Multiple Autoantigen Mimotopes of Infectious Agents Induce Autoimmune Arthritis and Uveitis in Lewis Rats

We found multimolecular antigenic mimicry of arthritogenic autoantigens and peptides from several other “self” or foreign antigens sharing amino acid sequence homologies. Many of these new mimotopes induced arthritis and/or uveitis upon immunization in Lewis rats, indicating a role for multiple antigens in the initiation of a certain autoimmune disease.     

In situ X-ray absorption spectroscopy at the K-edge of red phosphorus in polyamide 6,6 during a thermo-oxidative degradation

We present a new method for studying the influence of flame retardants as a function of time and temperature by measuring the X-ray absorption spectra of the corresponding additive. Here, red phosphorus in polyamide 6,6 was investigated at the phosphorus K-edge using synchrotron radiation. The thermo-oxidative degradation of the polymer was simulated by heating the sample up to 300°C. XANES

1 XANES, EXAFS: X-ray absorption spectroscopy investigating the near edge structure or the fine structure of the extended region, respectively.

spectra were monitored during the degradation process at different temperatures and at a constant reaction temperature as a function of time. The degradation reaction was analyzed by comparing the XANES spectra of red phosphorus and orthophosphoric acid, and the reaction was identified as an oxidation of red phosphorus to H₃PO₄. The results so obtained are confirmed by the EXAFS spectra of the additive in the polymer sample recorded before and after the thermo-oxidative degradation process, and by the EXAFS spectra of suitable reference compounds.     

Comparison of HLA-DR1-restricted T cell response induced in HLA-DR1 transgenic mice deficient for murine MHC class II and HLA-DR1 transgenic mice expressing endogenous murine MHC class II molecules

Transgenic mice expressing human HLA class II molecules provide a useful model for identifying HLA-restricted CD4+ epitopes. However, the influence of endogenous murine H-2-restricted T cell responses on HLA-restricted responses is not known. In the present study, we show that HLA-DR1 transgenic mice deficient for H-2 class II expression (HLA-DR1+/+/IAbeta0/0) exhibit an equivalent expression level of the transgene HLA-DR1 and a similar diversity in the TCR repertoire, but a slightly different number of CD4+ peripheral T cells, when compared to HLA-DR1 transgenic mice in which H-2 class II molecules were retained (HLA-DR1+/+/IAbeta+/+). More importantly, a strong antigen-specific HLA-DR1-restricted response was observed in nearly all HLA-DR1+/+/IAbeta0/0 mice immunized with HBV envelope protein (HBs) or capsid protein (HBc), whereas weak HBs- or HBc-specific HLA-DR1-restricted responses were detected in half of the immunized HLA-DR1+/+/IAbeta+/+ mice. Conversely, strong HBs- or HBc-specific H-2-restricted T cell responses were detected in HLA-DR1+/+/IAbeta+/+ mice but not in HLA-DR1+/+/IAbeta0/0 mice. Our results indicate that the coexpression of endogenous H-2 class II molecules reduces the intensity of HLA-DR1-restricted antigen-specific responses in transgenic mice, by favoring murine over human MHC recognition and education. Thus, HLA-DR1+/+/IAbeta0/0 mice represent a better model for identifying and characterizing HLA-DR1-restricted epitopes relevant for human disease.     

Autoimmune uveitis induced by molecular mimicry of peptides from rotavirus,bovine casein and retinal S-antigen

Antigenic mimicry of infectious agents and autoantigens is a proposed pathomechanism for autoimmune diseases. Here, we describe antigenic mimicry of a peptide from rotavirus, a nutritional protein from bovine milk (alphas2-casein) and a peptide thereof as well as a highly pathogenic peptide from retinal S-antigen (PDSAg), a major autoantigen in experimental autoimmune uveitis in Lewis rats. Immunization of rats with the peptides and the casein protein induced uveitis, an intraocular inflammation leading to decreased vision and even blindness. The peptides elicited cross-reactive T cell responses and uveitis in rats and were also recognized by lymphocytes and sera from uveitis patients. Oral tolerization with PDSAg, but not with rotavirus- and casein-derived peptides or casein protein, prevented PDSAg-induced uveitis in rats. Cofeeding of casein with cholera toxin induced uveitis in rats, suggesting that breaking oral tolerance to casein during gastrointestinal infections might also be able to initiate uveitis in humans.     

An indirect method for the estimation of osteoporotic fractures from injury and fracture profiles

Summary Study objective was to develop a valid epidemiological method for the estimation of osteoporotic fracture risk, using administrative databases and accounting for variable baseline risks of injury. Design is the secondary analysis of inpatient and outpatient utilization data. A baseline injury risk was estimated by the incidence of primary utilization of medical services for soft tissue injuries (ICD-9 diagnostic codes 910–929), and the risk profile was compared after normalization with the overall primary utilization rate for fractures (ICD-9 diagnostic codes 800–829). The setting is a county with approximately 100,000 inhabitants in the former East Germany. Participants were all inhabitants of the county who had a physician contact (inpatient or outpatient) during 1987–1988, as well as hospital inpatients for all of Germany in 1989. The number of fractures increased with age, especially in women, when compared to the number of fractures expected from the incidence of soft tissue injury. Similar patterns were identified in hospitalization data from East and West Germany. Estimating the prevalence of osteoporosis directly from certain osteoporotic fracture types associated with higher age is potentially biased, since it neglects the underlying risk of injury. Our model distinguished the osteoporotic fracture risk as the excess risk over an expected injury-related fracture risk for a given age and sex, and may allow a more valid quantification of osteoporotic fractures in different populations.

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Zusammenfassung Studienziel war die Entwicklung einer validen Methode zur Abschätzung des osteoporotischen Frakturrisikos unter Verwendung administrativer Daten und unter Berücksichtigung eines variablen Hintergrundrisikos für Unfälle. Studiendesign ist die sekundäre Analyse von Daten zur stationären und ambulanten Inanspruchnahme. Das Hintergrundrisiko für Unfälle wurde aus der Inzidenz der primären Inanspruchnahme der medizinischen Versorgung für Weichteilverletzungen (ICD-9 Kodierungen 910–929) geschätzt, und das Risikoprofil nach Normalisierung mit der allgemeinen primären Inanspruchnahme wegen Frakturen (ICD-9 Kodierungen 800–829) verglichen. Studienort war ein Landkreis mit etwa 100 000 Einwohnern in der ehemaligen DDR. Studienteilnehmer waren alle Einwohner des Kreises, welche 1987–1988 einen ambulanten oder stationären Arztkontakt hatten, sowie Krankenhausfälle in beiden deutschen Staaten im Jahr 1989. Die Anzahl der Knochenbrüche nahm mit dem Lebensalter zu, vor allem bei Frauen, verglichen mit der Anzahl, welche aus der Inzidenz der Weichteilverletzungen zu erwarten gewesen wäre. Ein ähnliches Muster war bei den Krankenhausfällen in Ost- und Westdeutschland zu beobachten. Die direkte Schätzung der Prävalenz der Osteoporose aus bestimmten osteoporotischen Frakturtypen, welche mit dem höheren Lebensalter verbunden sind, enthält potentiell einen systematischen Fehler, da ein Hintergrundrisiko für Unfälle vernachlässigt wird. Unser Modell identifiziert ein osteoporotisches Frakturrisiko als überschiessendes Risiko über ein nach Alter und Geschlecht zu erwartendes unfallbedingtes Frakturrisiko, und erlaubt potentiell eine validere Quantifizierung osteoporotischer Frakturen in verschiedenen Populationen.

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Résumé L'objective de la recherche était le développement d'une méthode valide pour l'estimation du risque d'une fracture ostéoporotique, utilisant données administratives et tenant compte des risques basales variables concernant les accidents. Le désigne de l'étude est l'analyse secondaire des données hospitalières et ambulatoires. Le risque basale des accidents fut estimé par l'incidence de l'utilisation première des services médicaux pour des blessures non-skeletals (ICD-9 codes 910–929) et cette risque fut comparé après normalisation avec la rate d'utilisation pour des fractures (ICD-9 codes 800–829). La recherche se concentrait sur un département de l'Allemagne de l'Est avec a peu près 100000 habitants. Les participants étaient tous les habitants du département qui avaient un contact avec un médecin (a l'hôpital ou ambulatoire) pendant les années 1987–1988, ainsi que tous les cas hospitalisés dans toute l'Allemagne en 1989. Le nombre de fractures augmentait avec l'âge, en particulier parmi les femmes, comparé avec le nombre attendu de l'incidence des blessures. Des profils de risque pareils ont pu être observés parmi les cas hospitalisés de l'Allemagne de l'Ouest et de l'Est. L'estimation directe de la prévalence de l'ostéoporose a la base de certains types «ostéoporotiques» des fractures, associés avec le troisième âge, peut être incorrecte, parce qu'il néglige le risque basale pour les accidents. Notre modèle distingue le risque ostéoporotique de fracture comme un risque plus haut que le risque de l'accident attendu pour un certain âge et gendre, et permet une quantification plus valide des fractures ostéoporotiques parmi des populations différentes.

     

Health and human rights--development of a questionnaire for measuring perceived human rights status

Zusammenfassung Gesundheit und Menschenrechte stellen in ihrer Verbindung ein wichtiges und innovatives Konzept für die zukünftige Public-Health-Forschung dar. Das Ziel der vorliegenden Studie war die Entwicklung eines Instrumentes zur Erfassung des empfundenen Menschenrechtsstatus und die Evaluation seiner psychometrischen Werte. Die Reliabilität und Validität dieses innovativen Fragebogens für Menschenrechte (MR) wurde an einer Gruppe von Public-Health-Studenten der Universität München (n=42) und an Teilnehmern der KORA-Frakturstudie (n=458) geprüft. Die Studien zeigten zufriedenstellende Ergebnisse für die zeitliche Stabilität (Pearson's r: 0,73; ICC: 0,69) und die interne Konsistenz (Cronbach's Alpha: 0,66–0,79). Die Prüfung der Validität mittels einer Faktoren-analyse und einer Zuordnungsstudie gab Hinweise darauf, dass der Menschenrechtsstatus ein nicht teilbares Konstrukt darstellt. Inhatlich zeigten sich in beiden Gruppen Defizite bei Items aus den Dimensionen Gerechtigkeit und Partizipation.

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Summary Health and human rights as interlinked concepts are a promising new avenue in public health. The aim of this study was the development of a reliable and valid instrument for the measurement of the human right status. The reliability and validity of this new questionnaire for human rights (HRS=human right scale) was measured within a group of Public Health students (n=42) and the participants of the KORA-fracture-study. Test-retest-reliability was 0.73 (ICC: 0.69) and Cronbach's alpha was 0.66–0.79. The evaluation of the validity with the help of a factor analysis and a reconstruction study pointed out, that the perceived human rights status has to be treated as an interlinked and not divisible concept. Both study groups showed deficits for items in the dimension justice and participation.

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Résumé La santé et les droits de l'homme représentent dans leur union un nouveau et important concept dans la recherche de la santé public. Le but de notre étude était le développment d'un questionnaire valide et reliable pour mesurer le status du droit de l'homme. La reliabilité et la validité furent mesuré parmis un groupe d' étudiants de santé public et les participants de l'étude KORA sur les fractures. L'analyse de l' étude montre des résultats satisfaisants pour la réliabilité (stabilité: 0.73; ICC 0.69 et alpha de Cronbach: 0.66–0.79). L'évaluation de la validité a indiqué, que le status du droit de l'homme représente une construction non divisible. Les deux groupes de l'étude montrent un déficit pour des critères dans les dimensions de la justice et de la participation.

     

Clinical and radiological appearance of early gastric cancer in comparision with endoscopical and surgery findings (an analysis of 40 cases) (author's transl)]

Forty cases of so-called early gastric cancer were investigated for their clinical symptomatology and radiological appearance. The essential symptoms are noncharacteristic abdominal pain and weight loss. Polypoid early cancer and depressed types which appear to be benign are problematical for x-ray diagnosis. In occult symptoms like depressed position or breaking off of mucosal folds in the surrounding of an ulcus, malignant growth is thought to occur. The x-ray diagnosis was compared with the gastroscopic diagnosis. The percentage of mucosal carcinomas which were secured preoperatively by biopsy could be increased considerably. In cases of polypoid early cancer the biopsy shows the most negative results. Often the basis of these polyps is cancerously degenerated only partially. Therefore we demand to take more tissue on different places. Especial problematically in x-ray diagnosis is the flat growing form of early gastric cancer if it is situated subcardially. Three of these cases could be neither diagnosed as benign nor as malign. Here the gastroscopy is superior to the x-ray diagnosis. A comparison with the results of surgery shows that half of the cases can be identified as malignant by the microscopical diagnosis only. The laparotomy without opening of the stomach can also lead to misinterpretations. The most important task of the x-ray diagnosis is the early detection of occult changes of gastric mucosa.     

Disinfection of contaminated metal implants with an Er:YAG laser

Infections related to orthopedic procedures are considered particularly severe when implantation materials are used, because effective treatments for biofilm removal are lacking. In this study, the relatively new approach for infection control by using an erbium:yttrium-aluminum-garnet (Er:YAG) laser was tested. This laser vaporizes all water containing cells in a very effective, precise, and predictable manner and results in only minimal thermal damage. For preliminary testing, 42 steel plates and 42 pins were seeded with mixed cultures. First, the minimally necessary laser energy for biofilm removal was determined. Subsequently, the effectiveness of biofilm removal with the Er:YAG laser and the cleansing of the metal implants with octenidine-soaked gauze was compared. Then, we compared the effectiveness of biofilm removal on 207 steel pins from 41 patients directly after explantation. Sonication and scanning electron microscopy were used for analysis. Laser fluences exceeding 2.8 J/cm² caused a complete extinction of all living cells by a single-laser impulse. Cleansing with octenidine-soaked gauze and irradiation with the Er:YAG laser are both thoroughly effective when applied to seeded pins. In contrast, when explanted pins with fully developed biofilms were analyzed, we found a significant advantage of the laser procedure. The Er:YAG laser offers a secure, complete, and nontoxic eradication of all kinds of pathogens from metal implants without damaging the implant and without the possible development of resistance. The precise noncontact removal of adjacent tissue is a decisive advantage over conventional disinfectants. Therefore, laser irradiation could become a valuable method in every debridement, antibiotics, and implant retention procedure.