Langerhans Cell Histiocytosis or Acute Cellular Rejection?

Background: Langerhans cell histiocytosis (LCH) is a rare malignant disorder of epidermal antigen presenting cells. It is characterized by infiltration of various tissues with dendritic cells (Langerhans cells, LC) that express CD1a or CD207 (langerin), often leading to organ dysfunction. A patient with LCH required liver transplantation (LT) for LCH-associated biliary-tract disease.

Novel cathepsin C inhibitor, BI 1291583, intended for treatment of bronchiectasis: Phase I characterization in healthy volunteers.

Novel treatments are needed to reduce inflammation, improve symptoms, address exacerbations, and slow disease progression in bronchiectasis. Cathepsin C (CatC) inhibition promises to achieve this through reduction of neutrophil-derived serine protease (including neutrophil elastase [NE] and proteinase 3 [PR3]) activation. Here, we present the phase I characterization of the novel CatC inhibitor, BI 1291583.

The preclinical and phase 1 development of the novel oral cathepsin C inhibitor BI 1291583.

https://bit.ly/47PZ8E5.

Occurrence of autoimmune pancreatitis after chronic immune thrombocytopenia in a Caucasian adolescent.

Autoimmune pancreatitis is a rare, distinct and increasingly recognized form of chronic inflammatory pancreatic disease secondary to an underlying autoimmune mechanism. We report on a 14-year-old boy who developed autoimmune pancreatitis, while he was under treatment with eltrombopag for chronic immune thrombocytopenia. Therapy with corticosteroids resulted in complete remission of both.

Hypopyon sign as an unusual complication of varicella infection in a girl with atopic dermatitis.

Varicella-zoster virus (VZV) infection, also known as chickenpox, is a common childhood affliction. Generalized small itchy single-standing vesicles on erythematous skin are typical. Both cutaneous and systemic complications of the VZV infection may commonly occur.

Extended clinical and immunological phenotype and transplant outcome in CD27 and CD70 deficiency.

Biallelic mutations in the genes encoding CD27 or its ligand CD70 underlie inborn errors of immunity (IEIs) characterized predominantly by Epstein-Barr virus (EBV)-associated immune dysregulation, such as chronic viremia, severe infectious mononucleosis, hemophagocytic lymphohistiocytosis (HLH), lymphoproliferation, and malignancy. A comprehensive understanding of the natural history, immune characteristics, and transplant outcomes has remained elusive. Here, in a multi-institutional global collaboration, we collected the clinical information of 49 patients from 29 families (CD27, n = 33; CD70, n = 16), including 24 previously unreported individuals and identified a total of 16 distinct mutations in CD27, and 8 in CD70, respectively.

Aminotenuazonic Acid: Isolation, Structure Elucidation, Total Synthesis and Herbicidal Activity of a New Tetramic Acid from Fruiting Bodies of Laccaria Species.

(5S,6S)-Aminotenuazonic acid, a new 3-acyltetramic acid, related to the well-known mycotoxin tenuazonic acid has been isolated from fruiting bodies of Laccaria bicolor. Its structure was mostly established by analysis of its 2D NMR and HR-(+)-ESI-MS spectra. A total synthesis starting from N-Boc-l-isoleucine gave (5S,6S)-aminotenuazonic acid in 8 % yield over nine steps (67 % de).

Automated classification of celiac disease during upper endoscopy: Status quo and quo vadis.

A large amount of digital image material is routinely captured during esophagogastroduodenoscopies but, for the most part, is not used for confirming the diagnosis process of celiac disease which is primarily based on histological examination of biopsies. Recently, considerable effort has been undertaken to make use of image material by developing semi- or fully-automated systems to improve the diagnostic workup. Recently, focus was especially laid on developing state-of-the-art deep learning architectures, exploiting the endoscopist's expert knowledge and on making systems fully automated and thereby completely observer independent.

The cereal pathogen Fusarium pseudograminearum produces a new class of active cytokinins during infection.

The fungal pathogen Fusarium pseudograminearum causes important diseases of wheat and barley. During a survey of secondary metabolites produced by this fungus, a novel class of cytokinins, herein termed Fusarium cytokinins, was discovered. Cytokinins are known for their growth-promoting and anti-senescence activities, and the production of a cytokinin mimic by what was once considered as a necrotrophic pathogen that promotes cell death and senescence challenges the simple view that this pathogen invades its hosts by employing a barrage of lytic enzymes and toxins.

Computer-aided texture analysis combined with experts' knowledge: Improving endoscopic celiac disease diagnosis.

Aim: To further improve the endoscopic detection of intestinal mucosa alterations due to celiac disease (CD).

Methods: We assessed a hybrid approach based on the integration of expert knowledge into the computer-based classification pipeline. A total of 2835 endoscopic images from the duodenum were recorded in 290 children using the modified immersion technique (MIT).

Pelianthinarubins A and B, Red Pyrroloquinoline Alkaloids from the Fruiting Bodies of the Mushroom Mycena pelianthina.

Pelianthinarubin A (1) and pelianthinarubin B (2), two previously unknown pyrroloquinoline alkaloids, have been isolated from fruiting bodies of Mycena pelianthina. The structures of these alkaloids have been deduced from their HR-(+)-ESIMS and 2D NMR data. The absolute configurations of the pelianthinarubins A (1) and B (2) were assigned by analysis of the NOE correlations and coupling constants and by comparison of the CD spectra of 1 and 2 and of hercynine obtained by degradation of 1 with suitable compounds of known absolute configuration.

Discovery, Structure Elucidation, and Biological Characterization of Nannocystin A, a Macrocyclic Myxobacterial Metabolite with Potent Antiproliferative Properties.

Microbial natural products are a rich source of bioactive molecules to serve as drug leads and/or biological tools. We investigated a little-explored myxobacterial genus, Nannocystis sp., and discovered a novel 21-membered macrocyclic scaffold that is composed of a tripeptide and a polyketide part with an epoxyamide moiety.

Follow-up of pediatric celiac disease: value of antibodies in predicting mucosal healing, a prospective cohort study.

Background: In diagnosing celiac disease (CD), serological tests are highly valuable. However, their role in following up children with CD after prescription of a gluten-free diet is unclear. This study aimed to compare the performance of antibody tests in predicting small-intestinal mucosal status in diagnosis vs.

Effect of ADRB2 polymorphisms on the efficacy of salmeterol and tiotropium in preventing COPD exacerbations: a prespecified substudy of the POET-COPD trial.

Background: The effect of β2-adrenergic receptor (ADRB2) polymorphisms on the treatment response to longacting bronchodilators in chronic obstructive pulmonary disease (COPD) is unclear. We aimed to establish whether ADRB2 polymorphisms differentially affected COPD exacerbation outcomes in response to tiotropium versus salmeterol.

Methods: We did a prespecified analysis of the ADRB2 polymorphisms Arg16Gly and Gln27Glu within the 1 year randomised, double-blind, double-dummy, parallel-group Prevention Of Exacerbations with Tiotropium in COPD (POET-COPD) trial, comparing the effects of treatment with tiotropium or salmeterol on exacerbations in 7376 patients with COPD.

Seasonal distribution of COPD exacerbations in the Prevention of Exacerbations with Tiotropium in COPD trial.

Background: There is still a lack of data on the seasonality of exacerbations of COPD based on large randomized studies using COPD exacerbations as primary end points. The objective of this study was to assess the seasonal pattern of moderate and severe exacerbations and analyze the influence of associated baseline factors. We also determined the timing of second exacerbations and the potential impact of the 2009 influenza A(H1N1) pandemic on exacerbations.

Isolation and structural elucidation of armeniaspirols A-C: potent antibiotics against gram-positive pathogens.

In an antibiotic lead discovery program, the known strain Streptomyces armeniacus DSM19369 has been found to produce three new natural products when cultivated on a malt-containing medium. The challenging structural elucidation of the isolated compounds was achieved by using three independent methods, that is, chemical degradation followed by NMR spectroscopy, a computer-assisted structure prediction algorithm, and X-ray crystallography. The compounds, named armeniaspirol A-C (2-4), exhibit a compact, hitherto unprecedented chlorinated spiro[4.

[Use of a lung function screening device for identifying patients at risk for COPD in general practice].

Background: Screening measures can facilitate the diagnosis of chronic obstructive pulmonary disease (COPD) and help save costs and time. We examined whether use of a lung function screener (Vitalograph copd-6™) can help general practitioners to identify patients at risk for COPD.

Methods: In 17,856 patients aged > 40 years (smokers/ex-smokers with cough and/or exertional dyspnoea) general practitioners measured prebronchodilator FEV1 [% of predicted] and FEV1/FEV6 with the lung function screening device.

[Early treatment of COPD with tiotropium].

Background: In a prespecified subgroup analysis of the 4-year trial "Understanding Potential Long-term Impacts on Function with Tiotropium", the efficacy of tiotropium versus control in patients with moderate COPD (GOLD II) was examined and compared with the pooled results of patients with more severe disease (GOLD III/IV).

Methods: Randomised, multicentre, double-blind, placebo-controlled, parallel-group study in 5993 patients over a period of 4 years. Patients received either tiotropium 18 µg or placebo once-daily.

Mechanical load-dependent cardiac ER stress in vitro and in vivo: effects of preload and afterload.

Proteins are folded in the endoplasmic reticulum (ER). ER stress initially leads to compensatory upregulation of ER chaperones and later to apoptosis, but the contribution of biomechanical load vs. neurohumoral stress to myocardial ER stress is unknown.

Age-dependent changes in contractile function and passive elastic properties of myocardium from mice lacking muscle LIM protein (MLP).

Aims: Muscle LIM protein (MLP) null mice are often used as a model for human dilated cardiomyopathy. So far, little is known about the time course and pathomechanisms leading to the development of the adult phenotype.

Methods And Results: We systematically analysed the contractile phenotype, myofilament calcium (Ca(2)(+)) responsiveness, passive myocardial mechanics, histology, and mRNA expression in mice aged 4 and 12 weeks.

Local and systemic effects of angiotensin receptor blockade in an emphysema mouse model.

Objectives: COPD with emphysema causes marked neurohumoral activation. Angiotensin II receptors are highly expressed within the lung and interfere with mechanisms involved in the progression of emphysema. This study examined the effects of an angiotensin II receptor blocker (ARB) on pulmonary and systemic manifestations of emphysema in a mouse model.

BNP controls early load-dependent regulation of SERCA through calcineurin.

Heart failure is characterised by reduced expression of sarcoplasmic reticulum calcium-ATPase (SERCA) and increased expression of B-type natriuretic peptide (BNP). The present study was performed to investigate causality of this inverse relationship under in vivo conditions in the transversal aortic constriction mouse model (TAC). Left ventricular SERCA-mRNA expression was significantly upregulated in TAC by 32% after 6 h, but not different from sham after 24 h.