tbuckley/cabot-search huggingface dataset:
Open access to research findings will deliver huge benefits but will not be cost free, report says
Authors: N. Hawkes
Journal: BMJ (2012)

Moving to an open access model for publishing research findings is likely to cost the United Kingdom £50m (€62m; $78m) to £60m a year in the transition period, a working group commissioned by the government has found.1

Although ultimately open access should be cost neutral, with payments made by authors to have their research published making up for a reduction in subscriptions paid to publishers, that will not be true in the short term, the group chaired by Janet Finch, professor of sociology at Manchester University, concludes.

That is because UK research is a small proportion of the world total (6%), and during the transition there will be a period of “double running” in which author payments and subscriptions for international journals are levied at the same time. “The danger is that we could make our own publications free but still pay subscriptions for others,” …
Increased expression of collagenase-3 (MMP-13) and MT1-MMP in oesophageal cancer is related to cancer aggressiveness
Authors: T Etoh
Journal: Gut (2000)

Collagenase-3 (matrix metalloproteinase-13, MMP-13) is a recently identified human MMP with broad substrate specificity which can be activated by membrane type 1 (MT1) matrix metalloproteinase in vitro. These may play a critical role in cancer aggressiveness.To examine the clinical significance of collagenase-3 expression and the cooperative role of MT1-MMP in human oesophageal carcinomas.Forty five individuals with oesophageal carcinoma who underwent surgery without preoperative treatment.The tumour/normal (T/N) ratios of collagenase-3 and MT1-MMP mRNA expression in 45 human oesophageal carcinomas were determined by northern blot analysis. The production and localisation of collagenase-3 and MT1-MMP proteins were investigated by immunohistochemistry, western blot analysis, and zymography.The mean T/N ratio of collagenase-3 mRNA was 3.5 and that of MT1-MMP 2.1. There was a significant correlation between collagenase-3 and MT1-MMP mRNA expression (p<0.001). Twenty two cases with a collagenase-3 T/N ratio >3.5 showed a significantly higher frequency of vascular involvement and lymph node metastasis, and tended to be at a more advanced stage than 23 cases with a T/N ratio < or =3.5 (p<0.05). Western blot analysis and zymography demonstrated production of collagenase-3 protein in tumour tissues but not in normal tissues. Immunohistochemical studies revealed that collagenase-3 was localised predominantly in tumour cells and MT1-MMP was detected in the same collagenase-3 positive cells; there was a significant association between collagenase-3 and MT1-MMP protein expression (p<0.05). With regard to prognosis, the survival time for subjects in the high collagenase-3 group (T/N ratio >3.5) was significantly worse (p<0.05).These data suggest that production of collagenase-3 together with MT1-MMP is implicated in tumour aggressiveness and prognosis in human oesophageal carcinomas.
Systemic Lupus Erythematosus
Authors: Thomas G. Benedek
Journal: JAMA (1987)

For the last 20 years, the monograph by Edmund Dubois (1966 and 1974 editions) has been the standard reference on lupus erythematosus, a disease about which information has been accruing rapidly. Lahita and 51 contributors have, in detail and with bibliographic thoroughness, produced the first challenge. The first three sections, on etiologic theories, animal models of the disease, and autoantigens and antibodies, constitute about one third of the text and provide an excellent presentation of the current understanding of the relevant immunology, immunopathology, and genetics. The following four sections are on clinical approach, organ system approach, drug-induced systemic lupus erythematosus (SLE), and therapeutic approaches. The general clinical section includes everything one might expect, with the exception of a chapter on the epidemiology of the disease. There is some duplication, such as presentation of the experimental mouse model of SLE in the chapter "Sex and Age in SLE" despite an exhaustive
Wire guided balloon assisted endoscopic biliary stent exchange.
Authors: D F Martin
Journal: Gut (1991)

A simple technique of endoscopic stent exchange using a biliary dilatation balloon is described. The technique is appropriate in patients with bile duct malignancy in whom clogging of a previously placed straight stent has occurred. Balloon assisted exchange has been used in 25 patients to date and minimises the risks of failure of stent reinsertion and the need for further procedures in patients with limited life expectancy.
Abstract 6: A triple-helix forming oligonucleotide targeting a genomic locus is capable of sequence specific mutagenesis in human lymphoblastoid TK6 cells
Authors: Reshat Reshat, Catherine Priestley, Nigel J. Gooderham
Journal: Cancer Research (2010)

Abstract It has been reported that DNA triplex formation induces mutagenesis as determined using plasmid-based reporter constructs (Wang et al 1996, Science, 271, p802). Triplex mediated mutagenesis has been shown to include point mutations, deletions, small insertions and homologous recombination. To the best of our knowledge, no study has successfully examined the mutagenic potential of a non-conjugated triplex-forming oligonucleotide (TFO) targeting a genomic sequence. In this study, we have designed a TFO that targets the hemizygous hypoxanthine-guanine phosphoribosyltransferase (HPRT) locus, in the human lymphoblastoid TK6 cell line, and assessed mutagenicity through resistance to 6-thioguanine. Our TFO, TFO27, has been designed to form a triplex with a purine tract in exon 3 of the HPRT gene. Triplex formation at the target motif was shown to occur at nanomolar concentrations, confirmed by Electrophoretic Mobility Shift Assays. A scrambled oligonucleotide, SCR27, failed to form a triplex at the target motif. A range of transfection reagents were evaluated for facilitated delivery of TFO27, and resulted in variable cellular toxicity. Transfection of high concentrations of oligonucleotide, with acceptable levels of cytotoxicity, resulted in HPRT mutation with TFO27 but not SCR27. Similar experiments failed to result in mutation at the non-targeted thymidine kinase (TK) locus, suggesting locus specificity for the mode of action of TFO27. The target specificity and sequence context of these mutagenic events is being determined to establish the mechanism of mutation. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 6.
Toxic Shock Syndrome: Clinical and Laboratory Features in 15 Patients
Authors: ROBERT W. TOFTE
Journal: Annals of Internal Medicine (1981)

Toxic shock syndrome is a recently recognized illness with serious morbidity and mortality that occurs primarily in healthy menstruating women who use tampons. Thirteen women and two men were evaluated; two of the women died in spite of seemingly appropriate therapy. All patients had a temperature of 38.9 degrees C or greater, hypotension of syncope, a skin rash with subsequent desquamation, mucous membrane inflammation, and laboratory evidence of multiple organ dysfunction. Staphylococcus aureus was isolated from the cervix or vagina in eight women and from soft-tissue infections in both men. Two patients were bacteremic. The significant heterogeneity in the clinical manifestations, laboratory abnormalities, and therapeutic requirements among patients may result in diagnostic confusion and inappropriate therapy. Although toxic shock syndrome appears to be associated with tampon usage and S. aureus, the pathogenesis remains unknown.
Liver Fluke Induces Cholangiocarcinoma
Authors: Banchob Sripa, Sasithorn Kaewkes, Paiboon Sithithaworn, Eimorn Mairiang, Thewarach Laha, Michael Smout, Chawalit Pairojkul, Vajaraphongsa Bhudhisawasdi, Smarn Tesana, Bandit Thinkamrop, Jeffrey M Bethony, Alex Loukas, Paul J Brindley
Journal: PLoS Medicine (2007)

Liver fl uke infection caused by Opisthorchis viverrini, O. felineus, and Clonorchis sinensis is a major public health problem in East Asia and Eastern Europe.Currently, more than 600 million people are at risk of infection with these trematodes [1].O. viverrini is endemic in Southeast Asian countries, including Thailand, Lao People's Democratic Republic, Vietnam, and Cambodia [2], and C. sinensis infection is common in rural areas of Korea and China.Opisthorchiasis has been extensively studied in Thailand, where an estimated 6 million people are infected with the liver fl uke (calculated from overall 9.4% prevalence within the population in 2001) [3].Infection with these food-borne parasites is prevalent in areas where uncooked cyprinoid fi sh are a staple of the diet.Due to poor sanitation practices and inadequate sewerage infrastructure, people infected with O. viverrini and C. sinensis pass parasite eggs in their faeces into natural water reservoirs, where the parasite eggs are eaten by intermediate host snails, for example, aquatic snails of the genus Bithynia, the fi rst intermediate host of O. viverrini.After hatching, free swimming parasites, called cercariae, are released from the infected snails.Cercariae then locate their next intermediate host, cyprinoid fi shes, encyst in the fi ns, skin, and muscles of the fi sh, and become metacercariae.The metacercariae are infective to humans and other fi sh-eating mammals upon ingestion of raw or undercooked fi sh in dishes such as koi-pla (Figure 1), and in turn the parasite's life cycle is completed (Figure 2).Most people with opisthorchiasis or clonorchiasis have no symptoms.Only 5%-10% of infected people, in general those with heavy fl uke infections, have non-specifi c symptoms such as right upper quadrant abdominal pain, fl atulence, and fatigue [4,5].Enlargement of the gall bladder can be detected by ultrasonography, and is reversed after elimination of fl ukes by praziquantel [6].Nonetheless, heavy, long-standing infection is associated with a number of hepatobiliary diseases, including cholangitis, obstructive jaundice, hepatomegaly, fi brosis of the periportal system, cholecystitis, and cholelithiasis [7][8][9][10].Moreover, both experimental and epidemiologic evidence strongly implicates liver fl uke infection in the aetiology of one of the liver cancer subtypes-cholangiocarcinoma (CCA), or cancer of the bile ducts [2,11].The pathology of clonorchiasis was recently reviewed in detail by Rim [12].Unlike O. viverrini, C. sinensis is not considered a Group I carcinogen (known to be carcinogenic in humans) [2], despite its widespread prevalence [13].In
P201 Health literacy and sleep apnoea
Authors: R. Ghiassi, M. R. Partridge
Journal: Thorax (2010)

<h3>Introduction</h3> We have previously demonstrated that 33% of new patients and 16% of serial users have difficulty completing the Epworth Sleepiness Scale (ESS). To explore reasons for this we assessed literacy in a further group of patients. <h3>Methods</h3> 122 Sleep Centre and Lung Function laboratory patients were approached and assessed for level of functional literacy in medicine using the REALM questionnaire. A score ≤60 suggests a literacy level that would struggle with patient education materials and prescription labels. Education and English language data were collected. <h3>Results</h3> 86/92 (93.3%) Sleep and 30/30 (100%) Lung function (LF) patients completed REALM. 5 (5.6%) in the Sleep group declined when shown the test. One did not complete due to time restrictions. Mean age was 51.2 ± 11.8 years Sleep and 56.1 ± 17 years LF. Mean age leaving formal education was 18.7 ± 2.9 years Sleep and 17.7 ± 2.9 years LF. In the Sleep cohort 24% (21/86) had a graduate and 15% (13/86) postgraduate education vs. LF 27% (8/30) graduate and 3% (1/30) postgraduate education. REALM scores are shown in Abstract P201 Table 1 grouped into the standard four ranges. 78% (Sleep) and 83% (LF) spoke English as their mother tongue; all patients used English as their everyday spoken language. <h3>Conclusions</h3> Assessing literacy in patients is not easy. We have previously shown how patients struggle to complete the ESS. Problems completing forms occur for many reasons and evidence suggests that clinicians overestimate patient literacy. We found evidence of impaired health literacy in 16.3% of Sleep and 10% of Lung function patients. That some Sleep patients declined to be tested once shown the questionnaire might suggest the 16.3% score is underestimated. Why Sleep patients should fare worse than LF patients is unclear especially when university and age leaving education were higher in the sleep cohort. All used English as their everyday language however fewer Sleep patients had English as their mother tongue. Cognitive deficits associated with undiagnosed obstructive sleep apnoea syndrome and increased sleepiness could conceivably be a contributory factor. This study suggests clinicians need to provide clinical material and information in a format that is comprehensible to a wide range of patients (such as pictorial format) and that Sleep patients may have special needs.
Phototoxic reaction and porphyrin fluorescence in skin after topical application of methyl aminolaevulinate
Authors: E. Angell-Petersen, C. Christensen, C.R. Müller, T. Warloe
Journal: British Journal of Dermatology (2006)

Photodynamic therapy using topical methyl aminolaevulinate (MAL) is a new treatment modality for skin disorders. MAL is metabolized into endogenous porphyrins, which act as photosensitizers when illuminated.To evaluate the severity and duration of skin photosensitivity after MAL application, and to investigate its relation to the presence of endogenous porphyrins.Placebo and 160 mg g(-1) MAL creams were randomly assigned to contralateral sites located at the forearms and fingertips of 16 healthy volunteers and were applied for 3 h. The porphyrin content in the skin was monitored by in situ fluorescence measurements following cream removal. Phototoxic reaction was evaluated after exposure to a high dose of red light.The porphyrin fluorescence in forearm skin peaked about 1 h after the cream removal, was halved after 8 h, and was reduced by > 90% within 24 h. Most forearm sites were photosensitive at 1 and 8 h following cream removal. Six subjects were still sensitive at 24 h, and at this time point the phototoxicity was coincidental with residual porphyrin fluorescence. In general, all reactions were mild or moderate, and included pain, erythema, oedema and transient hyperpigmentation. No photosensitivity or porphyrin fluorescence was detected at 48 h. At the fingertips photosensitivity was absent except for sporadic cases of mild pain.Topical MAL application and exposure to red light induced mild and moderate phototoxicity. The photosensitivity ceased within 24-48 h after cream removal, and its duration was associated with the degradation of porphyrins.
Omeprazole Therapy in Resistant Reflux Disease
Authors: Helge L. Waldum
Journal: Annals of Internal Medicine (1995)

Letters1 February 1995Omeprazole Therapy in Resistant Reflux DiseaseHelge L. Waldum, MD and Eiliv Brenna, MDHelge L. Waldum, MDSearch for more papers by this author and Eiliv Brenna, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-122-3-199502010-00019 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:We read with interest the article by Klinkenberg-Knol and coworkers [1] on omeprazole safety and the accompanying editorial by Freston [2]. Although the report by Klinkenberg-Knol and colleagues [1] offered a well-balanced description of gastrin values and micronodular neuroendocrine cell hyperplasia in the oxyntic mucosa of many patients receiving omeprazole maintenance treatment, the editorial [2] tended to underestimate the risks for hypergastrinemia. Thus, it was not considered that the maximal functional and trophic effects of gastrin in the rat and in humans on the enterochromaffin-like (ECL) cell are reached at a concentration of less than 500 pM ...References1. Klinkenberg-Knol EC, Festen HP, Jansen JB, Lamers CB, Nelis F, Snel P, et al. Long-term treatment with omeprazole for refractory reflux esophagitis: efficacy and safety. Ann Intern Med. 1994; 121:161-7. Google Scholar2. Freston JW. Omeprazole, hypergastrinemia, and gastric carcinoid tumors (Editorial). Ann Intern Med. 1994; 121:232-3. Google Scholar3. Waldum HL, Petersen H, Brenna E. Gastrin and gastric cancer. Eur J Gastroenterol Hepatol. 1992; 4:801-11. Google Scholar4. Lamberts R, Creutzfeldt W, Stuber HG, Brunner G, Solcia E. Long-term omeprazole therapy in peptic ulcer disease: gastrin, endocrine cell growth, and gastritis. Gastroenterology. 1993; 104:1356-70. Google Scholar5. Waldum HL, Lehy T, Brenna E, Sandvik AK, Petersen H, Schulze Sognen B, et al. Effect of the histamine-1 antagonist astemizole alone or with omeprazole on rat gastric mucosa. Scand J Gastroenterol. 1991; 26:23-35. Google Scholar Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByCOST-EFFECTIVE MANAGEMENT OF DYSPEPSIA AND GASTROESOPHAGEAL REFLUX DISEASE 1 February 1995Volume 122, Issue 3Page: 236-237KeywordsFoodGastrinHypergastrinemiaMucous membranesParietal cellsPernicious anemiaRespiratory system proceduresRisk managementSafetyStomach Issue Published: 1 February 1995 CopyrightCopyright © 1995 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Mother to Child: First Living Donor Lung Transplant
Authors: Marsha F. Goldsmith
Journal: JAMA (1990)

IN THE LATEST example of the lengths to which a mother will go in hopes of saving the life of a terminally ill child, 45-year-old Versell Johnson of Salt Lake City, Utah, donated one third of her right lung to replace the entire right lung of her 12-year-old daughter, Mazie Bond. The child suffered from bronchopulmonary dysplasia but "both mother and daughter are expected to resume normal activity within a few months," says Vaughn A. Starnes, MD, head of the heart-lung transplant program, Stanford (Calif) University Medical Center, who did the operation. Starnes is evaluating several more cases for possible living-donor transplantation. He estimates that several hundred children in the United States might benefit each year from a single lung transplant—from a live donor or a cadaver—to help them deal with the effects of bronchopulmonary dysplasia, pulmonary hypertension, and congenital diaphragmatic hernias. Starnes says the fact that children who receive
Abstract 3090: Oncogenic ETS transcription factors bind ETS/AP-1 sequences and activate a RAS/MAPK gene expression program in the absence of MAPK activation
Authors: Peter C. Hollenhorst, Mary W. Ferris, Megan A. Hull, Heejoon Chae, Sun Kim, Barbara J. Graves
Journal: Cancer Research (2012)

Abstract Deciphering the mechanism of transcription factor function in both normal and disease states requires understanding how these proteins are targeted to specific genomic binding sites, influence transcription, and how these functions are modified by signaling pathways. However, overlapping functions among the thousands of transcription factors encoded by the human genome have made it difficult to assign specific mechanisms. Approximately 50% of prostate cancers have chromosomal rearrangements resulting in the over-expression any one of four ETS-family transcription factors. It is not known why these four ETS family members are associated with prostate cancers, while the other 24 human ETS genes are not. We found that the four oncogenic ETS family members have a specific role in prostate cell migration that does not extend to other family members. Using chromatin immunoprecipitation coupled with next-generation sequencing (ChIP-seq), this specific biological function was matched to a specific set of genomic targets highlighted by the presence of both ETS and AP-1 binding sequences. ETS/AP-1 binding sequences are prototypical RAS-responsive elements where a MAPK can phosphorylate ETS proteins increasing transcriptional activation. We found that oncogenic ETS proteins could activate a RAS/MAPK transcriptional program when the MAPK pathway was inactive. These findings indicate that a specific function of ETS proteins over-expressed in prostate cancer is the activation of a RAS/MAPK gene expression program in the absence of activating mutations in the RAS/MAPK signaling pathway. We propose that this ETS/AP-1 regulated, RAS-responsive, transcriptional network will also play a critical role in other cancers that do not over-express an ETS protein, but have activating mutations in the RAS/MAPK pathway. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3090. doi:1538-7445.AM2012-3090
THE ORGANISM ASSOCIATED WITH SPECIFIC INFECTIOUS CYSTITIS AND PYELONEPHRITIS OF COWS
Authors: F. S. Jones, Ralph B. Little
Journal: The Journal of Experimental Medicine (1926)

A Gram-positive diphtheroid isolated from spontaneous cases of cystitis and pyelonephritis of cows on five farms has been studied. All the strains obtained were of the same general morphology. They possess similar cultural characteristics and to a great degree similar agglutination affinities. The organism is not pathogenic for the ordinary laboratory animals. It produces no toxin. Cows injected intravenously with broth cultures failed to develop the disease. On the other hand, small quantities of cultures introduced into the bladder by way of the urethra gave rise to a typical persistent cystitis. There is evidence for a transmission of the disease by contact infection, as when the same individual curries both normal and infected cows.
Upjohn libel case over "wild" claims opens in court
Authors: C Dyer
Journal: BMJ (1994)

The long awaited trial in Britain of the libel action brought by Upjohn, makers of the sleeping pill Halcion (triazolam) against the drug's long time critic Ian Oswald and the BBC opened in the High Court on Monday. Upjohn is suing Professor Oswald, emeritus professor of psychiatry at Edinburgh University, and the BBC over allegations that the company fraudulently concealed side effects of Halcion from drug regulatory authorities. The company is seeking substantial damages and injunctions to stop the claims from being repeated.

The case, which is expected to last three or four months, will be one of the longest and most complicated libel actions to come to trial in Britain. So voluminous and complex are the documents that the case is being tried by a judge alone, without a jury.

The High Court action will focus on whether Upjohn deliberately misled drug regulators about protocol 321, one of the earliest clinical trials of Halcion, which was carried out in 1972, and otherwise played …