Experimental vaccine induces Th1-driven immune responses and resistance to Neisseria gonorrhoeae infection in a murine model.

Female mice were immunized intravaginally with gonococcal outer membrane vesicles (OMVs) plus microencapsulated interleukin-12 (IL-12), and challenged using an established model of genital infection with Neisseria gonorrhoeae. Whereas sham-immunized and control animals cleared the infection in 10-13 days, those immunized with OMV plus IL-12 cleared infection with homologous gonococcal strains in 6-9 days. Significant protection was also seen after challenge with antigenically distinct strains of N. gonorrhoeae, and protective anamnestic immunity persisted for at least 6 months after immunization. Serum and vaginal immunoglobulin G (IgG) and IgA antibodies were generated against antigens expressed by homologous and heterologous strains. Iliac lymph node CD4+ T cells secreted interferon-γ (IFNγ), but not IL-4, in response to immunization, and produced IL-17 in response to challenge regardless of immunization. Antigens recognized by immunized mouse serum included several shared between gonococcal strains, including two identified by immunoproteomics approaches as elongation factor-Tu (EF-Tu) and PotF3. Experiments with immunodeficient mice showed that protective immunity depended upon IFNγ and B cells, presumably to generate antibodies. The results demonstrated that immunity to gonococcal infection can be induced by immunization with a nonliving gonococcal antigen, and suggest that efforts to develop a human vaccine should focus on strategies to generate type 1 T helper cell (Th1)-driven immune responses in the genital tract.

[Structural and morphological changes in the eyes of arterial hypertensive patients with and without anti-CCP-positive rheumatoid arthritis]. / Strukturelle und morphologische Veränderungen am Auge bei Patienten mit arterieller Hypertonie mit und ohne Anti-CCP-positiver rheumatoider Arthritis.

INTRODUCTION: To investigate the additive systemic inflammatory process of rheumatoid arthritis (RA) in arterial hypertension patients, structural and morphological changes of the retina and optic nerve head were assessed by modern topographic technologies. Similarities of underlying vascular mechanisms between RA and arterial hypertension are interesting and have not been researched in depth. The aim of this study is to evaluate changes of RA and arterial hypertension with the optic coherence topography (OCT) and Heidelberg retina tomography (HRT III), to validate RA changes in comparison to arterial hypertension only patients and, finally, if these methods are useful to detect the chronic inflammatory influence of the RA on the eye. METHODS: In this prospective study design, data of 18 patients with RA and arterial hypertension (55.3 ± 4.31 years old), positive for antibodies against cyclic citrullinated peptides, 21 patients with arterial hypertension (54.2 ± 4.18 years old) and 19 healthy subjects (53.1 ± 3.25 years old) were included. Intensive ophthalmologic and internistic screening tests were carried out in all subjects. All participants were investigated for the retinal nerve fiber layer (RNFL) and macula thickness with the OCT (Carl Zeiss AG Germany) and for stereometric parameters of the optic nerve head with the Heidelberg Retina Tomograph III (Heidelberg Engineering Germany). The pachymetry was conducted by the Orbscan II system (Bausch & Lomb). Statistical data were assessed by SPSS, v20.0. RESULTS: No significant differences were found in visual function, diastolic and systolic blood pressure. RNFL, and macular thickness (Stratus-OCT) were almost consistent between the groups and even the main stereometric parameters measured with HRT III showed no significant differences. CONCLUSION: Contrary to our study hypothesis no structural and morphological changes could be detected in patients with arterial hypertension without RA compared to healthy subjects. Furthermore, no RA-specific effects could be shown in comparison with the hypertension group. Thus, the used examination techniques are not suitable to prove the systemic inflammatory influence of RA on the eye.

The Vibrio harveyi GTPase CgtAV is essential and is associated with the 50S ribosomal subunit.

It was previously reported that unlike the other obg/cgtA GTPases, the Vibrio harveyi cgtAV is not essential. Here we show that cgtAV was not disrupted in these studies and is, in fact, essential for viability. Depletion of CgtAV did not result in cell elongation. CgtAV is associated with the large ribosomal particle. In light of our results, we predict that the V. harveyi CgtAV protein plays a similar essential role to that seen for Obg/CgtA proteins in other bacteria.

[Mathematical-technical model of passive and active vibrations of the basilar membrane]. / Eine mathematisch-technische Modellierung von passiven und aktiven Schwingungsformen der Basilarmembran.

On the basis of the physiological measurements made by v. Békésy and Johnstone, we developed a mathematical model to describe passive and active displacement patterns of the basilar membrane. Approximation of the model functions to the measured values is achieved with the aid of the linear least squares method. Using frequency mapping, the distribution of the basilar membrane displacement is presented in three-dimensional graphic form. The resulting application possibilities of this approach, for example, to electronic simulation of inner ear functions and speech processing systems, are discussed.

Rapid degradation of bacteriophage lambda O protein by ClpP/ClpX protease influences the lysis-versus-lysogenization decision of the phage under certain growth conditions of the host cells.

The initiator of bacteriophage lambda DNA replication, the O protein, is rapidly degraded in Escherichia coli by the ClpP/ClpX protease encoded by the host. Although the biochemical mechanism of this degradation has been investigated intensively, a physiological role for this process remained unknown since little effect of dysfunction of clpP and clpX genes on the lytic development of the phage was observed. Here we demonstrate that activities of clpP and clpX genes influence the lysis-versus-lysogenization decision of bacteriophage lambda under certain growth conditions of the host cells. This decision is influenced specifically by ClpP/ClpX-mediated O degradation and resultant inhibition of early lambda DNA replication because mutations in clpP and clpX genes have little effect on stability of other lambda proteins involved in the regulation of the phage developmental switch.

A Vibrio harveyi insertional mutant in the cgtA (obg, yhbZ) gene, whose homologues are present in diverse organisms ranging from bacteria to humans and are essential genes in many bacterial species.

The cgtA gene product is a member of the subfamily of small GTP-binding proteins that have been identified in diverse organisms ranging from bacteria to humans. In bacteria that sporulate or display another special developmental programme, this gene (referred to as cgtA, obg or yhbZ) appears to be involved in the regulation of these processes. However, this gene has also been found to be essential in all bacterial species investigated to date, although its role in bacteria that do not sporulate and do not undergo a specific development remains unknown. Here the authors characterize a Vibrio harveyi mutant bearing a transposon insertion into the cgtA gene. This mutant reveals a multiple phenotype: it grows more slowly than the wild-type strain in a rich medium; its growth is completely inhibited in minimal media; its survival in 3% NaCl is dramatically reduced; it is very sensitive to UV irradiation; it is more susceptible to mutation upon treatment with different mutagens; its luminescence is decreased; its quorum-sensing regulation is less effective than in the wild-type strain; and the elongated shape of the mutant cells may suggest problems with the regulation of cell division and/or DNA replication. These defects in diverse cellular processes found in the insertional cgtA mutant of V. harveyi indicate that in a bacterium that does not sporulate and does not display other special development programmes, the CgtA protein is involved in the regulation of many crucial biochemical reactions, possibly at the stage of signal transduction.

[Differential effect of bleomycin on squamous epithelium at various sites]. / Unterschiedliche Bleomycin-Wirkung auf Plattenepithel verschiedener Lokalisation.

By autoradiographic methods it was examined, whether a specific local effect on squamous epithelium can be proved in a animal model. For this purpose the proliferatory activity was considered in the epithelium of the murine tongue, of esophagus, of the skin in the area of foot and of tail as long as 72 hours after a single application of bleomycin. The result shows, that the proliferatory activity is impaired to a greater extent in the epithelium of the tongue and the esophagus in comparison on the squamous epithelium of foot and tail skin.

[Tissue specificity of the action of bleomycin. Autoradiographic studies]. / Gewebsspezifität der Bleomycinwirkung. Autoradiographische Untersuchungen.

The proliferative activity of different types of murine tissue up to 72 h after a single dose of bleomycin was studied via histoautoradiography to determine whether bleomycin has a tissue-specific effect. Bleomycin apparently not only has a general cytotoxic and/or cytostatic action, the strongest being on tissue with a high proliferation rate, but also, as a comparison of the effect of bleomycin on the proliferative activity of squamous epithelium (plantar region, tail, skin, esophagus, tongue) and of mucosal epithelium (stomach, ileum, colon) has indicated, the proliferative activity of squamous epithelium is impaired to a greater extent. This, therefore, distinguishes bleomycin from many other substances used in tumor therapy.

Five simultaneous steady states in a flipping two-compartment-system with optical antipodes.

The previously given systems-theoretic model for the synthesis of optical antipodes (AD and AL) in strongly asymmetric yield, which shows mono-bistable behaviour depending on the degree of "openess" of the chemical reaction system is reconsidered for two equal compartments (subscripts 1 and 2 on A) with coupling by diffusion. In this configuration three threshold values, j1, is less than j2 is less than j3, for the influx j of the common precursor substance appear. For j is less than j1 only one steady state (s.s.) with no optical activity (ADi = ALi, i-1;2) and equal distribution of the antipodes in both compartments (AD1 = AD2, AL1 = AL2) exists. For j is greater than j 1, this totally symmetric s.s. becomes unstable and a pair of s.s. with optical activity (AD1 is less than AL1, AD2 is less than AL2 or AD1 is greater than AL1, AD2 is greater than AL2) but no spatial asymmetry emerges (parallel flipping), i.e. both compartments be8have as a whole, showing a preponderance of either the D- or the L-form. For j is greater than j2 in addition two new s.s. are possible with antiparallel flipping (AD1 is less than AL1, AD2 is greater than AL2 or AD1 is greater than AL1, AD2 is less than AL2), i.e. in one compartment the D-form has the majority and in the other one the L-form, but these are stable only beyond a third threshold value j3. A third thinkable pair with no optical activity, but different sum concentrations in both cells, does not exist in this special circuitry, but can be obtained in a slightly changed arrangement. So for j is greater than j2, 5 different (4 stable, 1 unstable) s.s., exist for the same set of parameters, one of which is chosen by the system.