Characterization of a human pancreatic secretory trypsin inhibitor mutant binding to Legionella pneumophila as determined by a quartz crystal microbalance.

We describe the isolation from a large phagemid library of a human pancreatic secretory trypsin inhibitor (hPSTI) mutant that binds to Legionella pneumophila. To gain further insight into the binding kinetics of the isolated hPSTI mutant, an immunosensing system based on a quartz crystal microbalance (QCM) was used. In contrast to ELISA procedures, k(on) and k(off) rates could be derived from the QCM sensograms. Thus, it is possible to characterize specific intermolecular interactions between proteins and phages isolated from large phage display libraries by QCM.

Quartz crystal microbalance (QCM) as a device for the screening of phage libraries.

An immunosensing system based on a quartz crystal microbalance (QCM) is presented for the selection of both antigen specific recombinant antibodies and antigen specific human pancreatic secretory trypsin inhibitor (hPSTI) mutants isolated from large phage libraries. The QCM was integrated into a flow injection analysis system for the straightforward analysis of large sample numbers. Measurements were performed using a biotinylated antigen immobilized by streptavidin onto the gold surface of the quartz crystal and phages displaying recombinant antibodies or hPSTI mutants. The results obtained by the QCM were in accordance to those of a well established enzyme linked immunosorbent assay (ELISA). Therefore, the QCM is well suited for the detection of single high affinity clones isolated from large phage display libraries.

Isolated sacroiliitis as monosymptomatic form of ankylosing spondylitis--a possible cause of chronic back pain.

In a retrospective analysis of 770 cases of ankylosing spondylitis or allied disorders 146 patients (19 percent) were found to have isolated sacroiliitis without involvement of the spine. The mean disease duration of isolated sacroiliitis was 11.9 years. The conclusions were based on anamnestic, clinical and radiological data. Of those patients with isolated sacroiliitis 29 percent were female, compared to 11 percent of female patients with typical spinal disease. Cases restricted to the sacroiliac joints for a longer period can be observed frequently in younger patients and may be regarded as an abortive and monosymptomatic form of ankylosing spondylitis insofar as other seronegative spondarthritides can be excluded.

[Antinuclear antibodies in ankylosing spondylitis (author's transl)]. / Antinukleäre Antikörper bei Spondylitis ankylosans (Morbus Bechterew).

Antinuclear antibodies (ANA) were found in 19.1% of patients suffering from ankylosing spondylitis (n = 320). This figure is significantly higher than the results obtained in a control group. ANA were present in all stages of the disease, including the abortive form of isolated sacroiliitis. ANA were also found in different stages of activity. In addition, ANA-positive cases showed a higher inflammatory activity. In females ANA were more frequently found than in males. There was a positive correlation between ANA and HLA B27 in 87.2%.

[Immunological features in ankylosing spondylitis (author's transl)]. / Immunphänomene bei Spondylitis ankylosans (Morbus Bechterew).

Sera from 50 patients with various stages of ankylosing spondylitis were tested for the presence of antinuclear antibodies (ANA), anti-DNA antibodies, rheumatoid factor and antistreptolysin. Antinuclear antibodies (immunofluorescent technique) were detected in the sera of 10 patients (20%), associated in one case with anti-DNA antibodies (immunofluorescent technique). The disease activity in ANA-positive cases was low to moderate.

[Diagnosis of psoriatic osteoarthropathy: comparison of clinical, radiologic and scintigraphic findings]. / Zur Diagnose der Osteoarthropathia psoriatica: Gegenüberstellung von klinischen, radiologischen und szintigraphischen Befunden.

Among the group of seronegative spondarthritides psoriatic osteoarthropathy can be differentiated from rheumatoid arthritis as a separate disease with generalized osseous proliferation. 33 cases were evaluated and clinical data, X-ray films and nuclear bone scans were compared. Pathological alterations in the bone structure can be found by bone scintigraphy already at very early, even subclinical stages of the disease, thus allowing early diagnosis. In a high percentage of our cases pathological alterations could be demonstrated by scintigraphy long before they were revealed on X-ray films. Scintigraphic methods may help to evaluate the activity of the disease. Furthermore, in many of our cases, localization and concentration of the tracer in the skeleton were so typical, that they may be considered pathognomonic for psoriatic osteoarthropathy. Thus bone scanning appears to be a useful tool for the diagnostic evaluation and follow up in cases of psoriatic arthropathy, in particular if the low exposure to radiation is taken into account.

[Combination of ankylosing spondylitis with dermatomyositis and atypical gout (isolated gout kidney)]. / Kombination einer Spondylitis ankylosans (Sp.a.) mit Dermatomyositis und atypischer Gicht (isolierte Gichtniere).

In a 58-year-old man with the clinical and radiological signs of definite ankylosing spondylitis in its final stages, HLA B 27 positive, an onset of dermatomyositis was observed with characteristic clinical, histological, and pathological findings, and with high titers of ANA. It had been discovered years before that a gouty kidney with pyelonephritis accompanied the advanced ankylosing spondylitis. On the basis of these findings a triple association of etiologically different diseases could be diagnosed. After treatment with cortisone, allopurinol, and azathioprine appeared an acute and no longer controllable panmyelophthisis. That a malignant tumor could have caused the dermatomyositis was excluded by autopsy. Diagnostic questions concerning the gouty kidney as well as factors explaining the acute and deadly progress of a panmyelophthisis after the administration of a rather mild immunosuppressive agent are discussed.

[Spinal involvement in chronic Reiter's syndrome]. / Achsenskelettbefall bei chronischem Reitersyndrom.

From a retrospective analysis (1980-1984) we found 32 cases of chronic Reiter's syndrome with spinal involvement on the radiographs (as sacroiliitis, parasyndesmophytes, and rarely syndesmophytes). In these 32 case histories spinal pain was a rather frequent symptom, often beginning with the onset of the disease, whereas severe functional spinal impairment was seldom found. Joints were only mildly affected, organic symptoms were found chiefly in clinical history, but were often incomplete. Trigger infections were known in 40%, and 87% of the patients were HLA B27 positive. These 32 patients with mainly spinal symptoms represent 75% of all cases (n = 43) suffering from chronic Reiter's syndrome within the period of observation. Previous observations as well as our experience point to the fact that the chronic course of disease in Reiter's syndrome mainly affects the spinal structure with comparatively mild clinical symptoms.

[Special disco-vertebral forms of ankylosing spondylitis]. / Besondere discovertebrale Verlaufsformen bei der Spondylitis ankylosans.

In a retrospective study 10 cases (6 males, 4 females) of special disco-vertebral forms of ankylosing spondylitis were evaluated. In all cases radiographs showed bilateral sacroiliitis and destructive-sclerotic disco-vertebral lesions but hardly any syndesmophytes considered typical for ankylosing spondylitis. We found a rather striking diversity of morphologic changes caused by spondylodiscitis, polysegmental involvement, the simultaneous and successive appearance (in the cause of the disease) of shiny corner, as well as anterior spondylitis and spondylodiscitis. All cases had clinical and humoral signs of disease activity, and some even had extravertebral manifestations. Radiographs and clinical findings indicate that an inflammatory process causes the disco-vertebral lesions. The special forms of ankylosing spondylitis as described in this article are in accordance with the polymorphism frequently observed in this disease.

[Spondylodiscitis as a dominant early symptom of juvenile ankylosing spondylitis]. / Spondylodiszitis als dominierendes Frühsymptom bei juveniler Spondylitis ankylosans.

A 12-year-old female (HLA-B27 negative) presented with unilateral low back pain and sterno-clavicular arthritis. Six months after onset the clinical and radiological findings determined spondylodiscitis L1/2. On the basis of the clinical findings (oligoarthritis, symptomatic sacroilitis, spondylodiscitis), juvenile ankylosing spondylitis was suspected. The diagnosis was corroborated 18 months after the first occurrence of symptoms by the appearance of typical changes in the sacroiliac joint that are indicative of juvenile ankylosing spondylitis. Because of persisting antibodies against Borrelia burgdorferi, the possibility of B. burgdorferi-induced reactive arthritis with involvement of the axial division of the skeletal system was considered. After 3.5 years of observation the condition showed a benign course with radiologically observable consolidation of the spondylodiscitis. To our knowledge, this is the second case described of juvenile ankylosing spondylitis with spondylodiscitis as a dominating feature.

Mutations at four distinct regions of the rpoB gene can reduce the susceptibility of Helicobacter pylori to rifamycins.

The transformation of a panel of rpoB mutations (codons 525 to 586) from rifampin-resistant donor strains into Helicobacter pylori 2802A confirmed the MICs associated with the respective mutations. RpoB V149X random mutations were generated and induced different levels of resistance, depending on the replacement amino acid. Mutagenesis of the rpoB gene at codon position 701 (R701H) induced low-level resistance.