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A 48-year-old woman with a follicular, grade III, B-cell non-Hodgkin lymphoma developed clinical, immunopathological and histological features of paraneoplastic pemphigus. The skin symptoms flared after repeated cyclophosphamide infusions, and were preceded and accompanied by a progressive dyspnoea. Although the skin and oral mucosal disease went into remission with high-dose steroid and intravenous immunoglobulin therapy, the severe alveolitis led to death. Immunoblotting of human epidermal extracts showed that the patient's serum IgG reacted with the 210-kDa envoplakin, 190-kDa periplakin, as well as the recombinant protein of BP180 NC16a domain. IgG and IgA enzyme-linked immunosorbent assays for desmoglein 3 were positive, too. Indirect immunofluorescence studies on COS-7 cells transiently transfected with desmocollin 1-3 cDNAs showed that the patient's serum contained IgG and IgA antibodies to desmocollin 3 as well as IgG antibodies to desmocollin 2. Serum IgG and IgA strongly stained rat bronchial epithelium, corresponding to autoantibodies possibly involved in the pathomechanism of the severe lung disease. In this case, which was characterized by a mixed IgA/IgG antibody panel displaying known and unique antigenicity, the serious episodes of paraneoplastic pemphigus flared after cyclophosphamide treatment.

Mutations in genes keratin 5 (KRT5) and 14 (KRT14) encoding the basal type keratin intermediate filaments have been identified in epidermolysis bullosa simplex (EBS) families and are likely to cause skin fragility. Three novel keratin 14 mutations in cases from the Hungarian Epidermolysis Bullosa Centre are reported. In a 7-year-old boy with Dowling-Meara type EBS (DM-EBS), who had severe skin symptoms with extended herpetiform blisters, a novel amino acid substitution N123K in keratin 14 had been detected. A 26-year-old woman with mild DM-EBS with prominent palmoplantar hyperkeratosis and without active blister formation had a novel R125G mutation in keratin 14. In a 6-year-old girl, with Weber-Cockayne type EBS (WC-EBS) with palmoplantar blisters and moderate mental retardation, a novel V133L substitution was detected. Her pedigree showed autosomal dominant mode of inheritance; in the two other families, only the index patients were affected. The N123K and R125G mutations causing DM-EBS phenotypes are located within the helix initiation motif of the rod domain, whereas the very close V133L mutation underlying the WC-EBS phenotype is outside of this region. These novel amino acid substitutions provide further information for genotype–phenotype correlation in KRT14 mutations, and demonstrate the first molecular genetic data in EBS patients from Hungary.

Magyarország geopolitikai helyzetében a 20. században többször történt jelentős változás. Ezek a fordulópontok meghatározták a magyar katonai stratégia tartalmát is. A tanulmány azt vizsgálja, hogy a geopolitikai helyzet átalakulása hogyan hatott a katonai stratégia térszemléletére a trianoni békeszerződéstől napjainkig.

A 59-year-old male patient developed a necrotizing ulceration on the right shin. Both clinical and histopathologic examinations suggested pyoderma gangrenosum. After temporary improvement of skin symptoms under peroral glucocorticoid treatment, a hemorrhagic-purulent discharge started from the nose, he began to have fever, malaise, cough, and a chest X-ray revealed inflammation in the lung. Cerebral CT and MRI disclosed midline bone loss within the nasal septum and granulomatosus tissue masses protruding into the right orbit. The c-ANCA test was positive, serum IgA was elevated, and he had microhaematuria and proteinuria. In this severe case of Wegener's granulomatosis prolonged methylprednisone and cyclophosphamide treatment was initiated. Both the skin symptoms and the granulomatosus infiltrations resolved.

Congenital ichthyosiform erythroderma (CIE) belongs together with lamellar ichthyosis (LI) to the group of autosomal recessive congenital ichthyoses (ARCI). Mutations in the transglutaminase (TGase) 1 gene (TGM1) have been identified in several families with LI and in some families with CIE. We report a case of CIE with two new nonsense mutations: a C7780G transversion in exon 11 resulting in a premature stop codon at aminoacid residue Y503X and a C8533G transversion in exon 13 leading to a nonsense mutation at S669X. These mutations were also identified in a heterozygous pattern in the unaffected parents. These two termination-codons result in the translation of a truncated protein at the C-terminal end domain of the TGM 1 molecule. B.C1 monoclonal antibody failed to detect TGase 1 in the patient's skin sample, and TGase activity measured by monodansyl cadaverine-incorporation showed the reduced TGase activity at the distribution of TGase 1 in the epidermis.

Photooxidation of oxalic acid over TiO2 surface in the presence of silver ion was studied. Simultaneous deposition of silver and oxidation of oxalic acid were followed under irradiation of aqueous suspensions of pH 2.5–3.5. The rate of the reduction of Ag+ was increased by the progress of silver deposition until a considerable depletion of the silver ion in the liquid phase was achieved. Then it was slowed down when the transport of Ag+ from the bulk of the liquid phase to the surface of the semiconductor particle became the rate-determining process. It has been demonstrated that, after the completion of silver deposition, the small metal particles on TiO2 surface enhance the efficiency of the semiconductor by a factor of 5 for the photooxidation of oxalic acid.

The authors followed the frequency of fragrance contact sensitization in Hungary in a multicentre study in the years 1998 and 1999. A total of 3,604 patients were tested with fragrance mix (FM), and positive reactions were observed in 294 (8.2%). In 160 FM hypersensitive patients, the study was continued with patch testing of the mix constituents (cinnamic alcohol, cinnamic aldehyde, eugenol, amyl cinnamic aldehyde, hydroxycitronellal, geraniol, isoeugenol, oak moss absolute). Of the patients tested, 70.6% produced positive reactions to the constituents. FM contact sensitization was mainly observed in female patients (74.4%). The incidence of contact urticaria in FM hypersensitive patients was 6.1%. Simultaneous patch test trials of other environmental contact allergens, in both early and late evaluations, mainly confirmed hypersensitivity reactions to balsams. Female dominance of hypersensitivity reactions observed during testing the individual components of the mix was striking (82.4%). In positive skin reactions, cinnamic alcohol, isoeugenol and oak moss provoked skin symptoms most frequently. We also tested the 104 patients who produced negative reactions to FM with the constituent individual allergens, with 11.9% positive incidence. The clinical symptoms of the patients were above all manifest in the form of contact eczema, located on the hands, face, eyelids and axillae. With this study, the authors, members of the Hungarian Contact Dermatitis Research Group, call attention to one of the most frequent allergens in the environment.

Background A 42-year-old male patient suffering from the rare Comel–Netherton syndrome is reported, and the symptoms are discussed together with the results of light and electron microscopic examinations. Case report Our case presented peeling skin syndrome type B with spontaneous, lifelong skin shedding with underlying erythema; however, with more careful studies, the hidden features of Comel–Netherton syndrome were identified. Conclusion This is an example of a condition where there is no clear border between Comel–Netherton syndrome and peeling skin syndrome type B, lending credence to a close relationship between the two syndromes.

We have used a set of single-chain variable fragment antibodies (sc) genetically fused with an influenza hemagglutinin-derived peptide as a means to investigate the role of CR1 and CR2 in antigen presentation by B cells. When incubated with the B cell lymphoma 2PK3, peptide-containing sc specific for either CR1 or CR1/2 mediated activation of the hemagglutinin peptide-specific T cell line IP-12-7, as assessed by IL-2 production. Efficient presentation was dependent on the binding of the constructs to CR1/2, implying that receptor-mediated endocytosis is responsible for the effect. Cross-linkage of CR1/2 or CD19 by mAb did not increase the extent of T cell activation. However, when CR1/2 was co-ligated with the BCR--using either polyclonal goat anti-mouse IgG or recombinant protein LA--the antigen concentration required to activate T cells decreased by two orders of magnitude. Moreover, this enhancement was selective for the antigen included in these complexes and did not affect the presentation of a free peptide or of antigen bound to CR1/2 excluded from the complexes. These results suggest that B cells may bind various C3d-coated antigens at a time, but only the one which reacts with the BCR will be processed with high efficiency. This mechanism may ensure the specificity of cognate T cell help.

We have studied the effect of zinc ion on the uptake of histamine (HA) into cultured astroglial and cerebral endothelial cells and established that Zn2+ enhances the uptake of the amine dose-dependently and in remarkable extents by increasing the Vmax to about 3-fold (from 3.25 ± 0.42 to 8.50 ± 0.97 pmol/mg protein/min in astroglial cells) without altering the KM (0.20 ± 0.03 μM) significantly. The stimulatory effect of zinc ion showed strong sensitivity for VUF 8407, an inhibitory compound of astroglial and cerebral endothelial uptake of HA. In the presence of 20 μM VUF 8407 the zinc-enhanced uptake was reduced by about 50% in both cell types. Binding measurements revealed increased capacities of the zinc-exposed HA binding (Bmax= 0.41 ± 0.05 increased to 1.21 ± 0.16 pmol/mg protein in astroglial membranes and Bmax = 0.25 ± 0.03 enhanced to 1.05 ± 0.12 pmol/mg protein in cerebral endothelial membranes) but statistically unchanged affinity of the ligand for HA carrier (KD values calculated as 35.2 ± 3.4 nM and 45.1 ± 3.8 nM for astroglial bindings; whereas 25 ± 2.1 nM and 30 ± 2.6 nM for cerebral endothelial bindings of the amine). The compound VUF 8407 reduced the Bmax of zinc-exposed HA binding of astroglial membranes but did not modify the KD of the zinc-exposed membrane significantly. The ex vivo experiments confirmed our in vitro findings; an i.c.v. dose of 0.4 μmol/kg ZnSO4, 24 hr after the injection, enhanced the uptake of [3H]HA into dissociated hypothalamic and cerebellar cells to about 2- and 3-fold, respectively. Present data clearly showed that zinc exposures enhance the astroglial and the cerebral endothelial uptake of HA in vitro and it might be considered that zinc produces similar effects in vivo. Free zinc may participate in the regulation of the extraneuronal HA concentration and this metal ion (endogenous or exogenous) might be favored in the removal of the amine from the interstitial space especially in conditions with relatively high HA.

The reaction of acetylated alpha-allenic alcohols with LiBr in the presence of 1.5 mol % of Pd(OAc)(2) provides easy access to substituted (Z,E)-2-bromo-1,3-dienes in good yields with excellent diastereoselectivity. Both secondary and tertiary acetates as well as terminal and nonterminal allenes were studied to investigate the scope and the limitations of the reaction. A mechanism is proposed to clarify how a diastereomeric mixture of the starting compound is transformed into a single diastereomer of the product.

Five-coordinate complex formation of copper(II)–tetraphenylporphyrin (Cu(TPP)) and copper(II)–octaethylporphyrin (Cu(OEP)) have been studied in the presence of pyridine, 3-picoline and 4-picoline. Equilibrium constants in toluene were determined at various temperatures ranged between 10 and 60 °C from which thermodynamic parameters were determined. The entropy change is between −81 and −92 J mol −1 K −1 while the enthalpy values are also quite close to each other and range from −16 to −19 kJ mol −1 . Besides the above enumerated donors four other (acetonitrile, benzonitrile, 2-picoline and 2,6-lutidine) were used to quench the luminescent trip-multiplet manifold of the copper(II) porphyrins. These measurements were carried out at five different temperatures (20–60°C) by two different techniques: (1) steady state luminescence; and (2) laser flash photolysis. Thermodynamic parameters of the activated complexes were calculated: Δ S # ranges from −46 to −72 J mol −1 K −1 while Δ H ≠ changes is between 1.6 and 11.2 kJ mol −1 .

Background:Helicobacter pylori, the most important etiologic factor of gastritis and peptic ulcer, has recently been associated with several extradigestive diseases. Previous studies reported conflicting results on H. pylori eradication in chronic urticaria, in that some studies showed a benefit, while others found no effect. Methods: Peripheral blood mononuclear cells of 24 chronic urticaria patients (13 seropositive/11 seronegative for H. pylori) and 18 healthy controls (9 seropositive/9 seronegative) were stimulated with whole heat-inactivated H. pylori (8 × 105, 8 × 106 and 8 × 107 bacteria/well), phytohemagglutinin (2 µg/ml) and pokeweed mitogen (5 µg/ml). The proliferative response was determined by 3H-thymidine incorporation. Helicobacter-specific IgG antibody response was determined by ELISA. Results: There were significantly higher proliferative responses to various concentrations of whole heat-inactivated H. pylori antigen in 6- to 7-day cultures of peripheral blood mononuclear cells of chronic urticaria patients compared to healthy controls. We found a tendency to exhibit a higher proliferative response to either Helicobacter antigens or mitogens in seropositive compared to seronegative patients. Conclusion: Our results support the hypothesis that there is an increased lymphocyte reactivity in chronic urticaria, perhaps further enhanced by the presence of H. pylori which, therefore, may be involved as a trigger in the pathogenesis of chronic urticaria.

Electrosurgery and radiosurgery bear certain popularity in contemporary dentistry. Nevertheless, the inadequate treatment allocation may lead to tissue necrosis. A young female patient was referred to our department following root canal treatment (RCT) by radiosurgical device. Necrotised alveolar bone, lack of keratinized gingiva and increased tooth mobility were noticed. After considering all the treatment options, we attempted to keep the tooth. Therefore, the necrotised part of the alveolar process was removed and the gingival fringe was rejuvenated alongside root surface debridement. The tooth was then splinted with glass fibre reinforced composite and appropriate RCT was completed. After ten months of improvement periodontal reconstructive surgery with deproteinized bovine bone mineral and connective tissue graft was carried out. Substantial improvement was observed at the six month reassessment, including complete healing of the gingiva. The composite splint was then removed due to discontinued mobility. The tooth and the adjacent periodontium remained stable for seven years. Nevertheless, external root resorption was recently developed that was treated with glass ionomer cement filling and regenerative periodontal surgery using enamel matrix derivative (EMD). Ultimately, the tooth is still in place providing satisfactory function and aesthetics.

Five coordinate complex formation of zinc(II)–octaethylporphyrin (Zn(OEP)) and zinc(II)–tetraphenylporphyrin (Zn(TPP)) have been studied in the presence of seven systematically selected electron donor molecules. Stability constants in toluene were determined at various temperature ranged between 20 and 60°C by absorption and steady-state fluorescent measurements from which thermodynamic parameters were determined. Depending on the porphyrin and the axial ligand the entropy is changing between −127 and −61 J mol −1 K −1 while the enthalpy is ranging from −49 to −24 kJ mol −1 .

This contribution reviews recent studies devoted to understanding the mechanism of electron ejection in aqueous solutions of dicyanocuprate(I) in the presence of halide ions of high concentration using steady state and time resolved luminescence and absorption techniques. It has been demonstrated that electrons originate from two excited states: the lower energy level achieved by one-photon absorption, and the high energy state populated by biphotonic excitation.

Palladium(II)-catalyzed intramolecular 1,2-additions to allenes substituted with an internal nucleophile have been developed. Carboxylic acids, alcohols, N-substituted amides, and carbamates were used as internal nucleophiles in the palladium-catalyzed reaction, which afforded lactones, tetrahydropyrans, tetrahydrofurans, pyrrolidines, and oxazolidinones in good isolated yields. The reactions were performed in the presence of LiBr with Pd(OAc)2 as the catalyst. Two different reoxidants, p-benzoquinone or Cu(OAc)2, were used, the choice of oxidant being dependent on the substrate. The reaction proceeds through an external nucleophilic attack (Br-) on a (π-allene)palladium complex to produce a (π-allyl)palladium intermediate. Subsequent intramolecular attack by the second internal nucleophile gives the product. The intermediate (π-allyl)palladium complexes were isolated and characterized. The scope and limitation of the reaction were studied together with its mechanism and selectivity, under different react...

SummaryHistamine has been implicated as one of the mediators involved in regulation of proliferation in both normal and neoplastic tissues. Histidine decarboxylase, the only enzyme that catalyzes the formation of histamine from L-histidine, is an essential regulator of histamine levels. In this study, we investigated the gene and protein expression of histidine decarboxylase in melanoma. Reverse transcriptase polymerase chain reaction and in situ hybridization studies of WM-35, WM-983/B, HT-168, and M1 human melanoma cell lines both resulted in positive signals for histidine decarboxylase messenger RNA. A polyclonal chicken antibody was developed against human histidine decarboxylase and protein expression was confirmed by western blot analysis of the cell lysates, revealing a predominant immunoreactive band at approximately 54 kDa corresponding to monomeric histidine decarboxylase. Protein expression of histidine decarboxylase was also shown by flow cytometric analysis and strong punctate cytoplasmic staining of melanoma cell lines. Moreover, both primary and metastatic human melanoma tissues were brightly stained for histidine decarboxylase. When compared with the very weak or no reactions on cultivated human melanocytes both western blot and immunohistochemical studies showed much stronger histidine decarboxylase expression in melanoma cells. These findings suggest that expression of histidine decarboxylase is elevated in human melanoma.

In a 51-year-old female patient with intraepidermal neutrophilic IgA dermatosis (IEN) type of IgA pemphigus, circulating IgA, but not IgG, autoantibodies were detected to bind to the cell surface of the whole epidermis, being much stronger in the upper epidermis. In the patient's skin a heavy intraepidermal IgA staining was observed throughout the whole epidermis, accompanied by a weak IgG and a more prominent C3 staining. IgA from the patient's serum showed no reactivity either with epidermal proteins by immunoblot analysis, or with COS 7 cells transiently transfected with mammalian cell expression constructs containing full length human Dsc1, Dsc2 and Dsc3. Our patient's IgA specifically reacted with conformational epitopes of human desmoglein (Dsg) 1 but not Dsg 3, when studied in a previously established, here for IgA antibody detection modified enzyme-linked immunoabsorbent assay (ELISA) of baculovirus expression system. The immunoreactivity against keratinocyte cell surface was completely removed from the serum of the patient by pre-incubation with recombinant Dsg1 baculoprotein. This finding indicates that the sera possess only IgA antibodies against the extracellular domain of Dsg1 baculoprotein, but no antibodies against components of keratinocyte cell surface other than Dsg1. This is the first case of IgA pemphigus where Dsg1 has been identified as the autoantigen.

Trends in morbidity from syphilis in Hungary between 1952 and 1996 were analysed. The incidence of syphilis/100,000 inhabitants declined rapidly owing to the public health and therapeutic measures of the early 1950s (1952: total=73.6, early infections=60.2; 1962: total=13.7, early infections=8.7). After a temporary, slight increase until 1973 the number of reported syphilis cases declined continuously between 1978 and 1989 (1989: total=0.9, early infections=0.84). In 1994 a marked increase occurred when compared with 1993 (1993: total=early: 1.4. 1994: total=2.3, early infections=2.2). Incidence trends were statistically analysed using Chi-square test and linear regression. Chi-square analysis showed that the changes in the incidence of total and early syphilis are significant ( p

The synthetic peptide comprising the 317–341 region of human influenza A virus (H1N1 subtype) hemagglutinin elicits peptide-specific antibody and helper T cell responses and confers protection against lethal virus infection. Molecular mapping of the 317–329 region, which encompasses the epitope recognized by peptide-specific T cells, revealed that the minimal size required for T cell activation was the 317–326 segment. The most likely peptide alignment, which placed 320Leu to pocket 1 of the I-E d peptide binding groove, was predicted by molecular mechanics calculations performed with the parental and with the Ala-substituted analogs. In line with the prediction data, the results of the peptide binding assay, where the relative binding efficiency to I-E d molecules expressed on the surface of antigen-presenting cells was monitored, identified the 320–326 core sequence interacting with the major histocompatibility class II peptide binding groove. Functional analysis of Ala-substituted variants by functional assays and by calculating the surface-accessible areas of the single peptidic amino acids in the I-E d –peptide complexes demonstrated that 324Pro is a primary contact residue for the T cell receptor. Our results show that this type of analysis offers a suitable tool for molecular mapping of helper T cell epitopes and thus provides valuable data for subunit vaccine design.

Single-chain variable fragment (scFv) antibodies are genetically engineered molecules comprising the variable regions responsible for specific binding. scFv that recognize certain surface molecules on professional antigen presenting cells could therefore be suitable for targeting Ag to these cells. We have produced an scFv that recognizes murine complement receptors 1 and 2 (CR1/CR2) and genetically fused it with different numbers of influenza hemagglutinin peptides which contain both B and T cell epitopes. The CR1/CR2 specific hybridoma 7G6 was used for RT-PCR to obtain the variable regions, which were then combined to create an scFv fragment. The influenza hemagglutinin intersubunit peptide HA317-41 (IP) was engineered to the N terminus of the scFv in one, two or three copies. The so obtained IP1–37G6scFv still bound the complement receptors; the peptides in the construct were recognized by the peptide specific monoclonal IP2-11-1 on Western blots and ELISAs. The CR1/CR2 positive B lymphomas A20 and 2PK3 presented the peptide to an I–Ed restricted IP specific T cell hybridoma more efficiently when incubated with the IP17G6 constructs as compared to the free peptide. The results suggest that scFv could work as targeting devices in subunit vaccines.

A multicentre, randomized, open, prospective, parallel-group trial was carried out to compare the efficacy, tolerability and safety of topical treatment with tacalcitol ointment (4 μg/g, applied once daily) with that of short-contact dithranol therapy. The tolerability of tacalcitol was significantly (P=0.002) better and its efficacy was slightly better. Tacalcitol proved to be less (P

We have examined the structure and function of Ca2+ channels in excitable endocrine cell types, in rat adrenal glomerulosa cells and in two insulin producing cell types, the rat pancreatic beta cell and the INS-1 cell line. In previous studies on glomerulosa cells, we observed low (T-type) and high threshold (L-type) voltage dependent Ca2+ currents in addition to a K+ induced inward rectifying Ca2+ current (Igl). beta cells are known to exhibit T-, L- and N-type currents. We have now found that INS-1 cells also show low threshold (T-type) and high threshold Ca2+ currents. The latter was further resolved by organic inhibitors into L-type and P/Q-type currents and no Igl was detected. The expression of the pore-forming alpha 1 subunit of voltage dependent Ca2+ channels was studied by means of reverse transcription-polymerase chain reaction (RT-PCR), followed by restriction enzyme mapping and/or sequencing. Both in glomerulosa and pancreatic beta cells, the neuroendocrine (D) class of the alpha 1 subunit, known to be responsible for L-type current, represents the majority of the PCR product. Comparable amounts of the neuroendocrine (D) and the neuronal A-type alpha 1 subunits dominate the message in INS-1 cells. Different characteristics of Ca2+ currents in these cell types is discussed in view of the channel repertoire.

A 51-year-old female developed urticarial lesions of her right forearm which progressed into transient edema and subcutaneous swelling. Later a small infiltrated subcutaneous nodule also appeared and was removed in toto. Histopathological examination revealed the presence of Dirofilaria repens. This worm is the cause of an endemic zoonosis in the Mediterranean area. In the past decade many cases have been reported worldwide, but the condition appears rare in Hungary and skin findings have not been described.

Two different routes for ejection of hydrated electrons by photoexcited CuCl2- and CuCl32- have been observed: (1) a prompt (i.e. within the 5-ns laser pulse width) ejection directly from the charge-transfer excited states (characterized as CTTS or Rydberg states), and (2) a delayed ejection, with lifetimes of up to 105 ns, from the triplet states of the two complexes. These two processes have rather high quantum yields: 0.30−0.40 for the prompt ejection and 0.25−0.33 for the delayed ejection for the chlorocuprate(I) complexes. The delayed ejection process is the primary decay route for the two triplet species, 3CuCl2- and 3CuCl32-, which are formed by intersystem crossing from the charge-transfer excited states formed by absorption of light by the bis- and triscoordinated complexes in equilibrium in the ground state. Both of the chlorocuprate triplet excited states are weakly luminescent species. The triplet tris species, 3CuCl32-, has a strong absorption band at 390 nm (e ≈ 27 000 M-1 cm-1), and the b...

In HIV infection, the decrease in the number and functional activity of lymphocytes is accompanied by atopia and an increased level of total IgE and some specific IgE antibodies. This could be explained by the Th2 dominance induced by HIV replication and so a Th1-Th2 switch could have prognostic value. We investigated the characteristic T-helper phenotype dominance and its relationship to cytokine expression and IgE immune response in the early stage of asymptomatic HIV infection. In the separated lymphocytes of i. asymptomatic HIV positive persons; ii. HIV negative homosexuals; iii. atopic patients; and iv. healthy controls, expression of mRNA for IFNg (Th1) and IL-10 (Th2) were determined by semiquantitative RT-PCR. The serum level of antibodies for HIV 1/2 and total/specific IgE were also determined. Transcription of mRNA of IFNg and IL-10 were more pronounced in HIV positive and atopic groups than in the healthy control, without lymphocyte phenotype dominance. In HIV negative persons, however, a significant Th2 dominance was detected. There was no significant difference in the IgE level between the 4 investigated groups. In the HIV positive cases, IL-10 expression and total serum IgE do not support a switch to Th2 dominance. In the atopic group, aside from the total IgE level, down regulation of IFNg was not observed. These results suggest a general activation of the immune system in the early stage of HIV infection.

The photophysical and photochemical properties of two prominent groups of exciplexes generated by the excited transition metal complexes are discussed. The strong interaction between the excited tris-(α-diimine) ruthenium(II) complex and the ground state silver ion results in both bimolecular and termolecular exciplexes. Since the stabilization originates from the overlap between the low-lying π ∗ level of a coordinated ligand and the empty 5s orbital of the silver ion, these exciplexes are called ligand-centered exciplexes (LCEs). In contrast, coordinatively unsaturated dicyanocuprate(I) in the excited state associates with halide ions to create longer-lived, more highly luminescent metal-centered exciplexes (MCEs). The stepwise formation constants of exciplexes and the thermodynamic parameters of the excited state equilibrium determined by temperature-dependent measurements have been compared and discussed. The kinetics and energetics of LCEs and MCEs strongly depend on the ionic strength and the solvent properties. Although the exciplex constituents of the two groups and their interaction have a rather different nature, some common behavior of these transition metal complex exciplexes have been elucidated.

In the decade prior to the turn of the millennium, great interest was raised, and rightly so, by the STD (syphilis and HIV/AIDS) epidemic that developed in the Eastern-Central European Region. Its coincidence with the far-reaching political and economic changes that took place at that time suggested a link between the two events.Hungary, where these infections had had low incidence before the period investigated, also experienced an increase in STD incidence. The trend in syphilis infection during the 20 years between 1985-2004, that preceded the turn of the millennium and when finally Hungary joined the European Union, have been analyzed. Due to the nature of venereological epidemiological surveillance in Hungary, syphilis prevalence data are appropriate for further analysis from socio-demographic aspects. Behavioural changes underlying the specific features of the epidemics in Hungary had developed several years earlier and cannot be linked to the political and economic changes that started in the early 90s. The only exception is the phenomenon of growing migration that appeared simultaneously with the political changes and had a decisive impact on the spread and level of infection in some areas in the country. As shown by our data, trends seen in specific demographic groups (females, rural population) preceded the suddenly occurring political changes by about 15 years.

OBJECTIVES The aim of the study was to clinically and histologically evaluate the healing of human intrabony defects treated with open flap surgery (OFD) and application of a new, resorbable, fully synthetic, unsintered, nanocrystalline, phase-pure hydroxyapatite (nano-HA). MATERIALS AND METHODS Six patients, each of them displaying very advanced intrabony defects around teeth scheduled for extraction due to advanced chronic periodontitis and further prosthodontic considerations, were included in the study. Following local anaesthesia, mucoperiosteal flaps were reflected; the granulation tissue was removed, and the roots were meticulously debrided by hand and ultrasonic instruments. A notch was placed at the most apical extent of the calculus present on the root surface or at the most apical part of the defect (if no calculus was present) in order to serve as a reference for the histological evaluation. Following defect fill with nano-HA, the flaps were sutured by means of mattress sutures to allow primary intention healing. At 7 months after regenerative surgery, the teeth were extracted together with some of their surrounding soft and hard tissues and processed for histological analysis. RESULTS The postoperative healing was uneventful in all cases. At 7 months following surgery, mean PPD reduction and mean CAL gain measured 4.0 ± 0.8 and 2.5 ± 0.8 mm, respectively. The histological analysis revealed a healing predominantly characterized by epithelial downgrowth. Limited formation of new cementum with inserting connective tissue fibers and bone regeneration occurred in three out of the six biopsies (i.e. 0-0.86 and 0-1.33 mm, respectively). Complete resorption of the nano-HA was found in four out of the six biopsies. A few remnants of the graft particles (either surrounded by newly formed mineralized tissue or encapsulated in connective tissue) were found in two out of the six biopsies. CONCLUSION Within their limits, the present results indicate that nano-HA has limited potential to promote periodontal regeneration in human intrabony defects. CLINICAL RELEVANCE The clinical outcomes obtained following surgery with OFD + nano-HA may not reflect true periodontal regeneration.

For the determination of HIV-1 diversity and serotyping of HIV-1 subtypes, an enzyme immunoassay was developed based on synthetic peptides representing immunodominant epitopes of the V3 loop of HIV-1 subtypes A, B, C and E, respectively. Sera from 53 asymptomatic HIV-1 infected individuals were tested for their pattern of binding reactivity to the synthetic peptides. 45/52 (85%) of the sera reacted exclusively to V3 peptide representing HIV-1 B subtypes, 4/52 (7.6%) of the sera showed cross reacticity to A/B peptides and 1/52 (1.9%) of the sera reacted with both A and C peptides. No single reactivity with subtype A or E peptides have been observed. Results together with nucleotide sequence analysis of the V3 region of clinical isolates suggest that HIV-1 infection in Hungary has been induced predominantly by strains belonging to HIV-1 subtype B.

The concept that voltage-dependent Ca2+ influx is essential in the aldosterone stimulating action of angiotensin II (AII) has been recently challenged by the demonstration of the dihydropyridine (DHP) insensitive 'capacitative' Ca2+ uptake mechanism. The DHP-sensitivity of AII-induced aldosterone secretion is still to be explained. In rat glomerulosa cells the lag phase of AII-induced depolarization is more than 30 s, and there is no enhanced Ca2+ influx within the first min of stimulation. Yet we observed that DHPs as well as diltiazem influenced also the peak of cytoplasmic Ca2+ signal, although the peak (approximately 12 s) is attributed to Ca2+ release alone. Nifedipine reduced the Ca2+ transient induced by AII even after complete inhibition of Ca2+ channel activity. Recalling the loose attachment of InsP3 receptors (IP3R) to the plasma membrane, and the homology between the cytosolic domain of IP3R and the Ca2+ release channel (ryanodine receptor) of skeletal muscle, we proposed that DHP-sensitive L-type Ca2+ channels (DHP receptors) influence InsP3-induced Ca2+ release rather than Ca2+ influx in AII-stimulated cells. Although the dominant isoform is the neuroendocrine (D) one, the skeletal muscle isoform of L-type voltage-dependent Ca2+ channel is also expressed in rat glomerulosa cells. This isoform may be a candidate for protein-protein interaction between DHPR and subplasmalemmal IP3R, similarly to that occurring between DHP receptors and ryanodine receptors in skeletal muscle.

The photophysical and photochemical properties of exciplexes are summarized considering the electronic structure and role of energetics and kinetics in the formation and stabilization of these molecular entities. Exciplexes involving transition metal complexes, are known as transition metal complex exciplexes (TMCEs) and are classified on the basis of the reactive site of the excited metal complex and the properties of the ground state reactant. There are two main groups; ligand-centered exciplexes and metal-centered exciplexes. A survey of the literature of TMCEs is presented. Common features of exciplexes classified into different groups are revealed. A strategy for searching for new TMCEs is suggested.

Laser flash excitation of the CTTS band of CuBr(3)(2)(-) at 266 nm results in the formation of a luminescent species which decays through a coupled mechanism consistent with the formation of an emitting triplet tricoordinated exciplex in equilibrium with a nonemitting triplet dicoordinated species. The rate constants for some of the decay processes, as well as the formation constant of the radiative intermediate, are estimated. Hydrated electrons and Cu(II) ions are also efficiently produced in about a 1:1 molar ratio in a competing pathway with the copper(I) exciplex formation. Time-resolved absorbance spectra of the hydrated electron and the luminescent species were obtained, leading to the conclusion that the exciplex forms in high yield at high ligand concentrations. Another intermediate appears to be the Br(2)(-) radical anion.

An A/PR/8/34 (IHN1) influenza virus hemagglutinin (HA)-specific monoclonal antibody (Z38) was found to react with the solid phase adsorbed influenza virus expressing uncleaved (HA0) molecules but not to bind to virus particles bearing enzymatically cleaved hemagglutinin. Synthetic peptides corresponding to the uncleaved HA0 317-341 intersubunit region of subtypes H1-H3 (IP1-IP3) or comprising either the C-terminal 317-329 amino acids of HA1 (CP1) or the N-terminal 330-341 of HA2 (fusion peptide, FP) subunits of cleaved HA were used to characterize the fine specificity of Z38 mAb. Circular dichroism and Fourier-transform infrared spectroscopy showed that, compared to IP2 and IP3 comprising the H2 and H3 subtype fragments of the intact intersubunit region, IP1 has relatively low helicity but a tendency to adopt beta-turns in trifluoroethanol. The immunological and conformational properties of multiple antigenic peptides (MAPs) containing four copies of CP1 were also studied. Based on the appearance of an infrared component band at 1637 cm-1 (beta-turn band), the CP1 arms of MAPs also contain repeats of beta-turns. However, it is only the MAP1-FP construct comprising also the fusion peptide, which binds Z38 mAb as strongly as IP1 does. This puts emphasis on the role of the fusion region in modifying conformation and consequently the ability of peptides to elicit an antibody response. The results obtained for peptide conformation also suggests a beta-turn(s)/beta-sheet/beta-turn/beta-sheet conformational motif in the recognition by the hemagglutinin subtype-specific Z38 monoclonal antibody or by peptide-induced polyclonal antibodies.

The photophysical and photochemical properties of Ru (bpy) (CN)42− and RU(DMbpy) (CN)42− are reported, where bpy = 2,2′-bipyridine and DMbpy = 4,4′-dimethyl-2,2′-bipyridine. The luminescence quantum yields of the lowest energy d-π∗ state are (8 ± 1) × 10−3 and (7 ± 1) × 10−3 for the bpy and DMbpy complex, respectively, in aqueous solution at ambient temperature. Under these conditions the lifetimes are 125 and 115 ns. The luminescence lifetimes increase approximately threefold in D2O. The emission is quenched by methylviologen at diffusion controlled rate (kq(bpy) = (1.95 ± 0.4) × 1010 M−1 s−1, kq(DMbpy) = (1.85 ± 0.5) × 1010 M−1 s−1), and the cage escape efficiencies of MV+ are found to be 0.24 ± 0.02 and 0.25 ± 0.03 for the bpy and DMbpy derivatives, respectively. Photolysis of Ru(bpy) (CN)42− was also studied in chloroform and was compared with that of Fe (bpy) (CN)42−. UV irradiation of the Fe (bpy) (CN)42− complex in chloroform results in the iron(III) complex in anaerobic conditions, while the mixed ligand ruthenium(III) complex forms only in the presence of oxygen.

Cariprazine is a dopamine D(3)/D(2) receptor partial agonist antipsychotic candidate, which binds with high affinity to dopamine D(3) and D(2) receptors (with ∼10-fold higher in vitro affinity to D(3) vs. D(2) receptors) and with moderate affinity to 5-HT(1A) receptors. The main objective of the present molecular imaging investigation was to evaluate the uptake and reversible binding of 11-C labeled cariprazine in the nonhuman primate brain, in relation to the known distributions of dopamine D(2) and D(3) receptors. We examined the brains of two cynomolgus monkeys at baseline condition as well as during a pharmacological blocking condition, using unlabeled cariprazine or raclopride as blockers before injection of [(11) C]cariprazine. Of the total injected radioactivity, ∼7% entered the brain and ∼3-4% remained in the brain after 90 min, indicating good blood brain barrier penetration and slow washout. It was possible to block cariprazine binding with unlabeled cariprazine and raclopride indicating that [(11) C]cariprazine binds to dopamine D(3)/D(2) receptors. Nondisplaceable binding potential (BPND) measurements, using a simplified reference tissue model and cerebellum as the reference region, yielded values of ∼1.5 and 0.3 in the striatum and thalamus, respectively. Striatum BPND values were reduced by 80 and 85% following pretreatment with 0.1 mg/kg IV injection of unlabeled cariprazine and 1 mg/kg IV injection of unlabeled raclopride, respectively. The data confirm that cariprazine, a novel antipsychotic drug candidate, enters the nonhuman primate brain readily and binds to dopamine D(3)/D(2) receptors. Furthermore, in PET imaging [(11) C]cariprazine can effectively visualize dopamine D(3)/D(2) receptors in the nonhuman primate brain.

To present the safety profile, the early healing phase and the clinical outcomes at 24 weeks following treatment of human intrabony defects with open flap debridement (OFD) alone or with OFD and rhGDF-5 adsorbed onto a particulate β-tricalcium phosphate (β-TCP) carrier. Twenty chronic periodontitis patients, each with at least one tooth exhibiting a probing depth ≥6 mm and an associated intrabony defect ≥4 mm entered the study. Ten subjects (one defect/patient) were randomized to receive OFD alone (control) and ten subjects OFD combined with rhGDF-5/β-TCP. Blood samples were collected at screening, and at weeks 2 and 24 to evaluate routine hematology and clinical chemistry, rhGDF-5 plasma levels, and antirhGDF-5 antibody formation. Plaque and gingival indices, bleeding on probing, probing depth, clinical attachment level, and radiographs were recorded pre- and 24 weeks postsurgery. Comparable safety profiles were found in the two treatment groups. Neither antirhGDF-5 antibody formation nor relevant rhGDF-5 plasma levels were detected in any patient. At 6 months, treatment with OFD + rhGDF-5/β-TCP resulted in higher but statistically not significant PD reduction (3.7 ± 1.2 vs. 3.1 ± 1.8 mm; p = 0.26) and CAL gain (3.2 ± 1.7 vs. 1.7 ± 2.2 mm; p = 0.14) compared to OFD alone. In the tested concentration, the use of rhGDF-5/β-TCP appeared to be safe and the material possesses a sound biological rationale. Thus, further adequately powered, randomized controlled clinical trials are warranted to confirm the clinical relevance of this new approach in regenerative periodontal therapy. rhGDF-5/β-TCP may represent a promising new techology in regenerative periodontal therapy.

The influenza virus haemagglutinin has an important role in the infectious cycle of the virus and carries multiple B and T cell epitopes. It is synthesized as a single polypeptide chain but viral infectivity depends on its post-translational enzymatic cleavage. The cleavage site of a trypsin-like enzyme responsible for this modification is found in the most conserved intersubunit region of the molecule. In this study the role of this region in antibody recognition was investigated. Synthetic peptides comprising the intact and cleaved forms of the intersubunit segment were used to examine the specificity of virus- or peptide-induced antibodies. The immune response elicited by viral infection resulted in the appearance of antibodies capable of neutralizing the virus without interfering with its binding to the receptor. A monoclonal antibody (MoAb) of such functional properties was shown to recognize the intact intersubunit region both in the uncleaved haemagglutinin molecule and in a 25-mer synthetic peptide comprising the intact intersubunit region. Specificity and functional studies revealed the conformation-dependent recognition of the C-terminal segment of the haemagglutinin 1 subunit by this MoAb. The binding of the antibody was shown to inhibit the trypsin-mediated cleavage of the haemagglutinin molecule and the membrane fusion event. The enzymatic cleavage of the haemagglutinin was demonstrated to abolish antibody recognition of the infective virus suggesting an escape mechanism mediated by the functional destruction of this highly conserved region. The synthetic peptide corresponding to the intact intersubunit region is characterized by an ordered structure and is able to elicit an antibody response in BALB/c mice while its subfragments are nonimmunogenic. Furthermore, this peptide elicited a protective immune response demonstrated by in vivo experiments.

The objective of this paper is to examine the effect of alveolar ridge preservation (ARP) compared to unassisted socket healing. Systematic review with electronic and hand search was performed. Randomised controlled trials (RCT), controlled clinical trials (CCT) and prospective cohort studies were eligible. Eight RCTs and six CCTs were identified. Clinical heterogeneity did not allow for meta-analysis. Average change in clinical alveolar ridge (AR) width varied between −1.0 and −3.5 ± 2.7 mm in ARP groups and between −2.5 and −4.6 ± 0.3 mm in the controls, resulting in statistically significantly smaller reduction in the ARP groups in five out of seven studies. Mean change in clinical AR height varied between +1.3 ± 2.0 and −0.7 ± 1.4 mm in the ARP groups and between −0.8 ± 1.6 and −3.6 ± 1.5 mm in the controls. Height reduction in the ARP groups was statistically significantly less in six out of eight studies. Histological analysis indicated various degrees of new bone formation in both groups. Some graft interfered with the healing. Two out of eight studies reported statistically significantly more trabecular bone formation in the ARP group. No superiority of one technique for ARP could be identified; however, in certain cases guided bone regeneration was most effective. Statistically, significantly less augmentation at implant placement was needed in the ARP group in three out of four studies. The strength of evidence was moderate to low. Post-extraction resorption of the AR might be limited, but cannot be eliminated by ARP, which at histological level does not always promote new bone formation. RCTs with unassisted socket healing and implant placement in the ARP studies are needed to support clinical decision making. This systematic review reports not only on the clinical and radiographic outcomes, but also evaluates the histological appearance of the socket, along with site specific factors, patient-reported outcomes, feasibility of implant placement and strength of evidence, which will facilitate the decision making process in the clinical practice.

The almost uncountable infrastructural and other system elements make citizens’ life easier in post-modern societies. Normally these are all considered as obvious. Liveable urban places, their competitiveness and appreciation depends highly on the quality of the services available, such as the quality of public administration, finance system, energetic networks, economic capabilities, urban transportation systems, social entertainment, sport and recreation facilities and the like. The vulnerability of cities and their exposure to terrorist attacks arose after the 9/11 attacks. It give rise to many thoughts and associations if metropolises like New York, Washington DC, Tokyo, London, Paris, Madrid, Mumbai, New-Delhi, Bagdad, Istanbul, Athens are mentioned and since then, terrorism has become a frequent part of their obvious associations. How vulnerable the urban services can be that are now essential parts of their urban life? This study attempts to look beyond the terrorist threats of metropolises, cities and towns, and points out their defenceless exposures against their own infrastructural systems. Although an average city in Central-Europe has fortunately low risks from such points of view, other risk sources however, like accidents, natural disasters, and civilisation-based catastrophes are also retraceable. The authors attempt to find answers why urban studies in Central-Europe do not pay necessary attention to the city’s vulnerability analyses like their counterparts in the Western Countries do.

The molecular geometry, electronic structure and electronic spectra and the energy levels of the molecular orbitals responsible for the photophysical characteristics of a series of solvent tunable [Ru(x,x'-dmb)(CN)(4)](2-) complexes (where x,x'-dmb = x,x'-dimethyl-2,2'-bipyridine) were calculated by density-functional theory-based quantum chemical methods, with the purpose of proposing for experimental study the best candidate for sensitizing electron- and energy transfer processes or for light induced structural changes in the molecule. The methods applied include geometry optimization using the B3LYP functional combination and various basis sets, time-dependent density functional theory with the B3LYP and PBE0 functionals, with and without explicit inclusion of coordinated solvent H(2)O molecules and the conductor-like polarizable continuum model for solvation. The accuracy of the theoretical predictions was tested by experiments: the model compounds have been synthesized and characterized by various spectroscopic methods, such as (1)H-NMR, UV-Vis absorption and emission spectroscopy and by cyclic voltammetry. Excellent correlation was found between the theoretically calculated and the experimentally determined photophysical and photochemical characteristics. The electronic transition energies measured in water are superbly reproduced by TD-PBE0 and well by TD-B3LYP, but the performance of both functionals is worse if the solvent is acetonitrile.

Cariprazine is a novel antipsychotic drug candidate that exhibits high selectivity and affinity to dopamine D(3) and D(2) receptors and moderate affinity to serotonin 5-HT(1A) receptors. Targeting receptors other than D(2) may provide a therapeutic benefit for both positive and negative symptoms associated with schizophrenia. Positron emission tomography (PET) can be used as a tool in drug development to assess the in vivo distribution and pharmacological properties of a drug.The objective of this study was to determine dopamine D(2)/D(3) and serotonin 5-HT(1A) receptor occupancy in monkey brain after the administration of cariprazine.We examined three monkeys using the following PET radioligands: [(11)C]MNPA (an agonist at D(2) and D(3) receptors), [(11)C]raclopride (an antagonist at D(2) and D(3) receptors), and [(11)C]WAY-100635 (an antagonist at 5-HT(1A) receptors). During each experimental day, the first PET measurement was a baseline study, the second after a low dose of cariprazine, and the third after the administration of a high dose.We found that cariprazine occupied D(2)/D(3) receptors in a dose-dependent and saturable manner, with the lowest dose occupying ~5% of receptors and the highest dose showing more than 90% occupancy. 5-HT(1A) receptor occupancy was considerably lower compared with D(2)/D(3) occupancy at the same doses, with a maximal value of ~30% for the raphe nuclei.We conclude that cariprazine binds preferentially to dopamine D(2)/D(3) rather than to serotonin 5-HT(1A) receptors in monkey brain. These findings can be used to guide the selection of cariprazine dosing in humans.

Syphilis continues to have great public health importance because it increases the risk of human immunodeficiency virus (HIV) infection significantly; furthermore, statistical studies suggest that there are no chances of eradicating it in the foreseeable future. The T. pallidumGenome Sequencing Project also confirmed what had already been suggested by ongoing experimental efforts: this bacterium is a fastidious, microaerophilic, obligate parasite of humans. T. pallidumderives most essential macromolecules from the host, using interconversion pathways to generate others. The course of untreated syphilis consists of intermittent stages with sequential symptomatic and asymptomatic (latency) periods. This regular choreography, however, may be disturbed if the immunological competence of the host organism is severely compromised (HIV infection) by inappropriately administered prevention or antimicrobial therapy for another disease.