[Neurotisation of homologous lyophilized nerve transplants].
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Biomedical subjects
Publications and source records attributed to C Meier.
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Despite commonly applied clinical criteria, the early diagnosis of rheumatoid arthritis (RA) often remains difficult, thus delaying on suitable early treatment. In search for a test furthering the early and reliable diagnosis of RA, we have screened for novel disease specific autoantibodies. To this end proteins were isolated from synovial membranes and other tissues following a special protein purification protocol, and these were separated electrophoretically. Western blots were then used to screen sera of RA patients and of individuals suffering from other rheumatic diseases for antibodies to any of these proteins. The most prominent RA specific immunoreaction was with a 68k antigen, occurring in 110 of 167 RA patients (sensitivity is 66%). The antibody could also be identified in seronegative RA patients but not in healthy individuals (55 tested), in only 1 SLE patient of a group of 98 patients with other rheumatic diseases and in 1 out of 22 HIV patients, resulting in a specificity of 99%. Moreover, the anti-68k antibody could be correlated with a more severe course of RA. 13 out of 20 anti-68k positive RA patients (58%) had subcutaneous nodules, while only 2 out of 11 anti-68k negative (20%) did. The mean sedimentation rate of these antibody positive patients was 51 mm/h and 26 mm/h for the negative respectively. The 68k antigen was shown to be present in all human tissues investigated and is probably ubiquitously expressed. It is either located in the endoplasmatic reticulum or cytoplasm or both. Its isoelectric point is 5.1. It proved to be O-glycosylated and contains only one or a few sugar residues as the untreated and the deglycosylated antigen identical electrophoretical mobilities. The patient derived anti-68k antibodies were directed against the sugar residue: deglycosylation of the antigen completely abolished its immunoreactivity. N-acetylglucosamine competes with the antibody for binding the 68k antigen. The antigen physicochemical data of the 68k antigen argue against identity with one of the autoantigens in this molecular mass range already known to be associated with RA or other autoimmune diseases. It is neither identical to the 62k human antigen (EBNA-1) nor to RA33 (A2hnRNP), the 50k Sa antigen or the Hsp70 class of heats-hock proteins. It is argued that the particular method of protein purification applied in combination with separation via SDS-PAGE in the presence of urea, made it possible to detect a hitherto unidentified antigen. Considering the striking disease specificity of the anti-68k antibody it is now worthwhile to look for corresponding autoreactive T cells in order to analyse its role in the pathogenesis of RA.
In the presence of tetrodotoxin (0.5 microM) electrical stimuli of high current strength and long impulse duration evoke the outflow of previously incorporated 3H-noradrenaline from the mouse vas deferens. The mechanism of action is probably an electrotonic depolarization of nerve terminals. The effect of normorphine, calcium and magnesium was compared on transmitter outflow evoked by conducted action potentials and electrotonic depolarization of nerve terminals. It is suggested that in the presence of tetrodotoxin electrical stimulation induces an asynchronous quantal release of transmitter.
BACKGROUND: We wanted improve the nutritional status of patients with cystic fibrosis with enteral feeding via a percutaneous endoscopic gastrostomy (PEG). PATIENTS AND METHODS: In a period of 8 years 11 patients underwent a percutaneous endoscopic gastrostomy (PEG), 4 males and 7 females, in the median 14,9 years of age (7,4/20,8). So far we overlook a median duration of enteral feeding therapy of 19,5 months (10/53). MAIN RESULTS: In 9 of the 11 patients we found a distinct increase of the predicted anthropometrical values,e.g. the weight for height value increased statistically significant in the first 3 months by 10,3 % from 84,7 % to 95,5 % and showed a further increase to 97,8 % after 10 months of nocturnal enteral feeding (p < 0,05). The predicted values of the lung function got stabilized too, with an increase by 9 % of the FEV1 and 3 % of the vital capacity after 10 months. Here was no statistically significance found. In one patient with a poor social-economic background and a lack of compliance the PEG had to be removed surgically because of an abscess formation. Another patient developed an acute gastric ulcer which responded very well onto conservative therapy. In the other patients there were no further complications. CONCLUSION: We can conclude that in the treatment of patients with cystic fibrosis showing an unsatisfying nutritional status the long-term nocturnal enteral feeding via a PEG is a good and well tolerated method. The best results we achieved when the gastrostomy was placed at an early state of the disease. That's why we demand an early mentioning of this option of enteral feeding to the patients and their families since the involved mostly need a long time for their decision for that invasive procedure.
Novel lipophilic cycloSal-triesters 3 and 4 from the ara- and ribo-configurated 2'-fluorinated ddAs 1 and 2, respectively, were prepared. The title compounds 3 and 4 delivered the corresponding monophosphates and thus, increasing the bioactivity or convert a formerly inactive compound into a RT inhibitor.
Cytotoxic and antiretroviral activity of cycloSal-d4TMP derivatives were tested in a new AZT-resistant H9 cell subline (H9rAZT250). The results showed, that cycloSal-d4TMP derivatives overcame resistance of HIV-1 to d4T in H9rAZT250 cells, which exert decreased thymidine kinase (TK) gene expression.
An alternative synthesis of 3-methyl-cycloSal-nucleotides 3-6 using phosphoramidite chemistry is described. This protocol clearly shows advantages for the cycloSal-introduction into cytosine containing nucleoside analogues.
A hydrolysis study of 3-methyl-cycloSal-PCVMP 2 is described. Surprisingly, phosphotriester 5 released in this study not the expected PCVMP, but cycloPCVMP.
A new potential phosphoramidate prodrug approach for d4T 1 is described. In hydrolyses studies the cycloAmb-d4T-phosphoramidates 2 and 3 proved to deliver d4TMP following a tandem reaction.
A series of cycloSal-BVDUMP phosphate triesters has been prepared. The prototype compound was 3-methyl-cycloSal-BVDUMP 2. Furthermore, a series of 3'-O-acyl-modified derivatives having carboxylic acids with different lipophilicity or a L-configurated alpha-amino acid (phenylalanine) was prepared. The hydrolysis properties in phosphate buffer PBS as well as in PBS containing pig liver esterase (PLE) will be described. Finally, the biological activity against EBV has been determined.
Synthetic routes to benzyl-functionalized cycloSal-d4T monophosphates (7CH2X-cycloSal-d4TMP) have been developed. Their hydrolytic behavior in basic aqueous solution (pH = 7.3) was studied and their hydrolysis half-lives were determined. It turned out that two different degradation pathways are leading to different products: beside the formation of the expected d4TMP and a styrene type derivative, a phenyl-d4T-phosphodiester was obtained as well. The product distribution was specified.
CycloSal-d4TMP and two different bis(benzyl) phosphate triesters of the antivirally active nucleoside analog d4T were studied with regard to their chemical hydrolysis behavior at pH 7.3, in CEM/0 cell extracts, and their anti-HIV activity. In contrast to triesters 2-4, bis-(o-AB)-d4TMP 1 was found to be chemically exquisitely stable. All compounds led to the formation of d4TMP in cell extracts and all triesters achieved the TK-bypass.