Efficacious human metapneumovirus vaccine based on AI-guided engineering of a closed prefusion trimer.

The prefusion conformation of human metapneumovirus fusion protein (hMPV Pre-F) is critical for eliciting the most potent neutralizing antibodies and is the preferred immunogen for an efficacious vaccine against hMPV respiratory infections. Here we show that an additional cleavage event in the F protein allows closure and correct folding of the trimer. We therefore engineered the F protein to undergo double cleavage, which enabled screening for Pre-F stabilizing substitutions at the natively folded protomer interfaces.

Livestock production systems, their responses to the demand for animal-source food, and the implications for animal health services.

This paper reviews the rapidly changing global demands for animal-source foods, examines the agri-food systems behind these changes, and discusses the potential responses required by public-sector Veterinary Services to meet these new demands.

[Self-ligating edgewise brackets. An overview].

During the last years both the manufactures and the orthodontists seem to show an increased interest in self-ligating brackets. This paper aims to present the history of self-ligating systems, to describe the three mostly used bracketsystems and to review the relevant literature. It seems from the existing data that self-ligating brackets have certain advantages over conventionally ligated brackets.

A randomized clinical trial of alpha(1)-antitrypsin augmentation therapy.

We have investigated whether restoration of the balance between neutrophil elastase and its inhibitor, alpha(1)-antitrypsin, can prevent the progression of pulmonary emphysema in patients with alpha(1)-antitrypsin deficiency. Twenty-six Danish and 30 Dutch ex-smokers with alpha(1)-antitrypsin deficiency of PI*ZZ phenotype and moderate emphysema (FEV(1) between 30% and 80% of predicted) participated in a double-blind trial of alpha(1)-antitrypsin augmentation therapy. The patients were randomized to either alpha(1)-antitrypsin (250 mg/kg) or albumin (625 mg/kg) infusions at 4-wk intervals for at least 3 yr.

Effect of density and weight of load on the energy cost of carrying loads by donkeys and ponies.

Two experiments were designed to compare the energy used in carrying loads by donkeys and ponies. In the first experiment 3 donkeys and 3 ponies were compared on treadmills in the UK. Density of load (lead shot or straw) had no significant effect on the energy cost of carrying loads; however, the energy cost of carrying a load decreased significantly (p < 0.

Cigarette smoking and pulmonary diffusion defects in rheumatoid arthritis.

The pathogenesis of lung disease in rheumatoid arthritis (RA) has still to be defined. Risk factors associated with lung involvement in RA were investigated by means of pulmonary function studies in 40 RA patients without apparent lung disease. A decreased carbon monoxide (CO) diffusion capacity indicative of interstitial lung disease (ILD) was the main pulmonary function defect found in the first 20 patients.

Ozone-induced airway hyperresponsiveness in patients with asthma: role of neutrophil-derived serine proteinases.

Proteinase inhibitors may be of potential therapeutic value in the treatment of respiratory diseases such as chronic obstructive pulmonary disease (COPD) or asthma. Our aim was to study the role of neutrophils, and neutrophil-derived serine proteinases in an acute model in patients with asthma. Exposure to ozone induces an acute neutrophilic inflammatory reaction accompanied by an increase in airway hyperresponsiveness.

Effect of neutrophil serine proteinases and defensins on lung epithelial cells: modulation of cytotoxicity and IL-8 production.

Neutrophil accumulation in the lung may contribute to tissue injury as observed in inflammatory diseases. Both oxidative and non-oxidative mechanisms are involved in neutrophil-mediated tissue injury. Non-oxidative mechanisms include the release of neutrophil granule proteins such as the serine proteinases elastase and cathepsin G, and the non-enzymatic defensins.

The development of the 'Quality-of-life for Respiratory Illness Questionnaire (QOL-RIQ)': a disease-specific quality-of-life questionnaire for patients with mild to moderate chronic non-specific lung disease.

Chronic non-specific lung disease (CNSLD) encompasses asthma as well as chronic obstructive pulmonary disease (COPD). Recently in health care, there has been increasing awareness in the functional, psychological and social aspects of the health of patients; their quality of life (QOL). Quality-of-life research addressing CNSLD patients has been rather underdeveloped for a long period of time.

Effect of defensins on interleukin-8 synthesis in airway epithelial cells.

Neutrophils play an important role in inflammatory processes in the lung and may cause tissue injury through, for example, release of proteinases such as neutrophil elastase. In addition to neutrophil elastase, stimulated neutrophils also release small nonenzymatic and cationic polypeptides termed defensins. The aim of the present study was to investigate whether defensins induce interleukin (IL)-8 expression in cells of the A549 lung epithelial cell line and in human primary bronchial epithelial cells (PBEC).

The alveolar type II cell is a pluripotential stem cell in the genesis of human adenocarcinomas and squamous cell carcinomas.

Studies in a canine bronchogenic carcinoma model indicate that alveolar type II cells may differentiate from carcinogen-exposed epithelium of larger bronchi and generate adenocarcinomas with bronchioloalveolar and other growth patterns. In this study, we investigated whether type II cells are one of the major proliferating cells (= stem cells) in the genesis of two major subsets of bronchogenic carcinoma in humans. Adenocarcinomas (17 bronchioloalveolar; 3 papillary; and 10 other) and squamous cell carcinomas (n = 27) as well as (pre)neoplastic lesions in adjacent bronchi and bronchioles were examined for the presence of type II cell markers and cellular proliferation markers (PCNA; Ki-67) using light and electron microscopy and immunohistochemistry.

[Laboratory testing virtually centralized to benefit both patients and drug research].

Laboratory analyses in multicentre safety studies of new drugs usually are performed in central laboratories outside the Netherlands. Patient care requires local (hospital) laboratory tests. In the so-called Virtually Centralized Laboratory the Dutch local laboratories report their results after data communication and data transformation in such a way that they seem to form one laboratory.

Relationship between loss in parenchymal elastic recoil pressure and maximal airway narrowing in subjects with alpha1-antitrypsin deficiency.

Airway hyperresponsiveness is characterized by an increase in sensitivity and excessive airway narrowing to inhaled bronchoconstrictor stimuli. There is experimental evidence that maximal airway narrowing is related to lung elasticity in normal and asthmatic subjects. We hypothesized that reduced lung elasticity by parenchymal destruction increases the level of maximal airway narrowing in subjects with alpha1-antitrypsin deficiency.

Prognostic factors in resected non-small cell lung cancer: an immunohistochemical study of 39 cases.

Non-small cell lung carcinoma (NSCLC) is a histologically heterogeneous collection of tumours with variable clinical behaviour. Performance status, tumour stage and histological type have important prognostic implications, but the clinical outcome in an individual patient remains unpredictable. In search of other prognostic factors we studied the expression of several immunohistochemical markers in NSCLC, resected with curative intent.

Assessment of the progression of emphysema by quantitative analysis of spirometrically gated computed tomography images.

Rationale And Objectives: The authors assessed the progression of pulmonary emphysema by means of quantitative analysis of computed tomography images.

Methods: Twenty-three patients suffering from emphysema due to an alpha 1-antitrypsin deficiency, aged 45 +/- 7 years and exsmokers, were scanned twice with a 1-year time interval. At 90% of the vital lung capacity, slices with a thickness of 1.

Antibacterial activity of antileukoprotease.

Antileukoprotease (ALP), or secretory leukocyte proteinase inhibitor, is an endogenous inhibitor of serine proteinases that is present in various external secretions. ALP, one of the major inhibitors of serine proteinases present in the human lung, is a potent reversible inhibitor of elastase and, to a lesser extent, of cathepsin G. In equine neutrophils, an antimicrobial polypeptide that has some of the characteristics of ALP has been identified (M.

Stereological methods: a new approach in the assessment of pulmonary emphysema.

In order to develop a reliable and sensitive method for studying the development and progression of pulmonary emphysema, we compared stereological indices with the usual index for grade of emphysema, i.e., the mean linear intercept (Lm), in elastase-induced emphysema in mice.

The prognostic value of NCAM, p53 and cyclin D1 in resected non-small cell lung cancer.

Expression of the neural cell adhesion molecule, NCAM, in frozen sections has been associated with decreased postoperative survival in non-small cell lung carcinoma. Of the various isoforms of NCAM described, the highly sialylated isoform plays a role in the migration of embryonal cells from the neural crest and is expressed by highly malignant tumours such as small cell lung carcinomas. We investigated the clinical significance of expression of this NCAM isoform as a prognostic factor in a series of 96 non-small cell lung carcinomas resected with curative intent.

Lung sounds during allergen-induced asthmatic responses in patients with asthma.

We postulated that the distinct pathophysiologic mechanisms of airway narrowing during the early (EAR) and the late (LAR) asthmatic responses to inhaled allergens are reflected by the generation or transmission of lung sounds in asthma. Therefore, we measured FEV1 and recorded lung sounds in eight mildly asthmatic subjects before a standardized allergen challenge (PRE), during the EAR, during the recovery phase at 2 h (MID), during the LAR at 7 h, and after inhalation of a bronchodilator (POST). The recordings were made during flow- and volume-standardized quiet breathing, and during maximal forced breathing maneuvers.

Interstitial lung disease with pleural effusion caused by simvastin.

Simvastin, a HMG-CoA reductase blocker, is used for the treatment of certain forms of hypercholesterolaemia. Simvastin is prescribed to lower high serum levels of cholesterol by inhibiting a specific enzyme, hydroxy-methylglutarylCo-enzym-A (HMG-CoA) reductase. This ultimately leads to an increase of the number of LDL-receptors in the liver, and thus, to a decrease of the serum LDL-cholesterol.

Alveolar stem cells in canine bronchial carcinogenesis.

Alveolar type II cells are not present in normal epithelium of canine segmental bronchi but after carcinogen exposure they do occur in intra-epithelial lesions with all degrees of atypia and in invasive lesions with different glandular growth patterns. Immunohistochemistry for proliferation markers (PCNA; Ki-67) strongly suggest that such novel type II cells are pluripotential stem cells in canine bronchial carcinogenesis. Very likely, bronchial carcinogenesis is subject to an oncofetal mechanism of differentiation: bronchial epithelial retrodifferentiation followed by novel differentiation of alveolar tumor stem cells.

Complications in the use of the subcutaneous tunnelled intratracheal oxygen catheter.

Transtracheal oxygen delivery seems to be a safe procedure in the treatment of chronic obstructive pulmonary disease (COPD) with chronic hypoxaemia. Even so, serious complications do occur. Three patients in whom we used a subcutaneous tunnelled intratracheal oxygen catheter (ITO2C) are described.