tbuckley/cabot-search huggingface dataset:
Ganoderic Acid β Suppressed Th2 Responses and Induced Th1/Tregs in Cultures of Peripheral Blood Mononuclear Cells From Asthmatic Patients
Authors: Changda Liu, Ying Song, Nan Yang, Jody R. Tversky, Jessica Reid-Adam, Xiu-Min Li
Journal: Journal of Allergy and Clinical Immunology (2013)

It is well established that Th2 dominant responses play a central role in the pathogenesis of allergic diseases. In contract, Th1 and T regulatory immunity inhibit Th2 response and induces immune tolerance to harmless environmental antigens. Ganoderic acid β (GAβ) was isolated from Ganoderma lucidum, a widely used medicinal mushroom with immunomodulatory activity. Modulatory effect of GAβ was determined and compared with dexamethasone (Dex). GAβ was isolated by liquid-liquid extraction, silica gel column chromatography, and preparative HPLC. Specific allergy of each patient was identified by skin tests and antigen specific serum IgE testing, and included dust mite (Dermatophagoides farina), German cockroach, ragweed and cat allergens. PBMCs separated from 10 asthma patients were cultured with their specific antigen with or without GAβ or Dex for 3 and 6days. IFN-γ, IL-10, IL-12 levels in 3d culture supernatants, and IL-5 levels in the 6d culture supernatants were measured by ELISA. IFN-γ expression was determined by flow cytometry. Purified GAβ was identified LC-MS and NMR spectra. Dex (10-5 M) produced overall suppression. In contrast, GAβ (7×10-5 M) decreased only IL-5 production, and increased IFN-γ ,IL-10, and IL-12 production by specific-allergen stimulated PBMCs. GAβ also significantly increased CD8+ IFN-γ expression by allergen stimulated PBMCs from below normal to a normal range. GAβ suppressed IL-5, enhanced IFN-γ, IL-10, and IL-12 production, and restored Th1/Treg-Th2 balance cultures of PBMCs from asthmatic patients.
Mechanical vs. Reflex Effects of Diffuse Pulmonary Embolism in Anesthetized Dogs
Authors: M. HENRY WILLIAMS
Journal: Circulation Research (1956)

The effects of repeated pulmonary embolisms with glass spheres on systemic and right intracavitary pressures and on arterial oxygen saturation of anesthetized dogs are described. The results of studies of intact dogs and of the isolated perfused left lower lobe indicate that the hemodynamic effects were due to mechanical obstruction to the flow of blood through the lungs eventually followed by right heart failure. Evidence for reflex effects on the blood vessels or heart was lacking. The systemic arterial unsaturation which eventually developed after repeated embolisms was completely overcome by the inspiration of oxygen and was attributed to a reduction of the diffusing capacity of the lung.
Increased risk of tuberculosis transmission in families with microepidemics
Authors: R Vidal, M Miravitlles, JA Cayla, M Torrella, J de Gracia, F Morell
Journal: European Respiratory Journal (1997)

In the present study, we analysed: 1) prevalence of TB infection and incidence of disease among family contacts of a cohort of patients with TB; 2) differential characteristics of families with microepidemics and families with &lt; or = 1 new case of TB; and 3) efficacy of chemoprophylaxis in this group of contacts. Three thousand and seventy one family contacts of 635 patients with TB were studied. The study consisted of tuberculin skin testing and chest radiography in all cases, and bacteriological studies when active disease was suspected. Contacts were classified as belonging to: families with microepidemics (FME) (those with &gt; or = 2 new cases of TB); families with one new case; and families with with no new cases. Chemoprophylaxis was prescribed in contacts following standard recommendations; all were followed up for 12-18 months. Rates of TB infection and disease among families, as well as the incidence of TB disease between those compliant and noncompliant with chemoprophylaxis were compared. Among the 3,071 contacts, 1,264 (41%) were infected and 176 (6%) had TB. Twenty two families with FME (3%) yielded 55 new cases of TB. The prevalence of infection (excluding the TB cases) was 80% in families with FME, 52% in families with one new case, and 41% in families with no new case (odds ratio (OR) 3.7; 95% confidence interval (95% CI) 2.1-6.5). Sputum smears were positive in 53% of cases in FME and 24% in non-FME families (OR 3.4; 95% CI 1.7-6.5). Bronchial sample cultures were positive in 84% of patients from FME families but in only 40% of those from non-FME families (OR 7.5; 95% CI 3.6-15.8). Chemoprophylaxis was prescribed in 356 contacts, of whom 296 complied and generated only one new case of TB, whilst there were 13 new cases among the 60 who did not comply (OR 81.6; 95% CI 26.7-248.7). This study showed the prevalence of infection and incidence of tuberculosis among family contacts of patients with newly diagnosed tuberculosis to be very high. A small number of families with microepidemics accounted for most new cases of tuberculosis, which were also more infectious. The extremely high risk of transmission in these families, together with the proven efficacy of chemoprophylaxis, justifies prescription of chemoprophylaxis to all their members, regardless of age.
Prognostic Impact of Gene Expression–Based Classification for Neuroblastoma
Authors: André Oberthuer, Barbara Hero, Frank Berthold, Dilafruz Juraeva, Andreas Faldum, Yvonne Kahlert, Shahab Asgharzadeh, Robert Seeger, Paola Scaruffi, Gian Paolo Tonini, Isabelle Janoueix-Lerosey, Olivier Delattre, Gudrun Schleiermacher, Jo Vandesompele, Joëlle Vermeulen, Frank Speleman, Rosa Noguera, Marta Piqueras, Jean Bénard, Alexander Valent, Smadar Avigad, Isaac Yaniv, Axel Weber, Holger Christiansen, Richard G. Grundy, Katharina Schardt, Manfred Schwab, Roland Eils, Patrick Warnat, Lars Kaderali, Thorsten Simon, Boris DeCarolis, Jessica Theissen, Frank Westermann, Benedikt Brors, Matthias Fischer
Journal: Journal of Clinical Oncology (2010)

To evaluate the impact of a predefined gene expression-based classifier for clinical risk estimation and cytotoxic treatment decision making in neuroblastoma patients.Gene expression profiles of 440 internationally collected neuroblastoma specimens were investigated by microarray analysis, 125 of which were examined prospectively. Patients were classified as either favorable or unfavorable by a 144-gene prediction analysis for microarrays (PAM) classifier established previously on a separate set of 77 patients. PAM classification results were compared with those of current prognostic markers and risk estimation strategies.The PAM classifier reliably distinguished patients with contrasting clinical courses (favorable [n = 249] and unfavorable [n = 191]; 5-year event free survival [EFS] 0.84 +/- 0.03 v 0.38 +/- 0.04; 5-year overall survival [OS] 0.98 +/- 0.01 v 0.56 +/- 0.05, respectively; both P < .001). Moreover, patients with divergent outcome were robustly discriminated in both German and international cohorts and in prospectively analyzed samples (P <or= .001 for both EFS and OS for each). In subgroups with clinical low-, intermediate-, and high-risk of death from disease, the PAM predictor significantly separated patients with divergent outcome (low-risk 5-year OS: 1.0 v 0.75 +/- 0.10, P < .001; intermediate-risk: 1.0 v 0.82 +/- 0.08, P = .042; and high-risk: 0.81 +/- 0.08 v 0.43 +/- 0.05, P = .001). In multivariate Cox regression models based on both EFS and OS, PAM was a significant independent prognostic marker (EFS: hazard ratio [HR], 3.375; 95% CI, 2.075 to 5.492; P < .001; OS: HR, 11.119, 95% CI, 2.487 to 49.701; P < .001). The highest potential clinical impact of the classifier was observed in patients currently considered as non-high-risk (n = 289; 5-year EFS: 0.87 +/- 0.02 v 0.44 +/- 0.07; 5-year OS: 1.0 v 0.80 +/- 0.06; both P < .001).Gene expression-based classification using the 144-gene PAM predictor can contribute to improved treatment stratification of neuroblastoma patients.
Pertuzumab Monotherapy After Trastuzumab-Based Treatment and Subsequent Reintroduction of Trastuzumab: Activity and Tolerability in Patients With Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer
Authors: Javier Cortés, Pierre Fumoleau, Giulia Valeria Bianchi, Teresa M. Petrella, Karen Gelmon, Xavier Pivot, Shailendra Verma, Joan Albanell, Pierfranco Conte, Ana Lluch, Stefania Salvagni, Veronique Servent, Luca Gianni, Maurizio Scaltriti, Graham A. Ross, Joanna Dixon, Tania Szado, José Baselga
Journal: Journal of Clinical Oncology (2012)

The combination of pertuzumab and trastuzumab resulted in a clinical benefit rate (CBR) of 50% in patients with human epidermal growth factor receptor 2 (HER2) -positive breast cancer whose disease progressed during prior trastuzumab-based therapy. To define whether this previously observed encouraging activity was a result of the combination of pertuzumab and trastuzumab or of pertuzumab alone, we recruited a third cohort of patients who received pertuzumab without trastuzumab. We then investigated the impact of reintroducing trastuzumab to patients whose disease progressed on pertuzumab monotherapy.Twenty-nine patients with HER2-positive breast cancer whose disease progressed during prior trastuzumab-based therapy received pertuzumab (840 mg loading dose, then 420 mg every 3 weeks) until progressive disease or unacceptable toxicity. Seventeen patients with disease progression continued to receive pertuzumab (at the same dose), with the addition of trastuzumab (4 mg/kg loading dose and then 2 mg/kg weekly or 8 mg/kg loading dose and then 6 mg/kg every 3 weeks).All 29 patients enrolled for pertuzumab monotherapy experienced disease progression. The objective response rate (ORR) and CBR were 3.4% and 10.3%, respectively, during pertuzumab monotherapy. With the addition of trastuzumab, the ORR and CBR were 17.6% and 41.2%, respectively. Progression-free survival was longer with combination therapy than pertuzumab monotherapy (17.4 v 7.1 weeks, respectively). Treatment was well tolerated with minimal cardiac dysfunction.Although pertuzumab has some activity in patients with HER2-positive breast cancer that progressed during therapy with trastuzumab, the combination of pertuzumab and trastuzumab seems to be more active than monotherapy.
Histone Gene Complement, Variant Expression, and mRNA Processing in a Urochordate Oikopleura dioica that Undergoes Extensive Polyploidization
Authors: Mariacristina Chioda, Ragnhild Eskeland, Eric M. Thompson
Journal: Molecular Biology and Evolution (2002)

Considerable data exist on coding sequences of histones in a wide variety of organisms. Much more restricted information is available on total histone gene complement, gene organization, transcriptional regulation, and histone mRNA processing. In particular, there is a significant phylogenetic gap in information for the urochordates, a subphylum near the invertebrate-vertebrate transition. In this study, we show that the appendicularian Oikopleura dioica has a histone gene complement that is similar to that of humans, though its genome size is 40- to 50-fold smaller. At a total length of 3.5 kb, the H3, H4, H1, H2A, and H2B quintet cluster is the most compact described thus far, but despite very rapid early developmental cleavage cycles, no extensive tandem repeats of the cluster were present. The high degree of variation within each of the complements of O. dioica H2A and H2B subtypes resembled that found in plants as opposed to more closely related vertebrate and invertebrate species, and developmental stage–specific expression of different subtypes was observed. The linker histone H1 was present in relatively few copies per haploid genome and contained short N- and C-terminal tails, a feature similar to that of copepods but different from many standard model organisms. The 3′UTRs of the histone genes contained both the consensus stem-loop sequence and the polyadenylation signals but lacked the consensus histone downstream element that is involved in the processing of histone mRNAs in echinoderms and vertebrates. Two types of transcripts were found, i.e., those containing both the stem-loop and a polyA tail as well as those cleaved at the normal site just 3′ of the stem-loop. The O. dioica data are an important addition to the limited number of eukaryotes for which sufficiently extensive information on histone gene complements is available. Increasingly, it appears that understanding the evolution of histone gene organization, transcriptional regulation, and mRNA processing will depend at least as much on comparative analysis of constraints imposed by certain life history features and cell biological characteristics as on projections based on simple phylogenetic relationships.
Photochemotherapy (PUVA) of psoriasis using 3-carbethoxypsoralen, a non-carcinogenic compound in mice
Authors: L. DUBERTRET, D. AVERBECK, F. ZAJDELA, E. BISAGNI, E. MOUSTACCHI, R. TOURAINE, R. LATARJET
Journal: British Journal of Dermatology (1979)

Journal Article Photochemotherapy (PUVA) of psoriasis using 3‐carbethoxypsoralen, a non‐carcinogenic compound in mice Get access L. DUBERTRET, L. DUBERTRET Hòpital Henri Mondor, Centre de Photochimiotherapie, Creteil. Dr L. Dubertret, Service de Dermatologie, Hòpital Henri Mondor, 94010 Creteil, France. Search for other works by this author on: Oxford Academic Google Scholar D. AVERBECK, D. AVERBECK Institut Curie, Section de Biologie, Paris Search for other works by this author on: Oxford Academic Google Scholar F. ZAJDELA, F. ZAJDELA Institut Curie, Orsay, France Search for other works by this author on: Oxford Academic Google Scholar E. BISAGNI, E. BISAGNI Institut Curie, Orsay, France Search for other works by this author on: Oxford Academic Google Scholar E. MOUSTACCHI, E. MOUSTACCHI Institut Curie, Orsay, France Search for other works by this author on: Oxford Academic Google Scholar R. TOURAINE, R. TOURAINE Hòpital Henri Mondor, Centre de Photochimiotherapie, Creteil. Search for other works by this author on: Oxford Academic Google Scholar R. LATARJET R. LATARJET Institut Curie, Section de Biologie, Paris Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 101, Issue 4, 1 October 1979, Pages 379–389, https://doi.org/10.1111/j.1365-2133.1979.tb00015.x Published: 01 October 1979
Percutaneous evacuation (PEVAC) of multivesicular echinococcal cysts with or without cystobiliary fistulas which contain non-drainable material: first results of a modified PAIR method
Authors: H G Schipper
Journal: Gut (2002)

Background: Surgery is the treatment of choice in echinococcal cysts with cystobiliary fistulas. PAIR (puncture, aspiration, injection, and reaspiration of scolecidals) is contraindicated in these cases. Aim: To evaluate a modified PAIR method for percutaneous treatment of multivesicular echinococcal cysts with or without cystobiliary fistulas which contain non-drainable material. Patients: Twelve patients were treated: 10 patients with multivesicular cysts which contained non-drainable material and were complicated by spontaneous intrabiliary rupture, secondary cystobiliary fistulas, cyst infection, or obstructed portal or hepatic veins; and two patients with large univesicular cysts and a ruptured laminated membrane, one obstructing the portal and hepatic veins and one a suspected cystobiliary fistula. Methods: The methods used, termed PEVAC (percutaneous evacuation of cyst content), involved the following steps: ultrasound guided cyst puncture and aspiration of cyst fluid to release intracystic pressure and thereby to avoid leakage; insertion of a large bore catheter; aspiration and evacuation of daughter cysts and endocyst by injection and reaspiration of isotonic saline; cystography; injection of scolecidals only if no cystobiliary fistula was present; external drainage of cystobiliary fistulas combined with endoprosthesis or sphincterotomy; catheter removal after complete cyst collapse and closure of the cystobiliary fistula. Results: In all 12 patients initial cyst size was 13.1 (6–20) cm (mean (range)). At follow up 17.9 (4–30) months after PEVAC, seven cysts had disappeared and five cysts had decreased to 2.4 (1–4) cm (p=0.002). In eight patients with multivesicular cysts, a cystobiliary fistula, and infection, cyst size was 12.5 (6–20) cm, catheter time 72.3 (28–128) days, and hospital stay 38.1 (20–55) days. At 17.3 (4–28) months of follow up, six cysts had disappeared and in two cysts residual size was 1 and 2.9 cm, respectively (p=0.012). In four patients without a cystobiliary fistula, cyst size was 14.4 (12.7–16) cm, catheter time 8.8 (3–13) days, and hospital stay 11.5 (8–14) days. At 19.3 (9–30) months of follow up, one cyst had disappeared and three cysts were 85 (69–94)% smaller (2.2 (1–4) cm) (p=0.068). Conclusion: PEVAC is a safe and effective method for percutaneous treatment of multivesicular echinococcal cysts with or without cystobiliary fistulas which contain non-drainable material.
Comparative Effectiveness Research in Cancer Genomics and Precision Medicine: Current Landscape and Future Prospects
Authors: Naoko I Simonds, Muin J Khoury, Sheri D Schully, Katrina Armstrong, Wendy F Cohn, David A Fenstermacher, Geoffrey S Ginsburg, Katrina A B Goddard, William A Knaus, Gary H Lyman, Scott D Ramsey, Jianfeng Xu, Andrew N Freedman
Journal: JNCI Journal of the National Cancer Institute (2013)

A major promise of genomic research is information that can transform health care and public health through earlier diagnosis, more effective prevention and treatment of disease, and avoidance of drug side effects. Although there is interest in the early adoption of emerging genomic applications in cancer prevention and treatment, there are substantial evidence gaps that are further compounded by the difficulties of designing adequately powered studies to generate this evidence, thus limiting the uptake of these tools into clinical practice. Comparative effectiveness research (CER) is intended to generate evidence on the "real-world" effectiveness compared with existing standards of care so informed decisions can be made to improve health care. Capitalizing on funding opportunities from the American Recovery and Reinvestment Act of 2009, the National Cancer Institute funded seven research teams to conduct CER in genomic and precision medicine and sponsored a workshop on CER on May 30, 2012, in Bethesda, Maryland. This report highlights research findings from those research teams, challenges to conducting CER, the barriers to implementation in clinical practice, and research priorities and opportunities in CER in genomic and precision medicine. Workshop participants strongly emphasized the need for conducting CER for promising molecularly targeted therapies, developing and supporting an integrated clinical network for open-access resources, supporting bioinformatics and computer science research, providing training and education programs in CER, and conducting research in economic and decision modeling.
Innervation of melanocytes in human skin.
Authors: M Hara, M Toyoda, M Yaar, J Bhawan, E M Avila, I R Penner, B A Gilchrest
Journal: The Journal of Experimental Medicine (1996)

Communication between the nervous system and epidermal melanocytes has been suspected on the basis of their common embryologic origin and apparent parallel involvement in several disease processes, but never proven. In this study, confocal microscopic analysis of human skin sections stained with antibodies specific for melanocytes and nerve fibers showed intraepidermal nerve endings in contact with melanocytes. This intimate contact was confirmed by electron microscopy, which further demonstrated thickening of apposing plasma membranes between melanocytes and nerve fibers, similar to synaptic contacts seen in nervous tissue. Since many intraepidermal nerve fibers are afferent nerves that act in a "neurosecretory" fashion through their terminals, cultured human melanocytes were stimulated with calcitonin gene-related peptide (CGRP), substance P, or vasoactive intestinal peptide, neuropeptides known to be present in cutaneous nerves, to examine their possible functions in the epidermal melanin unit. CGRP increased DNA synthesis rate of melanocytes in a concentration- and time-dependent manner. Cell yields after 5 d were increased 25% compared with controls maintained in an otherwise optimized medium. Furthermore, stimulation by CGRP induced rapid and dose-dependent accumulation of intracellular cAMP, suggesting that the mitogenic effect is mediated by the cAMP pathway. These studies confirm and expand a single earlier report in an animal model of physical contact between melanocytes and cutaneous nerves and for the first time strongly suggest that the nervous system may exert a tonic effect on melanocytes in normal or diseased human skin.
An uncommon cause of haematochezia in an adult with skin rash
Authors: A Hokama, K Shimoji, M Nakamura, H Chinen, K Kishimoto, T Hirata, F Kinjo, J Fujita
Journal: Gut (2008)

1.<h3>Abstract</h3> Polarized light-based navigation in insects is facilitated by a specialised polarisation-sensitive part of the eye known as the dorsal rim area (DRA). Existing methods to study the anatomy of the DRA are in most cases destructive and very time consuming. Here, we present a novel method that allows for DRA localization using 3D volumetric images acquired through micro-computed tomography in combination with 2D photographs. We used the method on size polymorphic buff-tailed bumblebees, <i>Bombus terrestris</i>. We found that the size of the DRA can be easily acquired from photographs of the dorsal part of the eye. An allometric analysis of the size of the DRA in relation to body size in <i>B. terrestris</i> showed that the DRA region increases with body size but not at the same rate. Using our method, we localised the DRA in a 3D volume rendering of the eye using 2D photos localization of an individual’s DRA onto the volumetric image stack of the head allowed for individual-level descriptions of the ommatidial structures (lens, crystalline cones, rhabdoms) to be performed on three different eye regions (DRA, non-DRA, proximate to DRA). The only feature distinctly unique to the DRA ommatidia was the smaller dimension of crystalline cones in comparison to other regions. Using our novel methodology we provide the first individual-level description of DRA ommatidial features and a comparison of how the DRA area varies with body size in bumblebees.