Highly efficient antigen targeting to M-DC8+ dendritic cells via FcgammaRIII/CD16-specific antibody conjugates

Conjugates of peptide antigens with antibodies specifically recognizing surface molecules on dendritic cells (DC) represent an attractive approach to target antigens to antigen-presenting cells (APC) for the induction of specific T cell responses. The present study evaluates the potential of M-DC8(+) DC, a sub-population of professional APC in the blood, for an antibody-based vaccination strategy. We prepared, by chemical cross-linking, conjugates of peptide model antigens with antibodies directed against different cell surface molecules of DC. Antigen-peptide conjugates using an anti-CD16 (FcgammaRIII) antibody were most potent in inducing in vitro activation of a specific CD4(+) T cell response. They were at least 300 times more efficient than two other antibody-antigen conjugates and approximately 500 times more efficient than unconjugated antigen peptides. Our data demonstrate that specific antigen targeting via CD16 on M-DC8(+) DC is a promising vaccination approach for the efficient induction of specific CD4(+) T cell responses ex vivo, and perhaps in vivo.     

Beneficial effects of ambiguous precues: Parallel motor preparation or reduced premotoric processing time?

The present study was designed to investigate the mechanisms underlying movement preprogramming in situations where informative but ambiguous precue information is used. In a response precuing task that involved flexion or extension movements with the right or left index finger, a spatially compatible precue conveyed partial information about side, about direction, no parameter information (ambiguous condition), or no information at all. Advance movement preparation was indicated by reaction-time shortening for all informative precue conditions. The analysis of stimulus- and response-locked lateralized readiness potential onsets revealed a clear and exclusive motoric origin of the ambiguous-precue benefit. Additional analyses ruled out a strategic trial by trial choice of just one of the two ambiguous alternatives and provided evidence for a parallel preparation of both response alternatives when information only about direction or ambiguous precue information is provided.     

Studies on a German (Münster) version of the temperament auto-questionnaire TEMPS-A: construction and validation of the briefTEMPS-M

BACKGROUND: Based on classic German concepts of a continuum between depressive, hyperthymic, cyclothymic, and irritable temperaments and affective disorder (and adding an anxious type to the four), Akiskal and co-workers developed the Temperament Evaluation of Memphis, Pisa, Paris and San Diego both in interview (TEMPS-I) and auto-questionnaire (TEMPS-A) versions. It is the aim of the present analyses to validate a brief German version of TEMPS-A. METHODS: A total of 1056 students of the Westfalische-Wilhelms-Universitat in Munster, Germany, filled out the long 110-item version of the TEMPS-A (Munster translation by Erfurth: TEMPS-M) modified into a five gradation Likert format and with the items randomized. Based on this data we constructed a brief version of the TEMPS-M. In a second study, a sample of 151 students were recruited who filled out the briefTEMPS-M twice, approximately 1 month apart. RESULTS: Our psychometric procedures resulted in the retention of 35 items from the original 110. The proposed five-factor structure of the original TEMPS-A was upheld, with relatively few item reclassification (mainly due to some overlap between depressive and anxious traits). Internal consistency (Cronbach alpha values ranging from 0.69 to 0.84) and test-retest reliability were shown. Most importantly, all temperaments in the briefTEMPS-M correlated quite well (Pearson r values ranging from 0.49 to 0.72) with their respective original versions in the longer TEMPS-M. As for construct validity, significant correlation was shown with the Beck Depression Inventory for all but the hyperthymic temperament; the hyperthymic, cyclothymic and irritable correlated highest with the self-report Manic Inventory. LIMITATIONS: The study sample of university students was selective. CONCLUSIONS: We were able to construct a brief German version of the TEMPS-A auto-questionnaire. We submit this shorter version will be suitable for both clinical (psychiatric and general medical) and neurobiological research, as well as in studies on temperament features in selected populations, e.g., allowing comparisons between regions or different (German-speaking) countries.     

Genetic alterations in epithelial ovarian tumors analyzed by comparative genomic hybridization

The genetic changes involved in the pathogenesis of ovarian carcinoma are not completely understood. To investigate this matter, we studied paraffin-embedded, microdissected tissue of 47 ovarian epithelial tumors (9 adenomas, 11 tumors of low malignant potential [LMP], 14 serous carcinomas, and 13 nonserous carcinomas) using comparative genomic hybridization (CGH). (The primary data used in this study are available at our CGH online tumor database at http://amba.charite.de/cgh.) Chromosomal imbalances were found in 1 serous adenoma and in 7 LMP tumors. In the latter the alterations appeared randomly and showed no overlap with alterations found in invasive carcinomas. Although the mean aberration number of low-grade serous carcinomas was comparable to LMP tumors, the imbalances of the former occurred with high incidence (>50%) and were found at different localizations. High-grade serous carcinomas had more than twice as much chromosomal imbalances as low-grade serous carcinomas and also had pronounced alterations. In serous carcinomas, gains were found on 3q, 6p, 7, 8q, and 20, and losses were found on 4q, 6q, 12q, 13q, and 16q. Comparing serous and nonserous carcinomas, the mean aberration number was comparable, but the number of high incidence changes was lower, and the most frequent imbalances were losses on 13q and gains on 20p. Overlapping alterations occurring in serous and nonserous carcinomas were gains on 3q and 6p, as well as losses on 4q. Chromosomal imbalances associated with poor prognosis of ovarian carcinomas were gains on 6p, 7q, and 13q and losses on 15q, 17p, 18q, and 21q. Our data indicate that serous LMP tumors and invasive carcinomas have different genetic aberrations, indicating that invasive carcinomas do not arise from preexisting serous LMP tumors. On the other hand, there are common genetic abnormalities in serous and nonserous carcinomas, suggesting that they have very early lesions in common but take different paths of further development.     

Sickness Impact Profile Score versus a Modified Short-Form survey for functional outcome assessment: acceptability, reliability, and validity in critically ill patients with prolonged intensive care unit stays

BACKGROUND: Quality of life after surgical critical illness is an important measure of outcome. The Sickness Impact Profile Score (SIP) has been validated in critically ill patients, but the Modified Short-Form (MSF) has not been directly compared with it. METHODS: The SIP and MSF-36 were coadministered to 127 patients (surrogates) with a prolonged surgical critical illness at baseline at 1, 3, 6, and 12 months. Reliability, validity, and acceptability were determined for overall and subscores at each time point. RESULTS: The overall SIP and eight subscores, including physical health and psychosocial health, were all significantly improved at 1 year compared with baseline (p < 0.05). However, the MSF-36 was improved only in health perception (p < 0.05), but pain scores were higher (p < 0.05) than at baseline. Internal consistency of the MSF-36 was poor at 1 and 3 months. Correlation between the tools was excellent at baseline and 1 year but variable in overall and subscores at other time points. CONCLUSION: The SIP is more comprehensive, reliable, and acceptable in determining specific quality-of-life abnormalities, but the MSF-36 is easier to administer and correlates well at baseline and 1 year in patients with a prolonged critical illness.     

Morphologic and morphometric study of patellar resurfacing with woven carbon filamentous pads

Analysis of retrieved woven carbon filamentous pads, used for resurfacing of the patellar joint surface, disclosed a 4-zonal organizational pattern. Zone 1, facing the articular cavity, was devoid of carbon filaments and consisted of fibrous tissue. Foreign body granulation tissue and fibrous tissue occupied about one-third and ∼50%–60% of the interfilamentous space in zones 2 and 3, respectively. Carbon filaments formed 2%–9% of zone 2 and 14%–16% of zone 3. An interfacial membrane-like zone 4 separated the carbon filamentous pads from a trabecular bony shell. The bone volume within the latter was ∼25%. Given that the purpose of articular resurfacing with implants is repopulation of the defect by chondrocytes producing a cartilaginous matrix, the woven carbon filamentous pads did not fulfill this expectation. In an environment of an ongoing foreign body-induced granulomatous reaction, the stem cells permeating the interstices of the woven carbon filamentous pad are apparently incapable of maturing into highly differentiated cells (chondrocytes) synthesizing a highly complex (cartilaginous) matrix. Received: 10 August 1999     

The Association of Dietary Intake with Arterial Stiffness and Vascular Ageing in a Population with Intermediate Cardiovascular Risk—A MARK Study

The aim of this study was to analyse the association of diet with arterial stiffness and vascular ageing in a Caucasian population with intermediate cardiovascular risk. We recruited 2475 individuals aged 35–75 years with intermediate cardiovascular risk. Brachial-ankle pulse wave velocity (baPWV) was measured using a VaSera VS-1500^® device. Vascular ageing was defined in two steps. Step 1: The 20 individuals who presented kidney disease, peripheral arterial disease, or heart failure were classified as early vascular ageing (EVA). Step 2: The individuals with percentiles by age and sex above the 90th percentile of baPWV among the participants of this study were classified as EVA, and the rest of the individuals were classified as non-EVA. The diet of the participants was analysed with two questionnaires: (1) the diet quality index (DQI) questionnaire and (2) the Mediterranean diet (MD) adherence questionnaire. The mean age of the sample was 61.34 ± 7.70 years, and 61.60% were men. Adherence to the MD was 53.30%. The DQI was 54.90%. Of the entire sample, 10.70% (11.15% of the men and 9.95% of the women) were EVA. In the multiple linear regression analysis, for each additional point in the DQI questionnaire, there was a decrease of −0.081 (95%CI (confidence intervals) −0.105–−0.028) in baPWV; in the MD adherence questionnaire, there was a decrease of −0.052 (95%CI −0141–−0.008). When performing the analysis, separated by sex, the association remained significant in men but not in women. In the logistic regression analysis, there was an increase in MD adherence and a decrease in the probability of presenting EVA, both with the DQI questionnaire (OR (odds ratio) = 0.65; 95%CI 0.50–0.84) and with the MD adherence questionnaire (OR = 0.75; 95%CI 0.58–0.97). In the analysis by sex, the association was only maintained in men (with DQI, OR = 0.54; 95%CI 0.37–0.56) (with MD, OR = 0.72; 95%CI 0.52–0.99). The results of this study suggest that a greater score in the DQI and MD adherence questionnaires is associated with lower arterial stiffness and a lower probability of presenting EVA. In the analysis by sex, this association is only observed in men.