Atopic asthma after rhinovirus-induced wheezing is associated with DNA methylation change in the SMAD3 gene promoter.

Children with rhinovirus-induced severe early wheezing have an increased risk of developing asthma later in life. The exact molecular mechanisms for this association are still mostly unknown. To identify potential changes in the transcriptional and epigenetic regulation in rhinovirus-associated atopic or nonatopic asthma, we analyzed a cohort of 5-year-old children (n = 45) according to the virus etiology of the first severe wheezing episode at the mean age of 13 months and to 5-year asthma outcome. The development of atopic asthma in children with early rhinovirus-induced wheezing was associated with DNA methylation changes at several genomic sites in chromosomal regions previously linked to asthma. The strongest changes in atopic asthma were detected in the promoter region of SMAD3 gene at chr 15q22.33 and introns of DDO/METTL24 genes at 6q21. These changes were validated to be present also at the average age of 8 years.

Latent ion tracks were finally observed in diamond.

Injecting high-energy heavy ions in the electronic stopping regime into solids can create cylindrical damage zones called latent ion tracks. Although these tracks form in many materials, none have ever been observed in diamond, even when irradiated with high-energy GeV uranium ions. Here we report the first observation of ion track formation in diamond irradiated with 2-9 MeV C60 fullerene ions. Depending on the ion energy, the mean track length (diameter) changed from 17 (3.2) nm to 52 (7.1) nm. High resolution scanning transmission electron microscopy (HR-STEM) indicated the amorphization in the tracks, in which π-bonding signal from graphite was detected by the electron energy loss spectroscopy (EELS). Since the melting transition is not induced in diamond at atmospheric pressure, conventional inelastic thermal spike calculations cannot be applied. Two-temperature molecular dynamics simulations succeeded in the reproduction of both the track formation under MeV C60 irradiations and the no-track formation under GeV monoatomic ion irradiations.

Soluble urokinase-type plasminogen activator receptor in patients with suspected infection in the emergency room: a prospective cohort study.

OBJECTIVES: The soluble form of urokinase-type plasminogen activator (suPAR) was evaluated as an early prognostic marker of sepsis in patients with suspected infection. DESIGN: A single-centre prospective cohort study. METHODS: The cohort comprised 539 patients in the emergency department with suspected infection: 59 without systemic inflammatory response syndrome (SIRS) and without bacterial infection (group 1), 68 with bacterial infection and without SIRS (group 2), 54 with SIRS and without bacterial infection (group 3), 309 with sepsis (SIRS and bacterial infection) and without organ failure (group 4) and 49 with severe sepsis (SIRS, bacterial infection and organ failure) (group 5). suPAR was measured on admission using a commercial solid-phase enzyme-linked immunosorbent assay. RESULTS: The median soluble form of the receptor (suPAR) concentrations in groups 1-5 were 4.7, 5.0, 4.4, 4.8 and 7.9 ng mL(-1) , respectively (P < 0.001). The levels were significantly higher in nonsurvivors compared with survivors (8.3 vs. 4.9 ng mL(-1) , P < 0.001) and in patients with severe sepsis (group 5) compared with those in the other groups (7.9 vs. 4.8 ng mL(-1) , P < 0.001). Area under the receiver operating characteristics curve (AUC(ROC) ) for the prediction of case fatality was 0.79 (95% confidence interval [CI]: 0.72-0.86, P < 0.0001) and 0.75 for severe sepsis (95% CI: 0.68-0.81, P < 0.0001). At a cut-off level of 6.4 ng mL(-1) , suPAR had 76% sensitivity and 69% specificity for fatal disease; at a cut-off level of 6.6 ng mL(-1) , the sensitivity and specificity for severe sepsis were 67% and 72%, respectively. In multivariate models, high suPAR remained an independent predictor of case fatality and severe sepsis after adjusting for potential confounders. CONCLUSIONS: A high suPAR level predicts case fatality and severe sepsis in patients with suspected infection.

Genetic analyses of metabolic body weight, carcass weight and body conformation traits in Nordic dairy cattle.

Improving feed efficiency in dairy cattle by animal breeding has started in the Nordic countries. One of the two traits included in the applied Saved feed index is called maintenance and it is based on the breeding values for metabolic BW (MBW). However, BW recording based on heart girth measurements is decreasing and recording based on scales is increasing only slowly, which may weaken the maintenance index in future. Therefore, the benefit of including correlated traits, like carcass weight and conformation traits, is of interest. In this study, we estimated genetic variation and genetic correlations for eight traits describing the energy requirement for maintenance in dairy cattle including: first, second and third parity MBW based on heart girth measurements, carcass weight (CARW) and predicted MBW (pMBW) based on predicted slaughter weight, and first parity conformation traits stature (ST), chest width (CW) and body depth (BD). The data consisted of 21329 records from Finnish Ayrshire and 9780 records from Holstein cows. Heritability estimates were 0.44, 0.53, 0.56, 0.52, 0.54, 0.60, 0.17 and 0.26 for MBW1, MBW2, MBW3, CARW, pMBW, ST, CW and BD, respectively. Estimated genetic correlations among MBW traits were strong (>0.95). Genetic correlations between slaughter traits (CARW and pMBW) and MBW traits were higher (from 0.77 to 0.90) than between conformation and MBW traits (from 0.47 to 0.70). Our results suggest that including information on carcass weight and body conformation as correlated traits into the maintenance index is beneficial when direct BW measurements are not available or are difficult or expensive to obtain.

Genetic correlations between energy status indicator traits and female fertility in primiparous Nordic Red Dairy cattle.

Inclusion of feed efficiency traits into the dairy cattle breeding programmes will require considering early lactation energy status to avoid deterioration in health and fertility of dairy cows. In this regard, energy status indicator (ESI) traits, for example, blood metabolites or milk fatty acids (FAs), are of interest. These indicators can be predicted from routine milk samples by mid-IR reflectance spectroscopy (MIR). In this study, we estimated genetic variation in ESI traits and their genetic correlation with female fertility in early lactation. The data consisted of 37 424 primiparous Nordic Red Dairy cows with milk test-day records between 8 and 91 days in milk (DIM). Routine test-day milk samples were analysed by MIR using previously developed calibration equations for blood plasma non-esterified FA (NEFA), milk FAs, milk beta-hydroxybutyrate (BHB) and milk acetone concentrations. Six ESI traits were considered and included: plasma NEFA concentration (mmol/l) either predicted by multiple linear regression including DIM, milk fat to protein ratio (FPR) and FAs C10:0, C14:0, C18:1 cis-9, C14:0 * C18:1 cis-9 (NEFAFA) or directly from milk MIR spectra (NEFAMIR), C18:1 cis-9 (g/100 ml milk), FPR, BHB (mmol/l milk) and acetone (mmol/l milk). The interval from calving to first insemination (ICF) was considered as the fertility trait. Data were analysed using linear mixed models. Heritability estimates varied during the first three lactation months from 0.13 to 0.19, 0.10 to 0.17, 0.09 to 0.14, 0.07 to 0.10, 0.13 to 0.17 and 0.13 to 0.18 for NEFAMIR, NEFAFA, C18:1 cis-9, FPR, milk BHB and acetone, respectively. Genetic correlations between all ESI traits and ICF were from 0.18 to 0.40 in the first lactation period (8 to 35 DIM), in general somewhat lower (0.03 to 0.43) in the second period (36 to 63 DIM) and decreased clearly (-0.02 to 0.19) in the third period (64 to 91 DIM). Our results indicate that genetic variation in energy status of cows in early lactation can be determined using MIR-predicted indicators. In addition, the markedly lower genetic correlation between ESI traits and fertility in the third lactation month indicated that energy status should be determined from the first test-day milk samples during the first 2 months of lactation.

A 1-year prospective study on the relationship between physical activity, markers of bone metabolism, and bone acquisition in peripubertal girls.

We conducted a 1-yr prospective study to evaluate the association between physical activity and biochemical markers of bone formation and resorption with bone mineral acquisition in 155 peripubertal Caucasian girls (51 gymnasts, 50 runners, and 54 nonathletic controls). The bone mineral density (BMD) of the femoral neck, the greater trochanter, and the lumbar spine were measured by dual energy x-ray absorptiometry. Serum biochemical markers of bone formation (osteocalcin, bone-specific alkaline phosphatase, amino-terminal propeptide of type I procollagen) and bone resorption (degradation product of C-terminal telopeptide of type I collagen) were measured. The 1-yr increase in BMD (adjusted for age, height, Tanner stage, BMD at baseline, and increases in height and weight) of the femoral neck was 0.037 g/cm2 x yr [95% confidence interval (CI), 0.019-0.051 g/cm2 x yr), and that of the greater trochanter was 0.020 g/cm2 x yr (95% CI, 0.003-0.039 g/cm2 x yr) greater in gymnasts than in controls. The corresponding figures for gymnasts compared with runners were 0.038 g/cm2 x yr (95% CI, 0.009-0.041 g/cm2 x yr) and 0.033 g/cm2 x yr (95% CI, 0.006 to 0.043 g/cm2 x yr). The figures for the lumbar spine did not differ significantly between study groups. The baseline serum concentrations of formation markers and resorption marker accounted for 2.3-12.8% (P < 0.05) of the variation in the 1-yr increase in BMD at the femoral neck and lumbar spine. However, there was no significant difference between the levels of adjusted baseline bone turnover markers of the gymnasts, runners, and controls. The present data add considerable support to the argument that high impact mechanical loading is extremely important and beneficial for the acquisition of BMD of the hip during peripubertal years. Our results indicate also that a high rate of bone turnover, reflected as elevated bone markers, is only weakly associated with the 1-yr bone gain in peripubertal girls.

Reduced mildly oxidized LDL in young female athletes.

We investigated the effect of physical activity and sports participation on LDL oxidation in vivo and on lipid risk factors in 183 teenage girls (9-15 years): 64 gymnasts, 61 runners, and 58 controls. Oxidized LDL was measured as baseline levels of conjugated dienes in LDL lipids (ox-LDL). The gymnasts had a 15% lower ratio of LDL conjugated dienes to LDL cholesterol (ox-LDL:LDL ratio, P = 0.0052) compared to controls, and the difference persisted when the body mass index was included as a covariate (ANCOVA, P = 0.013). Also, the gymnasts had a 12% higher ratio of HDL cholesterol to total cholesterol than the controls (ANCOVA, P = 0.046). There were no differences in the other common lipid risk factors between the groups. The ox-LDL:LDL ratio correlated negatively with HDL cholesterol (r = -0.23, P=0.0021) and with physical activity METs (multiples of resting metabolic rate) (r = -0.21, P=0.0040). Our study strengthens the evidence that the atherogenic risk is influenced favourably by physical exercise and sporting activities as early as in adolescents. This risk reduction is associated with lower mildly oxidized LDL in adolescent girls.

Alpha-naphthyl acetate esterase activity in human foetal lymphocytes.

Human foetal mononuclear cells from thymus, spleen, liver, bone marrow and peripheral blood at 8-24 weeks of gestation were examined for cytochemical evidence of acid alpha-naphthyl acetate esterase (ANAE) activity. The focal brownish-red ANAE reaction product (T cell staining pattern) was observed in counterstained cytocentrifuged cell smears in the cytoplasm. ANAE-positive lymphoid cells were first observed in the thymus at 9 weeks of gestation. A gradual increase in frequency of ANAE-positive cells in foetal thymus was observed, from about 10% at 14-15 weeks to about 20% at 22-24 weeks of gestation. By 14 weeks of foetal age, spleen and liver contained a few ANAE-positive cells and after 15 weeks of gestation consistent occurrence of ANAE-positive cells was observed in foetal bone marrow and peripheral blood. These results demonstrate that ANAE-positive lymphocytes first appear in the foetal thymus and are subsequently found in the foetal liver, spleen, bone marrow and peripheral blood.

Is there a sex difference in the association of plasma insulin level and insulin sensitivity with serum lipids and lipoproteins?

Previous studies on the relationship between the plasma insulin level, insulin sensitivity (SI), serum lipids, and lipoproteins have been performed predominantly in men. Therefore, we investigated whether there is a sex difference in the association of insulin level during an oral glucose tolerance test and SI with lipids and lipoproteins among normoglycemic men and women aged 53 to 61 years. SI was determined by the minimal model from the frequently sampled intravenous glucose tolerance test (IVGTT). There were no correlations between total cholesterol or low-density lipoprotein (LDL) cholesterol and insulin level or SI. High-density lipoprotein (HDL) cholesterol correlated inversely with fasting insulin (r = -.26, P < .05 in men; r = -.29, P < .01 in women) and 2-hour insulin (r = -.31, P < .01 in men; r = -.39, P < .001 in women) and positively with SI (r = .28, P = .05 in men; r = .43, P < .001 in women). Total and very-low-density lipoprotein (VLDL) triglycerides correlated positively with fasting insulin (r = .43, P < .001 in men; r = .42, P < .001 in women) and 2-hour insulin (r = .50, P < .001 in men; r = .31, P < .01 in women) and inversely with (r = -.49, P < .001 in men; r = -.40, P < .001 in women). In multiple regression analyses including age, body mass index (BMI), waist to hip ratio, 2-hour glucose, fasting or 2-hour insulin, and SI, only BMI was associated with HDL cholesterol level in men.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum albumin and colorectal cancer risk.

OBJECTIVE: To study the relationship between serum albumin and colorectal cancer occurrence. DESIGN: A case-control study nested within a cohort followed from 1968 to 1991. SUBJECTS AND METHODS: The albumin concentration was determined from serum samples stored at -20 degrees C at baseline in 177 incident colorectal cancer cases and 288 controls matched for sex, age and study region. RESULTS: An elevated risk was present of cancer of the left, distal colon at high serum albumin concentrations. No significant association was observed for the right, proximal colon or the rectum. The relative risks of cancer of the distal and proximal colon among individuals in the highest and lowest quartiles of serum albumin were 17.03 (95% confidence interval 1.48-195) and 0.77 (95% confidence interval 0. 19-3.13), respectively. CONCLUSIONS: The present study lends support to the hypothesis that some dietary factor associated with serum albumin may be a risk factor for distal colon cancer.

Tumour markers and screening for gastrointestinal cancer: a follow up study in Finland.

BACKGROUND: Screening for gastrointestinal cancer is based mainly on a barium contrast x ray method and on identification of occult blood in stools. The methods are relatively expensive, not always acceptable to the participants, and there is only limited evidence of their effectiveness in reducing the mortality from gastrointestinal cancer. OBJECTIVE: To investigate the validity of several tumour markers as a screening test for stomach cancer and for colorectal cancer. METHODS: A registry of 36,265 serum samples drawn during 1968-72 was linked to the cancer registry. Follow up was during 1968-80 when 94 stomach cancers and 95 colorectal cancers were identified. One to two matched case-control design was applied, and the concentrations of CEA, CA 19-9, CA 50, and TATI were assessed. RESULTS: The mean values of the markers between the cases and the controls were almost the same for the total material. Case-control differences were found between the 11 sets with an interval of less than one year between drawing the sample and diagnosis of the cancer. The highest validity was found in CEA for colorectal cancer (specificity 91%; sensitivity 64%) and in CA 19-9 for stomach cancer (specificity 74%; sensitivity 73%). CONCLUSION: CEA, CA 19-9, CA 50, or TATI are not valid screening tests. Case-control differences were found with a potential one year screening interval, but they were not large enough for sufficient validity.

Ovarian hormone status, life-style factors, and markers of bone metabolism in women aged 50 years.

Fifty-year-old women (n = 519) attending a health examination were divided by their ovarian hormone status into four groups: premenopausal, perimenopausal, postmenopausal without ovarian hormone replacement therapy (HRT), and postmenopausal with HRT. Information on lifestyle factors was obtained with interviews and questionnaires. Bone mineral density at the calcaneus was assessed with single-photon absorptiometry, and several serum and urine markers of bone metabolism were measured. Postmenopausal women without HRT had significantly higher levels of fasting serum alkaline phosphatase, osteocalcin, total and ionized calcium, phosphate, and fasting urinary hydroxyproline than those in the three other study groups. No difference was found in bone mineral density between the premenopausal and postmenopausal groups. Postmenopausal women without HRT showed a marked correlation between serum osteocalcin and urine hydroxyproline. Both markers showed significant correlations with serum calcium, phosphate, and alkaline phosphatase. Multivariate analyses showed a statistically significant association of ovarian hormone status and body mass index with most measured markers of bone metabolism. The association between alcohol consumption and serum osteocalcin was highly significant. Cigarette smoking was associated with levels of serum alkaline phosphatase and total and ionized calcium. A weak association was found between coffee drinking and serum alkaline phosphatase.

Sympatho-adrenal activity and the clinical sedative effect of detomidine in horses.

Thirty-nine horses were given detomidine 10 micrograms/kg bodyweight (bwt) intravenously (iv) and six horses were given a corresponding volume of saline solution before minor procedures. Venous blood samples were collected for catecholamine and cortisol determination immediately before the detomidine or saline injection and 20 mins after it. The behaviour of the horse at the time of detomidine injection and the extent of sedation were evaluated. Plasma adrenaline, noradrenaline and the catecholamine metabolites, 3,4-dihydroxyphenylglycol (DHPG) and 3,4-dihydroxyphenylacetic acid (DOPAC), and cortisol concentrations decreased significantly after administration of detomidine, but they remained unchanged in the control group. A high plasma adrenaline concentration before detomidine injection, indicative of a high level of stress, seemed to correspond with a reduced sedative effect of detomidine. The extent of sedation also was related to the concentrations of adrenaline, noradrenaline and DHPG in plasma after the detomidine injection. The reductions in the plasma catecholamine concentrations may have been caused, in part, by decreased secretion of catecholamines due to the sedative effects of detomidine; but detomidine also influences the plasma catecholamine concentrations by reducing directly sympatho-adrenal activity.

Comparison of eight commercial on-site screening devices for drugs-of-abuse testing.

Eight commercially available on-site drugs-of-abuse testing devices for detecting cannabinoids (THC-COOH), opiates (OPI), cocaine (COC), amphetamines (AMP), metamphetamines (MET) and benzodiazepines (BZO) were evaluated. The used urine specimens suspected of being drug positive were all confirmed by gas chromatographic/mass spectrometry (GC/MS). For AMP and MET, sensitivities varied between 83 and 95% and specificities between 98 and 100%. Correspondingly, sensitivities between 88 and 98% and specificities between 95 and 100% were observed for THC-COOH. For BZO, sensitivities varied between 91 and 97% and specificities between 97 and 100%. Only a few confirmed positive samples were available for OPI and COC, the sensitivities being between 83 and 100% and 100%, respectively. On-site devices did not always find extremely high drug concentrations. False-negative results were found with AMP in particular. Pholcodine, commonly used as medicine, was observed to give false-positive results with most of the devices and was not, however, included in given cross-reactivity tables. It was found that the devices differed markedly with respect to interpretation of test results and to ease of test performance, leading to the suggestion that different criteria for selecting on-site devices for either emergency laboratories in hospitals or for police stations and prisons should be used. Since the overall specificity of any of the devices was not 100% and false positives were identified, we found it important to confirm any positive screening test result.

Problems with PEG-based precipitation methods in the determination of HDL2- and HDL3-cholesterol.

In this study a comparison of two polyethylene glycol (PEG)-based precipitation methods, that is, one using PEG-6000/DS-15000 and the other using two different concentrations of PEG-20000 are presented. The total HDL-cholesterol values measured with the PEG-6000 procedure were higher (13%) than those measured with PEG-20000 (r = 0.91) in 16 pooled serum samples tested. The HDL2- and HDL3-cholesterol values measured with the two methods differed markedly from each other in spite of the moderate correlation (HDL2: r = 0.74; HDL3: r = 0.26) observed. The advantage of the PEG-20000 method as compared with the other method was its simplicity and rapidity. The separation of HDL2/HDL3 is more or less arbitrary in both methods used and further studies are needed for the estimation of optimal conditions for subclass separation.

Serum concentrations of apolipoprotein A-I, apolipoprotein B, and lipoprotein(a) in a population sample.

Serum concentrations of apolipoprotein (apo) A-I, apo B, and lipoprotein(a) [Lp(a)] were studied with respect to age and sex in a Finnish population sample of 575 subjects (286 men and 289 women), ages 27-67 years. Apo A-I and apo B were measured with an immunoturbidimetric method calibrated against WHO International Reference Materials. Lp(a) was measured by RIA. Apo A-I and apo B concentrations were almost normally distributed (apo A-I: mean 1.38 g/L vs median 1.34 g/L for men, and 1.58 g/L vs 1.55 g/L for women; apo B: mean 1.21 g/L vs median 1.20 g/L for men and 1.09 g/L vs 1.05 g/L for women). The distribution of Lp(a) was remarkably skewed (mean 190 mg/L vs median 86 mg/L for men, and 169 mg/L vs 85 mg/L for women). The 95% intervals for apo A-I were 1.09-1.84 g/L for men and 1.06-2.28 g/L for women; for apo B, they were 0.63-1.88 g/L and 0.56-1.82 g/L, respectively. Apo A-I concentrations appeared to be unrelated to age, whereas apo B and Lp(a) concentrations were age-dependent. Cutoff values based on the 90th percentile for apo B and the 10th percentile for apo A-I are proposed for identifying subjects at increased risk of coronary heart disease.

Bone turnover markers during lactation, postpartum amenorrhea and resumption of menses.

Changes in bone turnover, and consequent bone loss and recovery during lactation and the postweaning period, are likely modulated by varying estrogen levels inherent in these time periods. To address this question we measured serum biochemical markers of bone formation (bone-specific alkaline phosphatase, amino-terminal propeptide of type I procollagen, osteocalcin), of bone resorption (type I collagen carboxy-terminal telopeptide), and serum female sex hormones (estradiol, luteinizing hormone and follicle-stimulating hormone) in 32 healthy mothers prospectively after delivery, 3 months postpartum, after postpartum amenorrhea and 1 year after resumption of menses. During postpartum amenorrhea (mean 5.7, SD 2.9 months) bone mineral density decreased significantly, some 2% at the lumbar spine and some 3% at the femoral neck, but subsequently recovered completely at the former site and partially at the latter. Bone turnover marker levels were elevated at parturition and still at the end of postpartum amenorrhea. Subsequent to parturition the bone resorption marker level showed a decreasing trend while the formation marker levels continued increasing, and eventually coincided with the resorption level within the very first months postpartum. Both lactation and hormonal status modulated bone turnover marker levels. Maternal age was positively associated with increased bone turnover. Interestingly, higher parity and longer history of previous lactation were associated with lower bone turnover marker levels postpartum as compared with previously nulliparous women of the same age. The regression models explained typically some 20-30% of the variability in the bone turnover marker levels. The dynamic pattern in bone turnover is dissimilar to that occurring at menopause and it indicates that the bone loss most likely occurs in the beginning of postpartum period. It also seems that estrogen has a specific influence on bone turnover only during the first months of lactation.