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The mammalian target of rapamycin (mTOR) is a protein kinase involved in the phosphatidylinositol 3-kinase (PI3K)/AKT signalling pathway. It plays a pivotal role in the control of cell proliferation, survival, and angiogenesis with multiple and frequent dysregulations of this pathway in human tumors. Temsirolimus is an intravenous drug, specifically inhibiting the mTOR pathway. Bendamustine is well known for its clinical activity in indolent non-Hodgkin-lymphoma (NHL) and has lately shown clinical activity in mantle cell lymphoma (MCL). Here, we present a case report of temsirolimus in combination with bendamustine and rituximab leading to a CR in a pretreated male. In addition, our in vitro data underlines the additive and synergistic efficacy in cell growth reduction of temsirolimus combined with bendamustine in MCL cell lines and in DLBCL cell lines. Furthermore, as an underlying mechanism of this additive, effects on cell cycle inhibition and apoptosis induction could be identified. [ABSTRACT FROM AUTHOR]

In this phase I/II study, we explored the combination of Temsirolimus with Bendamustine and Rituximab (BeRT) in patients with r/r follicular lymphoma (FL) or mantle cell lymphoma (MCL). Patients with 1-3 prior therapies received Bendamustine (90 mg/m2, day 1+2) and Rituximab (375 mg/m2, day 1) with Temsirolimus in doses from 25 to 75 mg added on day 1, 8, 15 of a 28-day cycle. Fifteen (11 MCL, 4 FL) patients were included in the phase I. Median age was 73 years and median pretreatment number was 2. No formal dose-limiting toxicity was observed. Dominant non-hematological side effects were fatigue in 11 (73%), nausea in 9 (60%), mucositis in 7 (47%) and vomiting in 6 patients (40%). Cough, diarrhea, pyrexia and rash were observed in five patients (33%) each. Grade 3/4 events included leukopenia in 6 (40%), neutropenia in 4 (27%) and thrombocytopenia in 2 patients (13%). An objective response was observed in 14/15 patients (93%), including 5 complete response (33%; all MCL). After a median follow-up of 19 months, 67% of patients are without signs of progression. Temsirolimus can be safely added to BR with promising preliminary activity. Recruitment in phase II is ongoing. [ABSTRACT FROM AUTHOR]

In most patients, mantle cell lymphoma (MCL) shows an aggressive clinical course with a continuous relapse pattern and a median survival of only 3-5 years. In the current study generation of the European MCL Network, the addition of high-dose Ara-C to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone)-like regimen followed by myeloablative consolidation achieved a significant improvement of progression-free survival in younger patients. In elderly patients, rituximab maintenance led to a marked prolongation of remission duration. Emerging strategies include mammalian target of rapamycin (mTOR) inhibitors, proteasome inhibitors, immune modulatory drugs, Bruton's tyrosine kinase inhibitors and others, all based on the dysregulated control of cell cycle machinery and impairment of several apoptotic pathways. Combination strategies are currently being investigated in numerous trials, but their introduction into clinical practice and current treatment algorithms remains a challenge. In the current survey, the application of the molecular targeted compounds were collected and evaluated by a representative national network of 14 haematological institutions. Optimised strategies are recommended for clinical routine. Future studies will apply individualised approaches according to the molecular risk profile of the patient. [ABSTRACT FROM AUTHOR]

Background: The erythropoiesis-stimulating agents (ESAs) epoetin alfa (EA) and darbepoetin alfa (DA) have comparable efficacy in treating chemotherapy-induced anaemia (CIA). Therapy choice depends on many factors, including cost. Previous estimates of ESA cost differences have been derived from claims data. These data lack clinical variables, such as baseline haemoglobin (Hb) level, which are likely to influence choice of ESA, dosing and costs. We estimated cost differences between DA and EA in patients with cancer receiving chemotherapy, using a propensity-score matched analysis of baseline patient characteristics with and without Hb values to assess the effect of this clinical variable on ESA cost estimates.Methods: Data were extracted from electronic medical records in two US databases between January 2004 and December 2006. The study sample included 6743 patients receiving chemotherapy, with one or more visits during the study period, who received an ESA during a chemotherapy episode. Episodes of chemotherapy care were constructed using a 90-day gap in administration to identify the start and end. Patients receiving both DA and EA during their initial chemotherapy episode or with missing data were excluded, representing 42% of patients with CIA receiving an ESA. Drug costs were calculated from the cumulative dose multiplied by 106% of the average sales price (ASP) for DA or EA. Two propensity-score matches were conducted: first using variables available in administrative billing claims systems, then adding the baseline Hb test result. Regression-adjusted cost differences were estimated with and without baseline Hb, using generalized linear models.Results: Using baseline Hb levels resulted in a better match of the baseline characteristics for the EA and DA treatment groups than the original sample or the matched sample without Hb variables. Mean ESA costs (year 2007 values) for the original sample were $US4171 for EA and $US3811 for DA (mean difference $US360; p < 0.001, standard error [SE] $US99). With propensity-score matching without Hb variables, mean estimated costs were $US3836 for EA and $US3599 for DA (mean difference $US237; p = 0.053, SE $US123). With propensity-score match including Hb variables, mean costs were $US3965 for EA and $US3536 for DA (mean difference $US429; p = 0.001, SE $US125). Cost differences in sensitivity analyses ranged between $US102 (p = 0.201) and $US261 (p = 0.003).Conclusions: Addition of baseline Hb level as a variable in propensity score and ESA cost models affects ESA treatment cost estimates in patients with cancer receiving chemotherapy. Cost comparisons based on observational data should use analytical methods that account for differences in clinical variables between treatment groups. [ABSTRACT FROM AUTHOR]

Lymphoplasmacytic lymphoma (LPL) is an indolent lymphoma with moderate sensitivity to conventional chemotherapy. This study investigated whether the addition of rituximab to standard chemotherapy improves treatment outcome in LPL and the subgroup of LPL patients fulfilling the criteria of Waldenstroem's macroglobulinemia (WM). A total of 69 patients with previously untreated LPL were enrolled into the trial; 64 patients were evaluable for treatment outcome. In all, 48 of the 64 LPL patients fulfilled the criteria of WM. Patients were randomly assigned to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone, n=34) or CHOP (n=30). R-CHOP resulted in significantly higher overall response (OR) rate (94 vs 67%, P=0.0085) in the LPL patients and in the WM subgroup (91 vs 60%, P=0.0188). With a median observation time of 42 months, R-CHOP induced a significantly longer time to treatment failure (TTF) with a median of 63 months for R-CHOP vs 22 months in the CHOP arm in the LPL patients (P=0.0033) and in the WM subgroup (P=0.0241). There was no major difference of treatment-associated toxicity between both treatment groups. These data indicate that the addition of rituximab to front-line chemotherapy improves treatment outcome in patients with LPL or WM.Leukemia (2009) 23, 153–161; doi:10.1038/leu.2008.261; published online 25 September 2008 [ABSTRACT FROM AUTHOR]

With the increasing incidence of Non-Hodgkin's lymphoma and still substantial disease related mortality, further improvement of therapeutic options is needed. Radioimmunotherapy (RIT) is a targeted treatment with the potential to augment the efficacy of conventional monoclonal antibodies. Out of numerous antibody – radioisotype combinations two have been approved so far: 90Y-Ibritumumab tiuxetan and 131I-Tositumomab. The tolerability of the drugs is excellent and the main side effect is protracted cytopaenia, which occurs 4–8 weeks after the treatment. Limitations of use are reduced bone marrow reserve, higher bone marrow involvement and preceding extensive radiotherapy. Results of initial trials showed promising phase I/II data for a variety of lymphoma entities. Especially in follicular lymphoma subsequent phase II/III studies now have established these drugs as single agent treatment for relapsed disease, with improved response rates when applied at an earlier disease stage. The recently released results of the so-called FIT trial helped us to additionally establish their role as consolidation treatment immediately after preceding cyclic chemotherapy. Current concepts evaluate the benefit of RIT in the context of Rituximab maintenance therapy and high dose therapy. In aggressive lymphoma, clinical efficacy of single agent treatment has been found, but nevertheless the development of the drugs in the context of consolidation treatment or as part of high dose regimens is favoured now. Upcoming results will help to identify the potential of these drugs when applied in entities like mantle cell lymphoma, diffuse large cell lymphoma or marginal zone lymphoma. Taken together, radioimmunotherapy is increasingly part of multimodal treatment algorithms, rather than a substitute for other treatment options. Moreover, given their side effect profile, radioimmunoconjugates are a highly attractive single agent option for patients with restrictions against other anti-lymphoma therapies. [ABSTRACT FROM AUTHOR]

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The article presents the reply of G. D. Hess to the article "Comments on: the Neutral, Barotropic Planetary Boundary Layer Capped by a Low-Level Inversion," by Juan Carlos Bergmann. The reply is included in the book "Boundary-Layer Meteorology," which discusses the purpose of some of the assumptions of the models and the research itself. The author discusses the turbulent closure models of the planetary boundary layer. The main purpose of the author was to examine the difference in model performance by using models of various levels of sophistication and compare the predictions against field observations.

Physical parameterisations of turbulent transfer processes in the atmospheric boundary layer, such as the stability parameterisations developed by Joost Businger, and recent advances in computing capabilities, have been important factors leading to the emergence of operational, numerical air quality forecasting systems. The present paper investigates the performance of the Australian Air Quality Forecasting System (AAQFS) in forecasting the peak 1 h ozone for the current or next day. These 24/36 h forecasts are generated for the Sydney and Melbourne regions and issued twice daily. Quantitative evidence is presented of the potential for the AAQFS to provide accurate numerical air quality forecasts. A second goal is to provide an initial benchmark for investigating the limits of predictability for air quality in the Sydney and Melbourne regions by looking at the dependence of the forecasts on the domain spatial scale (while maintaining the same model grid resolution), the starting time and length of the forecast (0000 UTC starts are 36-h forecasts and 1200 UTC starts are 24-h forecasts), and the sophistication of the photochemical mechanism (simple chemistry, Generic Reaction Set (GRS) and complex chemistry, Carbon Bond IV (CBIV)). The probability of detection by the forecast model is much better than persistence, showing considerable skill. The normalised bias, in general, decreases going from regional scale to sub-regional scale and becomes negative at the station scale. In Melbourne the gross error increases as the domain spatial scale decreases, but in Sydney there is a dip in the error at the sub-regional scale due to a sampling artifact. Better results are obtained at the smaller domain scales for 1200 UTC forecasts in Sydney. These are attributed to the shorter forecast period and secondarily to greater model spin-up effects at 0000 UTC. In Melbourne the results are ambiguous. Similar conclusions are derived from scatter plots of forecasts versus observations. Dividing the scatter plots into four sections by plotting vertical and horizontal lines (at 60 ppb) forms contingency tables for categorical forecasting. These plots show the increase in missed forecasts due to underprediction and the decrease in the number of extreme events detected as the spatial scale decreases. A comparison of the highly condensed GRS photochemical mechanism with the comprehensive CBIV mechanism indicates that, in general, GRS performs well for predicting ozone in urban situations provided that the background concentrations are appropriately specified. The potential to improve the forecasts at the smaller spatial scales, particularly for extreme events at high ozone concentrations, may require moving to a more complex mechanism as computer resources become available. [ABSTRACT FROM AUTHOR]

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The nicotinic acetylcholine receptor (nAChR) belongs to a group of five structurally related proteins that regulate signal transmission between approximately 10(12) cells of the mammalian nervous system. Many therapeutic agents and abused drugs inhibit the nAChR, including the anti-convulsant MK-801 and the abused drug cocaine. Many attempts have been made to find compounds that prevent inhibition by cocaine. Use of transient kinetic techniques to investigate the inhibition of the receptor by MK-801 and cocaine led to an inhibition mechanism not previously proposed. The mechanism led to the development of combinatorially synthesized RNA ligands that alleviate inhibition of the receptor. However, these ligands are relatively unstable. Here we determined whether much more stable 2'-fluoro-modified RNA ligands can be prepared and used to study the alleviation of receptor inhibition. Two classes of 2'-fluoro-modified RNA ligands were obtained: One class binds with higher affinity to the cocaine-binding site on the closed-channel form and, as predicted by the mechanism, inhibits the receptor. The second class binds with equal or higher affinity to the cocaine-binding site on the open-channel form and, as predicted by the mechanism, does not inhibit the receptor, and does alleviate cocaine and MK-801 inhibition of the nAChR. The stability of these 2'-fluoro-RNAs expands the utility of these ligands. [ABSTRACT FROM AUTHOR]

The presence of a low-level, capping inversion layer will affect the height and structure of the planetary boundary layer (PBL). Results from models of varying levels of sophistication, including analytical, turbulent kinetic energy (TKE), second-order closure (SOC), large-eddy simulation (LES) and direct numerical simulation (DNS) models, are used to investigate this influence for the neutral, barotropic PBL. Predicted and observed profiles of stress and geostrophic departure components, and integral measures, such as the parameters of Rossby-number similarity theory, are compared for the KONTUR, Marine Stratocumulus, JASIN, Leipzig, Pre-Wangara and Upavon field experiments. Analytical models of the equilibrium value of inversion height zi, which depend on the surface friction velocity u*, and both the Coriolis parameter f and the free-flow Brunt-Väisälä frequency N, are found to give reasonable estimates of the PBL height. They also indicate that only the KONTUR and Marine Stratocumulus experiments were strongly influenced by N. More quantitative comparisons would require larger, more comprehensive datasets. The effects of the presence of a capping inversion on the profile structure were found to be insignificant for h* = |f|zi/u* > 0.15. The simple analytical model performed quite well over all values of h*; it predicted the profiles of the longitudinal stress component (in the direction of the surface stress) better than the lateral component. The more advanced models performed well for small values of h* (for flow over the sea), but systematically underestimated the cross-isobaric angle for flow over land. These models predicted the profiles of the lateral stress component better than the longitudinal component. The profiles of the analytical model agreed with those of the advanced models when the constant eddy viscosity of the outer layer was increased. Agreement with DNS was achieved by increasing the eddy viscosity of the analytical model by a factor of 5. Zilitinkevich and Esau (2002, Boundary-Layer Meteorology, 104, 371–379) suggest that the neutral, barotropic values of A and B of Rossby-number similarity theory are not universal constants, but depend on the ratio N/|f|. The dependence for A and B is calculated using the analytical model and TKE models. Over the sea (h* ≅ 0.1; N/|f| ∼ 100, where we have used the Zilitinkevich-Esau relation to convert between h* and N/|f|) there is agreement between the model predictions and observations; however over land where the equilibrium boundary-layer height is greater (h* ≅ 0.35; N/|f| ∼ 10) the inconsistency between the advanced model predictions (TKE, SOC, LES, and DNS) and observations, as noted previously by Hess and Garratt, still exists. We attribute this disagreement to violations of the strict assumptions of steady, horizontally homogeneous, neutral, barotropic conditions implicit in the observations. At small values of zi and a strongly stable background stratification (h* ≅ 0.04; N/|f| ∼ 1000) both the TKE and analytical models predict that A and B depend significantly on h*, however observations are unavailable to confirm these predictions. Zilitinkevich and Esau call this case the `long-lived near-neutral PBL', and state that it is found in cold weather at high latitudes. [ABSTRACT FROM AUTHOR]

Data for the cross-isobaric angle α0, the geostrophic drag coefficient Cg, and the functions A and B of Rossby number similarity theory, obtained from meteorological field experiments, are used to evaluate a range of models of the neutral, barotropic planetary boundary layer. The data give well-defined relationships for α0, Cg, and the integrated dissipation rate over the boundary layer, as a function of the surface Rossby number. Lettau's first-order closure mixing-length model gives an excellent fit to the data; other simple models give reasonable agreement. However more sophisticated models, e.g., higher-order closure, large-eddy simulation, direct numerical simulation and laboratory models, give poor fits to the data. The simple models have (at least) one free parameter in their turbulence closure that is matched to atmospheric observations; the more sophisticated models either base their closure on more general flows or have no free closure parameters. It is suggested that all of the atmospheric experiments that we could locate violate the strict simplifying assumptions of steady, homogeneous, neutral, barotropic flow required by the sophisticated models. The angle α0 is more sensitive to violations of the assumptions than is Cg. The behaviour of the data varies in three latitude regimes. In middle and high latitudes the observed values of A and B exhibit little latitudinal dependence; the best estimates are A = 1.3 and B = 4.4. In lower latitudes the neutral, barotropic Rossby number theory breaks down. The value of B increases towards the Equator; the determination of A is ambiguous – the trend can increase or decrease towards the Equator. Between approximately 5° and 30° latitude, the scatter in the data is thought to be primarily due to the inherent presence of baroclinicity. The presence of the trade-wind inversion, thermal instability and the horizontal component of the Earth's rotation ΩH also contribute. Marked changes in the values of A and B occur in the region between the Equator and approximately 5° latitude, as the Coriolis parameter |f| approaches zero. Although the variation of A and B with latitude suggests some similarity to the results obtained from the direct numerical simulations, the presence of additional complexities in the real atmosphere that are not included in the numerical model, precludes a meaningful direct comparison. [ABSTRACT FROM AUTHOR]

The steady-state, horizontally homogeneous, neutral, barotropic case forms the foundation of our theoretical understanding of the planetary boundary layer (PBL). While simple analytical models and first-order closure models simulate atmospheric observations of this case well, more sophisticated models, in general, do not. In this paper we examine how well three higher-order closure models, E - ε - l, E - l, and LRR - l, which have been especially modified for PBL applications, perform in predicting the behaviour of the cross-isobaric angle α0, the geostrophic drag coefficient Cg, and the integral of the dissipation rate over the boundary layer, as a function of the surface Rossby number Ro. For comparison we also examine the performance of three first-order closure mixing-length models, two proposed by A. K. Blackadar and one by H. H. Lettau, and the performance of the standard model for second-order closure and a modification of it designed to reduce the overprediction of turbulence in the upper part of the boundary layer. [ABSTRACT FROM AUTHOR]

Provides information on a study that evaluated the feasibility and efficacy of Rituximab induced into a sequential salvage protocol for CD20[sup+] B cell non-Hodgkin's lyphoma in relapse or induction failure. Details on the patients and methodologies used; Results and discussion.

Here we describe the results of an interlaboratory test for RT-PCR-based BCR/ABL analysis. The test was organized in two parts. The number of participating laboratories in the first and second part was 27 and 20, respectively. In the first part samples containing various concentrations of plasmids with the ela2, b2a2 or b3a2 BCR/ABL transcripts were analyzed by PCR. In the second part of the test, cell samples containing various concentrations of BCR/ABL-positive cells were analyzed by RT-PCR. Overall PCR sensitivity was sufficient in approximately 90% of the tests, but a significant number of false positive results were obtained. There were significant differences in sensitivity in the cell-based analysis between the various participants. The results are discussed, and proposals are made regarding the choice of primers, controls, conditions for RNA extraction and reverse transcription. [ABSTRACT FROM AUTHOR]

The ability of layer I activation to facilitate the induction of long-term potentiation (LTP) in layer II/III horizontal connections of motor cortex (MI) was examined in rat brain slice preparations. Field potentials evoked in layer I and layer II/III horizontal pathways were recorded from radially aligned MI sites. While theta burst stimulation (TBS) of layer II/III pathways alone failed to induce LTP, simultaneous TBS of layer I and layer II/III inputs on alternate sides of the recording electrodes induced LTP in the layer II/III input in 8 out of 13 slices (mean change +20±6%; N=13). In the same cases, the layer I connections showed mixed effects: LTP in three cases, LTD in five cases, and no modification in five slices. Despite the facilitatory effect of layer I activation on layer II/III LTP induction, we found that the critical circuitry for this effect was outside layer I. Cutting the layer I fibers selectively in the slice did not prevent layer II/III LTP induction, while cuts preserving only layer I blocked layer II/III LTP after conjoint I+II/III TBS. Cholinergic fibers were evaluated as candidates for the facilitatory effect because they branch widely in both layers and they are thought to participate in synaptic modification. The cholinergic contribution to layer II/III LTP facilitation was investigated using bath application of muscarinic antagonists. Muscarinic blockade prevented facilitation of layer II/III LTP by layer I coactivation. Instead, conjoint stimulation in 10 µM atropine produced long-term depression (LTD) of layer II/III (–18±9%; N=11) as well as of layer I (–21±6%; N=11) horizontal responses. These results indicate that connections formed within layer I are ineffective in promoting LTP in the deeper-lying horizontal connections; the critical route by which layer I stimulation influenced LTP induction required the circuitry in the deeper layers, particularly the cholinergic system. Thus, it appears that diffuse cholinergic afferents provide an additional route to regulate activity-dependent synaptic modificaton in horizontal cortical connections. [ABSTRACT FROM AUTHOR]

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Copyright of Klinische Wochenschrift is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Klinische Wochenschrift is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Klinische Wochenschrift is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Klinische Wochenschrift is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Klinische Wochenschrift is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Minimal excitatory postsynaptic potentials (EPSP) were investigated in 13 neurons under single or double-pulse near-threshold microstimulation of the radial layer (Schaffer's collaterals) and stratum oriens in surviving hippocampal slices (area CA1) in guinea pigs. The amplitude of 23 EPSP (9 units; 12 pathways) rose after tetanization of Schaffer's collaterals over a 5-55 min period, taken as long-term potentiation (LTP). Statistical analysis conducted using four methods of quantal hypothesis based on a binomial approximation revealed an increase in mean quantal content (m) during LTP. The rise in quantal size was only statistically significant when using data obtained from a section of these methods (mainly for stretches of over 15 min following tetanization) and shows no correlation with intensity of LTP. The pronounced rise in m demonstrated using different methods matches data from experiments on intact animals and indicates a presynaptic location of the mechanisms underlying protracted persistence of residual tetanization lasting some tens of minutes. [ABSTRACT FROM AUTHOR]

Excitatory postsynaptic potentials (EPSP) were recorded from 14 neurons in guinea pig hippocampal slices (area CAl) after stimulating the stratum radiatum (Schaffer collaterals) and stratum oriens. An increase occurring in EPSP amplitude in 7 units (9 pathways) recorded 15-45 min after tetanic stimulation of Schaffer collaterals is viewed as long-term potentiation (LTP). Statistical analysis conducted according to two sets of quantal theory (histogram and variance methods) showed an increase in mean quantal content (m) during LTP. An increase in quantal size, found only when using the histogram method, did not correlate with LTP level. This increase is thought to be associated with the considerably greater sensitivity of the histogram method to noise level in comparison with the variance method, the latter being more reliable with signals of high noise level. The increase found in m using both methods matches findings previously obtained for the whole brain; it also points to presynaptic location of mechanisms responsible for raised synaptic efficacy during LTP. [ABSTRACT FROM AUTHOR]

Sera of patients with acute (AH) and chronic active hepatitis (CAH) were tested for anti-hepatitis B virus (HBV) x-protein (HBx) by immunoblotting, using recombinant MS2- and βgal-HBx fusion proteins as substrate. Antibodies against HBx were detected in 5 out of 17 patients with AH at an early stage of infection, and in 13 out of 35 patients with CAH. Positive sera from AH patients showed a relatively weak anti-HBx reactivity when compared to sera from CAH patients. In follow up studies we tested serial serum samples from patients positive for anti-HBx. Patients with AH were observed for 3 to 6 weeks and CAH patients for up to 51 months. In general anti-HBx reactivities appeared to be stable although significant differences in apparent antibody levels were noted when sera from individual patients were compared. Our data further support an early expression of HBx-antigen in HBV-infected individuals. There was no correlation between HBe-antigen and anti-HBx in CAH. [ABSTRACT FROM AUTHOR]

Intercalating agents, some of them in clinical use, were tested for their ability to inhibit the hepatitis B virus specific DNA polymerase reaction. Ethidium bromide was shown to be the strongest inhibitor among the compounds tested. Compounds in clinical use inhibited the DNA polymerase test only at high concentrations. The inhibitory activity of all compounds tested was increased when the MgCl content in the reaction mixture was lowered. UV absorption studies presented no evidence that this effect was due to complex formation of magnesium and the individual compounds. The therapeutic significance of these findings is not certain and needs further work. [ABSTRACT FROM AUTHOR]

The natural killer (NK) cell activity of mice in the peritoneal cavity is very low or undetectable and testing peritoneal NK cells is a useful model for studying the influence of activating substances upon local injection. Injection of tumor necrosis factor (TNF) at doses of 10-200 ng caused a marked activation of NK cell activity which was maximal after 24 h and declined rapidly on day 2. A similar effect was observed when interferons alpha and beta were injected, and there were additive results when interferon was injected together with TNF. The NK cell nature of the effector cells activated by TNF was substantiated by the finding that previous injection with anti-asialo GM 1 antibody prevented activation. Interferon could not be detected in the peritoneal wash fluid after injection of TNF suggesting interferon-independent activation. In further experiments after i.p. injection of TNF peritoneal exudate cells (PECs) only killed YAC-1 targets in a 4-h assay. There was no additional killing in an 18-h assay towards neither YAC-1 cells or P815 cells, suggesting that macrophages were not involved. Furthermore TNF was also active in vitro by activating NK cells in isolated human peripheral blood cells. However in the PECs stimulated in vitro no significant induction of cytotoxic capacities by TNF was measured. Our data suggest that the action of TNF is not restricted to the lysis of tumor cells but can also induce immunological properties in the host defense against virus infections and neoplasms. [ABSTRACT FROM AUTHOR]

In a prospective multicentre trial, the influence of schedule, compliance, age, sex and weight on the antibody response to hepatitis B vaccination was investigated. Comparison of the vaccination schedules 0, 1, 6 months (group 1; n=143) and 0, 1, 2, 12 months (group 2; n=141) was performed in months 3, 7 and 12. In addition, the antibody response was compared one month after the third and one and six months after the last vaccination. Seroprotection rates (anti-HB>10 IU/l) and antibody titres, given as geometric means (GMTs), were higher in group 1 at month 12 as well as one month after completion of three immunizations. More vaccinees of group 2, however, showed seroprotection at month 3 with higher GMTs. In addition, GMTs in group 2 were higher both one month and six months after the last vaccine dose. Determination of parallel corrected correlation factors demonstrated that age was the most important single factor, followed by body weight and sex. However, no more than 3 % of the variation in the GMT can be explained by the influence of age. Due to decreased compliance with the four-dose schedule with a drop-out rate of approximately 10 % of the vaccinees, the total percentage of initial vaccinees who in the end developed protective antibody levels was higher in the 0, 1, 6 months schedule. Thus, it can be concluded that subjects likely to comply will benefit from the 0, 1, 2, 12 months schedule as more rapid protection is obtained and the higher antibody levels after the booster vaccination at month 12 provide longer protection. However, vaccinees whose compliance might be questionable over a period of 12 months, should be selected for the vaccination 0, 1, 6 months schedule as compliance is at a higher level over this period and advantage can be taken of the booster effect of the third dose given in month 6. [ABSTRACT FROM AUTHOR]

Diagnosis of infection with the human immunodeficiency virus (HIV) relies on the demonstration of antibody to this virus. Occasionally, the combined analysis of sera using ELISA and western blot reveals false-positive results. We have compared a newly developed test to detect antibodies to the core (anti-p24) and surface (anti-p41) proteins of HIV with the established tests described above. Anti-p24 and anti-p41 were negative in three individuals positive for anti-HIV by ELISA and immunoblot; they had a low risk to acquire HIV infection and were clinically and immunologically normal and suspected false positive previously. In 62 individuals at risk, anti-p41 was always positive while anti-p24 was negative in 24/62 individuals including all but one patient with AIDS. The data indicate that this new test may replace the western blot as a reliable, widely available, and standardized confirmatory assay. In addition, preliminary evidence needs to be confirmed that quantitative analysis of anti-p24 might be of prognostic value in the course of HIV infection. [ABSTRACT FROM AUTHOR]

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Binomial distributions of amplitudes of excitatory postsynaptic potentials (EPSPs) mixed with Gaussian noise were simulated. The objective of Monte Carlo simulations was, firstly, to study influences of sampling size (N) and noise standard deviation (S) on estimates of mean quantal content (m), quantal size (v) and binomial parameters (n and p) by four methods of quantal analysis (histogram, variance, failures and combined method) based on the binomial model and, secondly, to modify these methods on the basis of comparison of estimated with simulated parameters. Reliable estimates (within ± 10% of the simulated values) were obtained for large sample sizes (N=500-1000) with S≤v by the histogram (deconvolution) method and with S≤2v by the other three methods. Similar results were obtained by averages from about 10 simulations if smaller samples were used (N=50-200). In electrophysiological experiments on slices, 'minimal' EPSPs were recorded from CA1 pyramidal cells after low-intensity stimuli to stratum radiatum or stratum oriens. Amplitudes of minimal EPSPs fluctuated in a manner predicted by the quantum hypothesis. Amplitude distributions of EPSPs in the nonfacilitated state were adequately described either by binomial statistics with an average p equal to about 0.4 (a range of 0.3-0.7) and an average n of about 3 (range 2-6) or by Poisson statistics with m of about 1. The quantal analysis suggests that typical values of m and v for a single activated fibre in stratum radiatum might be about 0.5-1 and 300-400 μV, respectively, with low p (0.1-0.3) and n (2-4). However, the estimates of binomial parameters should be considered as coarse approximations in view of the simulation results and a possible nonuniformity of parameter p. The comparison of results of various methods based on the binomial model, in both simulation and physiological experiments, indicates the reliability of estimates of basic quantal parameters (m and v) under realistic conditions of physiological experiments. The methods are considered to be sufficiently sensitive to make use of them for studies on mechanisms of long-term synaptic plasticity. [ABSTRACT FROM AUTHOR]

Excitatory postsynaptic potentials (EPSPs) were recorded in guinea pig hippocampal slices (area CA1) from 15 neurones after stimulation of stratum radiatum (str. rad.) and stratum oriens. EPSP amplitudes increased in 8 neurones (10 post-tetanic regions) recorded 15 to 45 min after tetanic stimulation of str. rad. The increase was considered to represent long-term potentiation (LTP). Quantal analysis was performed by two methods assuming binomial statistics: the histogram method using deconvolution of noise and the variance method. According to both methods, LTP was associated with an increase in mean quantal content (m) which correlated with LTP magnitude. A statistically significant increase in quantal size (v) was found only by the histogram method and the increase was not correlated with LTP magnitude. A separate analysis of EPSPs with small LTP magnitude demonstrated that with the histogram method only v was increased but not m. A smaller increase in m for the pooled data of both methods did not correlate with LTP magnitude for this EPSP subset. The increase in m for the whole EPSP set corresponds to previous results on the quantal analysis of LTP in in vivo preparations and favours a presynaptic location of major mechanisms underlying LTP maintenance. The increase in v indicates the existence of another mechanism responsible for the maintenance of a small part of LTP. This mechanism might involve either pre- or postsynaptic changes or both. [ABSTRACT FROM AUTHOR]

'Minimal' excitatory postsynaptic potentials (EPSPs) were recorded from 13 neurones in area CA1 of guinea pig hippocampal slices after double-pulse stimulation of stratum radiatum (str. rad.) and stratum oriens (str. or.). Amplitudes of EPSPs significantly increased in 8 neurones 5 to 55 min after 9 tetanizations in str. rad. The increase was considered to represent long-term potentiation (LTP). Altogether 26 EPSPs (42 post-tetanic regions) were statistically analysed by four methods of the quantum hypothesis assuming the binomial model of transmitter release: the deconvolution (histogram), the variance, the failures, and the combined (variance-failures) methods. The mean quantal content (m) significantly increased after LTP induction according to all methods used. Quantal size (v) also tended to increase but according to some methods, the increase was not statistically significant and it did not correlate with LTP magnitude. However, for an EPSP subset with a LTP magnitude of < 1.55, the increase in v correlated with LTP magnitude, whereas the increase in m did not. The relative contribution of the increase in v to LTP magnitude was larger for cases with small LTP than for the whole EPSP set. In general, the increase in m corresponds to previous studies and favours the presynaptic location of major mechanisms of LTP maintenance, i.e. an increase in the average number of transmitter quanta released by each presynaptic volley. The post-tetanic increase in v might reflect some additional mechanisms which presumably include an increase in the amount of transmitter in one quantum. [ABSTRACT FROM AUTHOR]

The results of immunological studies in serum and liver tissue from 26 patients with chronic HBsAg-positive hepatitis (15 CPH, 9 CAH, 2 MinH) are presented. Determination of serum immunoglobulins showed no significant differences between the three categories of HBsAg-positive CH. AGF, ANA and AMA were not demonstrable in our patients. HBsAg and anti-HBc were demonstrated in all patients, HBeAg in 16, anti-HBe in 6 patients. 2 children had anti-HBs antibodies. Elevated DNA polymerase activity was found in 8 of 12 HBeAg-seropositive and 0 of 9 HBeAg-sero-negative patients. HBcAg was present in liver tissue from 9 of 10 HBeAg-seropositive and 1 of 9 HBeAg-seronegative children. In some cases the classification of viral antigen expression patterns according to the studies of Bianchi and Gudat did not correspond to the histological diagnosis and the presence of serum HBeAg. Studies in 51 family members of 23 children showed a high incidence of HBsAg carriers among the siblings and frequent evidence of anti-HBs in the mothers. Altogether, contact with HBV was demonstrated in 28 of the relatives studied. [ABSTRACT FROM AUTHOR]

Extensive chemical kinetic measurements of acetylcholine receptor-controlled ion translocation in membrane vesicles isolated from the electroplax of Electrophorus electricus have led to the proposal of a minimum model which accounts for the activation, desensitization, and voltage-dependent inhibition of the receptor by acetylcholine, suberyldicholine, and carbamoylcholine. Comparison of chemical kinetic measurements of the dynamic properties of the acetylcholine receptor in vesicles with the properties of the receptor in cells obtained from the same organ and animal have been hampered by an inability to make the appropriate measurements with Electrophorus electricus electroplax cells. Here we report a method for exposing and cleaning the surface of electroplax cells obtained from both the Main electric organ and the organ of Sachs and the results of single-channel current recordings which have now become possible. The single-channel current recordings were made in the presence of either carbamoylcholine or suberyldicholine, as a function of temperature and transmembrane voltage. Both the channel open times and the single-channel conductance were measured. The data were found to be consistent with the model based on chemical kinetic measurements using receptor-rich membrane vesicles prepared from the Main electric organ of E. electricus. [ABSTRACT FROM AUTHOR]

Hepatitis B virus and the human immunodeficiency virus are similarly transmitted. Individuals with preexisting HIV infection have a higher chance to become HBsAg carriers than do anti-HIV negative persons. Cytotoxic T cells with specificity for HBcAg, that are under the control of HBcAg-specific helper T cells, are responsible for liver injury. There is good evidence that HIV infection lowers inflammatory activity, is associated with milder liver histology, high levels of viral replication and low seroconversion rates. In addition interferon alpha therapy is less effective in anti-HIV positive subjects. The immune response against HBsAg is helper T-cell dependent and vaccination against hepatitis B is of low effectiveness. In addition, vaccination against hepatitis B may activate the HIV disease and is, therefore, presently not to be recommended. [ABSTRACT FROM AUTHOR]

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Copyright of Naunyn-Schmiedebergs Archiv für Experimentelle Pathologie und Pharmakologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Many landscape indexes with ecological relevance have been proposed,including diversity indexes, dominance, fractal dimension, and patchsize distribution. Classified land cover data in a geographic information system (GIS) are frequently used to calculate these indexes. However, a lack of methods for quantifying uncertainty in these measures makes it difficult to test hypothesized relations among landscape indexes and ecological processes. One source of uncertainty in landscape indexes is classification error in land cover data, which can be reported in the form of an error matrix. Some researchers have used error matrices to adjust extent estimates derived from classified land cover data. Because landscape diversity indexes depend only on landscape composition - the extent of each cover in a landscape - adjusted extent estimates may be used to calculate diversity indexes. We used a bootstrap procedure to extend this approach and generate confidenceintervals for diversity indexes. Bootstrapping is a technique that allows one to estimate sample variability by resampling from the empirical probability distribution defined by a single sample. Using the empirical distribution defined by an error matrix, we generated a bootstrap sample of error matrixes. The sample of error matrixes was usedto generate a sample of adjusted diversity indexes from which estimated confidence intervals for the diversity indexes were calculated. We also note that present methods for accuracy assessment are not sufficient for quantifying the uncertainty in landscape indexes that are sensitive to the size, shape, and spatial arrangement of patches. More information about the spatial structure of error is needed to calculate uncertainty for these indexes. Alternative approaches should be considered, including combining traditional accuracy assessments withother probability data generated during the classification procedure. [ABSTRACT FROM AUTHOR]