Hydrothermal 15N15N abundances constrain the origins of mantle nitrogen.

Nitrogen is the main constituent of the Earth's atmosphere, but its provenance in the Earth's mantle remains uncertain. The relative contribution of primordial nitrogen inherited during the Earth's accretion versus that subducted from the Earth's surface is unclear1-6. Here we show that the mantle may have retained remnants of such primordial nitrogen. We use the rare 15N15N isotopologue of N2 as a new tracer of air contamination in volcanic gas effusions. By constraining air contamination in gases from Iceland, Eifel (Germany) and Yellowstone (USA), we derive estimates of mantle δ15N (the fractional difference in 15N/14N from air), N2/36Ar and N2/3He. Our results show that negative δ15N values observed in gases, previously regarded as indicating a mantle origin for nitrogen7-10, in fact represent dominantly air-derived N2 that experienced 15N/14N fractionation in hydrothermal systems. Using two-component mixing models to correct for this effect, the 15N15N data allow extrapolations that characterize mantle endmember δ15N, N2/36Ar and N2/3He values. We show that the Eifel region has slightly increased δ15N and N2/36Ar values relative to estimates for the convective mantle provided by mid-ocean-ridge basalts11, consistent with subducted nitrogen being added to the mantle source. In contrast, we find that whereas the Yellowstone plume has δ15N values substantially greater than that of the convective mantle, resembling surface components12-15, its N2/36Ar and N2/3He ratios are indistinguishable from those of the convective mantle. This observation raises the possibility that the plume hosts a primordial component. We provide a test of the subduction hypothesis with a two-box model, describing the evolution of mantle and surface nitrogen through geological time. We show that the effect of subduction on the deep nitrogen cycle may be less important than has been suggested by previous investigations. We propose instead that high mid-ocean-ridge basalt and plume δ15N values may both be dominantly primordial features.

[Immunogenicity of vaccines against viral hepatitis A and B in the population above 40 years of age -- impact of risk factors]. / Imunogenita vakcín proti virovým hepatitidám A a B u osob starsích 40 let -- vliv rizikových faktoru.

UNLABELLED: The immune reaction following vaccination against viral hepatitis A (HAV) and viral hepatitis B (HBV) can be influenced by a variety of factors. Among the most important are age, gender and body weight. STUDY OBJECTIVE: This prospective randomized study compared immunogenicity of available vaccines against HAV and HBV infections in the population above 40 years of age and the impact of risk factors. MATERIAL AND METHODS: The vaccinated subjects were divided into 3 groups based on the vaccine used. Within each group, the subjects were equally distributed by age, gender and body weight. The vaccine was always applied intramuscularly in the deltoid. Group 1 was given the combined vaccine Twinrix (GSK) against HAV and HBV infections in the left deltoid; group 2 was vaccinated with the Havrix vaccine against HAV (GSK) in the right deltoid and with the Engerix-B vaccine against HBV (GSK) in the left deltoid; group 3 received the Vaqta vaccine against HAV (Sanofi Pasteur) in the right deltoid and the HB VAX PRO against HBV (Sanofi-Pasteur) in the left deltoid. RESULTS: The following anti-HBs seroprotectivity rates: 92%, 80% and 71%, and anti-HAV seropositivity rates: 97%, 99% and 99%, were observed at 1 month after the end of the complete vaccination in groups 1, 2 and 3, respectively. The anti-HBs seroprotectivity rate was statistically significantly higher in group 1. The anti-HAV seropositivity rates were comparable (did not significantly differ) in all three study groups. CONCLUSION: The impact of age was revealed: the immune response decreases with increasing age. The lowest immunogenicity of the vaccines against HAV and HBV infections was observed in subjects above 60 years of age. Males achieved lower geometric mean titres (GMT) of antibodies and lower seroprotectivity rates compared to females. The impact of body weight was also observed, with the obese subjects showing the lowest immune response. The anti-HBs reactivity was significantly influenced by the vaccine used. The combined vaccine against HAV and HBV infections (Twinrix) induced higher anti-HBs seroprotectivity and comparable anti-HAV seropositivity when compared with the other monovalent study vaccines in the population above 40 years of age.

Long-term protective effect of post-exposure Havrix administration during viral hepatitis Type A outbreaks.

Administration of human normal immunoglobulin (HNIG) post-exposure has been routinely used in Slovakia for outbreak control of hepatitis A, but requires deep intramuscular injection, provides only short-lived protection and is a human blood product. The protective effect of post-exposure administration of an inactivated hepatitis A vaccine was evaluated during 10 outbreaks in Slovakia. Direct contacts of confirmed hepatitis A cases received either: a single dose of hepatitis A vaccine (n = 2171) or immunoglobulin (HNIG, n = 3837). In the HNIG group the number of hepatitis A confirmed cases dropped within the first 7 weeks, however the decrease was not as rapid or as marked as that observed in the vaccinated group where the number of hepatitis A cases dropped within the first 4 weeks after vaccination. Among contacts, 67 cases of hepatitis A were detected during the maximum incubation period of 45 days: 16 cases (0.7%) in the vaccine group and 51 cases (1.3%) in the HNIG group (p < 0.05). After two and three years respectively, 50 and 39 volunteers who had previously received one dose of hepatitis A vaccine received a booster dose and anti-HAV antibodies were measured. Differences in anti-HAV antibody GMCs before and after the booster were statistically significant. The longer time interval (3 years instead of 2) between primary vaccination and booster administration did not seem to impact the magnitude of the booster response. The results of this study show that active post-exposure immunisation with only one dose of inactivated vaccine confers high and long-term protection and effectively controls viral hepatitis A outbreaks.

The local and intermediate range structures of the five amorphous ices at 80 K and ambient pressure: a Faber-Ziman and Bhatia-Thornton analysis.

Using isotope substitution neutron scattering data, we present a detailed structural analysis of the short and intermediate range structures of the five known forms of amorphous ice. Two of the lower density forms--amorphous solid water and hyperquenched glassy water--have a structure very similar to each other and to low density amorphous ice, a structure which closely resembles a disordered, tetrahedrally coordinated, fully hydrogen bonded network. High density and very high density amorphous ices retain this tetrahedral organization at short range, but show significant differences beyond about 3.1 A from a typical water oxygen. The first diffraction peak in all structures is seen to be solely a function of the intermolecular organization. The short range connectivity in the two higher density forms is more homogeneous, while the hydrogen site disorder in these forms is greater. The low Q behavior of the structure factors indicates no significant density or concentration fluctuations over the length scale probed. We conclude that these three latter forms of ice are structurally distinct. Finally, the x-ray structure factors for all five amorphous systems are calculated for comparison with other studies.

[Seroprevalence of antibodies against hepatitis A virus and hepatitis B virus in nonvaccinated adult population over 40 years of age]. / Séroprevalence protilátek proti viru hepatitidy A, viru hepatitidy B u nevakcinované dospelé populace starsí 40 let.

STUDY OBJECTIVE: To determine prevalence rates of antibodies against hepatitis A virus (HAV) and hepatitis B virus (HBV) in the general adult male and female population over 40 years of age with no history of viral hepatitis A (VHA) and viral hepatitis B (VHB) who have never been vaccinated against hepatitis and to assess the cost-effectiveness of the pre-vaccination serological screening. MATERIAL AND METHODS: In 2003-2004, a total of 972 persons of three age categories: 41-50 years, 51-60 years, 61 and more years, were screened. Persons with a history of VHA and/or VHB and those who had been vaccinated against hepatitis were not included in the study. The following four indicators were determined from a 5 ml specimen of whole venous blood by electrochemiluminiscence assay: total anti-HAV antibodies, total anti-HBc antibodies, anti-HBs antibodies and HBsAg, as the most suitable markers of experienced hepatitis or previous vaccination. RESULTS: The prevalence rates of anti-HAV antibodies were lower in females compared to males for all of the three age categories. These antibodies were detected in 16.8%, 52.9% and 77.5% of 41-50-year-olds, 51-60-year-olds and > or = 61-year-olds, respectively. The total prevalence rate for the three age groups was 61.6%. The anti-HBc antibody seroprevalence rates were 1.9%, 5.3% and 6.1%, respectively. CONCLUSION: The results show high prevalence of VHA in higher age groups. Such a high seroprevalence of antibodies in nonvaccinated persons with no history of viral hepatitis is suggestive of a very frequent incidence of asymptomatic infection. For this reason, the prevaccination screening of anti-HAV antibodies is cost-effective in the population over 50 years of age but is not justified in persons under 40 years of age. Prevaccination screening for anti-HBc antibodies appears not to be cost-effective regardless of age in view of their low prevalence in the Czech population.

Structures of high and low density amorphous ice by neutron diffraction.

Neutron diffraction with isotope substitution is used to determine the structures of high (HDA) and low (LDA) density amorphous ice. Both "phases" are fully hydrogen bonded, tetrahedral networks, with local order similarities between LDA and ice Ih, and HDA and liquid water. Moving from HDA, through liquid water and LDA to ice Ih, the second shell radial order increases at the expense of spatial order. This is linked to a fifth first neighbor "interstitial" that restricts the orientations of first shell waters. This "lynch pin" molecule which keeps the HDA structure intact has implications for the nature of the HDA-LDA transition that bear on the current metastable water debate.

Control of laser high-harmonic generation with counterpropagating light.

Relatively weak counterpropagating light is shown to disrupt the emission of laser high-harmonic generation. Harmonic orders ranging from the teens to the low thirties produced by a 30-femtosecond pulse in a narrow argon jet are "shut down" with a contrast as high as 2 orders of magnitude by a chirped 1-picosecond counterpropagating laser pulse (60 times less intense). Alternatively, under poor phase-matching conditions, the counterpropagating light boosts harmonic production by similar contrast through quasiphase matching where out-of-phase emission is suppressed.

Inverse correlation between IgG-antihinge region and antierythrocyte autoantibody in chronic benign and malignant cold agglutination.

Previous reports provided evidence of an immunosuppressive role of natural anti-F(ab')2 antibodies. If suppressive anti-F(ab')2 antibodies also regulated the autoantibody production in cold agglutination, one would expect high titers of anti-F(ab')2 to be associated with low titers of cold agglutinins. Indeed, our previous studies revealed an inverse correlation between IgG-anti-F(ab')2 and cold agglutinins. Many previous experiments focused on anti-F(ab')2 of an antiidiotypic nature. Recent epitope mapping showed that anti-F(ab')2 of healthy persons is not an antiidiotype but recognizes a hinge region sequence. We attempted to answer the question whether this IgG-antihinge antibody is responsible for the previously described association between anti-F(ab')2 and cold agglutinins. IgG-antihinge and IgG-anti-F(ab')2 antibody was determined and statistically analyzed in the serum of 334 patients with cold agglutination. Our experiments revealed a strong correlation between the concentrations of antihinge and the previously described anti-F(ab')2 antibody. The anti-F(ab')2 activity was competitively inhibited by a synthetic hinge peptide. Moreover, patients with high antihinge titers had low cold agglutinin titers, and vice versa. A stratification according to cold agglutinin specificity and disease etiology showed that the inverse correlation is present only in anti-I and anti-i patients suffering from monoclonal B-lymphocyte proliferation. In conclusion, our results confirm the correlation previously described for anti-F(ab')2 antibody and antierythrocyte autoantibody and define for the first time an association between an idiotype-independent anti-IgG autoantibody and cold agglutinin.

A natural IgA-anti-F(ab')2gamma autoantibody occurring in healthy individuals and kidney graft recipients recognizes an IgG1 hinge region epitope.

Natural anti-IgG autoantibodies are found both in healthy individuals and in patients with certain diseases. One group of these Abs recognizes epitopes located in the F(ab')2 region of the IgG molecule. The immunoregulatory role of these Abs in healthy individuals, graft rejection, and disease was previously studied, usually with a focus on the characterization of anti-idiotypic Abs. In the present study, we characterize the epitope recognized by an anti-F(ab')2gamma autoantibody of the IgA isotype, which occurs in the serum of healthy individuals and kidney transplant recipients. The autoantibody described herein reacts strongly with F(ab')2gamma but only poorly with Fab(gamma) fragments, a binding pattern pointing to an epitope located in the hinge region. Using synthetic peptides, we identified a conformational epitope that overlaps the middle and part of the lower hinge region. Structural analyses of peptide constructs showed that a defined conformation of the first three residues of the lower hinge is required for a full expression of the epitope. Binding of IgA to the hinge region of IgG1 covers part of the physiologically active Fc domain, immobilizes the Fab arms, and thereby can be expected to exert immunoregulatory functions.

Family outbreak of alimentary tick-borne encephalitis in Slovakia associated with a natural focus of infection.

A family outbreak of tick-borne encephalitis involving 7 people, all of them hospitalized, was observed in the district of Povazská Bystrica (central Slovakia). The disease was associated with the drinking of unboiled goat milk and tick-borne encephalitis virus was recovered from Ixodes ricinus ticks collected from places where goats were grazing.

The natural human IgG anti-F(ab')2 antibody recognizes a conformational IgG1 hinge epitope.

Natural IgG anti-F(ab')2 Abs are part of the physiologic immune repertoire and have important immunoregulatory functions. Although previous work suggested that some of these Abs recognize epitopes located in the constant region of the F(ab')2 molecule, an exact epitope mapping has not been performed. We found that the anti-F(ab')2 Ab binds strongly to F(ab')2 but only weakly to Fab fragments. Fab fragments are lacking the core and lower hinge region. In our experiments, we show that the IgG anti-F(ab')2 Ab binds strongly to a synthetic double chain peptide (225-237/225'-237') comprising the core and lower hinge region of the human IgG1 molecule. In contrast, it binds only weakly to the same peptide in monomeric form (225-237) or to a short double chain hinge peptide (225-232/225'-232'). The double chain peptides comprise a cyclic region between the two cystine bridges and an exocyclic region. Previous nuclear magnetic resonance analyses showed that the cyclic portion of the short double chain hinge peptide adopts the same conformation as that found in the intact IgG1 molecule. The dichroic properties of the short and long double chain hinge peptides indicate that they have identical conformations in their cyclic regions, but have different conformations in their exocyclic regions. The conformational differences in the exocyclic regions explain the binding of the Ab to the long double chain hinge peptide and the lack of binding to the short one. The circular dichroism spectrum of the monomeric hinge peptide, which is not recognized by the Ab, is consistent with the absence of an ordered peptide structure. These findings lead us to conclude that the IgG anti-F(ab')2 Ab recognizes a conformational IgG1 hinge epitope.

Striking inverse correlation between IgG anti-F(ab')2 and autoantibody production in patients with cold agglutination.

Previous experiments showed that the physiologic IgG anti-F(ab')2 antibody suppresses the response of human autoreactive B cells. In the present study, we analyzed the IgG anti-F(ab')2 antibody in 293 patients with cold agglutination (CA). Their average IgG anti-F(ab')2 titer was not much different (211 +/- 8.3) from that of 279 healthy persons (195 +/- 6.7). However, CA patients with high anti-F(ab')2 titers had low CA autoantibody titers and vice versa (P = .0028; rho = -0.175). The stratification of patients according to the auto-antibody's specificity (anti-I, anti-i, anti-Pr) showed an inverse correlation between anti-F(ab')2 and CA in the anti-I group (P = .0057; rho = -0.180). Interestingly, the association was present only in patients whose disease was caused by noninfectious agents (P < .0001; rho = -0.423). The inverse correlation argues for an important role of the IgG anti-F(ab')2 in the regulation of autoantibody production in CA patients.

[Familial epidemics of tick-borne encephalitis in central Povazie]. / Rodinné epidémie kliest'ovej encefalitídy na strednom Povazí.

The authors describe two cases of tick-born encephalitis family epidemies in the natural focus of tick-born encephalitis (TbE) in the central part of Povazie in the district of Povazká Bystrica in the years 1989 and 1993. The infection took place due to consumption of raw goat milk. The best prevention against tick-born encephalitis is represented by vaccination. (Tab. 4, Ref. 6.)

Coexpression of CD4 and CD8 on mitogen-activated peripheral blood T cells from children with asthma: possible involvement of interleukin 4.

Mononuclear cells were isolated from the peripheral blood of 28 asthmatic and 18 healthy children aged 3 to 16 years. The cells were stimulated with phytohemagglutinin for 96 hours. Activated cells were detected microscopically by MTT staining. Expression of cell surface antigens was detected by indirect immune fluorescence using CD4-specific and CD8-specific monoclonal antibodies. Results indicate an enhanced expression of CD8 on mitogen-activated T cells from asthmatic children compared with cells from healthy controls (median 43% versus 27%). Further experiments revealed that CD8 is coexpressed with CD4 on activated lymphocytes. Coexpression is significantly enhanced with lymphocytes from asthmatic patients compared with normal controls. In addition, interleukin 4 is able to enhance this coexpression with lymphocytes from healthy but not asthmatic children suggesting an in vivo preactivation of lymphocytes from asthmatic patients with interleukin 4.

Frequency and transferability of trimethoprim and sulfonamide resistance in methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis.

A total of 374 Staphylococcus aureus and 126 Staphylococcus epidermidis strains from 14 countries were studied for their resistance to methicillin, trimethoprim (Tp) and sulfonamides (Su), alone and combined (TpSu). The frequency of resistance to Tp, Su and TpSu was much higher in methicillin-resistant S. epidermidis (MRSE) than in methicillin-resistant S. aureus (MRSA). Considerable differences, however, existed in isolates from different countries. Resistance to Tp, Su or TpSu in MRSA was low or absent in isolates from Switzerland, Spain, Japan, Mexico, Argentina and Chile, but high in isolates from Germany and Brazil. High level Tp resistance mostly resided on large plasmids. It could be transferred in 17 out of 97 strains. Su resistance was never cotransferred. Strains cured of their large Tp resistance plasmids remained Su-resistant, which suggests a chromosomal location of Su resistance.

Affinity of carumonam for penicillin-binding proteins.

Direct labeling experiments with [14C]-carumonam as well as competition binding assays with [14C]-benzylpenicillin and [14C]-ceftriaxone have demonstrated that penicillin-binding protein (PBP) 3 of Escherichia coli, Enterobacter cloacae and Pseudomonas aeruginosa has the highest affinity for carumonam (Ro 17-2301, AMA-1080). PBP 1a is inhibited only at significantly higher concentration whereas other PBPs display poor affinity. The IC50 values for binding to PBP 3 in E. coli and E. cloacae are in the range of the MIC-values (0.1-0.4 micrograms/ml), whereas those for P. aeruginosa are much lower than the MIC obtained in vitro. In accordance with the PBP affinity pattern observed for carumonam, filament formation resulted after exposure to concentrations greater than 1/2 MIC. Although PBP 1 and 2 of Staphylococcus aureus could be titrated with radioactive carumonam, very high concentrations were required and in line with the poor affinity for all four PBPs in S. aureus, this organism is resistant to carumonam.