tbuckley/cabot-search huggingface dataset:
Breast Cancer Researchers Cleared of Charges
Authors: Andrew A. Skolnick
Journal: JAMA (1997)

AFTER NEARLY 3 years of investigation, the US Department of Health and Human Services' Office of Research Integrity (ORI) has dismissed all scientific misconduct charges against Bernard Fisher, MD, former head of the National Surgical Adjuvant Breast and Bowel Project (NSABP), and 2 colleagues. <h3>Fisher Guided Study</h3> As chair of the project and principal investigator for nearly 3 decades, Fisher, who is Distinguished Service Professor of Surgery at the University of Pittsburgh School of Medicine, Pittsburgh, Pa, guided the international study that has helped shift the treatment of breast cancer for many women from mastectomy to lumpectomy combined with subsequent radiation therapy. In 1994, following pressure from Rep John Dingell (D, Mich), the National Cancer Institute (NCI)—the principal sponsor of the NSABP—charged Fisher, Lawrence Wickerham, MD, adjunct research associate professor of surgery at Pittsburgh, and Carol Redmond, ScD, currently on leave from her professorship of biostatistics at Pittsburgh's Graduate
Valvular Pulmonary Stenosis with Intact Ventricular Septum
Authors: S. GILBERT BLOUNT, JACK VAN ELK, OSCAR J. BALCHUM, HENRY SWAN
Journal: Circulation (1957)

Clinical and physiologic studies have been carried out in 25 patients following surgical correction of congenital valvular pulmonary stenosis. The patients were operated upon under conditions of hypothermia and circulatory occlusion and the approach to the valve was transarterial, permitting plastic repair of the stenotic pulmonary valve with unimpaired vision and a dry operative field. The systolic pressure gradient between the right ventricle and the pulmonary artery has been completely abolished in 17 of the 25 patients. The results as reported in this series are considered to be superior to those obtained with the blind transventricular approach and the operative mortality certainly compares favorably with the transventricular approach.
Gene Therapeutic Approach Using Mutation-adapted U1 snRNA to Correct a RPGR Splice Defect in Patient-derived Cells
Authors: Esther Glaus, Fabian Schmid, Romain Da Costa, Wolfgang Berger, John Neidhardt
Journal: Molecular Therapy (2011)

Retinitis pigmentosa (RP) is a disease that primarily affects the peripheral retina and ultimately causes visual impairment. X-chromosomal forms of RP are frequently caused by mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene. We show that the novel splice donor site (SDS) mutation c.1245+3A>T in intron 10 of RPGR cosegregates with RP in a five-generation Caucasian family. The mutation causes in-frame skipping of exon 10 from RPGR transcripts in patient-derived primary fibroblasts. To correct the splice defect, we developed a gene therapeutic approach using mutation-adapted U1 small nuclear RNA (U1). U1 is required for SDS recognition of pre-mRNAs and initiates the splice process. The mutation described herein interferes with the recognition of the SDS by U1. To overcome the deleterious effects of the mutation, we generated four U1 isoforms with increasing complementarity to the SDS. Lentiviral particles were used to transduce patient-derived fibroblasts with these U1 variants. Full complementarity of U1 corrects the splice defect partially and increases recognition of the mutant SDS. The therapeutic effect is U1-concentration dependent as we show for endogenously expressed RPGR transcripts in patient-derived cells. U1-based gene therapeutic approaches constitute promising technologies to treat SDS mutations in inherited diseases including X-linked RP.
LEISHMANIA DONOVANI IN THE PERIPHERAL BLOOD
Authors: Charles W. Young, Helen M. Van Sant
Journal: The Journal of Experimental Medicine (1923)

1. The effect of human red cells and serum on the growth of Leishmania donovani has been studied and a blood culture method devised, based on these findings. 2. The distribution of blood platelets and of the different varieties of leucocytes in the strata of centrifugalized diluted blood has been investigated, and also the distribution of Leishman-Donovan bodies, extracellular and intracellular, in these strata. 3. The effect of treatment with antimony on the cultivability of Leishmania donavani has been studied.
ARTERIAL WALL CHARACTERISTICS ARE ASSOCIATED WITH INCIDENT CARDIOVASCULAR DISEASE: AN ANALYSIS FROM THE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY
Authors: Eric Y. Yang, Lloyd Chambless, A. Richey Sharrett, Salim S. Virani, Zhengzheng Teng, Eric Boerwinkle, Christie M. Ballantyne, Vijay Nambi
Journal: Journal of the American College of Cardiology (2010)
Institutional Review Boards
Authors: Edward N. Brandt
Journal: JAMA (1983)

<h3>To the Editor.—</h3> I am writing in response to the SPECIAL COMMUNICATION entitled "Inconsistency and Institutional Review Boards" by J. Goldman and M. Katz (1982; 248:197) and the accompanying editorial, "Problems With Institutional Review Board Consistency," by R. Veatch (1982;248:179). Assuredly, the inevitable lag time between completion of a study and its eventual publication may leave the impression in readers that an important issue is going unattended by responsible federal officials. This letter is intended to place the Goldman and Katz study in the perspective of the correct time frame and to provide readers with current information on what is being done to assist institutional review boards (IRBs) in carrying out their "essential" mission. The system of local IRBs has been a requirement of Public Health Service policy since 1966. It was made a statutory requirement by the Congress in 1974 (PL 93-348). The fundamental soundness and effectiveness of IRBs
Ouantitation of Abdominal Pain
Authors: J. V. Gilkey
Journal: JAMA (1967)

ABSTRACT To the Editor:— In the Aug 14 issue (201:558, 1967) a Technique for Quantitating Abdominal Pain is described. Quite obviously it is tenderness, rather than pain, which the author is attempting to quantitate, and the difference in significance of the two terms is not an academic quibble, but an important point in diagnosis.Moreover, since the technique does not take into account variations in abdominal muscle tonus it could result in misleading and paradoxical pressure readings. For example, in progressive intra-abdominal disease irritation of the parietal peritoneum will cause involuntary localized splinting and a temporary increase in the amount of pressure necessary to cause discomfort. Because the cuff is interposed between the patient and the examiner's hand, the area of localized muscle spasm might go unrecognized.Dr. Shafer's aim is a worthy one but his proposed technique is potentially misleading.In patient-side diagnosis nothing can replace the thoughtful application
Ichthyosis, brittle hair, impaired intelligence, decreased fertility and short stature (IBIDS syndrome)
Authors: J. L. JORIZZO, D. J. ATHERTON, R. G. Crounse, R. S. Wells
Journal: British Journal of Dermatology (1982)

SUMMARY
The BIDS syndrome comprises brittle hair, intellectual impairment, decreased fertility and short stature. Hair from patients with the BIDS syndrome shows disordered cuticular scales on scanning electronmicroscopy, alternate bright and dark banding on polarizing microscopy and low sulphur content. This report describes a case in which ichthyosis occurred in combination with the other features of the BIDS syndrome.
Outcomes from studies of antineutrophil cytoplasm antibody associated vasculitis: a systematic review by the European League Against Rheumatism systemic vasculitis task force
Authors: C Mukhtyar, O Flossmann, B Hellmich, P Bacon, M Cid, J W Cohen-Tervaert, W L Gross, L Guillevin, D Jayne, A Mahr, P A Merkel, H Raspe, D Scott, J Witter, H Yazici, R A Luqmani
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objectives:</h3> We undertook a systematic literature review as a background to the European League Against Rheumatism (EULAR) recommendations for conducting clinical trials in anti-neutrophil cytoplasm antibody associated vasculitis (AAV), and to assess the quality of evidence for outcome measures in AAV. <h3>Methods:</h3> Using a systematic Medline search, we categorised the identified studies according to diagnoses. Factors affecting remission, relapse, renal function and overall survival were identified. <h3>Results:</h3> A total of 44 papers were reviewed from 502 identified by our search criteria. There was considerable inconsistency in definitions of end points. Remission rates varied from 30% to 93% in Wegener granulomatosis (WG), 75% to 89% in microscopic polyangiitis (MPA) and 81% to 91% in Churg–Strauss syndrome (CSS). The 5-year survival for WG, MPA and CSS was 74–91%, 45–76% and 60–97%. Relapse (variably defined) was common in the first 2 years but the frequency varied: 18% to 60% in WG, 8% in MPA, and 35% in CSS. The rate of renal survival in WG varied from 23% at 15 months to 23% at 120 months. Methods used to assess morbidity varied between studies. Ignoring the variations in definitions of the stage of disease, factors influencing remission, relapse, renal and overall survival included immunosuppressive therapy used, type of organ involvement, presence of ANCA, older age and male gender. <h3>Conclusions:</h3> Factors influencing remission, relapse, renal and overall survival include the type of immunosuppressive therapy used, pattern of organ involvement, presence of ANCA, older age and male gender. Methodological variations between studies highlight the need for a consensus on terminology and definitions for future conduct of clinical studies in AAV.
A method to study cell proliferation kinetics in human gastric mucosa.
Authors: O H Hansen, T Pedersen, J K Larsen
Journal: Gut (1975)

The purpose of this investigation was to study cell proliferation kinetics in human gastric mucosa. Biopsies were taken from the antral and fundic part of the stomach through a fibre-gastroscope and incubated in culture medium containing a DNA-precursor (3-H-thymidine). Autoradiographs were prepared by the dipping technique. The number of labelled cells and the total number of cells in all cross sections of foveolae containing one or more labelled cells were counted. The labelling index (LI), which is defined as the percentage of labelled cells in the progenitor cell region, was estimated. When only cross sections with labelled cells are taken into consideration, the labelling index will be a little overestimated. In order to reduce this error a formula for correction was worked out. Thirty-six patients with different gastric diseases were studied. The observer error was minimal, and the results were highly reproducible. It was not possible to demonstrate any correlation between the labelling indices in antral and fundic mucosa. A significantly increased epithelial proliferation was found in fundic mucosa from patients with gastric cancer and atrophic gastritis.
Issues concerning informed consent for medical research among non-westernized ethnic minority patients in the UK
Authors: S. Dein
Journal: Journal of the Royal Society of Medicine (2005)

The ethics governing research are evolving rapidly, and we need to be sure that the principles of good practice are applied in all social groups. When research involves people from ethnic minorities, a major but neglected issue is the validity of consent. Informed consent, a legal concept developed over the years in Western Europe and North America, demands much more than a signed document. It is a process of communication in which the underlying ethical concepts, especially that of respect for autonomy, are not shared by all cultures. Here is what the Helsinki Declaration, in its 2000 version, says about informed consent:


'In any research on human beings, each potential subject must be adequately informed of the aims, methods, sources of funding, any possible conflict of interest, institutional affiliations of the researcher, the anticipated benefits and potential risks of the research and the potential discomforts it may entail. The subject should be informed of the right to abstain from participation in the study or to withdraw at any time without reprisal'.1


Essentially informed consent consists of three steps. First, the research team provides full and transparent information about the nature of the project and the rights of the participant. Second, the participant must understand what is being asked and be competent to decide. Third, the person must decide freely whether or not to contribute. Because each element of this process may conflict with cultural values, research in certain UK minority groups has been problematic. In this paper we address the dilemmas of conducting research among individuals who, sometimes despite many years of living in the UK, adhere to their original religious and cultural values. Our own research experience has centred on elderly Bangladeshis in the UK, many of whom are illiterate.2 We acknowledge, however, that a large proportion of individuals from ethnic minority groups in the UK are well educated and in tune with the Western way of life.
Population and family studies of three disease-related polymorphic genes in systemic lupus erythematosus.
Authors: D F Huang, K A Siminovitch, X Y Liu, T Olee, N J Olsen, C Berry, D A Carson, P P Chen
Journal: Journal of Clinical Investigation (1995)

The contribution to systemic lupus erythematosus (SLE) of three lupus-associated polymorphisms (involving the C4A2 complement component, Humhv3005 and the T cell antigen receptor alpha chain gene) are investigated in 81 individuals from 14 multiplex SLE families, 41 unrelated lupus patients, and 88 unrelated healthy controls. The results show a strong association between C4A deletion and SLE in these families. While the current study confirms the previously reported association between hv3005 deletion and sporadic SLE, the study fails to support this association in familial SLE patients. Moreover, no correlation is detected between the occurrence of hv3005 deletion and C4A null alleles in lupus patients, suggesting that the effects of these genetic polymorphisms on predisposition to lupus are independent. The previously reported lupus-associated T cell receptor (TCR) alpha chain polymorphism is not detected in any of the individuals studied here. The combined data suggest that C4A null alleles predispose strongly to development of lupus, whereas the influence of hv3005 deletion is relatively weak. The results also suggest that contributions of weak susceptibility genes such as hv3005 to disease predisposition may be obscured by the effects of stronger genetic factors and thus need to be examined in patients lacking these factors.
Transesophageal endoscopic ultrasound-guided transcarotid fine needle aspiration of a positron emission tomography (PET)-positive mediastinal lymph node
Authors: F. Lococo, F. De Vincentis, A. Naldini, F. Tsiopoulos, A. Paglia, G. Fadda, A. Cesario, P. Granone, G. Costamagna, A. Larghi
Journal: Endoscopy (2012)

We report an unusual case of a positron emission tomography (PET)-positive para-aortic lymph node ([Fig. 1]) in a patient with breast cancer that was punctured with transesophageal endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) by traversing the carotid artery, with multiple needle passes performed.
Expression of resistance markers to methotrexate predicts clinical improvement in patients with rheumatoid arthritis
Authors: J Wolf
Journal: Annals of the Rheumatic Diseases (2004)

<b>Background:</b> Methotrexate is transported into the cell by the reduced folate carrier (RFC) and out of the cell by members of the multidrug resistance protein family (MRP). Transport proteins may affect the therapeutic efficacy of this drug in patients with rheumatoid arthritis. <b>Objective:</b> To investigate the potential benefit of the presence of RFC and the absence of functional MRP for the efficacy of methotrexate treatment. <b>Methods:</b> The study involved 163 patients (116 female, 47 male; mean age 59.5 years) on methotrexate (mean weekly dose 12.2 mg). RFC was determined using reverse transcriptase polymerase chain reaction, and MRP function by flow cytometry, using a calcein acetoxymethylesther/probenecid assay. Clinical response to methotrexate was evaluated by the EULAR response criteria and the ACR 20% improvement criteria. The clinical data were obtained at the beginning of methotrexate treatment and at the time of blood sampling during ongoing therapy. Patients were divided into four groups according to the presence (+) or absence (−) of RFC and functional (f) MRP. <b>Results:</b> fMRP+/RFC+ and fMRP−/RFC− patients more often had good EULAR response rates (60%, p = 0.014, and 53%, p = 0.035, respectively) in comparison with the fMRP−/RFC+ group (29%); fMRP+/RFC− patients had a low frequency of good disease activity responses. <b>Conclusions:</b> Absence of fMRP plus presence of RFC did not prove to be related to beneficial effects of methotrexate, but the lack or the presence of both fMRP and RFC led to a significantly better therapeutic outcome. Determination of these markers may predict responsiveness to methotrexate.
Dermatoscopy of facial actinic keratosis, intraepidermal carcinoma, and invasive squamous cell carcinoma: A progression model
Authors: Iris Zalaudek, Jason Giacomel, Karin Schmid, Silvia Bondino, Cliff Rosendahl, Stefano Cavicchini, Athanasia Tourlaki, Saturnino Gasparini, Peter Bourne, Jeff Keir, Harald Kittler, Laura Eibenschutz, Caterina Catricalà, Giuseppe Argenziano
Journal: Journal of the American Academy of Dermatology (2011)
Abstract 3819: DKK2 mediates osteolysis, invasiveness and metastatic spread in Ewing sarcoma.
Authors: Günther H. Richter, Stefan Burdach, Kristina Hauer
Journal: Cancer Research (2013)

Abstract Ewing sarcomas (ES) are malignant osteolytic bone and soft tissue tumors mostly affecting children and young adults, and are characterized by early lung and distant bone metastases. Here we identified the dickkopf 2 homolog (DKK2) as a highly over-expressed gene in ES, compared to normal tissues. DKK family members are increasingly recognized to be deregulated in bone metastasis. Using RNA interference, we show that DKK2 promotes anchorage-independent colony formation and proliferation of ES cells in vitro and tumorigenicity in vivo. Analysis of the invasion potential in vitro and in an orthotopic xenotransplantation model revealed a strong correlation of DKK2 expression and ES invasiveness that is possibly mediated by its downstream effector matrix metalloproteinase 1 (MMP1). Gene expression analyses proved DKK2 to differentially regulate genes such as CXCR4, PTHrP, RUNX2 and TGFβ1, that are associated with homing, invasion and growth of cancer cells in bone tissue as well as genes important for osteolysis, like HIF1α, JAG1, IL6 and VEGF. Moreover, we observed that DKK2 promotes bone infiltration and osteolysis in vivo, identifying DKK2 as a key factor for osteotropic malignancy. Interestingly, suppression of DKK2 expression increases neuronal differentiation, but at the same time decreases chondrogenic and osteogenic differentiation potential of ES cells. These data provide evidence that DKK2 is a key player in ES invasiveness and osteolysis, validating a critical role of DKK2 for malignancy and the differential phenotype of ES. Findings further suggest a broadly important role for a member of a family of antagonists of the Wnt pathway in driving bone invasion and osteolysis with potential implications for bone invasion in cancer generally. Citation Format: Günther H. Richter, Stefan Burdach, Kristina Hauer. DKK2 mediates osteolysis, invasiveness and metastatic spread in Ewing sarcoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3819. doi:10.1158/1538-7445.AM2013-3819
Parafibromin and APC as Screening Markers for Malignant Potential in Atypical Parathyroid Adenomas
Authors: C. Christofer Juhlin, Inga-Lena Nilsson, Kenth Johansson, Felix Haglund, Andrea Villablanca, Anders Höög, Catharina Larsson
Journal: Endocrine Pathology (2010)
Inappropriate use of photograph
Authors: C S Nanayakkara
Journal: BMJ (1993)

injected temazepam tablets.Since temazepam is such a popular drug of misuse, I fear that injection of tablets will become more commonplace as liquid and gel filled capsules become harder to obtain.Injecting tablets is likely to be much more dangerous than injecting the liquid from capsules; injecting gel filled capsules is known to be dangerous.2Probably the only way to prevent misuse of temazepam is not to prescribe it in any formulation.
Glucose-6-phosphate Dehydrogenase Activity Levels in Enzyme-deficient Greek Individuals
Authors: C. Choremis, Chr. Kattamis, L. Zannos-Mariolea, P. Paraschopoulou-Prevedouraki
Journal: BMJ (1963)

MEDICAL JOURNAL It is intended to follow up the cases considered to be definite, suspicious, or doubtful glaucoma, together with a random sample of those in whom no glaucoma was found, as a long-term project in the glaucoma clinic conducted by one of us (J.P. F. L.) at the Oxford Eye Hospital.Iris colour was recorded in each patient in the survey.The results are shown in Table VI.These suggest that the colour distribution is similar in the two groups-that is, the total sample and the cases of glaucoma, although there are fewer brown eyes in the latter.This is not a significant finding, because most of our brown-eyed persons happened to be in the younger age-groups.
Heterogeneity of antimitochondrial antibodies with the M2-M4 pattern by immunofluorescence as assessed by Western immunoblotting and enzyme linked immunosorbent assay.
Authors: M Fusconi, I Ghadiminejad, F B Bianchi, H Baum, G F Bottazzo, E Pisi
Journal: Gut (1988)

Seventy seven sera with antimitochondrial antibody exhibiting the M2-M4 pattern in immunofluorescence (56 from primary biliary cirrhosis (PBC), 21 from non-primary biliary cirrhosis patients) were studied by the combined use of Western immunoblotting with beef heart mitochondria and an enzyme linked immunosorbent assay (ELISA) with beef heart submitochondrial particles. Forty seven sera (10 without autoantibodies and 37 with different auto-antibodies) were included as controls. By immunoblotting, seven mitochondrial peptides reacting with antimitochondrial antibody positive sera were detected. These were of molecular weight 74 kD, 58 kD, 55 kD, 52 kD, 51 kD, 46 kD, and 43 kD. All primary biliary cirrhosis sera and 71% of antimitochondrial antibody-positive non-primary biliary cirrhosis sera reacted with one or more of these peptides, while none of the 47 antimitochondrial antibody negative sera reacted in immunoblotting. The 74 kD band was the most frequently detected (84% of primary biliary cirrhosis and 57% of non-primary biliary cirrhosis cases). All the primary biliary cirrhosis sera which failed to react with this peptide, showed a positive reaction with that of molecular weight 52 kD. 67/77 (87%) immunofluorescence antimitochondrial antibody positive sera reacted in the ELISA test (93% of primary biliary cirrhosis and 71% of non-primary biliary cirrhosis cases). All the 47 immunofluorescence antimitochondrial antibody negative sera were confirmed negative by ELISA. The ELISA values correlated with the immunofluorescence titres (p less than 0.05). By comparison of the results obtained by these two techniques, it emerged that the ELISA test (using our preparation of submitochondrial particles) was not able to detect the antibody directed against the mitochondrial peptide of 52 kD, which thus seems to be different from the other specificities.