IgE in unselected like-sexed monozygotic and dizygotic twins at birth and at 6 to 9 years of age: high but dissimilar genetic influence on IgE levels

BACKGROUND: IgE is a major determinant of allergic disease. Twin analysis of serum levels of IgE has been carried out previously in children and adults with heritability estimates of 30% to 70% on the basis of ANOVA. OBJECTIVE: This study included the analysis of serum IgE in a population of 126 twins, 27 monozygotic pairs and 36 dizygotic pairs, studied at birth (cord blood [CB] IgE) and consecutively at the age of 6 to 9 years of age (serum IgE). METHODS: IgE was determined by means of RIA. ANOVA, correlation analysis, and structural equation modeling by maximal likelihood analysis was used for genetic analysis. RESULTS: Structural equation modeling by maximal likelihood analysis showed the best-fitting model to be the AE model (A for additive genetic variance and E for environmental variance) both at birth and later in childhood. The estimated heritability was 0.92 (95% CI, 0.84-0.95) for CB IgE and 0.78 (95% CI, 0.60-0.87) for serum IgE. The correlation between CB IgE and serum IgE was 0.04. CONCLUSIONS: The study demonstrated a higher genetic dependency of serum IgE than previously recognized. The low correlation between the IgE levels at birth and later in childhood suggested that different effector mechanisms may be operating at different ages.     

Electrophysiological indices of processing aesthetics: Spontaneous or intentional processes?

Processes underlying aesthetic appreciation of formal graphic black and white patterns were investigated. In previous EEG studies on aesthetic and symmetry judgments, an early frontocentral negativity has been observed for not beautiful judgments, and interpreted as reflecting an impression formation. In addition, a lateralized late positivity, more pronounced in the aesthetic than in the symmetry judgment task, has been interpreted as reflecting evaluative categorization; and a sustained posterior negativity for not symmetric judgments, has been interpreted as reflecting a prolonged symmetry analysis. Here, we investigated whether these processes occur spontaneously, i.e. independent of an aesthetics task instruction or a judgment task demand. Participants were randomly assigned to two group conditions. In the Viewing condition, participants were instructed to view graphic patterns, and to detect a probe. In the Contemplation condition, participants were instructed to contemplate the beauty of the patterns, and to detect a probe. No aesthetics-related response was required in either condition. ERP results suggest that symmetry analysis occurred spontaneously. Evaluative categorization, reflected by a late positivity, required an aesthetics instruction and did not occur spontaneously. This process was elicited without an overt aesthetic judgment. An early frontocentral negativity for not beautiful patterns, interpreted as reflecting impression formation, did not occur (in contrast to previous studies that required an overt aesthetic judgment). Given the present data, aesthetic appreciation of graphic patterns requires different sub-processes. Aesthetic contemplation is reflected by a lateralized late positivity, whilst an aesthetic judgment is additionally reflected by an early frontocentral negativity. Aesthetic appreciation of beauty appears to require intention and is not spontaneous in character.     

Multicenter analytical evaluation of an automated immunoassay for total plasma homocysteine

A fully automated immunoassay for total plasma homocysteine assay was evaluated at four centers. To measure total homocysteine, oxidized forms of homocysteine in serum and plasma were reduced by dithiothreitol and assayed by a competitive fluorescence polarization technique. The assay had within-run precision from 0.9 to 3.0% and total precision from 2.8 to 4.1% for control materials with homocysteine concentrations of approximately 7, 12.5, and 25 micromol/L, a sensitivity of 0.35 micromol/L, good parallelism upon dilution, and analytical recovery ranging from 97.4 to 103.8%. The immunoassay correlated with four different HPLC assays for homocysteine, yielding a slope of 0.98, an intercept of -0.19 micromol/L, and a correlation coefficient of 0.966 for 440 paired samples. The reference range, determined with plasma samples from 609 males and 600 females, yielded a mean of 9.17+/-2.86 micromol/L, with a central 95% range of 4.78-15.43 micromol/L. The immunoassay is a suitable alternative to HPLC and may be useful in screening persons with high risk of coronary artery disease.     

Changes in Lower Leg Anterior Compartment Pressure Before,During, and After Creatine Supplementation

OBJECTIVE: To determine if 35 days of creatine supplementation (Cr) followed by 28 days of no supplementation altered lower leg anterior compartment pressure (ACP) at rest and after exercise. DESIGN AND SETTING: Subjects were divided into 2 treatment groups: (1) high dose (0.3 g Cr.kg body mass(-1).d(-1) for 7 days followed by 0.03 g Cr.kg body mass(-1).d(-1) for 28 days), or (2) low dose (0.03 g Cr.kg body mass(-1).d(-1) for 35 days). After 35 days, supplementation was terminated, and no Cr was ingested for 28 days. SUBJECTS: Sixteen physically active, healthy, college-aged males (O(2)max = 47.6 +/- 5.1 mL.kg(-1).min(-1)). MEASUREMENTS: At baseline, 7 days and 35 days of supplementation, and 28 days postsupplementation, ACP was measured preexercise and immediately, 1, 5, 10, and 15 minutes postexercise after a treadmill run at 80% O(2)max. RESULTS: For ACP, there was no significant group-by-time interaction, but there was a significant time effect for group when the data were combined. ACP was significantly increased at preexercise, immediately postexercise, and 1, 5, and 10 minutes from baseline to 7 days. ACP remained significantly elevated from baseline at 35 days immediately postexercise and 1 minute postexercise. After 28 days of no supplementation, ACP began to return to presupplementation levels, with only the 1-minute postexercise measurement significantly elevated from baseline. CONCLUSIONS: Creatine supplementation increased ACP at rest and after exercise, and ACP began to return to normal after 28 days of no supplementation.     

Long QT syndrome with a high mortality rate caused by a novel G572R missense mutation in KCNH2

In a four-generation family with long QT syndrome, syncopes and torsades de pointes ventricular tachycardia (TdP) were elicited by abrupt awakening in the early morning hours. The syndrome was associated with a novel KCNH2 missense mutation, G572R, causing the substitution of a glycine residue at position 572, at the end of the S5 transmembrane segment of the HERG K(+)-channel, with an arginine residue. This segment is involved in the channel pore and the mutation may cause a reduction in the rapidly activating delayed rectifier K+ current (Ikr), or changed gating properties of the ion channel, leading to prolonged cardiac repolarization. The electrocardiograms of affected persons showed prolonged QT interval and notched T waves. Despite treatment with atenolol, 200 mg twice daily, the proband still experienced TdP episodes. Three untreated relatives of the proband died suddenly, and unexpectedly, at 18, 32, and 57 years of age. The G572R mutation is thus associated with a high mortality rate, and the clinical presentation illustrates that some mutations may not be controllable by just beta-blockade.     

Effect of the 21-aminosteroid,U-74389F,on hyperoxic lung injury in rats

Hyperoxia (>95% oxygen) in rats caused an increase in lung weight and an accumulation of fluid in the thorax. The mean lung wet weight of air-breathing controls at 60 h was 1.2±0.01 g, and that of vehicle-treated, oxygen-exposed animals was 2.45±0.05 g. Treatment with the 21-aminosteroid U-74389F, 3, 10, and 30 mg/kg twice daily throughout oxygen exposure, produced 8, 42, and 18% inhibition of the oxygen-induced increase in lung weight, respectively. However, U-74389F did not inhibit the hyperoxia-induced accumulation of neutrophils in bronchoalveolar lavage fluid.

No pleural fluid could be aspirated from the thorax of air-breathing controls. The volume of pleural fluid in oxygen-exposed, vehicle-treated animals and animals treated with 3, 10, and 30 mg/kg U-74389F b.i.d. was 6.5±0.9, 2.6±0.6, 0.8±0.3, and 1.3±0.5 ml, respectively.

U-74389F or its biologs are of potential value for the treatment of lung diseases in which oxidant damage has been implicated.

     

Low-Dose ATG/GCSF in Established Type 1 Diabetes: A Five-Year Follow-up Report

Previously, we demonstrated low-dose antithymocyte globulin (ATG) and granulocyte colony-stimulating factor (GCSF) immunotherapy preserved C-peptide for 2 years in a pilot study of patients with established type 1 diabetes (n = 25). Here, we evaluated the long-term outcomes of ATG/GCSF in study participants with 5 years of available follow-up data (n = 15). The primary end point was area under the curve (AUC) C-peptide during a 2-h mixed-meal tolerance test. After 5 years, there were no statistically significant differences in AUC C-peptide when comparing those who received ATG/GCSF versus placebo (P = 0.41). A modeling framework based on mean trajectories in C-peptide AUC over 5 years, accounting for differing trends between groups, was applied to recategorize responders (n = 9) and nonresponders (n = 7). ATG/GCSF reponders demonstrated nearly unchanged HbA_1c over 5 years (mean [95% CI] adjusted change 0.29% [–0.69%, 1.27%]), but the study was not powered for comparisons against nonresponders 1.75% (–0.57%, 4.06%) or placebo recipients 1.44% (0.21%, 2.66%). These data underscore the importance of long-term follow-up in previous and ongoing phase 2 trials of low-dose ATG in recent-onset type 1 diabetes.     

Mixed solvent exposure and hearing impairment: an epidemiological study of 3284 men. The Copenhagen male study

Animal experiments and human studies have indicated an effecton auditory functions from exposure to organic solvents. Inthis study the relationship between self-assessed hearing problemsand occupational exposure to solvents was investigated in across-sectional design with 3284 participating men aged 53–74years. Exposure to solvents for five years or more resultedin an adjusted relative risk (RR) for hearing impairment of1.4 (95 per cent Cl: 1.1–1.9) in men without occupationalexposure to noise. Factors adjusted for were age, noise traumas,chronic middle ear infection and family history of hearing impairment.The prevalence of hearing impairment in men not exposed to organicsolvents was 24 per cent and the attributable risk from solventexposure was 9.6 per cent. Exposure for less than five yearshad no effect on hearing capacity. Occupational exposure tonoise for five years or more had an effect twice that of solvents,RR: 1.9 (95 per cent Cl: 1.7–2.1). In men exposed to bothsolvents and noise the effect of the latter dominated and noadditional effect from solvents was found. A subsample of 51men was examined with pure tone audiometry and 20 of 21 menwho reported abnormal hearing also fulfilled an audiometriccriterion for hearing impairment. In conclusion a damaging effecton hearing ability from long-term solvent exposure was foundin the present study. The relative effect was moderate but witha high background frequency of hearing problems in the unexposedsample the absolute effect, ie attributable risk, was considerableand of both clinical and preventive importance.     

Development of chicken antibodies to bovine interferon alpha

We have developed chicken polyclonal antibody to bovine interferon alpha (IFNalpha). Five hundred microg of recombinant bovine IFNalpha suspended with complete Freund's adjuvant was used in the first immunization round. A suspension of the same amount of IFNalpha and incomplete Freund's adjuvant was used for all subsequent boosters. The antibody was purified from egg yolks using polyethylene glycol precipitation. The first reactive antibody appeared several weeks after the first immunization. The antibody is specific for IFNalpha in immunoblotting, it is also useful in ELISA and immunohistochemistry. This method provides a fast, cheap and efficient alternative to development of monoclonal antibodies to conserved mammalian antigens.     

Prostatic central zone volume, lower urinary tract symptom severity and peak urinary flow rates in community dwelling men

PURPOSE: Previous studies have suggested that central zone prostatic volume may be more strongly correlated with lower urinary tract symptom severity and peak urinary flow rates than total prostatic volume. We determine whether prostatic central zone volume and central zone index volume correlate better with these measures than total prostate volume in an age stratified, community based random sample of healthy white men. MATERIALS AND METHODS: A cohort of 474 men were randomly selected from the 2,115 community dwelling men, 40 to 79 years old, who participated in the Olmsted County study of urinary symptoms and health status among men. All men had undergone transrectal ultrasound of the prostate. The total prostate and hypoechoic central zone volumes were caliper measured by 1 operator on static ultrasounds from baseline. Volumes were calculated with the prolate ellipsoid formula. The operator was blinded to clinical information and outcome. The associations between total prostate volume and central zone index (central zone volume/total volume), and American Urological Association (AUA) symptom index and peak urinary flow rates, respectively, were quantified with the Spearman rank correlation coefficient and least squares regression models. RESULTS: There was a moderately strong correlation between patient age and central zone volume (rs 0.54, p <0.001), total prostate volume (rs 0.45, p <0.001) and central zone index (rs 0.38, p <0.001). The AUA symptom index and peak flow rates correlated less strongly with central zone volume (rs 0.17, p = 0.001 and rs -0.20, p <0.001, respectively) and total volume (rs 0.16, p <0.001 and rs -0.16, p <0.001, respectively). Central zone index weakly correlated with AUA symptom index (rs 0.08, p = 0.103) and peak urinary flow rate (rs -0.08, p = 0.0823). In regression models predicting AUA symptom index and peak flow rates central zone volume added little information after accounting for age and total prostatic volume in predicting AUA symptom index (p = 0.55) and peak flow rate (p = 0.84). CONCLUSIONS: Central zone volume measured from static images optimized for total prostate volume no more closely correlated with lower urinary tract symptom severity or peak urinary flow rates than total prostate volume. Thus, the potentially greater imprecision in measuring central zone volume may not be offset by gains in strength of association with lower urinary tract symptom severity or peak urinary flow rates.