Rudolf Braun

University of Wisconsin–Madison | UW · Department of Pediatrics

Background: Acute Respiratory Distress syndrome (ARDS) is a clinical syndrome of noncardiac pulmonary edema and inflammation leading to acute respiratory failure. We used the oleic acid infusion pig model of ARDS resembling human disease to explore cytokine changes in white blood cells (WBC) and plasma proteins, comparing baseline to ARDS values. M...

Introduction: Survival and outcomes after cardiac arrest (CA) depend largely on the effectiveness of cardiopulmonary resuscitation (CPR). Traditional invasive methods of monitoring CPR can be challenging out-of-hospital and are lacking in more than 50% of in-hospital pediatric CA. Regional oxygen saturation (rSO 2 ) monitoring with Near Infrared Sp...

Introduction Hyperbaric air (HBA) was first used pharmaceutically in 1662 to treat lung disease. Extensive use in Europe and North America followed throughout the 19th century to treat pulmonary and neurological disorders. HBA reached its zenith in the early 20th century when cyanotic, moribund “Spanish flu pandemic” patients turned normal color an...

Introduction: Plasma potassium regulation is important for function of numerous cells in the body. Changes in potassium levels during exposure to an increased O2 concentration is thought to be the result of the changes in pH and increasing reactive oxygen species. However, the effects of hyperbaria on plasma potassium concentration are not well un...

Introduction: This study followed up on our findings, published in 2019, of stem progenitor cell mobilization following intermittent low level hyperoxia (42%) in an animal model. This most recent study in human participants used a never before tested small dose of intermittent hyperbaric air that has been used for many years as a placebo control i...

Chronic hypoxia (CH)-induced pulmonary hypertension (PH) results, in part, from TH17 cell-mediated perivascular inflammation. However, the antigen/s involved are unknown. Cellular immunity to collagen type V (col V) develops after ischemia-reperfusion injury during lung transplant and is mediated by naturally occurring "nTH17" cells. COL5A1 codifie...

Background Preterm birth affects approximately 1 in 10 pregnancies, and extreme preterm birth is associated with a 17‐fold increased risk of heart failure during childhood and early adulthood. Whether this is related to increase cardiac fibrosis is currently unknown. The objective of this study was to determine if fibrosis is present in an animal m...

Rationale Bronchopulmonary dysplasia (BPD) is the most common complication of preterm birth. It is induced by oxidative stress caused by hyperoxia exposure during the vulnerable saccular or early alveolar stage of lung development resulting in alveolar growth arrest and initiation of cellular senescence. Senescence is characterized by inhibition of...

Introduction: Rats exposed to postnatal hyperoxia develop right ventricular (RV) dysfunction, mild pulmonary hypertension, and dysregulated cardiac mitochondrial biogenesis when aged to 1 year, with the degree of cardiac dysfunction and pulmonary hypertension similar to that previously described in young adults born preterm. Here, we sought to und...

Premature birth is associated with increased risk for cardiac dysfunction and failure throughout life. Postnatal hyperoxia exposure in rodents is a well-established model of chronic lung disease of prematurity which recapitulates the pulmonary vascular and cardiovascular phenotype of premature birth, including decreased skeletal muscle fatigability...

Growing evidence suggests that environmentally relevant elevations in CO2 (<5,000 ppm) may pose direct risks for human health. Increasing atmospheric CO2 concentrations could make adverse exposures more frequent and prolonged through increases in indoor air concentrations and increased time spent indoors. We review preliminary evidence concerning t...

Rationale Bronchopulmonary dysplasia (BPD) is the most common complication of preterm birth. It is induced by hyperoxia exposure during the vulnerable saccular or early alveolar stage of lung development resulting in an arrest of alveolarization. Oxidative stress in the immature lung induced by this oxygen supplementation causes oxidative modificat...

Background In the United States an estimated 12% of births are preterm, meaning a significant number of infants are at increased risk for hypertension, type‐2 diabetes, and insulin resistance later in life. After a preterm birth, a common intervention used is oxygen therapy in order to improve oxygen delivery to systemic tissues. Although acutely l...

Rationale Macrophages are activated in response to insult. M1 macrophage polarization is associated with inflammation and tissue deterioration, whereas the M2 macrophage corresponds to wound repair and angiogenesis and has an anti‐inflammatory phenotype. Lipopolysaccharide (LPS) or interferon gamma (IFNγ) promote M1 differentiation and up‐regulate...

Mesenchymal stromal cell (MSC) derived exosomes mediate tissue protection and regeneration in many injuries and diseases by modulating cell protein production, protecting from apoptosis, inhibiting inflammation, and increasing angiogenesis. In the present study, daily intraperitoneal injection of MSC-derived exosomes protected alveolarization and a...

Rationale Preterm birth affects about 11% of pregnancies worldwide. The Institute of Medicine estimated the cost associated with premature birth to be $36 billion in 2016. Lungs in preterm infants are in the critical saccular stage of lung development and susceptible to the oxygen‐induced chronic lung disease known as bronchopulmonary dysplasia (BP...

Introduction Modern medicine has made enormous progress in the past 150 years including the development of vaccines and pharmaceutical therapies. However, to date there is little progress in developing therapies that speed the healing of injured tissues. Hyperbaric oxygen therapy (HBOT) is a FDA approved therapy for non‐healing wounds consisting of...

Images of all described western blots. Protein bands are above their respective loading control.

Premature birth affects more than 10% of live births, and is characterized by relative hyperoxia exposure in an immature host. Long-term consequences of preterm birth include decreased aerobic capacity, decreased muscular strength and endurance, and increased prevalence of metabolic diseases such as type 2 diabetes mellitus. Postnatal hyperoxia exp...

Infants born premature are at increased risk for development of bronchopulmonary dysplasia (BPD), pulmonary hypertension (PH), and ultimately right ventricular (RV) dysfunction, which together carry a high risk of neonatal mortality. However, the role alveolar simplification and abnormal pulmonary microvascular development in BPD affects RV contrac...

Obstructive sleep apnea (OSA) has been linked to increased mortality in pulmonary fibrosis. Its key feature, chronic intermittent hypoxia (CIH), can lead to oxidative stress and inflammation, known to lead to fibrotic pathology in other organs. We tested the effects of CIH in an animal model of bleomycin-induced lung fibrosis. Sprague Dawley rats w...

Rationale: Prematurity complicates 12% of births, and young adults with a history of prematurity are at risk to develop right ventricular hypertrophy and impairment. The long-term risk for pulmonary vascular disease, as well as mechanisms of right ventricular dysfunction and ventricular-vascular uncoupling following prematurity remain poorly defin...

Significance: Effective bench-to-bedside clinical translation of cellular therapies requires careful understanding of cell fate through tracking. Tracking cells is important to measure cell retention so that delivery methods and cell dose can be optimized and so that biodistribution and clearance can be defined to better understand potential off-t...

Background aims: In the field of cellular therapy, potential cell entrapment in the lungs following intravenous administration in a compromised or injured pulmonary system is an important concern that requires further investigation. We developed a rat model of inflammatory and fibrotic lung disease to mimic the human clinical condition of oblitera...

Most passenger leukocytes disembark the lung airway, but tissue-resident alveolar macrophages remain on board for the life of the transplant. See Furuya et al's article on page 2334.

Introduction Bronchopulmonary dysplasia (BPD) is a chronic lung disease of preterm infants exposed to oxygen therapy postnatally. Although it is a vital, life‐saving treatment, oxygen therapy is closely associated with long‐term consequences, including decreased alveolarization and reductions in pulmonary vasculature cross‐sectional area. Previous...

Background Approximately 12% of births in the United States are preterm, and this number is rising globally. Preterm birth is associated with increased long‐term risk for insulin resistance, metabolic syndrome, and cardiovascular disease. Infants born preterm often receive oxygen therapy, which, while life saving, can cause many changes in metaboli...

Background 12% of infants are born prematurely, and many require oxygen therapy and ventilation. Although life sustaining, oxygen therapy carries long‐term consequences. These children and young adults are at increased risk for metabolic disorders, including decreased insulin sensitivity, metabolic syndrome, and cardiovascular disease. However, the...

Introduction Bronchopulmonary dysplasia (BPD) is a chronic lung disease associated with premature birth. Hallmark pathologic features of BPD include increased alveolar wall thickness and reduced pulmonary vascular cross sectional area. Measurement of mean linear intercept (MLI) is a tool used to quantify alveolar size, where a higher MLI is suggest...

Introduction Bronchopulmonary dysplasia (BPD) is a chronic lung disease affecting pre‐term infants characterized by decreased alveolarization and impaired vascular development, and may contribute to the development of pulmonary hypertension (PH) and subsequent right ventricular dysfunction. Currently, little is known about the long‐term cardiac out...

Methods for generating and using omentum cells, and particularly stromal cells and/or omentum stem cells, in medical treatments such as tissue repair and regeneration to facilitate healing from traumatic injury to an abdominal organ, and immune modulation treatments such as suppression of immune responses and inflammation and prevention of tissue f...

Rationale: Obstructive sleep apnea aggravates asthma, but mechanisms are unknown. Chronic intermittent hypoxia is one hallmark feature of sleep apnea. Objective: We tested the effects of chronic intermittent hypoxia on allergen-induced inflammation in rats. Methods: Four groups (n= 9 -11/group) of ovalbumin-sensitized Brown-Norway rats underwent in...

Rationale: Obstructive sleep apnea (OSA) is common among patients with idiopatic pulmonary fibrosis (IPF), where it has been linked with increased mortality. Chronic intemittent hypoxia (CIH)—its hallmark feature—may be one culprit. We tested the effects of CIH exposure on lung collagen, gas exchange and lung function following intratracheal bleomy...

Many risk factors and post-transplant events have been linked to the development of bronchiolitis obliterans syndrome. Evolving research suggests that the development of cell-mediated and humoral reactivity to self-antigens (collagen V, K-α1 tubulin) in the lung allograft may play a very significant role in the bron-chiolar inflammation and fibrosi...

Rationale Obstructive sleep apnea (OSA) aggravates asthma, but the mechanisms are unclear. Chronic intermittent hypoxia (CIH) is one hallmark feature of OSA. We tested the effects of CIH on lower airways in an ovalbumin (OVA) rodent model. Methods Four groups (n=5–6/group) of Brown‐Norway rats underwent CIH (10% FiO2, 30 episodes/h, 10h/day for 30...

The omentum is a sheet-like tissue attached to the greater curvature of the stomach and contains secondary lymphoid organs called milky spots. The omentum has been used for its healing potential for over 100 years by transposing the omental pedicle to injured organs (omental transposition), but the mechanism by which omentum helps the healing proce...

Expansion of omentum in response to polyacrylamide bead injection into the peritoneal cavity of C57BL/6 mice. Pictures of the omentum attached to the stomach from a naïve mouse and from a day 7 bead- injected mouse. (TIF)

Interstitial pulmonary fibrosis is caused by the excess production of extracellular matrix (ECM) by Fb in response to TGF-β1. Here, we show that the peptidyl-prolyl isomerase Pin1 modulates the production of many pro- and antifibrogenic cytokines and ECM. After acute, bleomycin injury, Pin1−/− mice showed reduced, pulmonary expression of collagens,...

It is clear that γδ T cells, especially IEL, play more than an accessory role to αβ T cells in immune responses at mucosal borders. They are clearly unique and required for protective immune responses and repair of damaged epithelium. In fact, their role in epithelial surveillance, response and repair may reflect a fundamental role for this lineage...

Tolerance to collagen structures has been shown to inhibit the progression of autoimmune scleroderma and rheumatoid arthritis. More recently, tolerance induction to collagen type V (colV) in experimental models of lung transplantation was shown to ameliorate the complex pathology known as "chronic rejection." The link between colV autoimmunity and...

Rat lung allograft rejection is mediated by collagen type V (col(V)) specific T-helper-cell 17 (Th17) cells. Adoptive transfer of these cells is sufficient to induce rejection pathology in isografts, whereas tolerance to col(V) suppresses allograft rejection. Therefore, we tested whether regulatory T cells from tolerant rats could suppress the Th17...

The antibody HMB45 is used to diagnose lymphangioleiomyomatosis, a hyperproliferative disorder of lung smooth muscle cells with mutations in both alleles of either TSC1 or TSC2. A subset of these tumor cells expresses the melanoma-associated antigens gp100 and melanoma antigen recognized by T cells (MART-1). To explore the feasibility of targeting...

Aerosolized interferon-gamma (IFN-gamma) leads to transient conversion of sputum smears in multidrug-resistant pulmonary tuberculosis (MDR-TB). To test long-term conversion of sputum smears using the new Jena protocol. Four MDR-TB patients were treated with aerosolized recombinant IFN-gamma (rIFN-gamma) twice weekly for 8 weeks and anti-tuberculosi...

gammadelta T cells play a key role in the regulation of inflammatory responses in epithelial tissue, and in adaptive immunity, as gammadelta T cell deficient mice have a severely impaired capacity to clear lung pathogens. gammadelta T cells regulate the initial inflammatory response to microbial invasion and thereby protect against tissue injury. H...

The pathogenesis of primary graft dysfunction (PGD), a serious complication of lung transplantation, is poorly understood. Human studies and rodent models have shown that collagen type V (col[V]), stimulates IL-17-dependent cellular immunity after lung transplantation. To determine whether patients with end-stage lung disease develop pretransplant...

Bronchiolitis obliterans syndrome (BOS), a process of fibro-obliterative occlusion of the small airways in the transplanted lung, is the most common cause of lung transplant failure. We tested the role of cell-mediated immunity to collagen type V [col(V)] in this process. PBMC responses to col(II) and col(V) were monitored prospectively over a 7-ye...

Flow cytometry has evolved from single- and two-color analysis to the current use of 11-16 colors. The relatively bright excitation spectra of most fluorochromes have made color compensation a challenge especially when performed manually. We describe how by choosing filters with narrower bandwidths results in the color compensation values between F...

Background/Abstract Immune responses initiated by T cell receptor (TCR) and costimulatory molecule mediated signaling culminate in maximal cytokine mRNA production and stability. The transcriptional responses to co-stimulatory T cell signalling involve calcineurin and NF-AT, which can be antagonized by interference with the cis-trans peptidyl-proly...

Strenuous exercise may be a significant contributing factor for development of high-altitude pulmonary edema, particularly at low or moderate altitudes. Thus we investigated the effects of heavy cycle ergometer exercise (90% maximal effort) under hypoxic conditions in which the combined effects of a marked increase in pulmonary blood flow and nonun...

An immunological pathogenesis underlying dilated cardiomyopathy and myocarditis has been suggested on the basis of the subtype of lymphocyte infiltrates and the degree of HLA expression in cardiac tissue. In the present study, we investigated the relation between the peripheral CD4+T-cell subset and the degree of HLA expression in the heart. Fifty-...

Pulmonary fibrosis (PF) may develop following successful chemotherapy for malignancy, even if such therapy is not combined with radiotherapy. Bleomycin, which is known to induce acute pneumonitis and lung fibrosis, is especially associated with chemotherapy-induced PF, and bleomycin-induced pulmonary fibrosis can occur more than five years after su...

Eine pulmonale Fibrose kann als späte Folge einer erfolgreichen Chemotherapie mit und ohne Strahlentherapie relevant werden (besonders nach Bleomycin). Neben der bekannten frühen Bleomycin-assoziierten Pneumonitis mit Fibroseinduktion, sollten auch mehr als 5 Jahre nach erfolgreicher Chemotherapie Sauerstoffgaben sorgfältig abgewogen und zuvor mit...

Chromosomal aberrations were investigated in nuclei extracted from synovial tissue and first-passage synovial fibroblasts (P-1 SFB, 98% enrichment) or macrophages (P-1 Mphi) from patients with rheumatoid arthritis (n=10). The findings were compared with those in other rheumatic diseases (osteoarthritis, n=14; reactive arthritis, n=1), as well as wi...

The integrin CD103 is preferentially expressed on intraepithelial T lymphocytes, and cells expressing this integrin may play a regulatory role in the microenvironment of the epithelial cell layer. The relative number of CD103(+)/CD4(+) T cells in the bronchoalveolar lavage was significantly elevated in all patients diagnosed with interstitial lung...

Aminopeptidase N (CD13) is a cell surface metalloprotease involved in growth regulation, tumor invasion, and down-regulation of regulatory peptides. CD13 expression on eosinophils in bronchoalveolar lavage (BAL) of asthmatics 10 minutes and 18 hours after segmental allergen provocation was significantly increased (+225% to +294%) compared to blood...

T lymphocytes bearing the gammadelta-TCR accumulate during wound healing and inflammation. However, the role of gammadelta-T lymphocytes in fibrogenic tissue reactions is not well understood. Therefore, we addressed the question of whether human gammadelta-T cells express and synthesize connective tissue growth factor (CTGF), a factor known to regu...

T lymphocytes bearing the γδ-TCR accumulate during wound healing and inflammation. However, the role of γδ-T lymphocytes in fibrogenic tissue reactions is not well understood. Therefore, we addressed the question of whether human γδ-T cells express and synthesize connective tissue growth factor (CTGF), a factor known to regulate fibrogenesis and wo...

Infiltration of eosinophils into the airways plays a central role in the pathophysiology of asthma. Human blood eosinophils express apoptosis-inducing receptors (e.g. CD95R and CD69R) regulating both viability and survival and, thus, the extent of eosinophil infiltration into the airways. Signal transduction processes induced by occupation of the C...

Extrapolation to humans from rodent ozone exposure is limited by the anatomic differences between the species. Ferrets have similar pulmonary structures to humans, with well developed respiratory bronchioles and submucosal glands. We exposed adult ferrets, monkeys, and rats to 1 ppm ozone (O(3)) or filtered air for 8 h followed by 1 h in filtered a...

The concept of priming is widely used in cell biology and has come to mean the functional enhancement of a given cell by cytokines. 'Primed' cells have a number of other cellular alterations, although the relationship between functional and phenotypical diversity has not been established. Here, Claus Kroegel and colleagues discuss the dynamic natur...

Asthmatic airway inflammation due to chronic or repeated allergen exposure is maintained by a persistent inflammatory cell infiltration and results in a remodelling process which causes substantial structural and functional alteration in the airways of allergic asthmatic subjects. Recently, it has been suggested that a class of extracellular matrix...

Substance P (SP), a neurotransmitter of the central and peripheral nervous system, has been implicated as a mediator of the pulmonary inflammatory response through its stimulatory effects on neutrophils. We investigated the role of SP in priming the production of reactive oxygen species by human neutrophils with the cytochrome c reduction assay and...

5-lipoxygenase inhibitors and cysteinylleukotriene receptor antagonists belong to 2 new substance classes that suppress the biological action of leukotrienes in bronchial asthma. They have been shown to represent potent inhibitors of airway obstruction in bronchial asthma induced by allergen, aspirin, and exercise. In addition, several chronic trea...

Purpose: To evaluate the role of eosinophilic leukocyte infiltration in bronchogenic carcinoma. Methods: Eosinophil Cationic Protein (ECP) was measured consecutively in patients proved bronchogenic carcinoma (BC), classified on the grounds of their respective histology: squamous-cell carcinoma (SCC, n=22), adeno carcinoma (AC, n=2A), large-cell car...

Increased serum levels of eosinophil cationic protein (ECP) have been detected in adolescent patients with cystic fibrosis. However, ECP concentrations in adult patients with bronchiectasis unrelated to cystic fibrosis have not been studied. Eosinophil numbers and serum concentrations of ECP were determined in 14 patients with known or newly diagno...

Intense exercise causes a transient disruption in the lung blood-gas barrier. Pulmonary γδ intraepithelial lymphocytes (IEL) are sentinel cells that monitor the epithelium for damage and then, in part, regulate inflammation and epithelial growth/repair by secreting cytokines and growth factors, and therefore may play an important modulator role in...

We reported previously that treatment with antibody to transforming growth factor-beta (TGF-beta) caused a marked attenuation of bleomycin (BL)-induced lung fibrosis (LF) in mice. Decorin (DC), a proteoglycan, binds TGF-beta and thereby down-regulates all of its biological activities. In the present study, we evaluated the antifibrotic potential of...

The purpose of the study was to assess the sensitivity of acute ozone exposure on the ferret lung. Extrapolation to humans from rodent ozone exposure has been limited by the physiological and anatomical differences between the species. Ferret's have similar pulmonary structure to humans, such as well-developed respiratory bronchioles and large numb...

T lymphocytes expressing the αEβ7 integrin are localized and selectively retained in mucosal tissues. To investigate a potential relationship between αEβ7 expression and pulmonary inflammation, the distribution of αEβ7-bearing CD4+ and CD8+ T cells in peripheral blood and bronchoalveolar lavage (BAL) fluids obtained from patients with allergic asth...

Bleomycin produces pulmonary fibrosis in mice when given as a single intratracheal instillation or as multiple subcutaneous injections. Both models are associated with a significant deposition of collagen in the lungs but differ in the location of the initial lesions. Intratracheal instillation of bleomycin directs lesions to peribronchial or perib...

CD4, CD8, and gamma delta T-cells located in the epithelium express the integrin alpha E beta 7 that binds to E-cadherin on the epithelium. Gamma delta T-cells mediate specific cellular immune functions and can recognize damaged cells directly. It was, therefore, of interest to analyse the presence of gamma delta T-cells and the expression of alpha...

Neutrophil adhesion to microvascular endothelium at sites of acute inflammation is regulated by both chemotactic peptides and lipid-derived mediators. Tumour necrosis factor-alpha (TNF-alpha) is a pro-inflammatory peptide that up-regulates endothelial expression of intercellular adhesion molecule-1 (ICAM-1) and endothelial leucocyte adhesion molecu...

CD4, CD8, and γδ T-cells located in the epithelium express the inte- grin αEβ7 that binds to E-cadherin on the epithelium. γδ T-cells mediate specific cellular immune functions and can recognize damaged cells directly. It was, there- fore, of interest to analyse the presence of γδ T-cells and the expression of αEβ7 on γδ T-cells in the bleomycin (B...

Increasing evidence suggests an important role for cytokines in the regulation of eosinophilic inflammation. In the present study we investigated the distribution of leukocytes, lymphocyte subsets, their activation state, and the cytokine profile present in BAL fluid from patients with various lung diseases associated with eosinophilia. For this pu...

Eosinophils from sputum, nasal polyps, and bronchoalveolar lavages of asthmatics demonstrated a considerably increased CD11b expression, compared with blood eosinophils. Furthermore, the tissue eosinophils expressed ICAM-1 (CD54) and HLA-DR, whereas peripheral blood eosinophils did not. In vitro migration of peripheral blood eosinophils across IL-1...