Protein synthesis directed by DNA phage messengers.
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Biomedical subjects
Publications and source records attributed to K Weber.
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Synthetic peptides representing the conserved ends of the rod domain of desmin are shown to disassemble preformed desmin filaments when added in moderate molar excess. This argues for a similar importance of both ends of the rod for filament stability. Recent structural models of intermediate filaments suggest close proximity of the ends and perhaps even an interaction (N. Geisler, J. Schünemann, and K. Weber, 1992, Eur. J. Biochem. 206, 841-852; P. M. Steinert, L. N. Marekov, R. D. B. Fraser, and D. A. D. Parry, 1993, J. Mol. Biol. 230, 436-452). Since the disassembling activity of the peptides, in addition to their sequences, should be related in some way to their secondary structure, we have investigated the structures of a number of related peptides which all arise from the ends of the rod using electron microscopic and spectroscopic methods. All peptides showed the expected alpha-helical structure at low concentrations in the presence of trifluoroethanol, as revealed by circular dichroism. At higher concentrations the peptides showed extensive self-aggregation into various types of filaments. The filaments contain the peptides in beta-sheet conformation as shown by Fourier transform infrared spectroscopy.
In a prospective randomized multicenter trial for the therapy of erythema migrans, 40 patients received ceftriaxone 1 g daily for 5 days and 33 patients obtained phenoxymethylpenicillin, 1 million units 3 times daily, for 12 days. Follow-up was for a mean of 10 +/- 5 months. Eight oral penicillin recipients (24%) and six ceftriaxone recipients (15%) developed minor consecutive manifestations. Two ceftriaxone and one penicillin recipient(s) still had elevated IgG antibody titers 10 to 20 months after therapy. Borrelia burgdorferi could be isolated from the erythema migrans in 29 out of 56 patients (52%) before therapy and in one oral penicillin recipient but none of 24 other patients after therapy. Ceftriaxone was superior to oral penicillin in a subgroup of patients with more than one symptom prior to therapy (p less than 0.01), but not in the overall evaluation of clinical, serological and bacteriological outcome data. Ceftriaxone ought to be preferred to oral penicillin in patients with more severe early Lyme borreliosis.
Two patients received oral penicillin for erythema migrans disease (EMD) in 1973 and 1977. Five and seven years later, respectively, they developed EMD for a second time after being bitten by ticks. The first and second erythema migrans lesions appeared in different places. Tests of sera evaluated for antibodies to Borrelia burgdorferi before (in one case), during and after the second episode of EMD remained negative (patient 1) or yielded an at least four-fold rise of IgG antibody titers, but did not become positive (patient 2). These cases provide evidence that reinfection in EMD may occur without a significant elevation of specific antibody titers.
The persistence of Borrelia burgdorferi in patients treated with antibiotics is described. The diagnosis of Lyme disease is based on clinical symptoms, epidemiology and specific IgG and IgM antibody titers to B. burgdorferi in serum. Antibiotic therapy may abrogate the antibody response to the infection as shown in our patients. B. burgdorferi may persist as shown by positive culture in MKP-medium; patients may have subclinical or clinical disease without diagnostic antibody titers to B. burgdorferi. We conclude that early stage of the disease as well as chronic Lyme disease with persistence of B. burgdorferi after antibiotic therapy cannot be excluded when the serum is negative for antibodies against B. burgdorferi.
An indirect immunofluorescence technique for the determination of antibodies against ixodid tick spirochetes is described. Differences in the reactivity between Ixodes ricinus spirochete and Ixodes dammini spirochete antigens were not observed. Cross-reacting antibodies against Treponema pallidum and Treponema phagedenis can be eliminated by quantitative absorption with T. phagedenis. Cross-reactions with leptospira were not observed by immunofluorescence. In the IgM test, false negative reactions caused by high-titered specific IgG antibodies or false positive reactions caused by rheumatoid factor occur. This can be avoided by testing the IgM fraction (19S-IgM-test) or using sera previously treated with anti-IgG serum. Significantly elevated antibody titers against ixodid tick spirochetes were observed in 45% of 44 cases with erythema migrans disease, in 72% of 29 cases of lymphocytic meningoradiculitis, in all of nine patients with acrodermatitis chronica atrophicans and in all of four investigated patients with lymphocytoma (lymphadenosis benigna cutis).
In a randomized multicenter therapeutic trial, 32 patients with erythema migrans received oral azithromycin 500 mg once daily and 33 patients received phenoxymethylpenicillin (penicillin V) 1 million U three times daily for 10 days. Follow-up was for a median of 17 (range 3-32) months. Four weeks after initiation of therapy, 20 (62%) patients given azithromycin and 17 (51%) patients given penicillin V were completely free of all signs and symptoms and did not develop new ones subsequently (no significant difference). Three months after initiation of therapy, the corresponding figures were 25 (78%) azithromycin and 28 (85%) penicillin V recipients (no significant difference). There were only minor sequelae such as arthralgia, headache, fatigue, stiff neck and dysesthesia. Azithromycin led to a significantly faster resolution of the erythema migrans than penicillin V (p < 0.001). Significantly more patients with more severe compared with mild initial disease had an elevated IgM antibody titer prior to therapy (p < 0.001). Usually mild to moderate side effects occurred in 12 patients given azithromycin and five patients given penicillin V (p < 0.05). Azithromycin appears to be as effective as penicillin V for the treatment of early Lyme borreliosis and it seems to clear the erythema migrans more promptly.
Patients with erythema migrans can fail to respond to antibiotic therapy. Persistent or recurrent erythema migrans, major sequelae such as meningitis and arthritis, survival of Borrelia burgdorferi and significant and persistent increase of antibody titres against B. burgdorferi after antibiotic therapy are strong indications of a treatment failure. Most, if not all, antibiotics used so far have been associated with a treatment failure in patients with erythema migrans. Roxithromycin and erythromycin are definitely or probably ineffective. However, doxycycline, amoxicillin, cefuroxime, ceftriaxone, azithromycin and high-dose penicillin V perform comparably well.
OBJECTIVE: The aim of this study is to adapt measurements of IGF-I, IGFBP-2 and IGFBP-3 to dried blood filter disk assays. METHODS: Measurements of the three analytes in serum samples and in the corresponding blood spotted onto filter paper were compared by applying standard radioimmunoassays. RESULTS: In paired experiments, the quantity of all antigens measured on dried filter spots showed an excellent correlation to that in serum (R>0.88) and in addition this correlation was independent of the whole blood hematocrit value. Recovery of IGF-I, IGFBP-2 and IGFBP-3 in experiments using recombinant standards mixed with whole blood was well correlated with the recovery of the plasma fraction on the filter paper. All of the blood spot assays showed a inter- and intra-assay variation of less than 10% and the blood spots were stable over a period of more than 5 months stored at -20 degrees C. CONCLUSIONS: Taken together, these data clearly demonstrate that such a filter paper assay is a reliable procedure to monitor changes of IGF-I, IGFBP-2 and IGFBP-3 content in blood. The obvious advantages of this methods concerning storage, handling and shipping of blood probes helps to solve the logistics of centralised measurements of these three analytes.
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Wegener's granulomatosis is together with Churg-Strauss syndrome and microscopic polyangiitis a very rare cause of hemoptysis in childhood. We report on a 14 years old girl who developed arthralgia, purpura, glomerulonephritis and a diffuse alveolar haemorrhage with hemoptysis after a short time period of unspecific symptoms.