Microwave Realization of the Gaussian Symplectic Ensemble.

Following an idea by Joyner et al. [Europhys. Lett. 107, 50004 (2014)], a microwave graph with an antiunitary symmetry T obeying T^{2}=-1 is realized. The Kramers doublets expected for such systems are clearly identified and can be lifted by a perturbation which breaks the antiunitary symmetry. The observed spectral level spacings distribution of the Kramers doublets is in agreement with the predictions from the Gaussian symplectic ensemble expected for chaotic systems with such a symmetry.

Azelaic acid: Properties and mode of action.

Acne is a common skin disorder that can be problematic for adults as well as for adolescents. It has several key pathophysiological features such as follicular hyperkeratosis, elevated Propionibacterium acnes proliferation, and reactive inflammation, all of which should be targeted for an optimal outcome. Azelaic acid (AzA) has profound anti-inflammatory, antioxidative effects, and is bactericidal against a range of Gram-negative and Gram-positive microorganisms as well, including antibiotic-resistant bacterial strains. In addition, AzA's antikeratinizing effects are inhibitory toward comedones. AzA is effective overall in targeting multiple causes of acne and has been proven to be well tolerated in numerous clinical trials.

Dynamic proteome allocation regulates the profile of interaction of auxotrophic bacterial consortia.

Microbial ecosystems are composed of multiple species in constant metabolic exchange. A pervasive interaction in microbial communities is metabolic cross-feeding and occurs when the metabolic burden of producing costly metabolites is distributed between community members, in some cases for the benefit of all interacting partners. In particular, amino acid auxotrophies generate obligate metabolic inter-dependencies in mixed populations and have been shown to produce a dynamic profile of interaction that depends upon nutrient availability. However, identifying the key components that determine the pair-wise interaction profile remains a challenging problem, partly because metabolic exchange has consequences on multiple levels, from allocating proteomic resources at a cellular level to modulating the structure, function and stability of microbial communities. To evaluate how ppGpp-mediated resource allocation drives the population-level profile of interaction, here we postulate a multi-scale mathematical model that incorporates dynamics of proteome partition into a population dynamics model. We compare our computational results with experimental data obtained from co-cultures of auxotrophic Escherichia coli K12 strains under a range of amino acid concentrations and population structures. We conclude by arguing that the stringent response promotes cooperation by inhibiting the growth of fast-growing strains and promoting the synthesis of metabolites essential for other community members.

Thermodynamics of DNA binding of MM17, a 'single chain dimer' of transcription factor MASH-1.

MASH-1, a member of the basic helix-loop-helix (bHLH) family of transcriptional regulators, is a central factor for the regulation of the differentiation of committed neuronal precursor cells of the peripheral nervous system. We have previously produced MM17, a single chain version of this dimeric protein, by linking the C-terminal end of the first subunit to the N-terminal residue of the second subunit through a flexible peptide linker. We have now determined by isothermal titration calorimetry the thermodynamic parameters characterising the DNA binding reactions of MM17. The DNA binding specificity was relatively low and comparable to that observed for wild-type MASH bHLH. At 32 degrees C and pH 7, the concentration of MM17 at which 50% DNA binding occurred was determined as 22.8 and 152 nM for binding to MCK-S and the heterologous SP-1, respectively. Similarly to MASH bHLH the free energy of the association was only slightly temperature dependent, while both the entropy and the enthalpy change were strong functions of temperature. The free energy of DNA binding was independent of the pH for the pH range between 6 and 8. Dissection of the entropy change of the association reaction suggested that the two basic domains and the linker region between the subunits underwent a folding transition from a mainly unfolded to a predominantly ordered conformation. Therefore, like wild-type MASH bHLH, the DNA binding reaction of MM17 follows an induced fit mechanism.

Impedance analysis of supported lipid bilayer membranes: a scrutiny of different preparation techniques.

One topic of this study is the comparison of different preparation techniques to build up solid supported lipid bilayers onto gold substrates. The deposited lipid bilayers were investigated by a.c. impedance spectroscopy. Three different strategies were applied: (1) The gold surface was initially covered with a chemisorbed monolayer of octadecanethiol or 1,2-dimyristoyl-sn-glycero-3-phosphothioethanol (DMPTE). The second monolayer consisting of phospholipids was then deposited onto this hydrophobic surface by (i) the Langmuir-Schaefer-technique, (ii) from lipid solution in n-decane/isobutanol, (iii) by the lipid/detergent dilution technique or (iv) by fusion of vesicles. (2) Charged molecules carrying thiol-anchors for attachment to the gold surface by chemisorption were used. Negatively charged surfaces of 3-mercaptopropionic acid were found to be excellent substrates that allow the attachment of planar lipid bilayers by applying positively charged dimethyldioctadecylammoniumbromide (DODAB) vesicles or negatively charged 1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol vesicles in the presence of chelating Ca2+-ions. If positively charged first monolayers of mercaptoethylammoniumhydrochloride were used we were able to attach mixed 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol/1,2-dimyristoyl-sn-glycero- 3-phosphoethanolamine vesicles to form planar lipid bilayers via electrostatic interaction. (3) Direct deposition of lipid bilayers is possible from vesicles containing 1,2-dimyristoyl-sn-glycero-3-phosphothioethanol (DMPTE). A critical amount of more than 50 mol% of DMPTE was found to be necessary to form a solid supported lipid bilayer. Bilayers obtained with these different preparation techniques were scrutinized with respect to their capacitances, kinetics of formation and their long-term stabilities by impedance spectroscopy. The second feature of this paper is the application of the supported bilayers to study ion transport through channel-forming peptides. We used a DODAB-bilayer for the reconstitution of gramicidin D channels. By circular dichroism measurements we verified that the peptide is in its channel conformation. The ion transport of Cs+-ions through the channels was recorded by impedance analysis.

Non-Hodgkin's lymphoma after primary Hodgkin's disease in the German Hodgkin's Lymphoma Study Group: incidence, treatment, and prognosis.

PURPOSE: The cumulative incidence for non-Hodgkin lymphoma's (NHL) after primary Hodgkin's disease (HD) ranges between 1% and 6%. To investigate the course of disease for secondary NHL, we retrospectively analyzed patients treated within clinical trials of the German Hodgkin's Lymphoma Study Group (GHSG) since 1981. PATIENTS AND METHODS: From 1981 to 1998, the GHSG conducted three generations of clinical trials for the treatment of primary HD involving a total of 5,406 patients. Reference histology by an expert panel was obtained for 4,104 of the patients. Data on incidence, treatment, and outcome of secondary NHL were updated in March 1999. RESULTS: At first diagnosis of HD, the pathologists rejected 114 (2.1%) of 5,520 cases initially diagnosed as HD and rediagnosed them as primary NHL. Fifty-two (0.9%) of the remaining 5,406 patients developed a secondary NHL. One patient was excluded from further analyses because of insufficient documentation. Six patients had no further therapy because of patient refusal (n = 1) or rapidly progressive disease (n = 5). For the remaining 45 patients, overall response rate was 43% (36% complete response and 7% partial response). The actuarial 2-year freedom from treatment failure (FFTF) and overall survival (OS) for all patients was 24% and 30%, respectively, and for patients with diffuse large-cell lymphoma, it was 28% and 35%, respectively. Time of occurrence of secondary NHL after first diagnosis of HD and variables employed in the age-adjusted International Prognostic Factor Index (IPFI) significantly influenced treatment outcome. CONCLUSION: In the GHSG, the incidence of secondary NHL with 0.9% is relatively low compared with previously reported series. The prognosis of secondary NHL seems dismal and is significantly influenced by time of occurrence and the age-adjusted IPFI. In a subset of patients with secondary NHL, long-term disease-free survival could be achieved.

14-day variant of the bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone regimen in advanced-stage Hodgkin's lymphoma: results of a pilot study of the German Hodgkin's Lymphoma Study Group.

PURPOSE: This multicenter pilot study assessed the feasibility and efficacy of a time-intensified bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) regimen given in 14-day intervals (BEACOPP-14) with granulocyte colony-stimulating factor (G-CSF) support in advanced Hodgkin's lymphoma. PATIENTS AND METHODS: From July 1997 until March 2000, 94 patients with Hodgkin's lymphoma stage IIB, III, and IV were scheduled to receive eight cycles of BEACOPP-14. Consolidation radiotherapy was administered to regions with initial bulky disease or residual tumor after chemotherapy. RESULTS: All patients were assessable for toxicity and treatment outcome. Eighty-six patients received the planned eight cycles of BEACOPP-14. Consolidation radiotherapy was given in 66 patients. Chemotherapy could generally be administered on schedule. Dose reductions varied among drugs but were generally low. Acute toxicity was moderate, with World Health Organization grade 3/4 leukopenia in 75%, thrombocytopenia in 23%, anemia in 65%, and infection in 12% of patients. A total of 88 patients (94%) achieved a complete remission. Four patients had progressive disease. At a median observation time of 34 months, five patients have relapsed, one patient developed a secondary non-Hodgkin's lymphoma, and three deaths were documented. The overall survival and freedom from treatment failure rates at 34 months were 97% (95% confidence interval [CI], 93% to 100%) and 90% (95% CI, 84% to 97%), respectively. CONCLUSION: Acceleration of the BEACOPP baseline regimen by shortening cycle duration with G-CSF support is feasible and effective with moderate acute toxicity. On the basis of these results, the German Hodgkin's Lymphoma Study Group will compare the BEACOPP-14 regimen with BEACOPP-21 escalated in a prospective multicenter randomized trial.

Dose-response relationship of complementary radiotherapy following four cycles of combination chemotherapy in intermediate-stage Hodgkin's disease.

PURPOSE: To determine the appropriate irradiation dose after four cycles of modern combination chemotherapy in nonbulky involved field (IF/BF) and noninvolved extended-field (EF/IF) sites in patients with intermediate-stage Hodgkin's disease (HD). MATERIALS AND METHODS: HD patients in stage I to IIIA with a large mediastinal mass, E stage, or massive spleen involvement were treated with two double cycles of alternating cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) plus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by EF irradiation in two successive trials (HD1 and HD5). In the HD1 trial (1983 to 1988), 146 patients who responded to chemotherapy were randomized to receive 20 Gy (70 patients) or 40 Gy (76 patients) of EF irradiation in all fields outside bulky disease sites. A cohort of 111 patients who fulfilled the same inclusion criteria in the subsequent trial HD5 (1988 to 1993) were treated with 30 Gy. Bulky disease always received 40 Gy. RESULTS: Freedom-from-treatment-failure (FFTF) and survival (SV) curves showed no differences between the 20-, 30-, and 40-Gy groups. However, acute toxicities were more frequent in the 40-Gy arm. Analysis of relapse patterns showed that 18 of 26 relapsing patients either failed to respond in initial bulky sites (n = 5) or had an extranodal relapse (n = 9) or both (n = 4). After 5 years, the cumulative risk for relapse in bulky sites is 10%, despite 40 Gy of radiation. CONCLUSION: Our results strongly suggest that there is no relevant radiotherapy dose effect in the range between 20 Gy and 40 Gy in IF/BF and EF/IF after 4 months of modern polychemotherapy in patients with intermediate-stage HD. Relapse patterns indicate that patients destined to relapse need more systemic, rather than local, treatment. Based on our data, we conclude that 20 Gy is sufficient in EF/IF of intermediate-stage HD following four cycles of modern polychemotherapy.

BEACOPP, a new dose-escalated and accelerated regimen, is at least as effective as COPP/ABVD in patients with advanced-stage Hodgkin's lymphoma: interim report from a trial of the German Hodgkin's Lymphoma Study Group.

PURPOSE: The HD9 trial aims to evaluate whether moderate dose escalation and/or acceleration of standard polychemotherapy is beneficial for advanced-stage Hodgkin's disease (HD). Two variants of a novel bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) scheme (standard and escalated dose) are compared with cyclophosphamide, vincristine, procarbazine, and prednisone (COPP)/doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). PATIENTS AND METHODS: The randomized, three-arm trial recruited patients in stages IIB and IIIA with risk factors and stages IIIB and IV. BEACOPP in baseline dose contains all drug dosages of COPP/ABVD (except vincristine and procarbazine) rearranged in a shorter, 3-week cycle. Escalated BEACOPP uses higher doses of cyclophosphamide, doxorubicin, and etoposide with granulocyte colony-stimulating factor (G-CSF) support. After eight chemotherapy cycles, initial bulky and residual disease is irradiated. The trial is monitored and analyzed by means of a sequential strategy. RESULTS: An interim analysis with 505 assessable patients and a median follow-up of 23 months showed a significant inferiority (according to sequential monitoring strategy) of the COPP/ABVD regimen in progression rate and freedom from treatment failure (FFTF) compared with the pooled results of both BEACOPP variants. The 24-month FFTF rate was 75% for COPP/ABVD and 84% for BEACOPP pooled (P = .034). There was 12% progressive disease with COPP/ABVD and 6% with BEACOPP pooled. Differences in survival were not significant in sequential analysis. The acute toxicity of baseline BEACOPP resembled that of COPP/ABVD; escalated BEACOPP showed increased but manageable hematologic toxicity. CONCLUSION: Combined with local irradiation, BEACOPP in one or both variants shows superior disease control compared with COPP/ABVD, with acceptable acute toxicity. Further follow-up is required to assess the effect of dosage and the effect on survival and late toxicities.

Low-dose radiation is sufficient for the noninvolved extended-field treatment in favorable early-stage Hodgkin's disease: long-term results of a randomized trial of radiotherapy alone.

PURPOSE: To show that radiotherapy (RT) dose to the noninvolved extended field (EF) can be reduced without loss of efficacy in patients with early-stage Hodgkin's disease (HD). PATIENTS AND METHODS: During 1988 to 1994, pathologically staged patients with stage I or II disease who were without risk factors (large mediastinal mass, extranodal lesions, massive splenic disease, elevated erythrocyte sedimentation rate, or three or more involved areas) were recruited from various centers. All patients received 40 Gy total fractionated dose to the involved field areas but were randomly assigned to receive either 40 Gy (arm A) or 30 Gy (arm B) total fractionated dose for the clinically noninvolved EF. No chemotherapy was given. RT films were prospectively reviewed for protocol violations and recurrences retrospectively related to the applied RT. RESULTS: Of 382 recruited patients, 376 were eligible for randomized comparison, 190 in arm A and 186 in arm B. Complete remission was attained in 98% of patients in each arm. With a median follow-up of 86 months, 7-year relapse-free survival (RFS) rates were 78% (arm A) and 83% (arm B) (P =.093). The upper 95% confidence limit for the possible inferiority of arm B in RFS was 4%. Corresponding overall survival rates were 91% (arm A) and 96% (arm B) (P =.16). The most common causes of death (n = 27) were cardiorespiratory disease/pulmonary embolisms (seven), second malignancy (six), and HD (five). Protocol violation was associated with significantly poorer RFS. Nonirradiated nodes were involved in 42 of 52 reviewed relapses, infield areas in 18, marginal areas in 17, and extranodal sites in 16. CONCLUSION: EF-RT alone attains good survival rates in favorable early-stage HD. The 30-Gy dose is adequate for clinically noninvolved areas. Protocol violation worsens the subsequent prognosis. Relapse patterns suggest that systemic therapy can reduce the 20% long-term relapse rate.

Infradiaphragmatic versus supradiaphragmatic Hodgkin lymphoma: a retrospective review of 1,114 patients.

Infradiaphragmatic Hodgkin lymphoma (IDH) accounts for 4-13% of cases of stage I-II Hodgkin lymphoma (HD). It has been associated with distinct pre-treatment characteristics and outcomes when compared with supradiaphragmatic HD (SDH). The comparison of IDH vs SDH can only be made in early and intermediate stages (I-II), such a comparison is not possible for advanced stages (III-IV). This study retrospectively compared two groups of 1013 patients with stage I-II SDH and 101 patients with IDH (10%). These two sub-groups of patients were treated in 1988-1993 in 2 prospective randomized clinical trials in Germany for early and intermediate stages of Hodgkin lymphoma. IDH-patients were older (median 39 vs 31 years; p < 0.001), predominantly male (73% vs 52%; p < 0.001) and more often had involvement of 3 lymph node areas (LNA) (80% vs 55%; p < 0.001). Histology in IDH was more likely to be mixed cellularity (46.5% vs 23.6%, p < 0.001) or lymphocyte predominant (20 vs 10%, p = 0.003) and less likely nodular sclerosis (25% vs 63%, p < 0.001). In early-stage unfavorable disease, IDH was associated with a higher treatment failure rate (unadjusted hazard ratio 2, 95% CI, 1.3-3.4; p = 0.003). After controlling for age, sex, stage, histology, B-symptoms and involvement of 3 LNA, the adjusted hazard ratio was 1.25 (95% CI, 0.65-2.4; p = 0.51) so that IDH was no longer associated with a statistically significant treatment failure rate. Poorer outcomes with IDH as compared to SDH are attributable to its association with known adverse prognostic risk factors, but IDH, in itself, is not an independent adverse prognostic factor for treatment failure or survival.

BEACOPP and COPP/ABVD as salvage treatment after primary extended field radiation therapy of early stage Hodgkins disease - results of the German Hodgkin Study Group.

Patients with early stage favorable Hodgkin's disease who relapse after extended field radiotherapy have satisfactory results. We retrospectively analysed patients with relapsed HD after initial radiation therapy alone to determine treatment outcome and prognostic factors. Nine-hundred and forty five patients in localized stages without risk factors received either 40 Gy extended field RT or 30 Gy EF RT followed by an additional 10 Gy to involved lymph node regions. 107 patients relapsed and received salvage therapy. Characteristics of the 107 patients at relapse were as follows: median age was 34 years (range 18--75) with relapse occuring at a median of 19 months (range 4--98 months), 31% were female. The majority of patients (93%) were treated with conventional chemotherapy. Sixty-nine percent were treated with COPP/ABVD like regimens, 21% with BEACOPP, and 3% received various other regimens. Seven percent were treated with radiotherapy alone. Complete remission was achieved in 87% of all salvaged patients. The median follow-up after relapse was 45 months. FF2F (freedom from second treatment failure) and OS (overall survival) were 81% and 89%, respectively. In multivariate analysis age was the major prognostic factor for FF2F and OS (p<0.0001, for both). Further independent prognostic factors were B symptoms (p=0.05) and salvage chemotherapy (p=0.03) for FF2F, and B symptoms (p=0.03) and extranodal involvement (p=0.02) for OS. The long-term outcome of patients relapsing after EF RT is excellent. Age, B symptoms, extranodal involvement and salvage chemotherapy were identified as prognostic factors for second relapse and survival.

Fatigue in long-term survivors of Hodgkin's lymphoma; a report from the German Hodgkin Lymphoma Study Group (GHSG).

Although treatment regimens for Hodgkin's lymphoma have become more sophisticated, little is known about the prevalence of fatigue in long-term survivors. Therefore, we investigated the fatigue status of long-term survivors of Hodgkin's lymphoma and a control group using a pre-validated questionnaire. In 1995/1996, we contacted 1981 patients, who were enrolled in the German Hodgkin Studies HD 1-6. All patients were treated according to the treatment protocols HD1-3 (1981-1988) and HD 4-6 (1988-1993). The patients with a current status of complete remission were asked to complete a quality-of-life (QoL) questionnaire (European Organisation for Research and Treatment of Cancer Quality of Life Core 30 (EORTC QLQ C-30)) and a fatigue questionnaire (Multidimensional Fatigue Inventory (MFI)). The results were compared with the data from 935 controls, matched for age, gender and living area. Eight-hundred and eighteen questionnaires from the patients were available for analysis. The median time between the end of treatment and completing the questionnaire is 5.2 years. Fatigue levels of patients with Hodgkin's lymphoma are high, even years after treatment. Fatigue dimensions are significantly influenced by several clinical and non-clinical factors. Fatigue levels of Hodgkin's lymphoma patients are significantly higher than those of the control group. Further investigations are warranted to explore the effectiveness of treatment strategies for fatigue.

Calcium channels reconstituted from the skeletal muscle dihydropyridine receptor protein complex and its alpha 1 peptide subunit in lipid bilayers.

In the first part of this study, we show that sDHPR and pDHPR preparations reconstituted into lipid bilayers formed on the tips of patch pipettes exhibit two divalent cation-selective conductance levels of 9 and 20 pS, similar in single-channel conductance to VSCC reported in a variety of intact preparations (see Pelzer et al. and Tsien et al. for review). The larger conductance level is similar to the VSCC identified in intact rat t-tubule membranes and described in sDHPR and pDHPR preparations, and shares many properties in common with activity from L-type VSCC. It is sensitive to augmentation by the DHP agonist (+/-)-BAY K 8644 and cAMP-dependent phosphorylation, and to block by the phenylalkylamine (+/-)-D600 and the inorganic blocker CoCl2. Its open-state probability and open times are increased upon depolarization as expected for a voltage-dependent activation process. Upon depolarization beyond the reversal potential, however, open-state probability and open times decline again. A reasonable way to explain the bell-shaped dependence of open times and open-state probability on membrane potential is to assume voltage-dependent ion-pore interactions that produce closing of the channel at strong negative and positive membrane potentials. By contrast, the smaller conductance level may be similar to the 10.6-pS t-tubule VSCC described by Rosenberg et al. and may best be compared with T-type VSCC. It is largely resistant to augmentation by (+/-)-BAY K 8644 and cAMP-dependent phosphorylation or block by (+/-)-D600, but is sensitive to block by CoCl2. Its open times and open-state probability show a sole dependence on membrane potential where depolarization increases both parameters sigmoidally from close to zero up to a saturating level. Both elementary conductance levels do not exhibit significant inactivation over a wide potential range, which may suggest that skeletal muscle VSCC inactivation is either poorly or not voltage-dependent at all. This possibility seems in agreement with bilayer recordings on reconstituted intact t-tubule membranes and voltage-clamp recordings on intact fibers. It supports the idea that the decline of Ca2+ current in intact skeletal muscle fibers may be due to Ca2+ depletion from the t-tubule system and/or to inactivation induced by Ca2+ release from the sarcoplasmic reticulum. We consistently observe two conductance levels of 9 and 20 pS, either singly, or together in the same bilayer from solubilized DHPR samples and even highly purified DHPR preparations.(ABSTRACT TRUNCATED AT 400 WORDS)

Continuous deacetylation of cephalosporins.

Continuous deacetylation of cephalosporin C, 7-aminocephalosporanic acid, and of 2-methoxyethyl acetate in packed beds of an immobilized esterase is described by simple empirical equations relating conversion to space velocity and temperature. The choice of process conditions is discussed in relation to the effects of temperature on column efficiency, column life, growth of microbial contaminants, and the rates of thermal decomposition of the substrates. At the preferred temperature of 10°C columns were operated continuously for one month with only small losses in efficiency.

Impedance and shear wave resonance analysis of ligand-receptor interactions at functionalized surfaces and of cell monolayers.

The present paper scrutinizes the application of impedance spectroscopy and quartz-crystal microbalance (QCM) measurements in the analysis of composite layers of receptor containing lipid bilayers, and their interaction with external ligands or pore-forming peptides. The formation of supramolecular structures and their analysis will be discussed. Impedance measurement allows one to follow the adsorption of proteins on artificial membranes. This method is even more suitable for quantifying changes in membrane conductivity induced by channel peptides incorporated into the lipid membrane. The QCM is another sophisticated method for analyzing ganglioside-lectin and ganglioside-toxin interactions. A critical comparison between both methods will be given. Moreover, we will demonstrate that the QCM method, especially in combination with impedance analysis, is a completely new approach for determining electrical and viscoelastic properties of epithelial and endothelial cell monolayers that form controlled barriers in vivo.

Applications of impedance spectroscopy in biochemistry and biophysics.

The present study is intended to demonstrate the application of impedance spectroscopy to two very different fields of biophysical research. The core component of our measuring setup is a self-constructed continuous wave impedance spectrometer together with special measuring chambers which are individually designed for the systems under investigation. We directed our attention towards: i) the investigation of solid supported lipid bilayers in general, especially systems which are suitable for protein reconstitution such as dimethyldioctadecylammonium bromide (DODAB) immobilized onto a gold electrode, precovered with a negatively charged monolayer of 3-mercaptopropionic acid. Impedance spectroscopy allows to study the stability, the thickness and the electrode coverage of those artificial membranes as well as the observation of ion transport mediated by ionophores like gramicidin D incorporated into a DODAB-bilayer. ii) The characterization of the passive electrical properties of epithelial and endothelial cell monolayers in general and especially the determination of their transepithelial (transendothelial) electrical resistances as a measure for epithelial barrier function. From impedance spectra, as reported here, we are able to follow the formation and modulation of cell layer permeability to small ions.

Social background, attitudes and personality in a three-year follow-up study of alcohol consumers.

Eight hundred and forty-one men from the Canton of Zürich selected from a complete survey of males born in 1952 answered a questionnaire at age 19 and again three years later about their consumption of alcohol, drugs and cigarettes, social status, and social integration. The Freiburger Personality Inventory was used for personality assessment. Abuse of alcohol was connected with the following risk factors: lack of social integration, negative relations with parents, frequent relations with the peer group, heavy cigarette and cannabis consumption and lower social status of the father. Less important were: level of education, personality traits (emotional lability, extraversion), low fitness activities and the parental drinking pattern. Emotional lability was not increased in the heavy consumption group, but was rather a personality trait already existing before regular alcohol consumption began.

Alcohol, tobacco and cannabis: 12-year longitudinal associations with antecedent social context and personality.

In a 12-year longitudinal study of a birth cohort 1577 men were questioned at the age of 19 and again at 31 years. Personality, social background and substance use were connected with subsequent consumption of alcohol, tobacco and cannabis, using correlation and discriminant analysis on the total and on two split samples, respectively. The preceding level of substance use was the best predictor for later use. Antisocial attitudes, depressiveness and psychosomatic complaints were associated as non-specific indicators. The following predictors were specific for: Alcohol: parental consumption, self-description as aggressive-extraverted; Tobacco: broken home, low level of vocational training, extraversion; Cannabis: alienation from society. The results are related to various theoretical frameworks and discussed with regard to possible efforts for prevention.

Idiotype vaccine against Hodgkin's lymphoma: generation and characterization of an anti-idiotypic monoclonal antibody against the Hodgkin-associated (anti-CD 30) monoclonal antibody HRS-3.

The murine monoclonal antibody HRS-3 (Ab1; isotype IgG1-Kappa), that defines the CD30 antigen (m.w. 120,000) expressed by Hodgkin-Reed Sternberg cells was used to generate monoclonal anti-idiotype antibodies (Ab2) in syngeneic BALB/c mice. Ab2 were selected on the basis of their binding to HRS-3 immunoglobulin and F(ab')2 fragments and lack of reactivity with the whole immunoglobulin or F(ab')2 fragments of unrelated monoclonal antibodies of the same isotype and allotype. Such a putative anti-idiotypic Ab2, was designated antibody 12D3 and further characterized. 12D3 bound to the paratope of HRS-3, as determined by a 85% inhibition of binding of biotinylated HRS-3 to the cell surface of the CD30 positive Hodgkin cell line L450, and to semipurified CD30 positive cell lysates thereof at a concentration as low as 50 ng/well. These results demonstrate that 12D3 binds at or near the binding site of HRS-3 to the CD30 antigen. Purified 12D3 was coupled to keyhole limpet hemocyanine and used to immunize BALB/c mice and rabbits in order to obtain an Ab3 which binds to the CD30 antigen. These immune sera inhibited the binding of biotinylated 12D3 with HRS-3. Moreover, they showed binding activity with the CD30 positive L540 Hodgkin cell line as well as with the L540 cell lysates, indicating that an anti-anti-idiotopic antibody (Ab3) shares idiotopes with Ab1 (HRS-3). These data suggest that antibody 12D3 may be useful in the generation of an anti-idiotype vaccine against Hodgkin's lymphomas.