tbuckley/cabot-search huggingface dataset:
Genetic and Acquired Determinants of Individual Variability of Response to Antiplatelet Drugs
Authors: Andrew I. Schafer
Journal: Circulation (2003)

he efficacy of various antiplatelet agents in preventing cardiovascular and thrombotic complications has been established in large-scale clinical trials.Composite data from such studies tend to mask individual variability in responsiveness to the drugs being investigated.In fact, antiplatelet drugs that are effective and safe in one individual may be ineffective or harmful in another.
Macrolide-resistant Mycoplasma pneumoniae in adolescents with community-acquired pneumonia
Authors: Naoyuki Miyashita, Yasuhiro Kawai, Mika Kubo, Kazunobu Ouchi, Niro Okimoto
Journal: European Respiratory Journal (2012)

Background and objective:   Although the prevalence of macrolide-resistant (MR)  Mycoplasma pneumoniae  isolates in Japanese pediatric patients has increased rapidly, there have been no reports concerning MR  M. pneumoniae  infection in adolescents aged 16 to 19-years old. The purpose of this study was to clarify the prevalence and clinical characteristics of MR  M. pneumoniae  in adolescent patients with community-acquired pneumonia.    Methods:   A total of 61 cases with  M.   pneumoniae  pneumonia confirmed by polymerase chain reaction (PCR) and culture were analyzed. Thirty-two cases were pediatric patients less than 16 years old, 14 cases were 16 to 19-year-old adolescent patients and 15 cases were adult patients. Primers for domain V of 23S rRNA were used and DNA sequences of PCR products were compared with the sequence of an  M.   pneumoniae  reference strain.    Results:   Twenty-two of 32 pediatric patients less than 16-years old, eight of 14 adolescent patients aged 16 to 19-years old and five of 15 adult patients with  M. pneumoniae  pneumonia were found to be infected with MR  M. pneumoniae . Among 22 pediatric MR patients, 18 had an A-to-G transition at position 2063 (A2063G) and four had an A-to-G transition at position 2064 (A2064G). Among eight adolescent MR patients, six showed an A2063G transition and two showed an A2064G transition.    Conclusions:   The prevalence of MR  M. pneumoniae  is high among adolescent patients as well as pediatric patients less than 16-years old. To prevent outbreaks of  M. pneumoniae  infection, especially MR  M. pneumoniae , in closed populations including among families, in schools and in university students, physicians should pay attention to MR  M. pneumoniae .
Cutaneous arteritis with superior vena cava obstruction
Authors: P.DORRINGTON WARD, J. McIVOR, D. WOODROW, J.J. CREAM
Journal: British Journal of Dermatology (1979)

Superior vena cava (SVC) obstruction may occur in several disorders (Urschel & Paulson, 1966) and may be associated with arteritis in Behçet's disease (Chajek & Farinaru, 1975). We report a man who had arteritis and SVC obstruction without any of the known causes.
PRESENCE OF TWO TYPES OF L POLYPEPTIDE CHAINS IN GUINEA PIG 7S IMMUNOGLOBULINS
Authors: Victor Nussenzweig, Michael E. Lamm, Baruj Benacerraf
Journal: The Journal of Experimental Medicine (1966)

Guinea pig 7S immunoglobulins (gamma(1) and gamma(2)) consist of two groups of molecules (K and L) bearing different types of L chains (kappa and lambda). Approximately one-third of the molecules in normal guinea pig gamma(2)-globulin bear the lambda- type of L chains, and all or most of the others bear kappa-chains. kappa- and lambda-chains have similar molecular weights.
An Emergency Leucotomy
Authors: M. OC. Drury
Journal: BMJ (1950)

On January 17 the spinal fluid was under normal pressure.It contained no excess of cells; 30 mg. of protein per 100 ml.; no excess of globulin; 730 mg. of chlorides per 100 ml.On January 20 a repeat tap showed that the fluid contained no excess of cells; 30 mg. of protein per 100 ml.; no excess of globulin; 720 mg. of chlorides per 100 ml.; 65 mg. of sugar.No organisms were grown.Queckenstedt's test was negative.
Imiquimod 5% cream for the treatment of superficial and nodular basal cell carcinoma: randomized studies comparing low-frequency dosing with and without occlusion
Authors: W. Sterry, T. Ruzicka, E. Herrera, A. Takwale, J. Bichel, K. Andres, L. Ding, M.R.T.M. Thissen
Journal: British Journal of Dermatology (2002)

Summary Background Imiquimod 5% cream has been investigated for non-surgical treatment of superficial and nodular basal cell carcinoma (BCC) tumours. Objectives Two studies were conducted to examine the effect of occlusion at low dosing frequencies on the safety and efficacy of topical imiquimod 5% cream for the treatment of superficial and nodular BCC. Patients and methods Both open-label studies were conducted in Europe. Patients diagnosed with BCC were enrolled into either the superficial (93 patients) or nodular (90 patients) study, depending on the histological confirmation of the patient's tumour subtype. Patients were randomized to one of four groups to apply imiquimod 5% cream 2 or 3 days per week either with or without occlusion. Six weeks following a 6-week treatment period, the entire target tumour area was excised and histologically examined for evidence of residual tumour. Results In both studies, the highest histologically complete response rate was seen in the 3 days per week with occlusion groups, with complete response rates of 87% and 65% for the superficial and nodular studies, respectively. Occlusion did not have a statistically significant effect on response rate at either dosing frequency. Response rates for superficial and nodular BCC tumours treated 3 days per week without occlusion were 76% and 50%, respectively. Conclusions In the superficial study, the complete response rate of 87% in the 3 days per week with occlusion group was similar to that of daily and 5 days per week dosing without occlusion in a previous 12-week study and one study of daily dosing without occlusion for 6 weeks. All treatment groups had acceptable safety profiles in both studies. Occlusion did not have a statistically significant effect on efficacy for either superficial or nodular BCC tumours.
Incidence of Venous Thromboembolism in Patients With Ovarian Cancer Undergoing Platinum/Paclitaxel–Containing First-Line Chemotherapy: An Exploratory Analysis by the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group
Authors: Christina Fotopoulou, Andreas duBois, Alexandros N. Karavas, Ralf Trappe, Behnaz Aminossadati, Barbara Schmalfeldt, Jacobus Pfisterer, Jalid Sehouli
Journal: Journal of Clinical Oncology (2008)

Venous thromboembolism (VTE) has been associated with negative prognosis in cancer patients. Most series reporting on VTE have included different tumor types not differentiating between recurrent or primary disease. Data regarding the actual impact of VTE on primary advanced ovarian cancer (AOC) are limited.Between 1995 and 2002, the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study group (AGO-OVAR) recruited 2,743 patients with AOC in three prospectively randomized trials on platinum paclitaxel-based chemotherapy after primary surgery. Pooled data analysis was performed to evaluate incidence, predictors, and prognostic impact of VTE in AOC. Survival curves were calculated for the VTE incidence. Univariate analysis and Cox regression analysis were performed to identify independent predictors of VTE and mortality.Seventy-six VTE episodes were identified, which occurred during six to 11 cycles of adjuvant chemotherapy; 50% of them occurred within 2 months postoperatively. Multivariate analysis identified body mass index higher than 30 kg/m(2) and increasing age as independent predictors of VTE. International Federation of Gynecology and Obstetrics stage and surgical radicality did not affect incidence. Overall survival was significantly reduced in patients with VTE (median, 29.8 v 36.2 months; P = .03). Multivariate analysis identified pulmonary embolism (PE), but not deep vein thrombosis alone, to be of prognostic significance. In addition, VTE was not identified to significantly affect progression-free survival.Patients with AOC have their highest VTE risk within the first 2 months after radical surgery. Only VTE complicated by symptomatic PE have been identified to have a negative impact on survival. Studies evaluating the role of prophylactic anticoagulation during this high risk postoperative period are warranted.
The end of RIPK1‐RIPK3‐MLKL–mediated necroptosis in acetaminophen‐induced hepatotoxicity?
Authors: Xiao Yang, Xiaojuan Chao, Zheng‐Tao Wang, Wen‐Xing Ding
Journal: Hepatology (2015)

Potential conflict of interest: Nothing to report. To the Editor: We read with great interest the recently published article by Dara et al.1 in which they provided novel, mechanistic insights regarding the emerging role of receptor‐interacting protein kinase (RIPK)‐mediated necroptosis in acetaminophen (APAP)‐induced liver injury. Necroptosis is regulated by the RIPK1‐RIPK3‐MLKL (mixed lineage kinase domain‐like protein) signaling cascade and has been implicated in APAP‐induced liver injury.2 Dara et al. found that APAP‐induced necrosis was dependent on RIPK1, but not RIPK3, or MLKL. This finding suggests that necroptosis is not an important mediator of APAP‐induced liver injury. One major argument by Dara et al. for the lack of RIPK3 involvement in APAP‐induced cell death was that hepatocytes do not express RIPK3; however, their experimental design may have led to the failure to detect RIPK3 in primary mouse hepatocytes (PMHs). PMHs dedifferentiate rapidly in culture and thus quickly lose many hepatic proteins, such as macromolecule transporters, and drug‐metabolizing enzymes. It was unclear how long the PMHs were cultured by Dara et al., before the cells were harvested, but we found levels of RIPK3 protein in PMHs markedly decreased after 6 hours in culture. This may be the reason that Dara et al. failed to detect RIPK3 in PMHs. We used an RIPK3 antibody from ProSci, which was validated using RIPK3‐deficient liver tissues, and mouse embryonic fibroblasts.2 Although Dara et al. used the same antibody as we did, it is unclear why they failed to detect RIPK3 in the liver. Another finding from the study by Dara et al. was that RIPK1 acted upstream of c‐Jun N‐terminal kinase (JNK). This brings up the interesting question of whether RIPK1 directly interacts with and phosphorylates JNK, or is JNK activation a secondary effect of RIPK1 knockdown. Studies performed by our group and others, including Dara et al. themselves, indicate that the key necroptosis components (RIPK1, RIPK3, and MLKL) are primarily expressed in spleen and thymus, and not in the liver.4 This could mean that RIPK‐MLKL–mediated necroptosis may play a major role in regulating innate immunity. The innate immune system has been implicated in regulating the progression of APAP‐induced liver injury. The authors may like to comment on the possibility that RIPK1 knockdown in nonparenchymal cells, such as Kupffer cells and infiltrating neutrophils, also plays a protective role against APAP‐induced liver injury.
Developmental arrest of NK1.1+ T cell antigen receptor (TCR)-alpha/beta+ T cells and expansion of NK1.1+ TCR-gamma/delta+ T cell development in CD3 zeta-deficient mice.
Authors: H Arase, S Ono, N Arase, S Y Park, K Wakizaka, H Watanabe, H Ohno, T Saito
Journal: The Journal of Experimental Medicine (1995)

The relationship between the structure of the T cell antigen receptor (TCR)-CD3 complex and development of NK1.1+ T cells was investigated. The TCR complex of freshly isolated NK1.1+ TCR-alpha/beta+ thymocytes contained CD3 zeta homodimers and CD zeta-FcR gamma heterodimers, whereas that of the majority of NK1.1- T cells did not contain FcR gamma. The function of CD3 zeta and FcR gamma in the development of NK1.1+ T cells was determined by analyzing CD3 zeta- and FcR gamma-deficient mice. The NK1.1+ T cells from wild-type and CD3 zeta-deficient mice had equal levels of CD3 expression. However, the development of NK1.1+ TCR-alpha/beta+ T cells was almost completely disrupted in thymus and spleen in CD3 zeta-deficient mice, whereas no alteration was observed in FcR gamma-deficient mice. In contrast, the number of novel NK1.1+ TCR-gamma/delta+ thymocytes expressing a surface phenotype similar to NK1.1+ TCR-alpha/beta+ thymocytes increased approximately six times in CD3 zeta-deficient mice. These findings establish the distinct roles of the CD3 zeta chain in the development of the following different thymic T cell compartments: NK1.1- TCR+, NK1.1+ TCR-alpha/beta+, and NK1.1+ TCR-gamma/delta+ thymocytes, which cannot be replaced by CD3 eta or FcR gamma chains.
Azithromycin maintenance treatment in patients with frequent exacerbations of chronic obstructive pulmonary disease (COLUMBUS): a randomised, double-blind, placebo-controlled trial
Authors: Sevim Uzun, Remco S Djamin, Jan A J W Kluytmans, Paul G H Mulder, Nils E van't Veer, Anton A M Ermens, Aline J Pelle, Henk C Hoogsteden, Joachim G J V Aerts, Menno M van der Eerden
Journal: The Lancet Respiratory Medicine (2014)
Base Compositions of Genes Encoding α-Actin and Lactate Dehydrogenase-A from Differently Adapted Vertebrates Show No Temperature-Adaptive Variation in G + C Content
Authors: Rachael A. Ream, Glenn C. Johns, George N. Somero
Journal: Molecular Biology and Evolution (2003)

There is a long-standing debate in molecular evolution concerning the putative importance of GC content in adapting the thermal stabilities of DNA and RNA. Most studies of this relationship have examined broad-scale compositional patterns, for example, total GC percentages in genomes and occurrence of GC-rich isochores. Few studies have systematically examined the GC contents of individual orthologous genes from differently thermally adapted species. When this has been done, the emphasis has been on comparing large numbers of genes in only a few species. We have approached the GC-adaptation temperature hypothesis in a different manner by examining patterns of base composition of genes encoding lactate dehydrogenase-A (ldh-a) and alpha-actin (α-actin) from 51 species of vertebrates whose adaptation temperatures ranged from −1.86°C (Antarctic fishes) to approximately 45°C (desert reptile). No significant positive correlation was found between any index of GC content (GC content of the entire sequence, GC content of the third codon position [GC3], and GC content at fourfold degenerate sites [GC4]) and any index of adaptation temperature (maximal, mean, or minimal body temperature). For α-actin, slopes of regression lines for all comparisons did not differ significantly from zero. For ldh-a, negative correlations between adaptation temperature and total GC content, GC3, and GC4 were observed but were shown to be due entirely to phylogenetic influences (as revealed by independent contrast analyses). This comparison of GC content across a wide range of ectothermic (“cold-blooded”) and endothermic (“warm-blooded”) vertebrates revealed that frogs of the genus Xenopus, which have commonly been used as a representative cold-blooded species, in fact are outliers among ectotherms for the α-actin analyses, raising concern about the appropriateness of choosing these amphibians as representative of ectothermic vertebrates in general. Our study indicates that, whereas GC contents of isochores may show variation among different classes of vertebrates, there is no consistent relationship between adaptation temperature and the percentage of thermal stability-enhancing G + C base pairs in protein-coding genes.
Pneumococcal pneumonia – Are the new severity scores more accurate in predicting adverse outcomes?
Authors: Carla Ribeiro, Inês Ladeira, Gabriela Abreu, Ana Rita Gaio, M. Céu Brito
Journal: European Respiratory Journal (2011)

Background:  The severity scores are validated prognostic tools for community-acquired pneumonia mortality and treatment site decision.   Aim:  To compare the discriminatory power (DP) of 4 scores – the classic PSI and CURB65 and the most recent SCAP (Yandiola P et al. Chest 2009;135;1572-1579) and SMART-COP(Charles P et al.Clinical Infectious Diseases 2008; 47:375–84) – in predicting major adverse events: death, ICU admission, need for invasive mechanical ventilation or vasopressor support.   Methods:  A 5-year retrospective study of patients admitted for pneumococcal pneumonia (PP). The patients were stratified based on admission data and assigned to risk classes (low-medium-high) for each score, as validated by previous studies. Statistical analysis was done based on sensitivity, specificity and area under the curve (AUC) under the ROC curve.   Results:  We assessed 142 episodes of hospitalization for PP. We observed 2 deaths, 22 admissions to the ICU, 10 patients needed mechanical ventilation and vasopressor support. The AUC for each score/event is summarized on the following table.   Conclusions:  The rate of all adverse outcomes increased directly with increasing risk class in all scores. The new gravity scores (particularly the SCAP score) appear to have a higher DP to all adverse events in our study.
Double-blind, right/left comparison of calcipotriol and betamethasone valerate in treatment of psoriasis vulgaris
Authors: K. Kragballe, B.T. Gjertsen, D. de Hoop, P.C.M. van de Kerkhof, T. Karlsmark, O. Larko, C. Nieboer, J. Roed-Petersen, A. Strand, G. Tikjøb
Journal: The Lancet (1991)
Inhaled corticosteroids and mortality in chronic obstructive pulmonary disease
Authors: DD Sin, L Wu, JA Anderson, NR Anthonisen, AS Buist, PS Burge, PM Calverley, JE Connett, B Lindmark, RA Pauwels, Dirkje Postma, JB Soriano, W Szafranski, J Vestbo
Journal: Thorax (2005)

Clinical studies suggest that inhaled corticosteroids reduce exacerbations and improve health status in chronic obstructive pulmonary disease (COPD). However, their effect on mortality is unknown.A pooled analysis, based on intention to treat, of individual patient data from seven randomised trials (involving 5085 patients) was performed in which the effects of inhaled corticosteroids and placebo were compared over at least 12 months in patients with stable COPD. The end point was all-cause mortality.Overall, 4% of the participants died during a mean follow up period of 26 months. Inhaled corticosteroids reduced all-cause mortality by about 25% relative to placebo. Stratification by individual trials and adjustments for age, sex, baseline post-bronchodilator percentage predicted forced expiratory volume in 1 second, smoking status, and body mass index did not materially change the results (adjusted hazard ratio (HR) 0.73; 95% confidence interval (CI) 0.55 to 0.96). Although there was considerable overlap between subgroups in terms of effect sizes, the beneficial effect was especially noticeable in women (adjusted HR 0.46; 95% CI 0.24 to 0.91) and former smokers (adjusted HR 0.60; 95% CI 0.39 to 0.93).Inhaled corticosteroids reduce all-cause mortality in COPD. Further studies are required to determine whether the survival benefits persist beyond 2-3 years.
Gene Expression Alterations in Prostate Cancer Predicting Tumor Aggression and Preceding Development of Malignancy
Authors: Yan Ping Yu, Douglas Landsittel, Ling Jing, Joel Nelson, Baoguo Ren, Lijun Liu, Courtney McDonald, Ryan Thomas, Rajiv Dhir, Sydney Finkelstein, George Michalopoulos, Michael Becich, Jian-Hua Luo
Journal: Journal of Clinical Oncology (2004)

The incidence of prostate cancer is frequent, occurring in almost one-third of men older than 45 years. Only a fraction of the cases reach the stages displaying clinical significance. Despite the advances in our understanding of prostate carcinogenesis and disease progression, our knowledge of this disease is still fragmented. Identification of the genes and patterns of gene expression will provide a more cohesive picture of prostate cancer biology.In this study, we performed a comprehensive gene expression analysis on 152 human samples including prostate cancer tissues, prostate tissues adjacent to tumor, and organ donor prostate tissues, obtained from men of various ages, using the Affymetrix (Santa Clara, CA) U95a, U95b, and U95c chip sets (37,777 genes and expression sequence tags).Our results confirm an alteration of gene expression in prostate cancer when comparing with nontumor adjacent prostate tissues. However, our study also indicates that the gene expression pattern in tissues adjacent to cancer is so substantially altered that it resembles a cancer field effect.We also found that gene expression patterns can be used to predict the aggressiveness of prostate cancer using a novel model.
Skeletal muscle uptake of Tc 99m pyrophosphate in amyloidosis
Authors: James B. Johnston, Harry L. Rayner, Cynthia Trevenen, David Greenberg
Journal: American Journal of Hematology (1982)

Abstract In a patient with amyloidosis involving the heart, kidneys, and skeletal muscles, a Tc 99m pyrophosphate “bone” scan demonstrated intense uptake of tracer by the skeletal muscles; but not by the heart or kidneys. Using the alizarin red stain, prominent calcium deposits were detected histologically in association with the skeletal muscle amyloid. These findings suggest that certain amyloid deposits will take up Tc 99m pyrophosphate, but only if sufficient amounts of calcium are associated with the amyloid.
Angiofollicular lymph node hyperplasia arising from the intercostal space.
Authors: H Matsuda, M Mori, K Yasumoto, K Sugimachi
Journal: Thorax (1988)

Angiofollicular lymph node hyperplasia (Castleman's disease) was first described in 1956 by Castleman et al' as asymptomatic large, benign hyperplastic mediastinal lymph nodes that resembled thymoma.This disease has been reported in various sites and organs, but a careful search of published reports showed no case arising from the intercostal space.We report a case that arose in the chest wall. Case reportA 69 year old Japanese man was admitted to Kyushu University hospital for evaluation of a long standing abnor- mal shadow on his chest radiograph, first detected nine years previously on a routine chest radiograph.Initially it had been 1-3 cm in diameter, but three years later it had grown to 2-3 cm and by six years it was 3-4 cm.The patient had been in good health, without peripheral lymphadenopathy or abnor- mal palpable masses.On examination there was dullness to percussion with decreased breath sounds and diminished vocal fremitus at the base of the left lung.The erythrocyte sedimentation rate was 18 mm in one hour, and other laboratory data were within normal limits.A chest radiograph showed a uniform shadow