tbuckley/cabot-search huggingface dataset:
A single nucleotide deletion at the C1 inhibitor gene as the cause of hereditary angioedema: insights from a Brazilian family
Authors: M. F. Ferraro, A. S. Moreno, E. C. Castelli, E. A. Donadi, M. S. Palma, H. A. Arcuri, A. P. Lange, K. Bork, W. Sarti, L. K. Arruda
Journal: Allergy (2011)

To cite this article: Ferraro MF, Moreno AS, Castelli EC, Donadi EA, Palma MS, Arcuri HA, Lange AP, Bork K, Sarti W, Arruda LK. A single nucleotide deletion at the C1 inhibitor gene as the cause of hereditary angioedema: insights from a Brazilian family.Allergy 2011; 66: 1384–1390. Background: Hereditary angioedema is an autosomal dominant disease characterized by episodes of subcutaneous and submucosal edema. It is caused by deficiency of the C1 inhibitor protein, leading to elevated levels of bradykinin. More than 200 mutations in C1 inhibitor gene have been reported. The aim of this study was to analyze clinical features of a large family with an index case of hereditary angioedema and to determine the disease-causing mutation in this family. Methods: Family pedigree was constructed with 275 individuals distributed in five generations. One hundred and sixty-five subjects were interviewed and investigated for mutation at the C1 inhibitor gene. Subjects reporting a history of recurrent episodes of angioedema and/or abdominal pain attacks underwent evaluation for hereditary angioedema. Results: We have identified a novel mutation at the C1 inhibitor gene, c.351delC, which is a single-nucleotide deletion of a cytosine on exon 3, resulting in frameshift with premature stop codon. Sequencing analysis of the hypothetical truncated C1 inhibitor protein allowed us to conclude that, if transcription occurs, this protein has no biological activity. Twenty-eight members of the family fulfilled diagnostic criteria for hereditary angioedema and all of them presented the c.351delC mutation. Variation in clinical presentation and severity of disease was observed among these patients. One hundred and thirty-seven subjects without hereditary angioedema did not have the c.351delC mutation. Conclusion: The present study provides definitive evidence to link a novel genetic mutation to the development of hereditary angioedema in patients from a Brazilian family.
Long-Term Follow-Up of a Randomized Trial of Two Irradiation Regimens for Patients Receiving Allogeneic Marrow Transplants During First Remission of Acute Myeloid Leukemia
Authors: R.A. Clift, C.D. Buckner, F.R. Appelbaum, K.M. Sullivan, R. Storb, E.D. Thomas
Journal: Blood (1998)
Development and evaluation of an automated, Web-based tool for quantitative assessment of fluorescence in situ hybridization
Authors: Juho Konsti, Jorma Isola, Mervi Laakso, Mikael Lundin, Johan Lundin
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

4412 

Assessment of the HER2 status in breast cancer is routinely achieved by immunohistochemical analysis or in situ hybridization techniques. Quantification of fluorescence in situ hybridizations (FISH) is a laborious work, since it is most commonly done by visual counting of the hybridized markers. We have developed an automated method for quantification of HER2 fluorescence in situ hybridization. The algorithm, entitled FishJ, is based on a popular open source image manipulation tool, ImageJ, and is freely available for download. In addition to that, FishJ can be utilized through a web interface (www.webmicroscope.net/fishj) with an option of uploading FISH images for analysis.

In order to evaluate the FishJ algorithm, we tested it against traditional manual counting in breast cancer specimens from 42 patients. The hybridized tumor specimens were digitized within a virtual microscopy framework. Markers for the HER2 gene and chromosome 17 centromere (CEP17) were counted both manually and automatically with our macro. The correlation coefficient between the automatic and manual HER2/CEP17 ratios was 0.985. The corresponding percent-agreement was 95% and the kappa value 0.90.

The main findings of this study show that the automated determination of HER2 amplification using open-source software is possible and that the results are comparable to manual counting. In addition, the automatic counting saves sample processing time and provides possibilities to enhance inter- and intralaboratory reproducibility of results. A web-based, automated FISH quantification tool could potentially enable improved standardization of gene copy number evaluation.
Use of beta-blockers in COPD patients with heart-disease. BBEPOC study
Authors: Patricia Sobradillo, Antonia Fuster, Pedro Jorge Marcos, Ángel Ortega, Cruz González, Myriam Aburto, Juan Luis Rodríguez, Bernardino Alcázar, Myriam Calle, Luis Puente
Journal: European Respiratory Journal (2013)

There is strong evidence showing increased survival with beta-blockers (BB) treatment in patients with chronic heart failure and after acute myocardial infarction. There is high evidence showing the safety of cardioselective BB in COPD. AIMS: 1) To determine the frequency of use of BB COPD patients in whom BB are indicated because of an underlying heart disease 2) To determine whether the use of BB decreases the risk of more than 2 exacerbations in such patients. METHODS: Observational multicenter study. Indication for BB: ischemic heart disease or heart failure with LVEF  2 exacerbations per year” CONCLUSIONS: The use of BB in patients with heart disease is significantly lower when they also have COPD. The use of BB has a protective effect on the development of more than 2 complications per year, although this effect could be the consequence of other factors associated with the use of BB such as a better FEV1 or younger age.
A screening method to identify genes commonly overexpressed in carcinomas and the identification of a novel complementary DNA sequence.
Authors: Jennifer Byrne, Catherine Tomasetto, Jean-Marie Garnier, Nicolas Rouyer, Marie-Geneviève Mattei, Jean-Pierre Bellocq, Marie-Christine Rio, Paul Basset
Journal: Cancer Research (1995)

We describe a differential screening method for cDNA libraries which used a combination of subtracted and PCR-amplified cDNA probes, and which can be applied to the selection of genes expressed in multiple tissues. This technique was used to identify genes commonly overexpressed in breast and basal cell carcinomas. These represent stromally dependent, invasive tumors with and without metastatic capacity. Thus, this screening sought to identify genes involved in the early stages of tumor progression. We identified a total of 16 genes, including c-erbB-2 and tissue inhibitor of metalloproteinases 3 whose products have been implicated in tumorigenesis or invasion. We also identified a novel sequence (D52) showing little homology with others described in any species, which maps to the human chromosomal band 8q21. In situ RNA hybridizations of breast carcinoma sections indicated that the D52 gene was expressed in cancer cells, whereas other genes identified in the differential screening were expressed in fibroblastic or inflammatory cells within the tumor stroma. Thus, the procedure developed in this study selected genes expressed in a diversity of cell types, indicating its potential usefulness in other systems.
PEGylation in anti-cancer therapy: An overview
Authors: Prajna Mishra, Bismita Nayak, R.K. Dey
Journal: Asian Journal of Pharmaceutical Sciences (2015)

Advanced drug delivery systems using poly(ethylene glycol) (PEG) is an important development in anti-cancer therapy. PEGylation has the ability to enhance the retention time of the therapeutics like proteins, enzymes small molecular drugs, liposomes and nanoparticles by protecting them against various degrading mechanisms active inside a tissue or cell, which consequently improves their therapeutic potential. PEGylation effectively alters the pharmacokinetics (PK) of a variety of drugs and dramatically improves the pharmaceutical values; recent development of which includes fabrication of stimuli-sensitive polymers/smart polymers and polymeric micelles to cope of with the pathophysiological environment of targeted site with less toxic effects and more effectiveness. This overview discusses PEGylation involving proteins, enzymes, low molecular weight drugs, liposomes and nanoparticles that has been developed, clinically tried for anti-cancer therapy during the last decade.
Depression and Alzheimer's disease
Authors: Rovner Bw, Broadhead J, Spencer M, Carson K, Folstein Mf
Journal: American Journal of Psychiatry (1989)

In his classic case, Alzheimer described cognitive symptoms such as amnesia, aphasia, and apraxia and noncognitive symptoms such as delusions and agitation. Recent studies have suggested that depression also occurs in Alzheimer's disease. In this study, 144 patients who met criteria for Alzheimer's disease were examined for depression on a modified version of the Present State Examination. The prevalence rate of major depression was 17%. The depressed Alzheimer's disease patients were more cognitively impaired and more disabled than the nondepressed patients. Studies are needed to clarify the etiology and treatment of depression in Alzheimer's disease.
Multiplex real-time polymerase chain reaction is useful in diagnosing pathogens causing community-acquired pneumonia including atypical bacteria and viruses
Authors: Yutaka Yoshii, Kenichiro Shimizu, Miyuki Morozumi, Naoko Chiba, Kimiko Ubukata, Hironori Uruga, Shigeo Hanada, Kazuma Kishi, Hiroshi Wakui, Shunsuke Minagawa, Jun Kojima, Hiromichi Hara, Takanori Numata, Makoto Kawaishi, Jun Araya, Yumi Kaneko, Katsutoshi Nakayama, Kazuyoshi Kuwano
Journal: European Respiratory Journal (2014)

Background: We reported the utility of multiplex real-time polymerase chain reaction (MRT-PCR) to diagnose pathogens causing community-acquired pneumonia (CAP) in Japanese adults at ERS 2013. The number of samples was limited, so we extended the study to Jan 2014. Aims: To confirm usefulness of MRT-PCR in diagnosing causative pathogens in a large number of adult Japanese CAP patients as compared with conventional tests (sputum/blood culture, urine antigen for Streptococcus pneumoniae [S.p]/Legionella pneumophila [L.p], and paired serum of Mycoplasma pneumoniae [M.p] antibody) Methods: We prospectively enrolled adult CAP patients from Sep 2012 to Jan 2014. CAP was defined based on respiratory symptoms and laboratory/chest X-ray findings excluding noninfectious causes.We collected sputum, nasopharyngeal swab, urine, and blood samples of each patient. MRT-PCR can identify 6 bacteria and 11 viruses in sputum and nasopharyngeal swab samples. Causative pathogens were identified by each test. Results: We analyzed 92 patients (mean age, 60 years; 53 men). Sensitivity of MRT-PCR was significantly higher than that of conventional tests in all cases (78% vs. 56%; pl0.01). S.p was the most common causative pathogen of CAP by MRT-PCR (21 cases, 23%). Causative pathogens of 12 cases (13%) were atypical bacteria such as L.p, M.p, and Chlamydophila pneumoniae. Virus infection rate was also high (22%). Conclusions: Compared with conventional tests, MRT-PCR was useful for diagnosing CAP. It can simultaneously identify ≥2 pathogens including atypical bacteria and uncultivable viruses and maintain high sensitivity in a large number of patients.
Neuraminidase inhibitors: who, when, where?
Authors: J S Nguyen-Van-Tam, S Venkatesan, S G Muthuri, P R Myles
Journal: Clinical Microbiology and Infection (2014)

Although the neuraminidase inhibitors (NIs), oseltamivir and zanamivir were first licensed in 1999, their clinical effectiveness is still hotly debated. Two rigorous systematic reviews and meta-analyses of the data from clinical trials conducted in community settings against relatively benign influenza, both suggest that reductions in symptom duration are extremely modest, under one day. Whilst one of these reviews could find no evidence of reductions in complications, the most recent review reported clinically meaningful and statistically significant reductions in the likelihood of requiring antibiotics (44%) and hospitalizations (63%) in adult patients with confirmed influenza, treated with oseltamivir. A further meta-analysis of observational data from the 2009 influenza A(H1N1) pandemic suggested that, in hospitalised patients, NIs significantly reduced mortality in adults by 25% overall, and by 62% if started within 48 hours of symptom onset, compared with no treatment. But, the effectiveness of NIs in children is far less clear. Taken together, these data suggest that NIs should be reserved for patients with influenza who are at high-risk of complications, or when clinically assessed found to be markedly unwell, or rapidly deteriorating. In such patients, treatment should be initiated empirically, as soon as possible, preferably with follow-on virological confirmation.
Mistreatment of Women in Childbirth: Time for Action on This Important Dimension of Violence against Women
Authors: Rachel Jewkes, Loveday Penn-Kekana
Journal: PLoS Medicine (2015)

The mistreatment of women in childbirth has been documented by researchers for over three decades in all global regions.The scale of the problem is indicated by a systematic review conducted by Meghan Bohren and colleagues [1], which provides a foundation from which a typology of violence can be developed and used as a basis for developing measurement instruments and tools.This is a valuable complement to other work that is currently underway in this area [2].A multicountry study on the mistreatment of women during childbirth could be extremely valuable in generating comparable information on prevalence, risk groups and facilities, and the health consequences (physical and mental, including future health-seeking practices and expectations).It would provide the foundation needed for developing health policy, monitoring its impact, and advocating for proper resources.
Ocular Blast Injuries in Mass-Casualty Incidents
Authors: Yoshihiro Yonekawa, Henry D. Hacker, Roy E. Lehman, Casey J. Beal, Peter B. Veldman, Neil M. Vyas, Ankoor S. Shah, David Wu, Dean Eliott, Matthew F. Gardiner, Mark C. Kuperwaser, Robert H. Rosa, Jean E. Ramsey, Joan W. Miller, Robert A. Mazzoli, Mary G. Lawrence, Jorge G. Arroyo
Journal: Ophthalmology (2014)
Radioiodine Therapy: Malignant Thyroid Disease
Authors: P. Lind, I. Igerc, S. Kohlfürst
Journal: Clinical Nuclear Medicine (2008)

It was more than 60 years ago in 1943 that thyroid cancer was treated for the first time. The story of radioiodine started in 1935 at the Massachusetts Institute of Technology in cooperation with the Thyroid Unit of the Massachussetts General Hospital (Stanbury 1991). Diagnostic thyroid studies were performed for the first time in 1937 using iodine-128. In 1938, not more than 1 year later, I-130 and I-131 were discovered, followed by the first treatment of benign thyroid disease in 1941. In 1946 the Oak Ridge National Laboratory produced I-131 for routine use and from this time on I-131 treatment was increasingly performed not only in benign thyroid diseases but also in differentiated thyroid cancer (DTC). It was as early as 1949 that a patient with metastasizing thyroid cancer was treated for the first time in Europe. With 1 – 2 % of all malignancies, thyroid cancer is counted among the rare neoplastic diseases (Langsteger et al. 1993). The incidence of thyroid cancer is variable in different regions but is increasing worldwide. The figures range from 1.1 in the UK up to 15.4/100,000/year in Hawaii.
Modulation of melanosomal activity by cisplatin: Characterization of a novel cellular machinery that may evade chemosensitivity
Authors: Kevin G. Chen, Julio C. Valencia, Xing-Jie Liang, Werner Berens, Jill Paterson, Francois Rouzaud, Stephen Wincovitch, Susan H. Garfield, Vincent J. Hearing, Michael M. Gottesman
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

1487 

Melanomas, derived from melanocytes, are intrinsically resistant to many chemotherapeutic agents including cisplatin. However, the potential role of melanogenesis in this intrinsic cisplatin resistance (ICR) in melanomas is unknown. In this study, we report an altered melanogenesis pathway that may be involved in ICR. Briefly, the melanotic melanoma cell line MNT-1 and several other melanoma cell lines (included in the NCI-60 cell panel) showed an approximately 13-fold increase in ICR compared with KB-3-1 (epidermoid carcinoma) cells. The ICR phenotype was associated with an Alexa Fluor® 488-cisplatin-accumulation defect in MNT-1 cells. Transient treatments of MNT-1 cells with cisplatin resulted in altered melanogenesis, which was manifested as a pronounced decrease in cellular proliferation concomitant with a dramatic increase (by 7.3-fold) in intracellular pigmentation and an increase (8-fold) in secretion of melanin-containing melanosomes as well as other organelles (such as altered lysosomes and mitochondria). The rate-limiting melanogenic enzymatic activity mediated by tyrosinase was increased 11-fold in cisplatin-treated MNT-1 cells, compared with non-treated cells. In addition, mass spectrometric analysis of secretory organelles confirmed the presence of the components that are involved in melanosome export. Thus, these data suggest that ICR in melanomas is associated with decreased accumulation of cisplatin, which may be mediated by either active cisplatin export and/or melanosome-mediated drug secretion.
Utilizing population variation, vaccination, and systems biology to study human immunology
Authors: John S. Tsang
Journal: Trends in Immunology (2015)

•Genetic diversity and varied environmental exposures and life histories give rise to diverse immune states.•Genetic and phenotypic variations constitute natural 'perturbations' in humans.•These variations are essential to robustly establish correlations among parameters.•Population-based, systems-level studies of vaccination provide predictors of immune-response quality. The move toward precision medicine has highlighted the importance of understanding biological variability within and across individuals in the human population. In particular, given the prevalent involvement of the immune system in diverse pathologies, an important question is how much and what information about the state of the immune system is required to enable accurate prediction of future health and response to medical interventions. Towards addressing this question, recent studies using vaccination as a model perturbation and systems-biology approaches are beginning to provide a glimpse of how natural population variation together with multiplexed, high-throughput measurement and computational analysis can be used to uncover predictors of immune response quality in humans. Here I discuss recent developments in this emerging field, with emphasis on baseline correlates of vaccination responses, sources of immune-state variability, as well as relevant features of study design, data generation, and computational analysis. The move toward precision medicine has highlighted the importance of understanding biological variability within and across individuals in the human population. In particular, given the prevalent involvement of the immune system in diverse pathologies, an important question is how much and what information about the state of the immune system is required to enable accurate prediction of future health and response to medical interventions. Towards addressing this question, recent studies using vaccination as a model perturbation and systems-biology approaches are beginning to provide a glimpse of how natural population variation together with multiplexed, high-throughput measurement and computational analysis can be used to uncover predictors of immune response quality in humans. Here I discuss recent developments in this emerging field, with emphasis on baseline correlates of vaccination responses, sources of immune-state variability, as well as relevant features of study design, data generation, and computational analysis.
Abstract 17577: Searching for the Optimal Regimen of Potent P2Y12 Inhibitor in East Asian Patients with Acute Coronary Syndrome: A Pharmacodynamic Study
Authors: Jang-Young Kim, Ji Hyun Lee, Jun-Won Lee, Young Jin Youn, Min-Soo Ahn, Sung Gyun Ahn, Byung-Su Yoo, Seung-Hwan Lee, Junghan Yoon
Journal: Circulation (2014)

Introduction: The efficacy of prasugrel and ticagrelor has not been well evaluated in East Asian. We sought to compare the pharmacodynamic efficacy of prasugrel and ticagrelor by using VerifyNow P2Y12 assay (Accumetrics, San Diego, CA, USA). Methods: From 2012 January to 2014 April, we selected 83 patients who were administered ticagrelor 90 mg twice daily (n = 24), prasugrel 10 mg daily (n = 39), or prasugrel 5 mg daily (n = 20) after percutaneous coronary intervention due to acute coronary syndrome in our institute. After 3-4 weeks, on-treatment platelet reactivity (OPR) was measured by VerifyNow assay. According to the previous studies, we used 2 different criteria for the therapeutic window of OPR (East Asian criteria: 275≥PRU&gt;85; Western criteria: 208 ≥PRU&gt;85). We compared the OPR and the proportion of the therapeutic window between 3 groups. Results: The OPR was the lowest in the ticagrelor group, followed by the prasugrel 10 mg and prasugrel 5 mg groups (49.1 ± 29.9 vs. 83.7 ± 57.1 vs. 168.5 ± 60.8, p &lt; 0.001).When we used the East Asian criteria, the prasugrel 5 mg group had the highest proportion of patients in the therapeutic window of OPR followed by prasugrel 10mg and ticagrelor groups ( 90.0% vs. 46.2% vs. 12.5%, p &lt; 0.001). When using Western criteria, the prasugrel 5mg group still showed the highest proportion of patients with therapeutic window followed by prasugrel 10mg and ticagrelor groups (60.0% vs. 43.6% vs. 12.5%, p&lt;0.001). Conclusion: Short-term administration of prasugrel 5mg highly led the patients into the therapeutic window of OPR (in both of East Asian and Western criteria), compared with prasugrel 10mg and ticagrelor 180mg group. The prasugrel 5mg daily might be the optimal maintenance regimen for East Asian patients.
Women's Treatment Decisions for Genital Symptoms
Authors: R M Harrison
Journal: Journal of the Royal Society of Medicine (1982)

A study of illness behaviour and sexually transmitted diseases (STDs) investigated the ways in which women with symptoms potentially attributable to STD reached a decision on whether or not treatment should be sought. It was found that non-treatment of genital symptoms is partially explained by women classifying symptoms as normal: 53% among those not seeking treatment did so, compared to 12% and 10% in the two treated groups. When people are uncertain about symptoms there is a motivation to seek treatment. Thus, nearly all women in this category thought treatment necessary. Even among women who do seek treatment, the majority do so only after a period of waiting. Only 45% and 43% in the two treated groups reported seeking treatment immediately. The biological and sociological background relevant to treatment decisions indicate that it will be difficult to achieve changes in these percentages.