tbuckley/cabot-search huggingface dataset:
Hepatocyte Growth Factor Suppresses Vascular Endothelial Growth Factor-Induced Expression of Endothelial ICAM-1 and VCAM-1 by Inhibiting the Nuclear Factor-κB Pathway
Authors: Jeong-Ki Min, Young-Mi Lee, Jeong Hun Kim, Young-Myeong Kim, Sung Wan Kim, Soo-Young Lee, Yong Song Gho, Goo Taeg Oh, Young-Guen Kwon
Journal: Circulation Research (2005)

Vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) are potent angiogenic factors that have been used clinically to induce angiogenesis. However, concerns have been raised about VEGF because of its proinflammatory actions, which include enhancing the adhesion of leukocytes to endothelial cells. We have examined the possible antiinflammatory effects of HGF on the vasculature. HGF, unlike VEGF, did not alter leukocyte adhesion to endothelial cells. Instead it inhibited VEGF-induced leukocyte-endothelial cell interactions and the endothelial expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). In a skin inflammation model, VEGF-treated mice showed a significant increase of leukocytes infiltrated or adherent to the luminal surface of blood vessels, as compared with vehicle- or HGF-treated mice. The VEGF effect was markedly suppressed by coadministration of HGF. RT-PCR and promoter analysis revealed that HGF downregulated VEGF-mediated expression of ICAM-1 and VCAM-1 at the transcriptional level. Furthermore, these inhibitory effects coincided with suppression of IkappaB kinase activity, and this in turn prevented the activation of the inflammatory transcription factor NF-kappaB. Taken together, our results demonstrate that HGF suppresses VEGF-induced inflammation presumably by inhibiting the endothelial NF-kappaB pathway. This suggests that combined treatment with HGF and VEGF could be superior to treatment with either factor alone for enhancing therapeutic angiogenesis while avoiding inflammation.
Regression of Abdominal Aortic Aneurysms by Simultaneous Inhibition of Nuclear Factor κB and Ets in a Rabbit Model
Authors: Takashi Miyake, Motokuni Aoki, Hisao Masaki, Tomio Kawasaki, Masako Oishi, Kazusaburo Kataoka, Toshio Ogihara, Yasufumi Kaneda, Ryuichi Morishita
Journal: Circulation Research (2007)

Because current therapy to treat abdominal aortic aneurysm (AAA), and particularly to manage small AAA, is limited to elective surgical repair, we explored less invasive molecular therapy by simultaneous inhibition of the transcription factors nuclear factor (NF)kappaB and ets using a decoy strategy. Both NFkappaB and ets were shown to be markedly activated in human AAA. In addition, NFkappaB- and ets-positive cells were increased in the aneurysm wall, and a part of the expression of NFkappaB and ets was detected in migrating macrophages. Thus, we used chimeric decoy oligodeoxynucleotides (ODNs) containing consensus sequences of both NFkappaB and ets binding sites to treat AAA. Inhibitory effects of chimeric decoy ODNs on matrix metalloproteinase-1 and -9 expression were confirmed by ex vivo experiments using a human aorta organ culture. To examine the regressive effect in a rabbit already-formed AAA model, transfection by wrapping a delivery sheet containing chimeric decoy ODNs around the aneurysm was performed 1 week after incubation with elastase. Importantly, treatment with chimeric decoy ODNs significantly decreased the size of AAA. Interestingly, significant preservation of elastic fibers was observed with chimeric decoy ODN treatment, accompanied by a reduction of matrix metalloproteinase-2 and -9 and induction of macrophage apoptosis. Regression of AAA was also associated with an increase in elastin and collagen type I and III synthesis in the aneurysm wall. Minimally invasive molecular therapy targeted to the inhibition of NFkappaB and ets is expected to be useful for AAA through the rebalance of matrix synthesis and degradation.
Effect of Drinking on Adiponectin in Healthy Men and Women
Authors: Armin Imhof, Ines Plamper, Steffen Maier, Gerlinde Trischler, Wolfgang Koenig
Journal: Diabetes Care (2009)

OBJECTIVE Moderate alcohol consumption is associated with reduced incidence of type 2 diabetes and cardiovascular mortality and increases adiponectin concentrations, but effects might differ according to sex and beverage consumed. RESEARCH DESIGN AND METHODS A total of 72 healthy individuals (22–56 years) were enrolled in this randomized controlled crossover trial. After washout, two interventions for 3 weeks followed: ethanol (concentration 12.5%), beer (5.6%), or red wine (12.5%) equivalent to 30 g ethanol/day for men and 20 g/day for women or the same de-alcoholized beverages or water. Adiponectin was measured by sandwich enzyme-linked immunosorbent assay. RESULTS Among women, adiponectin significantly increased after consuming red wine (29.8%, P &amp;lt; 0.05) and increased among men after ethanol solution (17.4%, P &amp;lt; 0.05) and consuming beer (16.1%, P &amp;lt; 0.05). De-alcoholized beverages had no substantial effect on adiponectin concentrations. CONCLUSIONS Moderate amounts of ethanol-containing beverages increased adiponectin concentrations, but sex-specific effects might depend on type of beverage consumed.
Phase I Study of Weekly Intravenous Infusions of CPT-11, a New Derivative of Camptothecin, in the Treatment of Advanced Non-Small-Cell Lung Cancer
Authors: S. Negoro, M. Fukuoka, N. Masuda, M. Takada, Y. Kusunoki, K. Matsui, N. Takifuji, S. Kudoh, H. Niitani, T. Taguchi
Journal: JNCI Journal of the National Cancer Institute (1991)

7-Ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothecin (CPT-11) is a novel camptothecin derivative that has been selected for clinical evaluation because of its broad spectrum of anti-tumor activity in animal models and its unique inhibitory effects on mammalian DNA topoisomerase I. Seventeen patients with advanced non-small-cell lung cancer were treated with CPT-11 at weekly dose levels ranging from 50 to 150 mg/m 2 . At least three weekly doses were given to all patients except four, and a total of 74 weekly doses were given to the 17 patients. The dose-limiting toxic effects were myelosuppression (predominantly leukopenia) and unpredictable diarrhea. Gastroin-testinal toxic effects were severe and not well controlled by standard therapy in some patients. Interpatient variability of toxic effects was substantial (including two deaths) and did not correlate with the pharmacokinetic parameters of CPT-11 and 7-ethyl-10-hydroxycamptothecin, its major metabolite. Two previously untreated patients, who received doses of 100 and 125 mg/m 2 , had partial responses lasting 3.2 and 4.0 months, respectively. The maximum tolerated dose on this schedule was 100 mg/m 2 , which we also recommend as a starting dose for phase II studies. This schedule appears to allow a CPT-11 dose intensity which is double the dose intensity possible on a once-a-month schedule. However, careful supervision to assess gastrointestinal toxic effects and myelosuppression is indispensable because of wide individual differences in drug tolerance. [J Natl Cancer Inst 83: 1164–1168, 1991]
US health system doesn't give value for money, report says
Authors: Janice Hopkins Tanne
Journal: BMJ (2005)

More is spent per person on health care in the United States than in any of the other 29 industrialised countries in the Organization for Economic Cooperation and Development (OECD). The reason is higher prices in the United States, not malpractice litigation and defensive medicine, says an annual study published in Health Affairs (2005;24:903-14).

The study also refutes the argument that high spending in the US means that healthcare capacity is high. It says that many other OECD countries have a higher number of doctors, nurses and hospital beds per population and their spending is much lower than that in the US.

“It's the prices, stupid,” the authors argued in a previous paper ( Health Affairs 2003;22:89-105). US prices are higher because “there's no single entity to negotiate with providers on prices,” as there is in the United Kingdom and many other …
Chair of NICE backs call for all clinical trial data to be public
Authors: A. O'Dowd
Journal: BMJ (2014)

The head of the National Institute for Health and Care Excellence has told MPs that all clinical trial data should be made public, as there is a “moral imperative” to do so.

David Haslam, chair of NICE, appeared before the parliamentary health committee on 2 September as part of an evidence session for its inquiry into the institute’s work. NICE, the UK body that evaluates the benefits and cost effectiveness of medicines and treatments and makes recommendations about which of these the NHS should provide, has already signed up to the AllTrials campaign (www.alltrials.net). The initiative—backed by the charity Sense About Science, The BMJ , the James Lind Alliance, Ben Goldacre (author of Bad …
Radicals in the church
Authors: T.M.C.M. de Kok, J.G.F. Hogervorst, J.C.S. Kleinjans, J.J. Briedé
Journal: European Respiratory Journal (2004)

To the Editors: 

Public health is seriously threatened by exposure to ambient and indoor particulate matter (PM). Epidemiological studies have demonstrated that long-term exposure is associated with lung cancer and other pulmonary diseases 1. In vitro studies have demonstrated the involvement of polycyclic aromatic hydrocarbons (PAH), inflammation and oxidative stress in these adverse health effects 2–4. As free radicals are also known to play a crucial role in these processes, we developed an electron spin resonance (ESR)-based methodology to quantify the radical-generating capacity of PM. We applied this methodology in order to evaluate the effect of burning candles and incense, known sources of indoor air PM …
NATURAL HEALTH PRODUCTS AND DRUG DISPOSITION
Authors: Brian C. Foster, J. Thor Arnason, Colin J. Briggs
Journal: The Annual Review of Pharmacology and Toxicology (2004)

Botanicals such as herbal products (HPs) and nutraceuticals (NCs) are often regarded as low risk because of their long history of human use. Anecdotal and literature reports of adverse drug events (ADEs) and clinical studies with HPs are increasing, but many of the reports are incomplete and contradictory. These reports need to identify confounding factors and explain contradictory findings if they are to help health care professionals or patients understand what risks are involved. HPs are complex botanicals, not single-active ingredient (SAI) products. Studies can be confounded by different manufacturing processes and formulations, including cosmetics and food supplements; environment; chemotypes; misidentification or adulteration; and factors associated with the patient or user population such as use, total drug load, and genetics. Future studies need to be conducted with characterized product that includes all commercially available related products. Clinical trials should be relevant to the user population and take into account the confounding factors that may influence the interpretation of the findings.
Plasticity in Urokinase-Type Plasminogen Activator Receptor (uPAR) Display in Colon Cancer Yields Metastable Subpopulations Oscillating in Cell Surface uPAR Density—Implications in Tumor Progression
Authors: Lin Yang, Hector Avila, Heng Wang, Jose Trevino, Gary E. Gallick, Yasuhiko Kitadai, Takamitsu Sasaki, Douglas D. Boyd
Journal: Cancer Research (2006)

Abstract It is becoming increasingly clear that tumor growth and progression is not entirely due to genetic aberrations but also reflective of tumor cell plasticity. It follows therefore that proteins contributing to tumor progression oscillate in their expression a contention yet to be shown. Because the urokinase-type plasminogen activator receptor (uPAR) promotes tumor growth and invasion, we determined whether its expression is itself plastic. In fluorescence-activated cell sorting (FACS), three independent colon cancer clonal populations revealed the expected Gaussian distribution for cell surface uPAR display. However, subcloning of cells collected from the trailing edge of the FACS yielded subpopulations, displaying low cell surface uPAR number. Importantly, these subclones spontaneously reverted to cells enriched in uPAR display, indicating a metastable phenotype. uPAR display plasticity was associated with divergent in vivo behavior with weak tumor growth and progression segregating with receptor deficiency. Mechanistically, reduced uPAR display reflected not repressed gene expression but a switch in uPAR protein trafficking from membrane insertion to shedding. To our knowledge, this is the first demonstration that uPAR cell surface density is oscillatory and we propose that such an event might well contribute to tumor progression. (Cancer Res 2006; 66(16): 7957-67)
Pathology in the Soviet Union
Authors: F. Kash Mostofi
Journal: JAMA (1980)

Five pathologists from the United States visited the Soviet Union for three weeks in April 1978 to learn of the training in and the practice of pathology in that country. The major observations of the Americans were that (1) pathology is a medical specialty in the Soviet Union, with practice limited to anatomic pathology; (2) exfoliative cytology and clinical pathology are not part of pathology; (3) interest, both clinical and experimental, in occupational, environmental, and geographic pathology is conspicuous; (4) an autopsy rate of 90% to 95% is customary; and (5) there is an organized and hierarchical framework for practice, with career patterns established early and change infrequent.
Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians
Authors: Yoon Shin Cho, Chien-Hsiun Chen, Cheng Hu, Jirong Long, Rick Twee Hee Ong, Xueling Sim, Fumihiko Takeuchi, Ying Wu, Min Jin Go, Toshimasa Yamauchi, Yi-Cheng Chang, Soo Heon Kwak, Ronald C W Ma, Ken Yamamoto, Linda S Adair, Tin Aung, Qiuyin Cai, Li-Ching Chang, Yuan-Tsong Chen, Yutang Gao, Frank B Hu, Hyung-Lae Kim, Sangsoo Kim, Young Jin Kim, Jeannette Jen-Mai Lee, Nanette R Lee, Yun Li, Jian Jun Liu, Wei Lu, Jiro Nakamura, Eitaro Nakashima, Daniel Peng-Keat Ng, Wan Ting Tay, Fuu-Jen Tsai, Tien Yin Wong, Mitsuhiro Yokota, Wei Zheng, Rong Zhang, Congrong Wang, Wing Yee So, Keizo Ohnaka, Hiroshi Ikegami, Kazuo Hara, Young Min Cho, Nam H Cho, Tien-Jyun Chang, Yuqian Bao, Åsa K Hedman, Andrew P Morris, Mark I McCarthy, Ryoichi Takayanagi, Kyong Soo Park, Weiping Jia, Lee-Ming Chuang, Juliana C N Chan, Shiro Maeda, Takashi Kadowaki, Jong-Young Lee, Jer-Yuarn Wu, Yik Ying Teo, E Shyong Tai, Xiao Ou Shu, Karen L Mohlke, Norihiro Kato, Bok-Ghee Han, Mark Seielstad
Journal: Nature Genetics (2011)
Clostridium difficile-associated diarrhoea: bovine anti-Clostridium difficile whey protein to help aid the prevention of relapses
Authors: S. C Numan, P. Veldkamp, E. J Kuijper, R. J van den Berg, J. T van Dissel
Journal: Gut (2007)

Antibiotic treatment can usually help in symptomatic recovery in Clostridium difficile -associated diarrhoea (CDAD), but recurrent episodes of diarrhoea remain a major problem.1–4 Besides increasing the dose or extending the course of antibiotics, and using alternating or pulsed regimens, there are no effective alternatives to prevent relapses.5 Previously, we reported on anti- Clostridium difficile whey protein concentrate (anti-CD-WPC) made from the milk of cows immunised against C difficile and its toxins. Anti-CD-WPC is prepared using standard techniques used in the milk industry, and contains a high concentration of sIgA directed against C difficile and its toxins. It neutralises the cytotoxicity of C difficile toxins in vitro and protects hamsters against otherwise lethal C difficile -associated cecitis.6

The aim of this study was to assess the preliminary efficacy of anti-CD-WPC in aiding the prevention of relapses in patients with CDAD confirmed by positive faecal C difficile toxin assay and …
Montelukast and Churg-Strauss syndrome
Authors: R Solans
Journal: Thorax (2002)

Several cases of eosinophilic conditions including Churg-Strauss syndrome (CSS) have recently been reported in asthmatic patients being treated with antileukotriene receptor antagonists. One patient with CSS who experienced a clinical relapse after treatment with montelukast and two asthmatic patients who developed CSS while receiving montelukast treatment are described. In one case reduction in the dose of oral steroid preceded the onset of CSS. To our knowledge, no case of CSS relapse has previously been reported in association with leukotriene antagonists.
Tumor necrosis factor-α is a marker of familial combined hyperlipidemia, independently of metabolic syndrome
Authors: Paolo Pauciullo, Marco Gentile, Gennaro Marotta, Angela Baiano, Stefania Ubaldi, Fabrizio Jossa, Gabriella Iannuzzo, Fulvio Faccenda, Salvatore Panico, Paolo Rubba
Journal: Metabolism (2008)
P09.04 * CAROTID PLAQUE MRI AND STROKE AFTER RADIOTHERAPY: A LONG-TERM PROSPECTIVE COHORT STUDY
Authors: J. Wilbers, F. Meijer, A. Kappelle, W. Boogerd, L. Dorresteijn, E. van Dijk, S. Steens
Journal: Neuro-Oncology (2014)

PURPOSE: Radiotherapy(RT) induced carotid artery vasculopathy and ischemic strokes are long-term complications after radiotherapy of the neck. The exact underlying pathofysiology of this RT induced atherosclerosis is not understood. The current study evaluated the presence and MRI characteristics of radiotherapy induced long-term carotid wall and cerebral complications in survivors of head and neck cancer (HNC). METHODS: Prospective multicenter long-term cohort study of 43 patients (mean age 60 years, SD 13) treated with RT of the neck because of head and neck cancer. Cerebrovascular risk factors were assessed at baseline (before RT). At follow-up (mean 7 years after RT) patients were evaluated with a MRA / MRI of the carotid arteries and the brain. First endpoint was frequency and characteristics (degree of stenosis, location, composition) of vessel wall changes. Secondary endpoints were frequency of white matter lesions, atrophy and (silent) brain infarctions. RESULTS: We found a vessel wall thickening in 55% of the irradiated common carotid arteries versus 18% in the non-irradiated. (p = 0.003). In the internal carotid arteries vessel wall thickening was found in 24% of the irradiated versus 6% of the non-irradiated arteries. (p = 0.02). Mean length of vessel wall thickening in the irradiated common and internal carotid arteries was 48.9 and 20 mm, respectively. In 50% of the irradiated common carotid arteries degree of stenosis was between 0 and 50%. MRI of the brain showed focal white matter lesions in 47% and mild atrophy in 33% of patients. CONCLUSION: Our study showed a significant increase in vessel wall changes on a long carotid segment in irradiated versus non-irradiated carotid arteries with a follow-up of 7 years after radiotherapy. An important proportion of patients also had intracranial vascular brain changes.
Abnormal platelet von willebrand factor (vWF) as a marker of abnormal function in megakaryocytic dysplasia
Authors: F. de Cataldo, F. Baudo, R. Redaelli, A. R. Corno
Journal: American Journal of Hematology (1995)

The myelodysplastic syndromes (MDS) are neoplastic disorders of the hemopoietic system; multilineage involvement is also evidenced by specific cellular dysfunctions. The von Willebrand factor (vWF), synthesized and processed in the megakaryocytes (MK), is stored in the alpha granules of the platelets. The platelet vWF multimeric pattern was studied in 18 patients with MDS, and in 4 with pernicious anemia (PA), to investigate whether the processing of vWF is abnormal in the megakaryocytic dysplasia. An abnormal multimeric pattern was observed in 10/18 MDS and 4/4 PA patients. The abnormality of this specific protein is the discrete expression of the basic disorder, and is reversible when hemopoiesis is normalized. Although the data do not allow any conclusion, abnormal synthesis is the likely explantation of the abnormality.
External antigen uptake by Langerhans cells with reorganization of epidermal tight junction barriers
Authors: Akiharu Kubo, Keisuke Nagao, Mariko Yokouchi, Hiroyuki Sasaki, Masayuki Amagai
Journal: The Journal of Experimental Medicine (2009)

Outermost barriers are critical for terrestrial animals to avoid desiccation and to protect their bodies from foreign insults. Mammalian skin consists of two sets of barriers: stratum corneum (SC) and tight junctions (TJs). How acquisition of external antigens (Ags) by epidermal Langerhans cells (LCs) occur despite these barriers has remained unknown. We show that activation-induced LCs elongate their dendrites to penetrate keratinocyte (KC) TJs and survey the extra-TJ environment located outside of the TJ barrier, just beneath the SC. Penetrated dendrites uptake Ags from the tip where Ags colocalize with langerin/Birbeck granules. TJs at KC–KC contacts allow penetration of LC dendrites by dynamically forming new claudin-dependent bicellular- and tricellulin-dependent tricellular TJs at LC–KC contacts, thereby maintaining TJ integrity during Ag uptake. Thus, covertly under keratinized SC barriers, LCs and KCs demonstrate remarkable cooperation that enables LCs to gain access to external Ags that have violated the SC barrier while concomitantly retaining TJ barriers to protect intra-TJ environment.
Increased Aldosterone Secretion in Response to Blood Loss
Authors: GORDON L. FARRELL, ROBERT S. ROSNAGLE, ELIZABETH W. RAUSCHKOLB, Robert Banks, Milena Saleliar
Journal: Circulation Research (1956)

A marked increase in the adrenal secretion of the potent electrolyte-active steroid, aldosterone, was observed in the dog in response to loss of blood. The proportionate increase in adrenal output of alclostcrone exceeded that of hydrocortisone. The physiologic mechanism by which the increased aldosterone release is mediated remains obscure. The stimulus to increased aldosterone secretion was not a change in the serum electrolytes. Expansion of the volume of the vascular system by the infusion of large amounts of plasma substitutes failed to uniformly prevent the increased aldosterone output.
Identification of a Melanoma Marker Derived from Melanoma-Associated Endogenous Retroviruses
Authors: Johannes Humer, Andrea Waltenberger, Andreas Grassauer, Martin Kurz, Julia Valencak, Ronald Rapberger, Silvia Hahn, Roswitha Löwer, Klaus Wolff, Michael Bergmann, Thomas Muster, Bernd Mayer, Hubert Pehamberger
Journal: Cancer Research (2006)

Abstract We previously described the expression of melanoma-associated endogenous retrovirus (MERV) proteins and viral particles in human melanomas and metastases. The objective of the present study was to determine whether a humoral immune response to MERV proteins occurs in melanoma. Candidate B-cell epitopes on MERV proteins were predicted using bioinformatic screening. The reactivity of MERV peptides corresponding to the predicted epitopes with antibodies prevalent in sera of melanoma patients was analyzed. An immunodominant peptide located in the env protein of MERV was identified. Subsequent analyzes using 81 samples from stage I to stage IV melanoma patients and 95 sera from healthy subjects revealed statistically significant differences in seroprevalence of antibodies in melanoma sera samples when compared with reference samples from healthy subjects. The prevalence of anti-MERV antibodies in melanoma patient sera was confirmed by immunofluorescence on env-transfected cells. These data indicate the potential of this candidate peptide as target for diagnosis and immunotherapy. (Cancer Res 2006; 66(3): 1658-63)