Diagnostische Bewertung des Nachweises von Gliadin-Antikörpern bei Cöliakie

Zusammenfassung Die Methoden der Komplement-bindung und der Präcipitinreaktion in Agar mit Gliadin als Antigen wurden vergleichend auf ihre Anwendbarkeit in der Diagnostik der Cöliakie geprüft.Beim Präcipitinversuch kamen pseudopositive Reaktionen bei 285 Kontrollen nie vor, bei der Komplementbindung zweimal bei 189 Kontrollen.Zwölf sichere Cöliakiefälle ergaben vergleichend geprüft acht bzw. neun positive Reaktionen, wobei die negativen Befunde für die beiden Verfahren nicht das gleiche Serum jeweils betrafen. Wurde die positive Reaktion in nur einer Methode als ausreichend betrachtet, so war das Ergebnis: elf positive Reaktionen auf zwölf Fälle.Während bei klinisch bestätigter Cöliakie die Übereinstimmung der beiden Methoden gut war, war dies bei den bloßen Verdachtsfällen nicht der Fall. Hier gab es bei der Komplementbindung mehr positive Resultate als bei der Präcipitinreaktion.Es wird vorgeschlagen, beide Methoden nebeneinander anzuwenden und sie bei negativem Ausfall zu wiederholen, wobei die gegebenen diätetischen Richtlinien einzuhalten sind. Als Antigen kann ein Glycerinextrakt aus Gluten verwendet werden, wenn gereinigtes Gliadin nicht zur Verfügung steht. Extrakte mit heißem Wasser geben zu viele pseudopositive Reaktionen.

---

Summary Complement fixation tests and precipitin reactions in agar with gliadin as antigen were compared in cases of celiac disease.Pseudopositiv reactions did not occur in 285 controll cases when the precipitin test of Ouchterlony was used, but were seen in two cases of 189 controlls with the complement fixation test.If only one of the two reactions was positive and this was considered as a sufficient proof for the formation of gliadin antibodies those were found in 11 of 12 cases of clinically confirmed celiac disease. In those cases the agreement of the two methods was good, but not so in not confirmed cases where complement fixation tests gave more positive results than the precipitin reaction.It is proposed to use both methods for diagnostic help and to repeat the tests if the reactions are negativ.

     

Prevalence of Eikenella corrodens in dental plaque.

The prevalence of Eikenella corrodens in dental plaque and saliva samples of 282 volunteers was determined by a semiquantitative method with a selective medium. E. corrodens was recovered in 58.9% of plaque samples and 0.3% of saliva samples. This prevalence rate was not significantly altered (P greater than 0.05) by variables of sex, race, smoking habits, clinic attended by the patient, general health status, or age; however, patients 7 to 14 years old had a significantly higher prevalence rate (90.5%; P less than 0.05). E. corrodens should be considered as a potential pathogen in infections associated with and wounds inoculated by the human gingival flora.     

The bingo model of survivorship. V. The problems of conformation to the empirical evidence

We discuss the statistical and biological problems of adapting the theoretical bingo model to the analysis of empirical data. A distinction is made between an idealized pathogenetic model, which aims to represent the disease in as much authentic detail as the present state of knowledge allows and in components that have literal interpretation, and an empirical model, which deals with those effects of the pathogenetic model that one may hope to observe clinically. We review a variety of empirical models distinguishable by the amount of data available on intermediate degrees of damage short of total destruction. The relationship of damage to time is explored, and we consider the criteria and usefulness of linearization of this relationship where the diachronic ("longitudinal") data are few and extend over a comparatively short time. Every time a patient is examined, the degree of cumulative damage is assessed in each of the body systems of interest. Thus the examination will furnish a set of measurements, which is obtained on each of several examinations, taken over a period that for preference is long relative to the survival of the system. Specific disorders discussed include dentition and enlargement of the aorta with age in the Marfan syndrome.     

Location of immunodominant antigenic determinants on fragments of the tick-borne encephalitis virus glycoprotein: Evidence for two different mechanisms by which antibodies mediate neutralization and hemagglutination inhibition

A model showing the topological distribution, functions, and serological specifities of eight distinct, monoclonal antibody-defined epitopes on the tick-borne encephalitis (TBE) virus glycoprotein has been presented in a previous publication [Heinz et al., 1983]. Virology 126, 525–537.) In the present report the influence of conformational change, chemical modification, and fragmentation on the antigenic reactivity of each epitope has been analyzed by the use of blocking enzyme immunoassays and “Western blotting.” One of the two major antigenic domains (A), composed of three different epitopes, completely lost its antigenicity upon incubation at pH 5.0 or by treatment with guanidine-HCl/urea, SDS, reduction and carboxymethylation, as well as by proteolytic (trypsin, α-chymotrypsin, thermolysin) and chemical (CNBr) fragmentation. The second major antigenic domain (B), however, defined by four distinct monoclonal antibodies, three of which are hemagglutination (HA)-inhibiting, neutralizing, and protective, was shown to be resistant to low pH, guanidine-HCl/urea treatment, and proteolytic cleavage of the native protein. Also, polyclonal immune sera from mice and rabbits contained antibody populations reactive with antigenic determinants which are resistant and others which are sensitive to conformational change and fragmentation. Glycoprotein fragments with molecular weights of about 9000, generated by proteolysis of the native protein, were immunoreactive with neutralizing and protective monoclonal antibodies (defining domain B) as well as with a polyclonal mouse immune serum. Thus, these fragments appear to contain antigenic determinants which are immunodominant on the native protein and play an important role in the induction of a protective immune response against TBE virus. In addition, these results show that antibody binding to antigenic domains which are topologically and structurally completely unrelated may result in neutralization and/or HA inhibition. As the presence of two receptor-binding sites is unlikely, different effector mechanisms may account for the effects of these antibodies. The antigenic reactivity of domain A is sensitive to the same treatments which also inactivate HA activity of TBE virus, whereas domain B is resistant. These treatments include a change of domain A induced by incubation at slightly acidic pH which also results in inactivation of virus infectivity. Antibodies to domain A therefore presumably block viral activities by direct binding at or near the putative receptor-binding site whereas antibodies to domain B may cause loss of biological activities by inducing a conformational change of the receptor-binding site.     

Dopamine and methionine-enkephalin in human brain

The contents of dopamine (determined radioenzymatically) and methionine-enkephalin (assayed by a radioimmunoassay) were measured in several areas of the human brain. The peptide was principally localized in dopamine-rich structures. In patients with Parkinson's disease, in contrast to the general dopamine deficiency, the reduction in methionine-enkephalin was restricted to the mesencephalon, putamen and lateral pallidum.     

Gestosis and the psychosomatic phenomenon--an empirical investigation.

Patients suffering from psychosomatic diseases in the strict sense of the term (asthma, ulcers, colitis etc.) have characteristic object relations which we call the 'relation blanche'. The present investigation aims at finding out whether similar features can be observed in patients suffering from early and late gestosis. The results indicate that there is a definite connection between gestosis and the group of strictly psychosomatic diseases, thus confirming our hypothesis that gestosis does not primarily represent a neurotic conflict situation nor a psychotic breakdown.     

Fluoropyrimidine chemotherapy in a rat model: comparison of fluorouracil metabolite profiles determined by high-field 19F-NMR spectroscopy of tissues ex vivo with therapy response and toxicity for locoregional vs systemic infusion protocols

A Sprague-Dawley rat model with DS sarcoma transplanted in the thigh was used to compare transcatheter locoregional i.a. and systemic i.v. administration of 5-fluorouracil (FU) at 12 dose-rate schedules: 25, 50 and 100 mg/kg; bolus, 1, 5 and 24 h infusions. In experiment A tumor (62/67 animals) as well as liver and kidney (56/67 animals) were excised 1 h after a single bolus or 1 h infusion or at the end of 5 and 24 h infusions. (19)F-NMR spectroscopy at 11.7 T was used to quantitate FU and its metabolites in ca. 1 g of tissue at 4 degrees C. In experiment B analogous FU treatments were repeated for 5 days (rats 80+11 controls). Tumor volumes vs time, various blood parameters and survival times were recorded, and a log growth rate parameter log GR, a response index RI, and a toxicity index TI were calculated. The i.a. vs i.v. ratios for tumor concentrations of FU and total anabolites (F-Nucl) were >1 for nearly all treatments and increased with infusion time at the higher doses. F-Nucl in tumor correlated linearly with total fluorine concentration (Tot. F range 30-1100 nmol/g) over all treatments (r=0.92, slope=0.45, p<0.0001). For non-bolus i.v. treatments [FU+F-Nucl] decreased linearly with decreasing FU dose rate (r(2)=0.74, zero intercept), while i.a. treatments showed non-linear behavior. For non-bolus treatments the mean log GR per treatment group showed a negative correlation (r=-0.87) with log[F-Nucl]. The most effective non-toxic treatments were 25 mg/kg over 5 or 24 h; the i.a. route was superior to i.v. on the basis of [FU+F-Nucl], RI, the reduction in log GR, and Kaplan-Meier survival statistics. For liver and kidney Tot. F (>83% FU catabolites) reached ca. 3-4 and 6-7 micromol/g, respectively, at the highest dose rates for either route; F-Nucl were detected only for Tot. F>500 nmol/g and increased exponentially as Tot. F increased (toxic treatments). The concentrations of the main catabolite (alpha-fluoro-beta-alanine, FBAL) in tumor did not correlate with Tot. F but rather with FBAL levels in kidney (r=0.90, all treatments), indicating that uptake of liver-derived FBAL from the circulation is the major source of FBAL in tumor.     

Zur darstellung tritiummarkierter polymethacrylsäuremethylester

A method is described for the preparation of identical fractions of tritium marked and unmarked fractions of polymethacrylate of higher molecular weights. The labeling is done by TOH on polymethacrylic acid and does not change the molecular weight distribution. Further the influence of labeling by the method of WILZBACH on fractionated polymethacrylate is reported. The molecular weight distributions before and after the exposing to tritium gaz of 3 curie are determined. These data make it is possible to gain information concerning the number of bonds broken and of the position of the active hydrogen atoms in the polymer chain.     

Autosomal dominant inheritance of left ventricular outflow tract obstruction

Most nonsyndromic congenital heart malformations (CHMs) in humans are multifactorial in origin, although an increasing number of monogenic cases have been reported recently. We describe here four new families with presumed autosomal dominant inheritance of left ventricular outflow tract obstruction (LVOTO), consisting of hypoplastic left heart (HLHS) or left ventricle (HLV), aortic valve stenosis (AS) and bicuspid aortic valve (BAV), hypoplastic aortic arch (HAA), and coarctation of the aorta (CoA). LVOTO in these families shows a wide clinical spectrum with some family members having severe anomalies such as hypoplastic left heart, and others only minor anomalies such as mild aortic valve stenosis. This supports the suggestion that all anomalies of the LVOTO spectrum are developmentally related and can be caused by a single gene defect.     

Mast cell myositis: a new feature of allergic asthma?

There is some evidence that, in asthma, mast cells infiltrate the airway smooth muscle layer and, as a consequence, alter the functional and structural properties of myocytes. This inflammation so-called mast-cell myositis, probably contributes to both bronchial hyperresponsiveness and airway remodelling. Previous observations have pointed out the presence of mast cells within airway smooth muscle of atopic patients and recent data obtained in asthmatic patients demonstrate that this infiltration is more important in asthmatic patients with atopy. Although the mechanism of such a mast cell attraction remains to be fully understood, experimental data demonstrate that, upon stimulation by tryptase or cytokines, smooth muscle cells can attract mast cells through the production of TGF-beta1 or SCF. Once at the site of inflammation, activated mast cells are responsible for an important extracellular deposition of inflammatory products that may facilitate the increase in smooth muscle mass. In addition, comparison of asthmatic patients with and without atopy suggests that mast cell myositis is closely related with atopy.