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Bronchopulmonary dysplasia (BPD) is a common chronic lung condition in preterm infants that results in abnormal lung development and leads to considerable morbidity and mortality, making BPD one of the most common complications of preterm birth. We employed RNA sequencing and 16S rRNA gene sequencing to profile gene expression in blood and the composition of the fecal microbiota in infants born at <29 weeks gestational age and diagnosed with BPD in comparison to those of preterm infants that were not diagnosed with BPD. 16S rRNA gene sequencing, performed longitudinally on 255 fecal samples collected from 50 infants in the first months of life, identified significant differences in the relative levels of abundance of Klebsiella, Salmonella, Escherichia/Shigella , and Bifidobacterium in the BPD infants in a manner that was birth mode dependent. Transcriptome sequencing (RNA-Seq) analysis revealed that more than 400 genes were upregulated in infants with BPD. Genes upregulated in BPD infants were significantly enriched for functions related to red blood cell development and oxygen transport, while several immune-related pathways were downregulated. We also identified a gene expression signature consistent with an enrichment of immunosuppressive CD71 + early erythroid cells in infants with BPD. Intriguingly, genes that were correlated in their expression with the relative abundances of specific taxa in the microbiota were significantly enriched for roles in the immune system, suggesting that changes in the microbiota might influence immune gene expression systemically. IMPORTANCE Bronchopulmonary dysplasia (BPD) is a serious inflammatory condition of the lung and is the most common complication associated with preterm birth. A large body of evidence now suggests that the gut microbiota can influence immunity and inflammation systemically; however, the role of the gut microbiota in BPD has not been evaluated to date. Here, we report that there are significant differences in the gut microbiota of infants born at <29 weeks gestation and subsequently diagnosed with BPD, which are particularly pronounced when infants are stratified by birth mode. We also show that erythroid and immune gene expression levels are significantly altered in BPD infants. Interestingly, we identified an association between the composition of the microbiota and immune gene expression in blood in early life. Together, these findings suggest that the composition of the microbiota may influence the risk of developing BPD and, more generally, may shape systemic immune gene expression., (Copyright © 2019 Ryan et al.)

Background: Consumption of baked egg by raw egg allergic children is associated with immune changes suggesting development of tolerance. However, causation has not been tested using a double blind randomized controlled trial (RCT). We aimed to compare clinical and immunological outcomes after baked egg (BE) consumption in young BE tolerant egg allergic children., Methods: In a double blind RCT, BE tolerant egg allergic children consumed 10 g BE (1.3 g protein) 2 to 3 times per week for 6 months ( n  = 21 intervention group) or similar egg free baked goods ( n  = 22 control group) while maintaining an otherwise egg free diet. The final assessment was a raw egg oral food challenge (OFC) 1 month after ceasing the intervention product. Egg specific IgE and IgG4 were assessed at baseline and 7 months., Results: After the intervention there was no difference in raw egg tolerance between groups, (23.5% (4/17) intervention group and 33.3% (6/18) control group). This was independent of age and amount of BE consumed (aOR 0.50 CI 0.11-2.40 p  = 0.39). Both groups demonstrated decreased egg specific serum IgE titres and decreased whole egg specific IgE/IgG4 ratios., Discussion: We conducted this trial because inclusion of baked egg protein in the diet of egg allergic children appears to move children towards a more tolerant immune profile. Strengths of our study include design of the blinded intervention, the consistent dosing protocol and the regular monitoring of symptoms and intake. However, the study was limited by small sample size resulting in insufficient power to show statistically significant results., Conclusion: Our study suggests that short term, regular consumption of BE by BE tolerant 1 to 5 year old children with IgE mediated raw egg allergy may not induce, accelerate or slow development of tolerance to raw egg in this selected population. Trials with larger sample sizes are required to further test this hypothesis., Trial Registration: The trial was registered on 7 th February 2012 with the Australian New Zealand Clinical Trials Registry (ACTRN 12612000173897).

Background: Oral food challenges for diagnosis and management of egg allergy using fresh egg are common; however, to limit the risk of foodborne infection, many allergy units use pasteurized raw egg. Pasteurization and drying processes have the potential to affect the structure of egg proteins in egg powder and thus the allergenicity when compared to fresh egg. Our aim was to compare the binding of serum IgE from egg-allergic children to in vitro digested and undigested pasteurized whole raw egg powder with unpasteurized fresh whole raw egg., Methods: Egg proteins from in vitro digested or undigested pasteurized whole raw egg powder, fresh whole egg, egg white and egg yolk were separated by SDS-PAGE, transferred onto nitrocellulose membrane and incubated overnight with pooled sera from egg-allergic children., Results: In both the raw egg samples and the pasteurized whole egg powder, protein bands corresponding to known molecular weights of the major egg allergens were present. Pasteurized whole raw egg powder was bound by serum IgE in a similar manner to unpasteurized whole raw egg and was unaffected by in vitro digestion. Serum IgE also bound egg yolk, indicating sensitization to both egg yolk and egg white proteins., Conclusions: The main egg allergens are present in pasteurized whole raw egg powder, and serum IgE of egg-allergic children binds to them in a similar pattern to those in fresh whole raw egg. Pasteurized whole raw egg powder is a suitable substitute for raw egg in clinical practice for oral food challenges., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Food allergies are one of the first manifestations of allergic disease and have been shown to significantly impact on general health perception, parental emotional distress and family activities. It is estimated that in the Western world, almost one in ten children have an IgE-mediated allergy. Cow's milk and egg allergy are common childhood allergies. Until recently, children with food allergy were advised to avoid all dietary exposure to the allergen to which they were sensitive, in the thought that consumption would exacerbate their allergy. However, recent publications indicate that up to 70% of children with egg allergy can tolerate egg baked in a cake or muffin without apparent reaction. Likewise, up to 75% of children can tolerate baked goods containing cow's milk, and these children demonstrate IgE and IgG4 profiles indicative of tolerance development. This article will review the current literature regarding the use of heated food allergens as immunotherapy for children with cow's milk and egg allergy.

Early nutritional events have the potential to affect health outcomes in later life including the development of allergy. Food allergy is usually the first manifestation of allergy. Breast-feeding has been associated with a protective effect against the development of allergy, but the evidence is contradictory and the mechanisms involved are not clear. We hypothesize that milk cytokines, such as transforming growth factor beta (TGF-beta), play a role in regulating immune responses to dietary antigens. Using a rat pup model of gastrostomy feeding, the immune response profile, at weaning and post-weaning, of allergy-prone Brown Norway rats fed formula supplementation with TGF-beta was assessed. We show that feeding formula to allergy-prone rat pups results in increased total IgE immunoglobulin, beta-lactoglobulin (BLG) IgG1 antibody, and mucosal mast cell activation, as measured by serum rat mast cell protease II (RMCPII) levels in the gut. Supplementation of formula with physiological levels of TGF-beta down-regulated the BLG IgG1 response as well as total IgE and mucosal mast cell activation. Supplementation of formula also resulted in an increase in Th1 cytokines, interleukin (IL)-18, IL-12p40, IL-12p35, and interferon gamma (IFN-gamma) and an increase in IL-10. In conclusion, TGF-beta supplementation of formula moved the immune response profile of allergy prone (Th2 type) rat pups toward a Th1 profile in the suckling period. Importantly, this immune profile persisted after weaning when TGF-beta was no longer present in the diet.

Ulcerative colitis and Crohn's disease, collectively termed inflammatory bowel diseases (IBD), are chronic inflammatory diseases of the intestine that afflict more than 4 million people worldwide. Intestinal inflammation is characterized by an abnormal mucosal immune response to normally harmless antigens in the gut flora. In Crohn's disease, the pathogenic mucosal immune response is a typical T helper (TH1) type cell response, whereas ulcerative colitis is predominantly associated with a TH2 response. We are interested in the role of dendritic cells in early immunologic events leading to T cell activation and chronic intestinal inflammation. Using a murine adoptive transfer model of IBD, we found an accumulation of dendritic cells in colon and mesenteric lymph nodes during the early stage of IBD before the appearance of epithelial lesions and tissue degradation. In situ immunostaining and flow-cytometric analysis revealed that approximately 50% of colonic dendritic cells were CD11b B220 myeloid dendritic cells and 50% expressed the CD11b B220 plasmacytoid phenotype. In corresponding mesenteric lymph nodes, approximately 16% were plasmacytoid dendritic cells. Colonic myeloid dendritic cells were shown to express the co-stimulatory molecule CD40. Both, colonic myeloid and plasmacytoid dendritic cells released interferon-alpha in situ and stimulated T cell proliferation ex vivo. Our results show that dendritic cells can mature in the intestine without migrating to mesenteric lymph nodes. Mature intestinal dendritic cells may form a nucleation site for a local T cell response and play an important role in the pathogenesis of IBD.

Transforming growth factor-beta (TGF-beta) is present at high concentrations in maternal milk. In milk TGF-beta2 is the predominant isoform. For function TGF-beta2 requires TbetaRIII to facilitate efficient binding to the TGF-beta receptor types I and II signalling complex. We have shown that TGF-beta receptor types I (TbetaRI), II (TbetaRII) and III (TbetaRIII) are coexpressed in the suckling rat intestine. Immunostaining for TbetaRIII was also observed in the intestinal lumen prior to weaning. TbetaRIII (or betaglycan) has been reported in serum, cell culture medium and extracellular matrix. To determine whether a soluble form of TbetaRIII is present in milk, the rat milk aqueous phase was analysed by slot-blot and Western blot. Soluble TbetaRIII was detected in milk throughout lactation. Western blot analysis of rat milk revealed a high molecular weight band of glycosylated protein of >200 kDa, with a core protein of approximately 110-120 kDa that comigrated with recombinant TbetaRIII. Immunoabsorption of soluble TbetaRIII (sTbetaRIII) from milk resulted in partial depletion of active TGF-beta from milk, suggesting that the receptor may interact with ligand in milk. In addition rat pups suckled on mother's milk demonstrated an enhanced labelling of TbetaRIII in the gut, as compared with pups fed on a rat milk substitute (RMS). These findings suggest that milk sTbetaRIII is functional, and may modulate milk-derived TGF-beta function in the developing intestine.

Background: Inflammatory process has been found to play an important role in the pathogenesis of coronary heart disease (CHD) and in the prognosis of CHD patients. AIM. The aim of this study was to investigate the prognostic value of C-reactive protein (CRP), fibrinogen, interleukin (IL)-6 and tumour necrosis factor-alpha (TNF-alpha) in patients with unstable angina pectoris (UAP), including factor analysis to assess their joint effects., Methods: The study comprised 263 consecutive patients (159 men, 104 women; median age 68 years) with UAP. Blood samples for the acute-phase protein and cytokine determinations were drawn on admission., Results: Coronary mortality during the median follow-up time of 17 months was 6-fold higher in the highest tertile for CRP and IL-6 and 3.5-fold higher in the highest tertile for fibrinogen and TNF-alpha than in the respective combined lower tertiles. Factor analysis produced two underlying factors, ie the 'inflammation' factor, including CRP, fibrinogen and IL-6, and the 'injury' factor, including troponin T, creatine kinase MB mass and TNF-alpha. In Cox models, both of these factors were independent predictors of the risk of coronary death and major coronary events (coronary death or nonfatal myocardial infarction)., Conclusions: Elevated levels of acute-phase proteins and cytokines, particularly CRP and IL-6, are strong predictors of the risk of serious coronary events in patients with UAP.

Purpose: The aim of this study was to determine the nutritional status of Finnish elite male ski jumpers (N = 21) and age-matched controls (N = 20)., Methods: Nutritional status was assessed by estimating body composition with dual-energy x-ray absorptiometry (DXA), dietary intake with 4-d food records, and assessment of nutritional status was complemented with biochemical and hematological indices., Results: Mean (SD) age (19.7 (3.6) vs 19.8 (3.9) yr, P = 0.675) and stature (176.4 (6.0) vs 178.5 (5.5) cm, P = 0.259) were similar in ski jumpers and in controls, respectively. However, ski jumpers had a lower mean (SD) body weight (61.9 (4.8) vs 71.5 (9.0) kg, P < 0.001) and body fat percentage (8.6 (1.9) vs 16.1 (7.2)%, P < 0.001) than controls. The amount of bone-free lean soft tissue and bone mineral content (BMC) did not differ between the groups, but age- and bone-free lean soft tissue-adjusted bone mineral density (BMD) in lumbar spine (L2-4) and in proximal femur was greater in ski jumpers. Mean (SD) energy intake was lower in ski jumpers than in controls (7.4 (3.3) vs 11.0 (2.6) MJ, P = 0.001), respectively, whereas the percentage of energy derived from carbohydrates was higher in athletes. Despite the markedly lower energy consumption, intake of thiamin, riboflavin, folate, vitamin C, calcium, and iron was similar in both groups, whereas intake of vitamins D and E, magnesium, and zinc was lower in ski jumpers than in controls (P-values range from 0.012 to 0.004). Biochemical and hematological indices showed no abnormalities in either group., Conclusions: These data suggest that despite the lower body weight and energy intake, nutritional status of the elite Finnish ski jumpers was not compromised as compared with that of nonathletic controls.

The growth mitogenic properties of IGF-I on tissues of the gastrointestinal tract are well established; however, IGF effects on enzyme maturation are less clear. To test whether IGF-I peptide administration stimulates disaccharidase activity, we administered IGF-I or the more potent analog, long [Arg3]IGF-I, at doses ranging between 2 and 12.5 micrograms g-1 d-1 to suckling Wistar rat pups by either continuous s.c. infusion or by three times daily orogastric gavage. Peptides were administered for approximately 6 d starting on d 6 or 12 postpartum with six to nine rats per group. The results of the study demonstrated that systemically but not orally administered IGF-I stimulated duodenal wet tissue weight (up to 85%) and length (up to 36%). Enzyme maturation was assessed by measuring disaccharidase biochemically in tissue homogenates. Enzyme activity was also localized histocytochemically in cryostat-sectioned duodenum. After systemic infusion of IGF-I, intestinal lactase activity increased proportional to mucosal mass in both age groups. Systemic infusion of the more potent analog, long [Arg3]IGF-I, precociously induced the decline in lactase activity and accelerated the appearance of sucrase activity in the rat pups infused during the later suckling period. These findings indicate that enzyme maturation can be accelerated by systemically derived IGF-I peptides. Orogastrically IGF-I peptides, delivered at pharmacologic doses, did not affect intestinal growth or digestive enzyme maturation in suckling rat pups treated between 6 and 18 d postpartum, indicating the efficacy of IGF-I peptides may depend on the route of delivery and postnatal age of the recipient.

High body iron stores have been proposed as a risk factor for advanced atherosclerosis. We investigated the prevalence of early atherosclerotic changes, and their relation to conventional CHD risk factors and body iron status. A cross-sectional study was carried out in 206 men aged 50 to 60 years (6% random population sample). Intima-media thickness (IMT) of the carotid artery was evaluated with high-resolution B-mode ultrasonography. Statistical analyses were performed separately for men with and without cardiovascular disease (CVD). Among all the study participants, 6.6% had IMT > 1.3 mm in the common carotid artery, whereas 53.8% had IMT > 1.5 mm in the carotid bifurcation. Respective values were 4.8% and 46.8% for those without CVD, and 8.5% and 62.2% for those with CVD. Mean IMT in the carotid bifurcation, the predilection site for atherosclerosis, was 1.85 mm (95% CI 1.72; 1.98) in the men with CVD, as compared to 1.65 mm (95% CI 1.56; 1.73) in the men free of CVD. Serum LDL cholesterol (beta = 0.26), saturated fat intake (beta = 0.20), blood haemoglobin (beta = -0.29), systolic blood pressure (beta = 0.21) and smoking (beta = 0.19), jointly explained 23% of the variance in the carotid bifurcation IMT in the men without CVD. Neither serum ferritin, transferrin nor dietary iron levels were associated with carotid bifurcation atherosclerosis. On the other hand, in the men with CVD, age (beta = 0.34) and physical activity (beta = -0.25) jointly explained 16.5% of the IMT variance in the carotid bifurcation.(ABSTRACT TRUNCATED AT 250 WORDS)

The serum values of tissue polypeptide antigen (TPA) were measured in a prospective series of 100 patients with jaundice, 54 patients with suspicion of chronic pancreatitis or a pancreatic tumour, and 19 patients with unjaundiced cholestasis to assess its value in diagnosing pancreatic cancer. There were altogether 25 patients with a cancer of the pancreas including 2 patients with a cancer of the papilla of Vater. The highest serum TPA values were noticed in patients with pancreatic cancer, but raised values were also seen in patients with malignant or benign liver diseases, and with cholangiocarcinoma. The sensitivity of TPA was 52% with a specificity of 85% and an efficiency of 80%. In comparison to CEA, CA 50 and CA 242, TPA showed lower sensitivity but higher specificity. When TPA was combined with the other markers, the specificity and efficiency improved clearly in all combinations, being highest in that of TPA and CA 242 (specificity 94.5%, efficiency 87.2%). The results suggest that the TPA test has a useful complementary role in the clinical use of the current serum tumour markers in the diagnosis of pancreatic cancer.

Objective: To determine the prevalence of hypertriglyceridemia and the mean serum triglyceride concentrations in different degrees of glucose tolerance--non-insulin-dependent diabetes mellitus (NIDDM), impaired glucose tolerance (IGT), and normal glucose tolerance (NGT). In addition, we analyzed the correlates of serum triglyceride concentration to explain why it is more prevalent in diabetic subjects., Research Design and Methods: This study was a cross-sectional survey of 4000 people aged 45-64 yr randomly drawn from the population register of the Finnish population of the provinces of North Karelia and Kuopio in eastern Finland and Turku/Loimaa area in southwestern Finland and stratified by four 10-yr age- and sex groups. The final material comprised 96 subjects with NIDDM, 102 subjects with IGT, and 323 subjects with normal glucose tolerance classified on the basis of two 2-h oral glucose tolerance tests. The prevalence of hypertriglyceridemia by the glucose tolerance status and the variation in serum triglycerides associated with selected life-style and biochemical factors were executed as the main outcome measures., Results: The prevalence of hypertriglyceridemia (greater than or equal to 2.3 mM) was 47.6% (95% confidence interval [CI] 32.5-62.7%) in NIDDM men, 21.9% (95% CI 7.6-36.2%) in IGT men, and 15.4% (95% CI 9.3-21.5%) in NGT. In women, hypertriglyceridemia was found in 51.9% (95% CI 38.6-65.2%) among those with NIDDM, 25.7% (95% CI 15.5-35.9%) among those with IGT, and 10.7% (95% CI 6.3-15.1%) in women with NGT. After adjusting for body mass index (BMI) and age, the difference in the prevalence of hypertriglyceridemia between the glucose tolerance groups remained significant in both men (P = 0.008) and women (P = 0.0001). High serum total cholesterol, high BMI, high waist-hip ratio, and low high-density lipoprotein (HDL) cholesterol were significantly associated with high serum triglycerides in all glucose tolerance groups. No synergistic effect between these parameters and glucose tolerance status was found. In multiple linear regression analyses, fasting plasma insulin, diabetes status, and serum uric acid were significant predictors of serum triglyceride concentration after taking into account age, BMI, and HDL and total cholesterol. The association between BMI and serum triglycerides in the regression analysis was significant only when plasma insulin was not included in the model., Conclusions: Hypertriglyceridemia is common in subjects with NIDDM and IGT and is often associated with low HDL cholesterol, high total cholesterol, hyperinsulinemia, and elevated serum uric acid concentration.

Gluten intolerance (coeliac disease) is characterised by the development of a small intestinal lesion following exposure to the gliadin fraction after consumption of wheat and related cereals. Cellular immune mechanisms are thought to be responsible for gliadin toxicity, but the toxic sequence/s within gliadin have not been clearly established. A panel of synthetic gliadin peptides was tested using peripheral blood mononuclear cells from coeliac patients and two assays for cell-mediated immunity. Using the indirect leucocyte migration inhibition factor and the macrophage procoagulant activity assays, gliadin peptides which were located in the aminoterminal or the proline-rich domain of the alpha/beta gliadin molecule were coeliac-active. Peptides predicted by T cell algorithms or on the basis of homology to adenovirus Ad12 Elb protein and which were located in the proline-poor gliadin domains were inactive. Protein sequence studies which indicate significant homology in the proline-poor gliadin domains with a number of non-coeliac-toxic seed proteins also supported the hypothesis that the proline-rich domains may be more important in the pathogenesis of coeliac disease.

A recommendation concerning basic urine examinations and bacteriological cultures was published in 1983 in Finland including three clinical indication groups with different screening strategies. Close cooperation between laboratory experts and clinicians as well as much training in urine sediment cytology were essential before the new principle became widely accepted. Decreased workload in laboratories in clinically less significant cases was shown with the use of the full capacity and qualities of complete urinalysis when needed. Standardized test procedures combined with sediment staining improved the clinical efficiency of urine microscopy.