase-2, caspase-3, caspase-4, caspase-6, caspase-7, caspase-8, caspase-9, caspase-10, and caspase-13. Colony formation was evaluated by soft agar assay. Results: P10(4) exerted a potent cytotoxic activity on different neuroblastoma and melanoma cell lines through induction of both extrinsic and intrinsic caspase cascades and subsequent apoptosis. Moreover, the clonogenic potential of cells that survived P10(4) treatment was strongly reduced. Next, we tested the effects of P10(4) in nude mice injected with both a human and a murine neuroblastoma cell lines i.v. P10(4) significantly increased the life span and the long-term survival of treated mice over controls. No side effects were observed, even at doses higher than those used for therapeutic purposes. Conclusions: Our data suggest that P10(4) holds promise as an anticancer compound and, because of its lack of interaction with DNA, is unlikely to give rise to drug resistance.
The early allergic response in small airways of human precision-cut lung slices
Authors: A. Wohlsen, C. Martin, E. Vollmer, D. Branscheid, H. Magnussen, W-M. Becker, U. Lepp, S. Uhlig
Journal: European Respiratory Journal (2003)

To study the role of small airways in the early allergic response (EAR), the method of human precision-cut lung slices (PCLS) was developed and used to examine the bronchoconstriction elicited by passive sensitisation and allergen provocation. Viable human PCLS of 250-µm thickness containing airways &lt;1.5 mm in outer diameter were prepared from lung lobes obtained from lung resection and taken into culture. According to the low release of lactate dehydrogenase and the constant ciliary beat frequency, human PCLS were viable for at least 3 days. Following overnight passive sensitisation with serum from allergic individuals, administration of grass-pollen extract or activating immunoglobulin E antibody resulted in immediate airway contraction that was quantified by videomicroscopy. The extent of the EAR increased with decreasing airway size (outer airway diameter), with the strongest response occurring in the terminal bronchioles. Histamine receptor antagonism was ineffective, and leukotriene or thromboxane receptor antagonism attenuated the early allergic response only in some cases. However, simultaneous blockade of leukotriene and thromboxane receptors almost completely prevented the early allergic response in the precision-cut lung slices from all individuals, suggesting such a dual treatment as a potential future asthma therapy.
A history of war: The role of inter-group conflict in sex differences in aggression
Authors: Dominic D. P. Johnson, Mark van Vugt
Journal: Behavioral and Brain Sciences (2009)

Abstract Human aggression has two important dimensions: within -group aggression and between -group aggression. Archer offers an excellent treatment of the former only. A full explanation of sex differences in aggression will fail without accounting for our history of inter-group aggression, which has deep evolutionary roots and specific psychological adaptations. The causes and consequences of inter-group aggression are dramatically different for males and females.
TCT-755 Beneficial Vascular Remodeling and Hemodynamic Improvement following Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension
Authors: Hiroto Kinutani, Noriaki Emoto, Yu Taniguchi, Hiromasa Otake, Toshiro Shinke, Junya Shite, Kenichi Hirata
Journal: Journal of the American College of Cardiology (2012)
Carbonated Soft Drink Consumption and Risk of Esophageal Adenocarcinoma
Authors: Susan T. Mayne, Harvey A. Risch, Robert Dubrow, Wong-Ho Chow, Marilie D. Gammon, Thomas L. Vaughan, Lauren Borchardt, Janet B. Schoenberg, Janet L. Stanford, A. Brian West, Heidi Rotterdam, William J. Blot, Joseph F. Fraumeni
Journal: JNCI Journal of the National Cancer Institute (2006)

Carbonated soft drinks (CSDs) have been associated with gastroesophageal reflux, an established risk factor for esophageal adenocarcinoma. As both CSD consumption and esophageal adenocarcinoma incidence have sharply increased in recent decades, we examined CSD as a risk factor for esophageal and gastric cancers in a U.S. multicenter, population-based case-control study. Associations between CSD intake and risk were estimated by adjusted odds ratios (ORs), comparing the highest versus lowest quartiles of intake. All statistical tests were two-sided. Contrary to the proposed hypothesis, CSD consumption was inversely associated with esophageal adenocarcinoma risk (highest versus lowest quartiles, OR = 0.47, 95% confidence interval = 0.29 to 0.76; Ptrend = .005), due primarily to intake of diet CSD. High CSD consumption did not increase risk of any esophageal or gastric cancer subtype in men or women or when analyses were restricted to nonproxy interviews. These findings indicate that CSD consumption (especially diet CSD) is inversely associated with risk of esophageal adenocarcinoma, and thus it is not likely to have contributed to the rising incidence rates.
Frequent Loss of HLA-A2 Expression in Metastasizing Ovarian Carcinomas Associated with Genomic Haplotype Loss and HLA-A2-Restricted HER-2/<i>neu</i>-Specific Immunity
Authors: Håkan Norell, Mattias Carlsten, Tomas Ohlum, Karl-Johan Malmberg, Giuseppe Masucci, Kjell Schedvins, Wolfgang Altermann, Diana Handke, Derek Atkins, Barbara Seliger, Rolf Kiessling
Journal: Cancer Research (2006)

Abstract Defective expression of HLA class I molecules is common in tumor cells and may allow escape from CTL-mediated immunity. We here investigate alterations in expression of HLA class I and their underlying molecular mechanisms in ovarian cancer patients. The HLA class I and HLA-A2 expression levels on noncultured tumor cells of 12 patients diagnosed with ovarian carcinoma were investigated by flow cytometry. Molecular analyses of antigen-processing machinery (APM) components were done in metastatic cancer cells, and the HLA genotype was determined in both these and the primary tumor. HER-2/neu-specific immunity was evaluated by enzyme-linked immunospot assays. The metastatic tumor cells from all patients expressed low levels of HLA class I surface antigens. In six of nine HLA-A2+ patients, HLA-A2 expression was heterogeneous with a subpopulation of tumor cells exhibiting decreased or absent HLA-A2 expression. One patient-derived tumor cell line completely lacked HLA-A2 but exhibited constitutive expression of APM components and high HLA class I expression that was further inducible by IFN-γ treatment. Genotyping showed a haplotype loss in the metastatic tumor cells, whereas tumor tissue microdissected from the primary tumor exhibited an intact HLA gene complex. Interestingly, HLA-A2-restricted HER-2/neu-specific T-cell responses were evident among the lymphocytes of this patient. Abnormalities in HLA class I antigen expression are common features during the progression of ovarian cancer, and haplotype loss was, for the first time, described as an underlying mechanism. (Cancer Res 2006; 66(12): 6387-94)
Cutaneous sarcoidosis during interferon alfa and ribavirin treatment of hepatitis C virus infection: two cases
Authors: O. Cogrel, M.S. Doutre, V. Marliere, M. Beylot-Barry, P. Couzigou, C. Beylot
Journal: British Journal of Dermatology (2002)

Interferon-induced sarcoidosis is well documented. We report two new cases of sarcoidosis in two patients with hepatitis C virus infection treated with interferon alfa and ribavirin. These patients developed cutaneous sarcoidosis about 3 months after the beginning of the combination therapy. Spontaneous regression of the lesions was noted after discontinuation of the treatment. There have been more than 20 observations of the appearance or aggravation of this granulomatosis with interferon alfa and more recently with the combination of interferon alfa plus ribavirin. Dermatological signs are found in 50% of cases, and are often diagnostic. Other clinical symptoms of sarcoidosis resemble side-effects of interferon. The evolution is fairly stereotypical and is marked by a regression of the lesions following a dose reduction or curtailment of interferon. Interferon alfa acts by stimulating the T-helper (Th) 1 immune response. In addition to its antiviral action, ribavirin also enhances the Th1 response. Indeed, the superiority of the combination of interferon alfa and ribavirin in terms of antiviral action is corroborated by the enhancement of a Th1-type immune reaction by this combination. At the same time, this immune cell reaction triggers a greater granulomatous reaction.
Circulating fibrocytes are increased in children and young adults with pulmonary hypertension
Authors: M.E. Yeager, C.M. Nguyen, D.D. Belchenko, K.L. Colvin, S. Takatsuki, D.D. Ivy, K.R. Stenmark
Journal: European Respiratory Journal (2011)

Chronic inflammation is an important component of the fibroproliferative changes that characterise pulmonary hypertensive vasculopathy. Fibrocytes contribute to tissue remodelling in settings of chronic inflammation, including animal models of pulmonary hypertension (PH). We sought to determine whether circulating fibrocytes were increased in children and young adults with PH. 26 individuals with PH and 10 with normal cardiac anatomy were studied. Fresh blood was analysed by flow cytometry for fibrocytes expressing CD45 and procollagen. Fibrocyte numbers were correlated to clinical and haemodynamic parameters, and circulating CC chemokine ligand (CCL)2 and CXC chemokine ligand (CXCL)12 levels. We found an enrichment of circulating fibrocytes among those with PH. No differences in fibrocytes were observed among those with idiopathic versus secondary PH. Higher fibrocytes correlated to increasing mean pulmonary artery pressure and age, but not to length or type of treatment. Immunofluorescence analysis confirmed flow sorting specificity. Differences in plasma levels of CCL2 or CXCL12, which could mobilise fibrocytes from the bone marrow, were not found. We conclude that circulating fibrocytes are significantly increased in individuals with PH compared with controls. We speculate that these cells might play important roles in vascular remodelling in children and young adults with pulmonary hypertension.
The impact of the neisserial DNA uptake sequences on genome evolution and stability
Authors: Todd J Treangen, Ole Herman Ambur, Tone Tonjum, Eduardo PC Rocha
Journal: Genome biology (2008)

Abstract Background Efficient natural transformation in Neisseria requires the presence of short DNA uptake sequences (DUSs). Doubts remain whether DUSs propagate by pure selfish molecular drive or are selected for 'safe sex' among conspecifics. Results Six neisserial genomes were aligned to identify gene conversion fragments, DUS distribution, spacing, and conservation. We found a strong link between recombination and DUS: DUS spacing matches the size of conversion fragments; genomes with shorter conversion fragments have more DUSs and more conserved DUSs; and conversion fragments are enriched in DUSs. Many recent and singly occurring DUSs exhibit too high divergence with homologous sequences in other genomes to have arisen by point mutation, suggesting their appearance by recombination. DUSs are over-represented in the core genome, under-represented in regions under diversification, and absent in both recently acquired genes and recently lost core genes. This suggests that DUSs are implicated in genome stability rather than in generating adaptive variation. DUS elements are most frequent in the permissive locations of the core genome but are themselves highly conserved, undergoing mutation selection balance and/or molecular drive. Similar preliminary results were found for the functionally analogous uptake signal sequence in Pasteurellaceae. Conclusion As do many other pathogens, Neisseria and Pasteurellaceae have hyperdynamic genomes that generate deleterious mutations by intrachromosomal recombination and by transient hypermutation. The results presented here suggest that transformation in Neisseria and Pasteurellaceae allows them to counteract the deleterious effects of genome instability in the core genome. Thus, rather than promoting hypervariation, bacterial sex could be regenerative.
Innovation, the new panacea
Authors: Kamran Abbasi
Journal: Journal of the Royal Society of Medicine (2013)

Innovation is hard to avoid, especially in healthcare. Even this issue of JRSM, which contains two articles concerned with innovation, has caught the bug.1,2 Innovation is the modern panacea. It will bring new products and novel approaches to clinicians and policy-makers. It will improve healthcare by delivering better quality care. Money is also a key theme here; indeed money and innovation seem to be inseparable. Successful innovations will save taxpayers' money while some of these innovations will make a few entrepreneurs and their financial backers unimaginably rich. There is a financial push and pull.

Still, innovation has many forms and several meanings. It might simply be a genius idea that requires support to make it reality. Another interpretation might be the ability of clinicians to be free of the bounds of ‘standard practice’, albeit in accordance with strict rules. Maurice Saatchi explains why his parliamentary bill to permit this particular form of innovation, focused on cancer care, is required and the arguments that he believes make it compelling.1

The challenge for medical journals is how to capture innovation. Innovation, by dictionary definition, is ‘something new which is introduced, a new idea or a method’. The problem is that medical journals, as much as they seek to, tend to struggle to present genuinely new ideas or methods.

By the time a randomized controlled trial is published, the idea or the method is no longer new; the innovatory phase has passed or reached a late stage. Yet, medical journals do not have established means of presenting the exciting early phase of innovation, which is unlikely to have been assessed by a randomized controlled trial, the gold standard methodology to evaluate any new intervention.

Some journals publish research letters, short papers or pilot studies. But none of these solutions is sufficient to capture the broad range of innovation in healthcare, from new products to new services. If we accept the inextricable link between innovation and costs, for example, how should a report capture the efficiency savings in a convincing way without embarking on a full economic analysis? There is no quick solution, which is why medical journals are a no entry zone for innovation.

Other journals have grappled with this challenge and failed. But it is a challenge that JRSM is willing to take on. Over the coming months we will consult with our editorial board and experts in innovation to devise a way of presenting assessments of new innovations in healthcare. Like others, we might fail, but we will not fear failure, for every successful innovation there will be several thousand that flounder.

Failure, by some accounts, is the new success; innovation, for its part, is the new panacea.
A functional polymorphism in the 5′ UTR of GDF5 is associated with susceptibility to osteoarthritis
Authors: Yoshinari Miyamoto, Akihiko Mabuchi, Dongquan Shi, Toshikazu Kubo, Yoshio Takatori, Susumu Saito, Mikihiro Fujioka, Akihiro Sudo, Atsumasa Uchida, Seizo Yamamoto, Koichi Ozaki, Masaharu Takigawa, Toshihiro Tanaka, Yusuke Nakamura, Qing Jiang, Shiro Ikegawa
Journal: Nature Genetics (2007)
Hodgkin’s disease occurring in a child after liver transplantation
Authors: V. Conter, B. Tschümperlin, B. Gridelli, A. Lucianetti, S. Ascani, D. Bauer, R. Burnelli, S. Poggi, V. Ramaccioni, M. Milani, S.A. Pileri
Journal: Annals of Oncology (1998)
Induction of Syndecan-1 Expression in Stromal Fibroblasts Promotes Proliferation of Human Breast Cancer Cells
Authors: Takashi Maeda, Caroline M. Alexander, Andreas Friedl
Journal: Cancer Research (2004)

Infiltrating carcinomas characteristically elicit a reactive stromal response, and accumulating evidence indicates that tumor stroma fibroblasts reciprocally promote tumor development and growth. The cell surface heparan sulfate proteoglycan, syndecan-1 (Sdc1), is thought to function as a coreceptor for growth factor and extracellular matrix interactions, and Sdc1 expression is induced in reactive stromal cells in both mice and man. Mice with a targeted mutation in Sdc1 show reduced tumor development in response to oncogene expression and altered responses to other pathological stimuli that are associated with the induction of stromal Sdc1. Here, we test the hypothesis that Sdc1 is required for the growth-promoting activities of reactive stroma. We found that when highly invasive carcinoma cells (MDA-MB-231) were placed in contact with mouse embryonic fibroblasts (MEFs) in a coculture model, Sdc1 expression was induced. Sdc1 was not induced by less invasive or normal cell lines (T47D and NMuMG). Furthermore, the growth of MDA-MB-231 cells was enhanced by 42% when cocultured with Sdc1+/+ MEFs compared with Sdc1-/- MEFs. When T47D cells were cocultured with fibroblasts that expressed transfected Sdc1, these Sdc1-positive fibroblasts stimulated growth of the breast epithelial cells by 85% compared with untransfected controls. The growth-promoting effect was completely abolished when fibroblasts were transfected with mutant Sdc1 lacking heparan sulfate attachment sites. In conclusion, we have demonstrated that a growth-promoting loop exists between breast cancer cells and their stroma that depends on the activity of glycanated Sdc1.
Pyelonephritic Escherichia coli Expressing P Fimbriae Decrease Immune Response of the Mouse Kidney
Authors: James C. Rice, Tao Peng, Jeff S. Spence, Hui-Qun Wang, Randall M. Goldblum, Blaise Corthésy, Bogdan J. Nowicki
Journal: Journal of the American Society of Nephrology (2005)

P fimbriae are proteinaceous appendages on the surface of Escherichia coli bacteria that mediate adherence to uroepithelial cells. E. coli that express P fimbriae account for the majority of ascending urinary tract infections in women with normal urinary tracts. The hypothesis that P fimbriae on uropathic E. coli attach to renal epithelia and may regulate the immune response to establish infection was investigated. The polymeric Ig receptor (pIgR), produced by renal epithelia, transports IgA into the urinary space. Kidney pIgR and urine IgA levels were analyzed in a mouse model of ascending pyelonephritis, using E. coli with (P+) and without (P-) P fimbriae, to determine whether P(+) E. coli regulate epithelial pIgR expression and IgA transport into the urine. (P+) E. coli establish infection and persist to a greater amount than P(-) E. coli. P(+)-infected mice downregulate pIgR mRNA and protein levels compared with P(-)-infected or PBS controls at > or =48 h. The decrease in pIgR was associated with decreased urinary IgA levels in the P(+)-infected group at 48 h. pIgR mRNA and protein also decline in P(+) E. coli-infected LPS-hyporesponsive mice. These studies identify a novel virulence mechanism of E. coli that express P fimbriae. It is proposed that P fimbriae decrease pIgR expression in the kidney and consequently decrease IgA transport into the urinary space. This may explain, in part, how E. coli that bear P fimbriae exploit the immune system of human hosts to establish ascending pyelonephritis.
The Cone Visual Pigments of an Australian Marsupial, the Tammar Wallaby (Macropus eugenii): Sequence, Spectral Tuning, and Evolution
Authors: S. S. Deeb
Journal: Molecular Biology and Evolution (2003)

Studies on marsupial color vision have been limited to very few species. There is evidence from behavioral, electroretinographic (ERG), and microspectrophotometric (MSP) measurements for the existence of both dichromatic and trichromatic color vision. No studies have yet investigated the molecular mechanisms of spectral tuning in the visual pigments of marsupials. Our study is the first to determine the mRNA sequence, infer the amino acid sequence, and determine, by in vitro expression, the spectra of the cone opsins of a marsupial, the tammar wallaby (Macropus eugenii). This yielded some information on mechanisms and evolution of spectral tuning of these pigments. The tammar wallaby retina contains only short-wavelength sensitive (SWS) and middle-wavelength sensitive (MWS) pigment mRNAs. This predicts dichromatic color vision, which is consistent with conclusions from previous behavioral studies ( Hemmi 1999). We found that the wallaby has a SWS1 class pigment of 346 amino acids. Sequence comparison with eutherian SWS pigments predicts that this SWS1 pigment absorbs maximally (λmax) at 424 nm and, therefore, is a blue rather than a UV pigment. This (λmax) is close to that of the in vitro–expressed wallaby SWS pigment (λmax of 420 ± 2 nm) and to that determined behaviorally (420 nm). The difference from the mouse UV pigment (λmax of 359 nm) is largely accounted for by the F86Y substitution, in agreement with in vitro results comparing a variety of other SWS pigments. This suggests that spectral tuning employing F86Y substitution most likely arose independently in the marsupials and ungulates as a result of convergent evolution. An apparently different mechanism of spectral tuning of the SWS1 pigments, involving five amino acid positions, evolved in primates. The wallaby MWS pigment has 363 amino acids. Species comparisons at positions critical to spectral tuning predict a λmax near 530 nm, which is close to that of the in vitro–expressed pigment (529 ± 1 nm), but quite different from the value of 539 nm determined by microspectrophotometry. Introns interrupt the coding sequences of the wallaby, mouse, and human MWS pigment sequences at the same corresponding nucleotide positions. However, the length of introns varies widely among these species.