Hepatitis C virus upregulates B-cell receptor signaling: a novel mechanism for HCV-associated B-cell lymphoproliferative disorders.

B-cell receptor (BCR) signaling is essential for the development of B cells and has a critical role in B-cell neoplasia. Increasing evidence indicates an association between chronic hepatitis C virus (HCV) infection and B-cell lymphoma, however, the mechanisms by which HCV causes B-cell lymphoproliferative disorder are still unclear. Herein, we demonstrate the expression of HCV viral proteins in B cells of HCV-infected patients and show that HCV upregulates BCR signaling in human primary B cells. HCV nonstructural protein NS3/4A interacts with CHK2 and downregulates its activity, modulating HuR posttranscriptional regulation of a network of target mRNAs associated with B-cell lymphoproliferative disorders. Interestingly, the BCR signaling pathway was found to have the largest number of transcripts with increased association with HuR and was upregulated by NS3/4A. Our study reveals a previously unidentified role of NS3/4A in regulation of host BCR signaling during HCV infection, contributing to a better understanding of the molecular mechanisms underlying HCV-associated B-cell lymphoproliferative disorders.

Inflow based investigations on the efficiency of a lamella particle separator for the treatment of stormwater runoffs.

The present design of stormwater tanks is based on the creation of storage volume to retain stormwater and the prevention or reduction of stormwater overflows. The treatment of stormwater is often improved with mechanical equipment. The general layout rules do usually not include the appropriate choice of design inflow related to the chosen treatment equipment. In the following investigations it was the task to analyze the hydraulic efficiency and the overflow behaviour of a lamella particle separator inside a stormwater tank under different design approaches regarding the chosen design inflow. Therefore six scenarios with different precipitation yield approaches were chosen and applied to a given constant sized catchment to calculate the design inflows. For a given minimum particle size, the necessary number of lamellas were determined for the scenarios and standard stormwater tanks were dimensioned. These stormwater tanks were modelled in the hydrologic model SMUSI to investigate the overflow behaviour of the different tank sizes. The number of overflow events, their duration and maximum flow rates were the results of the modelling. Comparisons to the design inflows were carried out. The treated particles sizes at the overflow events were determined reversible and compared to the original chosen minimum particle sizes.

The imbalanced mixed lymphocyte reaction between maternal and fetal lymphocytes as well as between the lymphocytes of adult children and their parents is mediated by activated CD8+ T cells.

PROBLEM: The mixed lymphocyte reaction (MLR) between maternal and fetal lymphocytes as well as between adult children and their parents is imbalanced in bidirectional mixed lymphocyte cultures. The present investigation was aimed at examining which type of T cells has primary responsibility for this phenomenon. METHODS: Two-way mixed lymphocyte cultures between lymphocytes of five female and five male adults and five male and five female newborns against lymphocytes of their parents were performed. Unrelated adults served as the controls. Before and after 72 hr incubation the mixed leukocytes cultures (MLCs) were sorted by flow cytometry according to the surface markers CD4 and CD69 or CD8 and CD69. The single cell populations within the four resulting fractions were discriminated by fluoresence in situ hybridization (FiSH) using xy-DNA probes. RESULTS: Before incubation the share of CD8(+) CD69(+) cells in the MLCs between mothers and their newborn infants was significantly shifted toward the newborn cells (P < 0.01). After 72 hr incubation the CD8(+) CD69(+) ratio in the MLCs between mother and newborn cells and between adult children (male as well female) and their parents showed a significant shift of the CD8(+) CD69(+) cells toward the children's direction. All other MLCs showed a balanced cell population for all investigated cell types, both before and after incubation. CONCLUSION: The imbalanced MLR between maternal and fetal lymphocytes and lymphocytes of adult children against their parents is mediated by a specific imbalance of the activation of CD8(+) but not of CD4(+) T cells.

[Vertical changes in the lateral teleroentgenographic image after functional orthodontic therapy]. / Vertikale Veränderungen am Fernröntgenseitenbild nach funktionskieferorthopädischer Therapie.

We looked for vertical changes in lateral cephalometric X-rays of patients who had been treated with Andresen and Häupl appliances to correct distal occlusion. Thus, a therapy using functional appliances for orthodontic correction has the following effects on the vertical proportions of the visceral cranium. 1. The alveolar processes show additional vertical growth in the area of the incisors of the upper jaw and the molars of the lower jaw. 2. In conjunction with 1, increased vertical growth of the anterior facial heights compared to the posterior facial height causes an opening of the bite which, however, is not significant in terms of the Jarabak ratio. 3. Functional therapy has an effect on the spina plane, and, in addition, causes active vertical growth in the area of both upper facial heights, i.e., of the entire nasomaxillary complex. This additional growth is a little bit more pronounced anteriorly than posteriorly. Therefore the effect of functional orthodontic appliances on the nasomaxillary complex seems to be more complex than previously believed. 4. We did not observe any additional growth in the area of the ascending rami and/or condyles of the lower jaw during activator treatment. Our studies showed that the influence of functional orthodontic therapy on the vertical growth of the lower jaw is rather insignificant; the significant vertical changes were seen in the area of the mandibular molars and of the anterior facial heights. 5. Our findings thus support the assumption that the main vertical effect of the activator can be described as a relative inhibition of the development of the nasomaxillary complex with simultaneous normal progression of mandibular growth.(ABSTRACT TRUNCATED AT 250 WORDS)

[The periodontal findings during orthodontic treatment. A cross-sectional study]. / Parodontale Befunde während kieferorthopädischer Behandlung. Eine Querschnittsuntersuchung.

The study was designed to evaluate the adverse influence of removable or fixed orthodontic appliances on the periodontal status of patients, thus predisposing to periodontal disease. PLI (Plaque Index), PBI (Papillary Bleeding Index), SFFR (Sulcus-Fluid-Flow-Rate) and probing depth were the parameters used to evaluate the periodontal health of the patients in the study group. The results of the investigation were: 1. There was no significant difference between wearers of removable appliances and the untreated control group. 2. Wearers of fixed orthodontic appliances showed increased values of the Papillary Bleeding Index (PBI) and the Sulcus-Fluid-Flow-Rate (SFFR) in contrast to the control group. 3. The small patient population did not allow for definite conclusions to be made on the relationship between the age of the patients and the results of the investigation. 4. The most striking observation of the study was a decreased ability to maintain oral hygiene with a consequent decline in periodontal health. Orthodontic movements however should be carried out basically on teeth with a healthy periodontium.

[Possibilities for the use of zonography in orthodontics]. / Anwendungsmöglichkeiten der Zonographie in der Kieferorthopädie.

The "Zonarc" is a panoramic device in maxillofacial radiology that is programmed to cover different image layers. In this study human skulls of various sizes and various stages of development were examined with the aid of this equipment. The following projections were used: DENT program, JLA (special) program (TMJ side view, mouth open and closed), JSA program (TMJ sagittal, mouth open and closed). The positioning of the skulls as well as the correct adjustment of the equipment have been described on the basis of this investigation. The quality of reproduction of the skeletal tissue is discussed. The results indicate that the projections JLA and JSA can be used to advantage in orthodontic diagnosis. However one has to take the cost factor into consideration.

[Zonarc panoramic X-rays of the human TMJ in different stages of development]. / Röntgenologische Darstellung menschlicher Kiefergelenke mit dem Panoramaschichtgerät Zonarc.

21 human skulls in various stages of development were evaluated with the radiological equipment "Zonarc". The following projections were used: DENT program (OPG), JLA (special) program (TMJ-S program), JSA program (TMJ-PA program). The positioning of the skulls as well as the correct adjustment of the equipment have been described on the basis of this investigation. The quality of reproduction of the skeletal tissue is discussed.

Absorption of protein in the early postoperative period in chronic conscious dogs.

Postoperative alterations in amino acid exchange across the intestinal tract and in the capacity for protein absorption were investigated in a chronic canine model. Changes in postoperative splanchnic amino acid exchange consisted of a temporary decrease of total splanchnic amino acid release, including a significant reduction in alanine production, and an increase in glutamine consumption. Contrary to results under stable metabolic conditions, branched chain amino acids were also taken up by the intestine in the early postoperative period. The changes in postoperative amino acid exchange were not, however, reflected by a corresponding alteration in protein transport capacity. The absorptive capacity for a protein hydrolysate remained stable during the early postoperative period.

Evidence of the incorporation of normally nonaggregating hemoglobins into crystalline aggregates of deoxy hemoglobin S.

Changes in the solubility of both components of binary mixtures of sickle-cell deoxyhemoglobin (Hb degrees S) and some normally nonaggregating hemoglobins were determined by direct compositional analysis of the solution phage following sedimentation of crystalline aggregates generated from them. Increases in turbidity associated with the suspension of the crystals in solution were also monitored for each mixture. Correlations between changes in species solubility and "excess' turbidity levels were observed which define two distinct forms of interaction between hemoglobin additives and Hb degrees S. The R-state quaternary structures, COHbS and metHbS in the absence of organic phosphate, are excluded from the aggregate phase and act to lower the solubility of Hb degrees S through increased excluded volume contributions to the activity of the solution phase. Increases in turbidity which parallel this solubility change reflect the increased population of highly asymmetric Hb degrees C crystals in solution. Deoxyhemoglobin A and metHbS fixed in the deoxy conformation lower the solubility of Hb degrees S in a more complex manner, which may include the establishment of a minimum solubility. The solubility of these additives also decreases, as does the turbidity due to the resultant crystals, when the proportion of additive exceeds 40% of the total. Analysis of the composition of pellets isolated from both hybrid and nonhybrid mixtures with Hb degrees A confirms its incorporation into the aggregates. Such "mixed" crystals appear to have solubility and morphological properties different from those of Hb degrees S alone. Comparison of phase composition data from mixtures prepared with varying initial concentrations of Hb degrees S suggests that the degree of HbA incorporation into HbS aggregates is a function of the amount of Hb degrees S itself available for self-aggregation and the stage of crystal development at which HbA participates.

The effects of diverse proteins on the solubilization of various hydrophobic probes by protein.detergent complexes.

The solubilization behavior of various protein.detergent complexes with respect to a particular water-insoluble organic substance ("hydrophobic probe") dimethylaminoazobenzene, was reported in earlier studies. The present report describes further the solubilization of other hydrophobic probes (e.g. Sudan II, naphthalene, anthracene and azobenzene) in various protein.sodium dodecyl sulfate complexes, in order to enlarge the scope of our understanding of these phenomena, which undoubtedly play a part in the transport of different water-insoluble organic substances in the living organisms. Solubilization by the various protein.SDS complexes is found to be specific for each probe. The amount of a particular probe solubilized is nearly always equal to the amounts which are solubilized by pure SDS micelles equivalent in amount to the SDS bound. Serious exceptions are found with two heme proteins (e.g. myoglobin and hemoglobin) and a few others. The hemeprotein.SDS complexes also exhibit regions of flat plateaus in the solubilization curves, whereas the binding equilibria show progressively larger amounts of SDS bound. The solubilization of probes by cationic detergent (cetylpyridinium chloride and cetyltrimethylammonium bromde).protein complexes indicate that the solubilization phenomena are related to the environment of the binding sites (the cationic detergents are known to bind at different sites on the protein than the anionic detergents, i.e. SDS in the present case). With anionic detergents the effective chain length of the pseudo-micellar protein.detergent clusters is sufficient to cause an increase in solubilizing effectiveness of about 1.5 between the complexes and pure micelles. When small probes such as naphthalene are used such ratios are found. With larger probes the effectiveness ratio is reduced to 1.0 or even less as a result of steric interference with the formation of the protein.detergent.probe clusters. The solubilization energy exhibited by each protein.detergent complex is largely determined by the individual protein, and by the charge on the detergent.

Differences in the solubilizing effectiveness of the sodium dodecyl sulfate complexes of various proteins.

The detailed reversible binding isotherms of sodium dodecyl sulfate (NaDodSO4) with 13 different initially native proteins are reported; the data were obtained at 20 degrees C and pH 7.1, ionic strength 0.033, with amounts bound with some proteins up to 1.1 g per g of protein. Although the isotherms of some of the proteins do not vary widely, extreme variations between certain classes are found. Thus, for example, hemoglobin and myoglobin both have high affinities and high binding capacities, while gamma-globulin, apoferritin, and transferrin have low initial affinities, and change drastically at higher concentrations. The protein-NaDodSO4 complexes solubilize the water-insoluble dye dimethylaminoazobenzene (DMAB) as effectively as micelles of pure NaDodSO4 when only small amounts (0.2 to 0.5 g/g of NaDodSO4) are bound. In most cases this effectiveness falls progressively as larger amounts are bound, and may even cease altogether at limits characteristic of the individual protein. With some of the latter, a second region of renewed solubilization occurs when substantially higher amounts of NaDodSO4 are present. In all cases, solubilization by ordinary micelles in normal amount occurs when the free NaDodSO4 concentration exceeds the critical micelle concentration, but the binding of NPADodSO4 to the protein also increases, in competition with formation of micelles. With some, but not all proteins the NaDodSO4 bound at concentrations above the cmc also solubilizes DMAB. In such cases the solubilizations by the protein-NaDodSO4 complexes and by the simple micelles are additive. The significance of the differences in binding and solubilizing encountered among these proteins is discussed in terms of surface structure, cooperativity of binding, and protein composition. No certain correlations with content of most amino acids, subunit structure, solubility, and hydrophobicity have been found, but there is a weak inverse dependence of solubilizing effectiveness on molecular size and indications of a strong dependence on content of cationic groups.

Electrooptical properties of reduced protein-sodium dodecyl sulfate complexes.

Two independent electrooptical properties, the specific Kerr constants and the electric birefringence relaxation times, of the saturated sodium dodecyl sulfate complexes of a series of reduced polypeptides of known molecular weight are reported. Both the Kerr constants and the relaxation times are unique functions of the molecular weight of the polypeptide chain. The specific Kerr constants depend upon the square of the polypeptide molecular weight. The relaxation times of the complexes, which are proportional to the rotational diffusion constants, are dependent on the molecular weight to approximately the first power. The latter finding is inconsistent with the compact prolate ellipsoid model for sodium dodecyl sulfate-protein complexes proposed by Reynolds and Tanford ((1970) J. Biol. Chem. 245, 5161) in which the cross section is constant and the length depends on linearly on molecular weight; for this model the relaxation times would depend on approximately the 2.5 power of the molecular weight in the range of sizes investigated. Combination of the present results with other properties in the literature rules out a number of other models characterized by compactness and near inflexibility. No firm conclusions can be drawn as to the suitability of the free-draining flexible model of Shirahama, Tsujii, and Takagi ((1974) J. Biochem. (Tokyo) 75, 309).