tbuckley/cabot-search huggingface dataset:
Serum levels of soluble vascular endothelial growth factor receptor-2 in patients with systemic sclerosis
Authors: M. Jinnin, T. Makino, I. Kajihara, N. Honda, K. Makino, A. Ogata, H. Ihn
Journal: British Journal of Dermatology (2009)

Background Although vascular endothelial growth factor (VEGF)-A/VEGF receptor 2 (KDR) signalling may play a major role in the microangiopathy of systemic sclerosis (SSc), serum levels of soluble KDR (sKDR) in this disease have not yet been determined. Objectives To evaluate the possibility that serum sKDR levels can be a specific disease marker of SSc. Methods Serum sKDR levels of 42 patients with SSc, 10 patients with Raynaud's phenomenon (RP) and 22 healthy controls were measured with specific enzyme-linked immunosorbent assays. Quantitative real-time polymerase chain reaction (PCR) was performed to determine KDR mRNA levels. Results In females, the serum sKDR levels were significantly higher in patients with SSc, especially limited cutaneous SSc, than in patients with RP or healthy controls. Quantitative real-time PCR with RNA from skin sections revealed that KDR mRNA levels were also increased in the skin of patients with SSc with elevated serum sKDR levels. A significantly lower prevalence of pulmonary fibrosis, higher percentage vital capacity, and a higher incidence of telangiectasia were seen in female patients with SSc with elevated serum sKDR levels than those with normal levels. Conclusions These results suggest that the skin can be one of the sources of elevated serum sKDR levels, and that serum sKDR levels are useful for diagnosis and may be a marker of microangiopathy in patients with SSc, especially females. The VEGF-A/KDR signalling system may be involved in the pathogenesis of the disease.
Vitrectomy with Internal Limiting Membrane Repositioning and Autologous Blood for Macular Hole Retinal Detachment in Highly Myopic Eyes
Authors: Chi-Chun Lai, Yen-Po Chen, Nan-Kai Wang, Lan-Hsin Chuang, Laura Liu, Kuan-Jen Chen, Yih-Shiou Hwang, Wei-Chi Wu, Tun-Lu Chen
Journal: Ophthalmology (2015)
Sensation of leg effort at rest is related to lower peripheral muscle strength in patients with COPD
Authors: Glenn Leemans, Kris M.H. Ides, Lieve De Backer, Hilde Vaerenberg, Kevin De Soomer, Dirk Vissers, Wilfried De Backer
Journal: European Respiratory Journal (2012)

Introduction   Sensation of leg effort (SLE) is known as a limiting factor in exercise capacity during a maximal exercise test in patients with COPD. The Borg scale scores this discomfort of the peripheral muscles before and during an exercise test. A high score in a maximal exercise test is known to correlate with lower skeletal muscle strength. However some patients experiencesome SLE l already at rest before the exercise test and other do not.   Objective   To evaluate if SLE at rest before exercise also could be related to peripheral muscle strength.   Methods   Data of 26 patients in a pulmonary rehabilitation program was analysed. The Borg scale SLE before the maximal incremental exercise test. Isometric quadriceps force was assessed by a computerized dynamometer during a voluntary maximal isometric contraction with the hip at 90° and the knee at 60° flexion. The highest value was taken.   Results   SLEis light to moderate inversely correlated with isometric quadriceps force which is expressed as the percentage of strength compared to that of a healthy individual (Pearson r=0.408; p=0.039).   Conclusions   Lower quadriceps force seems to relate to higher leg effort compared to those patients who do not experience any leg discomfort at all. However due to the great range in quadriceps force, it is necessary to objectively measure quadriceps force to have a good clinical impression of patient9s peripheral muscle strength.
Inhibitory Effect of Polychlorinated Biphenyls on Liver Tumorigenesis in Rats Treated With 3′-Methyl-4-dimethylaminoazobenzene, N-2-Fluorenylacetamide, and Diethylnitrosamine2
Authors: Sachio Makiura, Haruko Aoe, Seiichi Sugihara, Kazuya Hirao, Masayuki Arai, Nobuyuki Ito
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Inhibitory Effect of Polychlorinated Biphenyls on Liver Tumorigenesis in Rats Treated With 3′-Methyl-4-dimethylaminoazobenzene, N-2-Fluorenylacetamide, and Diethylnitrosamine Get access Sachio Makiura, Sachio Makiura Search for other works by this author on: Oxford Academic PubMed Google Scholar Haruko Aoe, Haruko Aoe Search for other works by this author on: Oxford Academic PubMed Google Scholar Seiichi Sugihara, Seiichi Sugihara Search for other works by this author on: Oxford Academic PubMed Google Scholar Kazuya Hirao, Kazuya Hirao Search for other works by this author on: Oxford Academic PubMed Google Scholar Masayuki Arai, Masayuki Arai Search for other works by this author on: Oxford Academic PubMed Google Scholar Nobuyuki Ito Nobuyuki Ito 3Department of Oncological Pathology, Cancer Center Institute, Nara Medical University, Kashihara, Nara 634, Japan. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 53, Issue 5, November 1974, Pages 1253–1257, https://doi.org/10.1093/jnci/53.5.1253 Published: 01 November 1974 Article history Received: 25 March 1974 Accepted: 18 July 1974 Published: 01 November 1974
The effect of intravenous immunoglobulin on oxygen-dependent metabolism of blood cells in patients with community acquired pneumonia
Authors: Usman Farkhutdinov, Albert Mirchaidarov, Rafagat Farkhutdinov
Journal: European Respiratory Journal (2012)

Active oxygen forms (AOF) determine the microbicidal activity of phagocytes. Their low generation may be one of the reasons of latent inflammatory process.

The aim was to study the effect of i.v. immunoglobulin immunovenin (IMV) on the production of AOF in in-vitro experiments and in patients with community acquired pneumonia (CAP).

Methods: The method of chemiluminescence (ChL) registration was used to study the effect of various doses of IMV (0.005 mg/ml, 0.01 mg/ml, 0.05 mg/ml) on the production of AOF in the blood of healthy subjects. In the clinical part of the research AOF generation was studied in 35 patients with CAP. 17 patients with CAP received standard therapy. In 18 patients IMV was added to the treatment.

Results: In in-vitro experiments IMV dose of 0.005 mg/ml increased ChL intensity of blood by 18.4± 0.3% (p<0.05) the doses of 0.01 mg/ml and 0.05 mg/ml increased ChL intensity by 48.6± 2.1% (p <0.05) and 64.5± 3.4%(p<0.05) times respectively. In comparision with normal findings ChL intensity of blood in patients with CAP has been found to be reduced by 1.5 times. The use of IMV in patients has increased production of AOF in blood and resulted in positive dynamics of clinical findings. In the case of standard therapy low ChL intensity of blood maintained, the inflammatory process often had a prolonged course.

Conclusion: IMV may be used in the treatment of patients with CAP owing to its influence on AOF. It allows to increase AOF production by phagocytes and decrease the incidence of latent inflammatory processes.
Memory function in disease-free survivors of childhood acute lymphocytic leukemia given CNS prophylaxis with or without 1,800 cGy cranial irradiation.
Authors: R K Mulhern, A L Wasserman, D Fairclough, J Ochs
Journal: Journal of Clinical Oncology (1988)

Previous studies have found that CNS prophylaxis of children with leukemia, especially young children receiving cranial irradiation, causes neuropsychologic deficits. In the present study, 40 children in continuous complete remission from acute lymphocytic leukemia (ALL) were given a battery of tests to assess memory functioning 5 years after CNS prophylaxis. All children were free of CNS disease at diagnosis and had been randomly assigned to receive CNS prophylaxis with either 1,800 cGy cranial irradiation (CRT) plus intrathecal (IT) methotrexate (MTX) or IT MTX plus intravenous (IV) high-dose MTX (HDMTX). No treatment- or age-related differences were seen on 16 standardized memory measures. However, scores of the combined sample were significantly lower than age-corrected norms on a test of visual-spatial memory and on four scales of verbal memory. Differences in methods or intensity of CNS prophylaxis and study group selection criteria are proposed to explain our findings and to resolve discrepancies with previous reports. The long-term neuropsychological sequelae in these survivors of ALL may be attributable to some common factor, such as the disease itself or systemic and IT chemotherapy.
Comparison and Evaluation of Some Experimental Designs for Use in Carcinogen Screening&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: R M Elashoff, D L Preston, T R Fears
Journal: JNCI Journal of the National Cancer Institute (1979)

The development and evaluation of experimental designs for routine in vivo screening of chemicals for potential carcinogenic activity were considered. Such designs have played an important role in the Carcinogenesis Bloassay Program of the National Cancer Institute (NCI). In particular, the current one-stage 50-animal/group screen used by the NCI was considered. A specific two-stage alternative was proposed in which 35 animals/group were used; this alternative allowed for retesting of equivocal compounds. The proposed designs were evaluated in terms of sensitivity, specificity, and throughout. Despite the large number of tests made for each compound, the false-positive rate was found to be less than 0.07 for the current screen and less than 0.05 for the proposed two-stage alternative. The power of the one-stage and two-stage screens was comparable. The two-stage screen was shown to make about 30% more decisions per test period with a savings of around 28% in the expected number of animals needed per compound tested.
Liver-specific expression of the agouti gene in transgenic mice promotes liver carcinogenesis in the absence of obesity and diabetes.
Authors: Alexander I Kuklin, Randall L Mynatt, Mitchell L Klebig, Laura L Kiefer, William O Wilkison, Richard P Woychik, Edward J Michaud
Journal: Molecular Cancer (2004)

The agouti protein is a paracrine factor that is normally present in the skin of many species of mammals. Agouti regulates the switch between black and yellow hair pigmentation by signalling through the melanocortin 1 receptor (Mc1r) on melanocytes. Lethal yellow (A y ) and viable yellow (A vy ) are dominant regulatory mutations in the mouse agouti gene that cause the wild-type protein to be produced at abnormally high levels throughout the body. Mice harboring these mutations exhibit a pleiotropic syndrome characterized by yellow coat color, obesity, hyperglycemia, hyperinsulinemia, and increased susceptibility to hyperplasia and carcinogenesis in numerous tissues, including the liver. The goal of this research was to determine if ectopic expression of the agouti gene in the liver alone is sufficient to recapitulate any aspect of this syndrome. For this purpose, we generated lines of transgenic mice expressing high levels of agouti in the liver under the regulatory control of the albumin promoter. Expression levels of the agouti transgene in the liver were quantified by Northern blot analysis. Functional agouti protein in the liver of transgenic mice was assayed by its ability to inhibit binding of the α-melanocyte stimulating hormone (αMSH) to the Mc1r. Body weight, plasma insulin and blood glucose levels were analyzed in control and transgenic mice. Control and transgenic male mice were given a single intraperitoneal injection (10 mg/kg) of the hepatocellular carcinogen, diethylnitrosamine (DEN), at 15 days of age. Mice were euthanized at 36 or 40 weeks after DEN injection and the number of tumors per liver and total liver weights were recorded. The albumin-agouti transgene was expressed at high levels in the livers of mice and produced a functional agouti protein. Albumin-agouti transgenic mice had normal body weights and normal levels of blood glucose and plasma insulin, but responded to chemical initiation of the liver with an increased number of liver tumors compared to non-transgenic control mice. The data demonstrate that liver-specific expression of the agouti gene is not sufficient to induce obesity or diabetes, but, in the absence of these factors, agouti continues to promote hepatocellular carcinogenesis.
Towards a paradigm shift in cancer screening: informed citizens instead of greater participation
Authors: G. Gigerenzer
Journal: BMJ (2015)

Germany aims to stop nudging the public on screening



Policy on screening people for cancer poses a dilemma: should we aim for higher participation rates or for better informed citizens? The dilemma is that both cannot be had. A focus on informing citizens risks lowering participation rates, because well informed people may realise that for most cancers it is unclear whether the benefits of screening exceed its harms. Historically, screening policies opted for increasing participation and accordingly took measures that made people overestimate the benefits and underestimate the harms.1 But that is set to change, at least in Germany.

The goal of increasing participation rates has been moderately successful. For instance, German breast cancer screening campaigns set a goal of participation of 70% of eligible women and reached over 50%. Similarly, the NHS Breast Screening Programme in England aimed for an 80% participation rate and reached over 70%.2 But campaigns for this screening test and most other cancer screening tests have caused …
Pyoderma gangrenosum with pathergic phenomenon in pregnancy
Authors: B. Sassolas, Y. le Ru, P. Plantin, G. Lair, P-F. Dupre, G. Cochard, G. Guillet
Journal: British Journal of Dermatology (2000)

Journal Article Pyoderma gangrenosum with pathergic phenomenon in pregnancy Get access B. Sassolas, B. Sassolas Departments of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar Y. le Ru, Y. le Ru Departments of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar P. Plantin, P. Plantin Department of Dermatology, CHIC, 29000 Quimper, France E‐mail: Bruno.Sassolas@univ‐brest.fr Search for other works by this author on: Oxford Academic Google Scholar G. Lair, G. Lair Departments of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar P‐F. Dupre, P‐F. Dupre Gynecology, and Search for other works by this author on: Oxford Academic Google Scholar G. Cochard, G. Cochard Hyperbaric Unit, Centre Hospitalier Universitaire de Brest, 29609 Brest, France Search for other works by this author on: Oxford Academic Google Scholar G. Guillet G. Guillet Departments of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 142, Issue 4, 1 April 2000, Pages 827–828, https://doi.org/10.1046/j.1365-2133.2000.03444.x Published: 01 April 2000
Validity and reliability of Turkish version of St. George's respiratory questionnaire
Authors: Mehmet Polatli, Arzu Yorgancioglu, Ömer Aydemir, Nilgün Yilmaz Demirci, Gamze Kirkil, Sibel Atis Nayci, Nurdan Kokturk, Atilla Uysal, Gonca Gunakan
Journal: European Respiratory Journal (2013)

The importance of the evaluation of health status in COPD is recently highlighted in many studies. In this study, we aimed to test the validity and reliability of the Turkish version of St. George Respiratory Questionnaire (SGRQ). The study was conducted in 7 centers in Turkey. Three hundred twenty one COPD patients (40-75 years-old) were included to the study. Turkish versions of breathlessness, Cough, and Sputum Scale (BCSS), mMRC (Modified Medical Research Council) dyspnea scale, St George Respiratory Questionnaire (SGRQ), COPD assessment test (CAT) and Short Form Health Survey (SF-36) were carried out to the patients. The statistical analysis of SGRQ was performed by using the coefficient of internal consistency, discriminate analysis for different stages and the correlation with the other scales. The mean age was 62.4 ± 8.9 years and the mean FEV1 was 51.9 ± 19.2% pred. The coefficient of internal consistency (Cronbach alpha) was 0.8815. The correlation between the total score measured initially and that obtained 2 weeks later was found to be highly significant (r=0.90, p<0.0001). According the results of the testing the validity of both total score and the components of SGRQ, the correlation between the total score of SGRQ and CAT was 0.782 (p<0.0001), SGRQ and SF-36 was between -0.481 ile -0.819 (p<0.0001). The total and component scores were able to discriminate different disease stages and a significant correlation was found to be with pulmonary function tests.

CONCLUSION: St George Respiratory Questionnaire (SGRQ) Turkish version is a reliable and valid assessment tool for COPD patients in clinical practice.
Sensitive Detection of Mono- and Polyclonal ESR1 Mutations in Primary Tumors, Metastatic Lesions, and Cell-Free DNA of Breast Cancer Patients
Authors: Peilu Wang, Amir Bahreini, Rekha Gyanchandani, Peter C. Lucas, Ryan J. Hartmaier, Rebecca J. Watters, Amruth R. Jonnalagadda, Humberto E. Trejo Bittar, Aaron Berg, Ronald L. Hamilton, Brenda F. Kurland, Kurt R. Weiss, Aju Mathew, Jose Pablo Leone, Nancy E. Davidson, Marina N. Nikiforova, Adam M. Brufsky, Tadeu F. Ambros, Andrew M. Stern, Shannon L. Puhalla, Adrian V. Lee, Steffi Oesterreich
Journal: Clinical Cancer Research (2015)

Given the clinical relevance of ESR1 mutations as potential drivers of resistance to endocrine therapy, this study used sensitive detection methods to determine the frequency of ESR1 mutations in primary and metastatic breast cancer, and in cell-free DNA (cfDNA).Six ESR1 mutations (K303R, S463P, Y537C, Y537N, Y537S, D538G) were assessed by digital droplet PCR (ddPCR), with lower limits of detection of 0.05% to 0.16%, in primary tumors (n = 43), bone (n = 12) and brain metastases (n = 38), and cfDNA (n = 29). Correlations between ESR1 mutations in metastatic lesions and single (1 patient) or serial blood draws (4 patients) were assessed.ESR1 mutations were detected for D538G (n = 13), Y537S (n = 3), and Y537C (n = 1), and not for K303R, S463P, or Y537N. Mutation rates were 7.0% (3/43 primary tumors), 9.1% (1/11 bone metastases), 12.5% (3/24 brain metastases), and 24.1% (7/29 cfDNA). Two patients showed polyclonal disease with more than one ESR1 mutation. Mutation allele frequencies were 0.07% to 0.2% in primary tumors, 1.4% in bone metastases, 34.3% to 44.9% in brain metastases, and 0.2% to 13.7% in cfDNA. In cases with both cfDNA and metastatic samples (n = 5), mutations were detected in both (n = 3) or in cfDNA only (n = 2). Treatment was associated with changes in ESR1 mutation detection and allele frequency.ESR1 mutations were detected at very low allele frequencies in some primary breast cancers, and at high allele frequency in metastases, suggesting that in some tumors rare ESR1-mutant clones are enriched by endocrine therapy. Further studies should address whether sensitive detection of ESR1 mutations in primary breast cancer and in serial blood draws may be predictive for development of resistant disease. See related commentary by Gu and Fuqua, p. 1034.
Tuberculosis (TB) among intravenous drug users (IDUs) in Georgia
Authors: Nana Kiria, Nino Lomtadze, Mamuka Japaridze, Maia Kavtaradze, Nino Kiria
Journal: European Respiratory Journal (2013)

Background: IDU is widespread problem in Georgia and regardless of HIV status drug users are at increased risk of developing active TB. It is necessary to conduct the screening and effectively address the TB cases among IDUs.  Intervention: From January 2010 to December 2012 IDUs were screened for TB symptoms using the special questionnaire at harm reduction and VCT sites to assess the prevalence of TB among IDUs through the screening program. TB suspect cases were referred to TB units for farther investigation and diagnosis.  Findings: 7023 IDUs were screened for TB symptoms, 43(0.6%) from them were female and 6980 (99.4%) male. 83(1.2%) from the screened IDU-s were HIV-positive and 3983(56,7%) were diagnosed to have Hepatitis B or C. 638 (8.6%) were classified as TB suspects.265 (3,7%)suspected TB cases were presented at TB units for further examination. TB was diagnosed in 52 (19,6%) cases. 38 (73.1%) had pulmonary TB and 14 (26.9%) had extra-pulmonary. Conclusions: IDU and TB represent public health problem in Georgia. Active case finding is one of the useful tools for addressing TB problem among this group. Given the high risk for TB among IDUs, interventions such as active case finding, is urgently needed to detect TB cases as early as possible and treat them adequately.
Immunopotentiation With BeG: Dimensions of a Specific Antitumor Response2
Authors: Eugenia Hawrylko
Journal: JNCI Journal of the National Cancer Institute (1975)

The dimensions of a BCG-potentiated antitumor response against the poorly immunogenic murine mastocytoma, P815 (MA), are described for a model in which the tumor immunogen is injected into subcutaneous sites previously infected with BCG; a distantly located tumor challenge is subsequently monitored for evidence of regression. A comparison of concomitant immunity and the immunity elicited by injection of varying doses of live MA into sites previously infected with BCG revealed similar antitumor effects. The subcutaneous site was the most effective route for immunization with BCG and irradiated tumor cells. Antitumor immunity was maximally expressed at intravascular sites and in the footpad. Complete tumor suppression was limited to footpad challenge with 104–105 MA. Not only did the iv injection of BCG and immunogen fail to elicit immunity against subcutaneous challenge, but also systemically administered immunogens abrogated antitumor immunity elicited by subcutaneous immunization. These effects were reversed by prior splenectomy. Immunity was specific for the evoking tumor immunogen, but challenge with the specific tumor did not elicit nonspecific resistance against another 3-methylcholanthreneinduced tumor. In another strain of mice, immunity potentiated by BCG against the highly antigenic tumor, Meth A, was more effective than that potentiated against the poorly immunogenic MA.
Abrogation of Macrophage-dependent Injury in Experimental Glomerulonephritis in the Rabbit
Authors: Stephen R. Holdsworth, T. James Neale, Curtis B. Wilson
Journal: Journal of Clinical Investigation (1981)

Macrophages were shown by the use of glomerular cell culture and morphologic techniques to be present in large numbers within the glomeruli of rabbits with acute serum sickness (AcSS) and in a passive model of the autologous phase of antiglomerular basement membrane (GBM) antibody-induced glomerulonephritis (PAGBMN). To determine the part played by these cells in the glomerular injury, animals were treated with a sheep anti-rabbit macrophage serum (AMS) or normal sheep serum (NSS). NSS administration had no effect on the development of either model of glomerulonephritis. The use of AMS reduced the number of circulating monocytes and prevented the accumulation of macrophages within glomeruli in both models (AcSS/NSS, mean 126/glomerulus, range 40-251; AcSS/AMS, mean 8, range 1-44; PAGBMN/NSS, mean 52, range 27-69; PAGBMN/AMS, mean 5, range 2-7). The AMS-treated rabbits had only minor histologic lesion and profound reduction in proteinuria (AcSS/NSS, mean 516 mg/24 h, range 200-991; AcSS/AMS, mean 41, range 3-161; PAGBMN/NSS, mean 335, range 55-975; PAGBMN/AMS, mean 10, range 2-24). Similar studies in the heterologous phase of glomerular injury induced by the same anti-GBM antibody revealed no effect of the AMS on this polymorphonuclear leukocyte-related phase of injury, demonstrating the selectivity of the antisera. Complement depletion, with cobra venom factor, did not affect the development of glomerulonephritis nor the accumulation of macrophages in either model. Inhibition of macrophage accumulation can largely prevent these forms of experimental glomerulonephritis, thereby implicating macrophages as mediators of glomerular injury and consequent proteinuria.