tbuckley/cabot-search huggingface dataset:
Treatment of extensive lentigo maligna melanoma of the scalp by brachytherapy moulage technique
Authors: M.M. Sachse, G. Wagner, H. Aydin, S. Pohlmann, F. Heinicke, A. Liebmann
Journal: British Journal of Dermatology (2010)

Journal Article Treatment of extensive lentigo maligna melanoma of the scalp by brachytherapy moulage technique Get access M.M. Sachse, M.M. Sachse Department of Dermatology, Phlebology and Allergology Search for other works by this author on: Oxford Academic Google Scholar G. Wagner, G. Wagner Department of Dermatology, Phlebology and Allergology Search for other works by this author on: Oxford Academic Google Scholar H. Aydin, H. Aydin Department of Radiooncology, Hospital Bremerhaven‐Reinkenheide, 27574 Bremerhaven, Germany Search for other works by this author on: Oxford Academic Google Scholar S. Pohlmann, S. Pohlmann Department of Radiotherapy and Radiooncology, University Hospital Leipzig AöR, Leipzig, Germany E‐mail: michael.sachse@klinikum‐bremerhaven.de Search for other works by this author on: Oxford Academic Google Scholar F. Heinicke, F. Heinicke Department of Radiotherapy and Radiooncology, University Hospital Leipzig AöR, Leipzig, Germany E‐mail: michael.sachse@klinikum‐bremerhaven.de Search for other works by this author on: Oxford Academic Google Scholar A. Liebmann A. Liebmann Department of Radiotherapy and Radiooncology, University Hospital Leipzig AöR, Leipzig, Germany E‐mail: michael.sachse@klinikum‐bremerhaven.de Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 164, Issue 1, 1 January 2011, Pages 219–221, https://doi.org/10.1111/j.1365-2133.2010.10064.x Published: 01 January 2011
The longitudinal course of chronic mucus hypersecretion (CMH) over 43 years of adult life within a nationally representative birth cohort
Authors: James Allinson, Rebecca Hardy, Gavin Donaldson, Seif Shaheen, Diana Kuh, Jadwiga Wedzicha
Journal: European Respiratory Journal (2014)

Background   CMH is thought to contribute to COPD development yet the longitudinal course of CMH is little studied. We report the longitudinal CMH pattern during 43 years of adult life within the MRC National Survey of Health and Development(NSHD) birth cohort.   Methods   The MRC NSHD recruited subjects born in one week in March 1946 within England, Scotland and Wales. MRC questionnaire defined CMH was recorded in the following years (age,yrs):1966(20),1971(25),1982(36),1989(43),1999(53)&2009(63). From those with complete data we calculated prevalence and classified CMH presence as follows:  Not yet=no current/prior;  Incident=first report;  Ongoing=continued since first report;  Remission=prior but not current;  Relapse=current with prior remission.   Results   1417 subjects(47%male) had complete data sets. Table1&Figure1 show a remitting relapsing pattern of CMH. Of the 259(18.3%)(56%male) reporting CMH≥once, 0.8% had CMH six times, 57.9% had CMH only once.   Conclusion   During this birth cohort9s adult life, CMH followed a dynamic course. Studying such dynamism may help delineate both CMH susceptibility and its role in COPD development.
4-1BBL mediated balance of Th17/Treg in patients with allergic asthma
Authors: Xiangyan Ai, Shiguo Chao, Xiaoxia Hou
Journal: European Respiratory Journal (2012)

Objective:  To investigate the expression of 4-1BBL in peripheral blood of patients with allergic asthma and its role in the balance of Th17/Treg cells.  Methods:  We detected the plasma soluble 4-1BBL (s4-1BBL) levels with ELISA and membrane expression of 4-1BBL (m4-1BBL) on monocytes with flow cytometry in patients with allergic asthma and controls. The peripheral blood mononuclear cells (PBMCs) of patients with asthma were in vitro stimulated with or without 4-1BB agonistic mAb for 72h, the concentrations of IL-17 and TGF-β in supernatant were measured with ELISA and the percentages of Th17 and Treg cells were measured with flow cytometry.  Results:  The s4-1BBL concentrations of patients with asthma (202.47 ± 60.68 µg/L) were decreased than controls (298.29 ± 40.32 µg/L, p 0.05)  C  onclusions:  Both s4-1BBL and m4-1BBL decreased in peripheral blood of patients with allergic asthma. In vitro agonistic 4-1BB antibody stimulation enhanced TGF-β but inhibited IL-17 production by PBMCs. Thus 4-1BBL/4-BB may restore Th17/Treg balance in allergic asthma more likely by changing the function of Th17 and Treg cells.
Ventilatory function impairment and risk of cardiovascular death and of fatal or non-fatal myocardial infarction
Authors: P Lange, J Nyboe, G Jensen, P Schnohr, M Appleyard
Journal: European Respiratory Journal (1991)

The relationship of ventilatory function to cardiovascular events was studied in 12,511 men and women, enrolled in 1976-1978 in a prospective population study. Until the end of 1983, 388 subjects died because of a cardiovascular disease, 133 died within 30 days of developing myocardial infarction (fatal myocardial infarction), while 238 had a non-fatal myocardial infarction. Cox proportional hazards models were employed for the analysis. In the models including tobacco smoking, cholesterol level, blood pressure, diabetes mellitus and body-mass index as covariates, forced expiratory volume in one second in percentage of predicted (FEV1% pred), forced vital capacity in percentage of predicted (FVC% pred), and the ratio between FEV1 and FVC (FEV1/FVC) were significantly related to the risk of cardiovascular death, e.g. compared with subjects with FEV1% pred or FVC% pred greater than or equal to 80 the risk of death from cardiovascular disease among subjects with FEV1% pred or FVC% pred less than 60 was approximately twice as high. There was a nonsignificant trend towards an increased risk of fatal myocardial infarction with reduction of FVC% pred, but in general the regression models did not show consistent relationship between lung function impairment and risk of myocardial infarction. In the regression models, which only included age and sex as covariates, reduced FVC% pred and FEV1% pred were significantly related to both cardiovascular mortality and to fatal myocardial infarction, but not to the non-fatal infarction, whereas the FEV1/FVC ratio was not related to fatal or to non-fatal myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)
Mild pH alteration leads to intracellular retention of IL-8 by airway epithelial cells
Authors: Angela Hackett, Brian Flanagan, Paul McNamara
Journal: European Respiratory Journal (2013)

Background: 

In children with severe neurodisability, chronic microaspiration can lead to recurrent lower respiratory tract infections and cause pulmonary fibrosis. Previous research on acid lung injury has focused on the effects of very low pH on airways, primarily through direct instillation of acid onto airway epithelial cells (AECs). This is not physiologically relevant to injury caused by chronic microaspiration where mild but persistent airway acidification occurs.

Aim: 

To investigate the effects of mildly acidic conditions on inflammatory (IL-8) protein secretion by AECs

Methods: 

A549 cells were cultured to 70% confluence in 96 well plates. DMEM media was adjusted to appropriate pH using 1M hydrochloric acid. Cells were exposed to media for 24h at pH6.5, pH6 and pH5.5. E.coli LPS, alone or with Brefeldin A, were used as positive controls for IL-8 production and intracellular protein retention.

AEC IL-8 mRNA expression was measured by RT-PCR (Taqman). Extracellular (cell supernatants) and intracellular (whole cell lysate) protein concentration was measured by ELISA (R&D). Intracellular IL-8 expression was normalised to total protein concentration measured by BCA assay.

Results: 

Increased IL-8 mRNA expression but not IL-8 protein secretion, was observed at pH6.5, pH6 and pH5.5 at 24h. Intracellular IL-8 protein increased as media acidity increased at pH6.5, pH6 and pH5.5.

Conclusions: 

Mild acidification of A459 cells causes intracellular retention of IL-8 protein indicating that lowering pH of airways may disrupt intracellular protein trafficking. This may be due to activation of stress response pathways.
Contrasts between patients with affective disorders and patients with schizophrenia on a neuropsychological test battery
Authors: T E Goldberg, J M Gold, R Greenberg, S Griffin, S C Schulz, D Pickar, J E Kleinman, D R Weinberger
Journal: American Journal of Psychiatry (1993)

This study was designed to ascertain the degree and specificity of cognitive impairments in patients with schizophrenia and patients with affective disorders.Cognitive function was assessed with a neuropsychological test battery in consecutively admitted patients with schizophrenia (N = 57), unipolar depression (N = 29), and bipolar disorder (N = 16).The performance of the schizophrenic group was significantly below that of the groups with affective disorders on measures of attention and psychomotor speed, verbal and visual memory, and problem solving and abstraction. IQ was lower in the schizophrenic group and appeared to have deteriorated from a normal premorbid level that was not different from that of the affective disorder groups, as determined by the Wide Range Achievement Test--Revised reading test, a putative measure of premorbid intelligence. When IQ was controlled, differences between the groups in problem solving and visual memory remained. Psychiatric symptoms had a larger impact on test performance in the affective disorder groups than in the schizophrenic group.These results suggest that patients with schizophrenia perform systematically worse on cognitive measures than patients with affective disorders, which is consistent with their generally poorer outcome. The results also indicate that schizophrenia and affective disorders are qualitatively distinguishable in neuropsychological terms, given differences in apparent intellectual deterioration, profiles of cognitive impairment, and associations between cognitive performance and psychopathology.
Investigating the role of BAFF in murine models of allergic asthma
Authors: Anika Lorenz, Mandy Busse, Kathleen Dalüge, Ann-Kathrin Behrendt, Gesine Hansen, Almut Meyer-Bahlburg
Journal: European Respiratory Journal (2014)

Introduction: The cytokine B cell activating factor of the TNF family (BAFF) is crucial for peripheral B cell survival. It is well known that elevated BAFF levels are associated with autoimmune diseases but its role in allergic diseases including asthma is barely understood.

Aims and objectives: To better comprehend the role of BAFF in allergic asthma we analyzed BAFF in murine asthma models.

Methods: Wildtype (WT) and B cell deficient (μMT) mice were immunized with ovalbumin (OVA) or house dust mite (HDM). Bronchoalveolar lavage fluid (BALF) was measured morphometrically, airway hyperreactivity (AHR) by invasive lung function and BAFF via ELISA.

Results: Asthmatic WT mice showing lung eosinophilia and severe AHR have significantly elevated BAFF serum levels compared to controls. Additionally, in OVA-induced respiratory tolerant mice, BAFF levels are lower than in allergic mice. Kinetic studies demonstrate that BAFF levels increase, the more often allergen is administered intranasally suggesting local BAFF production in the asthmatic lung. Furthermore, BAFF determination in BALF showed increased levels in allergic compared to control mice. To test, whether BAFF is related to elevated IgE levels during asthma, BAFF production in μMT mice was analyzed. Allergen treated μMT mice develop a similar allergic phenotype compared to WT mice and show increased BAFF levels in serum and BALF even in IgE absence.

Conclusions: In asthma models, allergic mice show elevated systemic and local BAFF, which increases with frequency of allergen uptake via the lung and is independent of IgE presence. Thus, BAFF inhibition, recently permitted for treatment of systemic lupus erythematodes, might represent a new therapeutic target in asthma.
High- and Low-Dose Interferon Alfa-2b in High-Risk Melanoma: First Analysis of Intergroup Trial E1690/S9111/C9190
Authors: John M. Kirkwood, Joseph G. Ibrahim, Vernon K. Sondak, Jon Richards, Lawrence E. Flaherty, Marc S. Ernstoff, Thomas J. Smith, Uma Rao, Mary Steele, Ronald H. Blum
Journal: Journal of Clinical Oncology (2000)

PURPOSE: Pivotal trial E1684 of adjuvant high-dose interferon alfa-2b (IFNα2b) therapy in high-risk melanoma patients demonstrated a significant relapse-free and overall survival (RFS and OS) benefit compared with observation (Obs). PATIENTS AND METHODS: A prospective, randomized, three-arm, intergroup trial evaluated the efficacy of high-dose IFNα2b (HDI) for 1 year and low-dose IFNα2b (LDI) for 2 years versus Obs in high-risk (stage IIB and III) melanoma with RFS and OS end points. RESULTS: A total of 642 patients were enrolled (608 patients eligible), of whom a majority (75%) had nodal metastasis (50% had nodal recurrence). Unlike E1684, E1690 allowed entry of patients with T4 (&gt; 4 mm) deep primary tumors, regardless of nodal dissection, and 25% of the patients entered onto this trial had deep primary tumors (compared with 11% in E1684). At 52 months’ median follow-up, HDI demonstrated an RFS benefit exceeding that of LDI compared with Obs. The 5-year estimated RFS rates for the HDI, LDI, and Obs arms were 44%, 40%, and 35%, respectively. The hazards ratio for the intent-to-treat analysis of HDI versus Obs was 1.28 (P 2 = .05); for LDI versus Obs, it was 1.19 (P 2 = .17). By Cox analysis, the impact of HDI on RFS achieved significance (P 2 = .03). The RFS benefit was equivalent for node-negative and node-positive patients. Neither HDI nor LDI has demonstrated an OS benefit compared with Obs at this time. A major improvement in the median OS of patients in the E1690 Obs arm was noted in comparison with E1684 (6 years v 2.8 years). An analysis of salvage therapy for patients who relapsed on E1690 demonstrated that a significantly larger proportion of patients in the Obs arm received IFNα-containing salvage therapy compared with the HDI arm; this therapy was unavailable to patients during E1684, and patients with undissected regional nodes were not included in E1684. This study did not specify therapy at recurrence. Analysis of treatments received at recurrence demonstrated significantly more frequent use of IFNα2b at relapse from Obs than from HDI, which may have confounded interpretation of the survival benefit of assigned treatments in E1690. CONCLUSION: The results of the intergroup E1690 trial demonstrate an RFS benefit of IFNα2b that is dose-dependent and significant for HDI by Cox multivariable analysis.
In Vitro Induction of Human Skin Ornithine Decarboxylase by the Tumor Promoter 12-&lt;italic&gt;O&lt;/italic&gt;-Tetradecanoylphorbol-13-Acetate&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Ajit K. Verma, Charles L. Loprinzi, R. K. Boutwell, P. P. Carbone
Journal: JNCI Journal of the National Cancer Institute (1985)

A method was developed for the in vitro induction by 12-O-tetradecanoylphorbol-13-acetate (TPA) of ornithine decarboxylase (ODC) activity in human skin punch biopsy samples. Addition of TPA to 1 ml serum-free minimum essential medium containing a single 3-mm human skin punch biopsy sample obtained from a surgical specimen resulted in an induction of ODC activity with a peak activity at 5 hours after TPA addition. In vitro induction of human epidermal ODC activity was dependent on the TPA concentration in the medium; about a twofold increase in ODC activity was observed 6 hours after the addition of 0.1 microM TPA, and about a fivefold increase in ODC activity was observed with 1 microM TPA. TPA also caused about a fivefold to sixfold increase in ODC activity in 3-mm skin punch biopsy samples from healthy volunteers. Human skin punch biopsy samples remained responsive to TPA induction of ODC activity even when stored in serum-free medium at 4 degrees C for 24 hours. A similar degree of induction of ODC activity by TPA was observed whether whole unfractionated human epidermis or a soluble epidermal extract was used for ODC assays. Increased ODC activity was the result of the increase in enzymatically active ODC protein, quantitated by a [3H]difluoromethylornithine-binding assay. Thus human skin, like mouse skin, is responsive to TPA for ODC induction.
Clinical phenotypes in patients with concomitant obstructive sleep apnea and chronic obstructive pulmonary disease
Authors: Yuji Kusunoki, Ryuko Furutate, Kumiko Hattori, Takeo Ishii, Takashi Motegi, Kouichi Yamada, Akihiko Gemma, Kozui Kida
Journal: European Respiratory Journal (2012)

Rationale: Concomitant obstructive sleep apnea syndrome (OSAS) and COPD (overlap syndrome, OLS) may result in the presentation of different clinical phenotypes of each disease.

Objectives: To examine the clinical phenotypes of COPD in OLS cases.

Methods: We conducted a prospective cohort study including 204 patients recruited in 8 years. All the subjects underwent the examinations: pulmonary function tests; polysomnography (PSG); blood chemistry tests, including a KL-6 test; nutritional assessments; computed tomography (HRCT) to assess emphysema (LAA%); and 6-minute walk tests (6MWT). Subjects with symptomatic airflow obstruction were classified as COPD patients, and the apnea-hypopnea index (AHI) was calculated for assessing OSAS. We analyzed the association between the variables recorded during the examinations.

Results: The overall cohort included 138 male subjects and 23 female subjects (mean age, 54.8 years). The mean FEV1:FVC ratio, mean body mass index (BMI), and mean AHI were 0.77, 25.3, and 30.3, respectively. The AHI values were as follows: 0–5 (n = 9), 5–15 (n = 36), 15–30 (n = 50), and >30 (n = 66). The subjects were divided into the OLS group (n = 34), OSAS alone group (n = 118), COPD alone group (n = 0), and neither group (n = 9). The mean age, BMI, and AHI in the OLS were 66.4, 24.5, and 34.7, respectively. AHI was significantly associated with BMI in the OSAS alone group. This association was not seen in the OLS group, in which there was a trend that low FEV1% predicted was associated with low AHI and AHI was significantly associated with KL-6 (p < 0.0002).

Conclusions: We concluded that OLS did not affect the clinical phenotypes of OSAS and COPD.
Harnessing Allostery: A Novel Approach to Drug Discovery
Authors: Shaoyong Lu, Shuai Li, Jian Zhang
Journal: Medicinal Research Reviews (2014)

Allostery is the most direct and efficient way for regulation of biological macromolecule function, ranging from the control of metabolic mechanisms to signal transduction pathways. Allosteric modulators target to allosteric sites, offering distinct advantages compared to orthosteric ligands that target to active sites, such as greater specificity, reduced side effects, and lower toxicity. Allosteric modulators have therefore drawn increasing attention as potential therapeutic drugs in the design and development of new drugs. In recent years, advancements in our understanding of the fundamental principles underlying allostery, coupled with the exploitation of powerful techniques and methods in the field of allostery, provide unprecedented opportunities to discover allosteric proteins, detect and characterize allosteric sites, design and develop novel efficient allosteric drugs, and recapitulate the universal features of allosteric proteins and allosteric modulators. In the present review, we summarize the recent advances in the repertoire of allostery, with a particular focus on the aforementioned allosteric compounds.
FDA Approval: Ibrutinib for Patients with Previously Treated Mantle Cell Lymphoma and Previously Treated Chronic Lymphocytic Leukemia
Authors: R. Angelo de Claro, Karen M. McGinn, Nicole Verdun, Shwu-Luan Lee, Haw-Jyh Chiu, Haleh Saber, Margaret E. Brower, C.J. George Chang, Elimika Pfuma, Bahru Habtemariam, Julie Bullock, Yun Wang, Lei Nie, Xiao-Hong Chen, Donghao (Robert) Lu, Ali Al-Hakim, Robert C. Kane, Edvardas Kaminskas, Robert Justice, Ann T. Farrell, Richard Pazdur
Journal: Clinical Cancer Research (2015)

On November 13, 2013, the FDA granted accelerated approval to ibrutinib (IMBRUVICA capsules; Pharmacyclics, Inc.) for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. On February 12, 2014, the FDA granted accelerated approval for the treatment of patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy. Ibrutinib is a first-in-class Bruton's tyrosine kinase (BTK) inhibitor that received all four expedited programs of the FDA: Fast-Track designation, Breakthrough Therapy designation, Priority Review, and Accelerated Approval. Both approvals were based on overall response rate (ORR) and duration of response (DOR) in single-arm clinical trials in patients with prior treatment. In MCL (N = 111), the complete and partial response rates were 17.1% and 48.6%, respectively, for an ORR of 65.8% [95% confidence interval (CI), 56.2%-74.5%]. The median DOR was 17.5 months (95% CI, 15.8-not reached). In CLL (N = 48), the ORR was 58.3% (95% CI, 43.2%-72.4%), and the DOR ranged from 5.6 to 24.2 months. The most common adverse reactions (≥ 30% in either trial) were thrombocytopenia, diarrhea, neutropenia, bruising, upper respiratory tract infection, anemia, fatigue, musculoskeletal pain, peripheral edema, and nausea.
BAL neutrophilia increases mortality in lung transplant patients despite azithromycin treatment
Authors: Elly Vandermeulen, Stijn Verleden, David Ruttens, Robin Vos, Dirk Van Raemdonck, Geert Verleden, Bart Vanaudenaerde
Journal: European Respiratory Journal (2013)

Introduction: Azithromycin can attenuate bronchoalveolar lavage (BAL) neutrophilia and can prevent or treat bronchiolitis obliterans syndrome (BOS). An increasing number of patients is found to have BAL neutrophilia despite azithromycin treatment, which might have an impact on BOS-free and overall survival.  Methods: Medical records of all patients transplanted between 2002 and 2012 were retrospectively investigated. Three groups of patients were created. Group A: patients already treated with azithromycin before the onset of BOS having an increased BAL neutrophilia (>15%) (n=81); control group B: patients under azithromycin therapy with low BAL neutrophilia (  Results: Group A had a significantly worse outcome compared to group C, in terms of BOS (p  Discussion: Elevated BAL neutrophilia, despite treatment with azithromycin, implies a detrimental effect towards BOS and survival. This group of patients which constitutes 28% of our study population is steadily growing without an effective therapy being available up to now.
Recurrent late-onset sepsis in the neonatal intensive care unit: incidence, clinical characteristics and risk factors
Authors: M.-H. Tsai, S.-M. Chu, C.-W. Lee, J.-F. Hsu, H.-R. Huang, M.-C. Chiang, R.-H. Fu, R. Lien, Y.-C. Huang
Journal: Clinical Microbiology and Infection (2014)