Inhibition of the conjugation of PABA with glycine in vitro by sulfamoyl benzoic acids, sulfonamides, and penicillins and its relation to tubular secretion.

Elimination of drug molecules via tubular secretion is an important pharmacokinetic parameter especially for oral dosage forms where an extremely short half-life would prevent their application. We have studied the inhibition in vitro of the glycination of p-aminobenzoic acid (PABA) using rat liver microsomal preparations. The I50 values, the concentration of the inhibitor that leads to 50% inhibition of glycine conjugation of PABA as compared to the control, have been determined for sulfamoyl benzoic acids, sulfonamides, and penicillins. Statistically significant regression equations were derived explaining the observed variation in I50 values as a function of lipophilicity and steric bulk of the substituents for the combined set of sulfamoyl benzoic acids and sulfonamides (n = 33). For the penicillins studied, only steric effects seem to be important for the explanation of the I50 values. Finally, regression analysis and the use of neural networks allowed the classification of compounds by their in vitro I50 values as being tubular secreted or not. Therefore, it can be concluded that the inhibition in vitro of the glycine conjugation of PABA is a useful model for the estimation of tubular secretion and drug interaction potential of acidic drug molecules in this process in vivo.

[Distribution of the Rhesus haplotype frequencies in the Düsseldorf administrative center (North Rhine-Westphalia)]. / Zur Verteilung der Rhesus-Haplotypenfrequenzen im Regierungsbezirk Düsseldorf (Nordrhein-Westfalen).

The Rhesus haplotype frequencies and their regional distribution have been studied in the administrative area of Düsseldorf, North Rhine-Westphalia. The area studied is characterised by a heterogeneous distribution of the haplotypes without clinical trends and by missing Hardy-Weinberg conditions.

[Distribution of Rhesus haplotype frequencies in the Cologne (North Rhine-Westphalia) administrative district]. / Zur Verteilung der Rhesus-Haplotypenfrequenzen im Regierungsbezirk Köln (Nordrhein-Westfalen).

The Rhesus haplotype frequencies and their regional distribution have been studied in the administrative area of Cologne, North Rhine-Westphalia. The area studied is characterised by a heterogeneous distribution of the haplotypes and by missing Hardy-Weinberg conditions. There are higher CDe- and lower cde-haplotype frequencies in the south-western part. The distribution of the very rare cDue haplotype could be correlated with higher B frequencies in the administrative areas of Cologne and Düsseldorf.

[Distribution of ABO allele frequencies in the Düsseldorf regional district (Northern Rhine-Westphalia)]. / Zur Verteilung der AB0-Allefrequenzen im Regierungsbezirk Düsseldorf (Nordrhein-Westfalen).

The AB0 allele frequencies and their regional distribution have been studied in the administrative area of Düsseldorf, North Rhine-Westphalia. The o allele shows relatively low and the B allele relatively high frequencies in the eastern and south-eastern parts of the region. The high B frequencies are interpreted as a consequence of the immigration from north-eastern Germany and Poland at the end of the 19th and the beginning of the 20th century (labourers) and after 1945.

[Distribution of ABO allele frequencies in the Cologne registration district (Nordrhein-Westfalen)]. / Zur Verteilung der ABO-Allelfrequenzen im Regierungsbezirk Köln (Nordrhein-Westfalen).

The AB0 allele frequencies and their regional distribution have been studied in the administrative area of Köln, North Rhine-Westphalia. The B allele shows relatively high frequencies ( > 0.0800) on both sides of the river Rhein, in the eastern parts of the area and--separated from the Köln region by a region of lower B frequencies--in the Aachen region. The possible causes for the different B frequencies are discussed.

Incidence and disease associations of a proteinase 3-antineutrophil cytoplasmic antibody idiotype (5/7 Id) whose antiidiotype inhibits proteinase 3-antineutrophil cytoplasmic antibody antigen binding activity.

OBJECTIVE: To evaluate the potential of a monoclonal proteinase 3-antineutrophil cytoplasmic antibody (PR3-ANCA) antiidiotype autoantibody (5/7 anti-Id) as a candidate for specific immunotherapy in Wegener's granulomatosis (WG), and to estimate the immunodiagnostic value of the corresponding idiotype (5/7 Id). METHODS: We analyzed the incidence of 5/7 Id in patients with ANCA-associated vasculitides (WG, microscopic polyangiitis, Churg-Strauss syndrome), in disease controls (systemic lupus erythematosus patients), and in healthy donors. We then investigated the presence of 5/7 Id in relation to disease stage, clinical activity, and organ manifestations in 86 patients with WG. Finally, we investigated the ability of the 5/7 anti-Id reagent to inhibit the binding of PR3-ANCA to corresponding antigen in 19 WG patients. RESULTS: The incidence of 5/7 Id was significantly more frequent in WG patients (43 of 86; 50%). We did not find a significant correlation between the prevalence of idiotype expression and disease activity or organ manifestations. Further, we demonstrated in vitro suppression of PR3-ANCA antigen binding activity by 5/7 anti-Id in 11 of 19 WG patients who were positive for 5/7 Id. CONCLUSION: This study shows that 5/7 Id is a common idiotype with a significantly increased incidence in WG and that 5/7 anti-Id inhibits PR3-ANCA antigen binding activity. Based on these observations, we conclude that 5/7 anti-Id is a promising tool for the development of a specific immunotherapy for WG.