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Biomedical subjects

R Scharf

Publications and source records attributed to R Scharf.

At least 37 records · Page 2Linked to original sources
PubMed1992

Aziridine-2-carboxylic acid. A reactive amino acid unit for a new class of cysteine proteinase inhibitors.

The three-membered ring of aziridine-2-carboxylic acid, which is susceptible to opening by nucleophiles, has been analyzed as a potential useful handle for the design of specific irreversible inhibitors of cysteine proteinases. For this thiol-reactive amino acid, an imino analogue of proline, a second-order rate constant of 17.07 M-1.s-1 for inactivation of papain was determined. Thus, the aziridine moiety proved to be remarkably more reactive than activated double bonds, e.g. N-ethylmaleimide, or halides such as alpha-iodopropionic acid or chloroacetic acid. Since it does not alkylate histidine under conditions in which quantitative alkylation occurs with N-ethyl-maleimide, it could represent an interesting reactive amino acid unit for the synthesis of a new class of irreversible inhibitors, at least in terms of specificity of the chemical reaction involved in the inactivation process.

Aziridines↗
PubMed1991

Fully synthetic immunogens. Part III. Synthesis of hinge-peptide/gastrin conjugates and their immunological properties.

As core molecule for the multiple attachment of antigenic peptides we have selected the human IgG1 hinge fragment 225-232/225'-232'. Two types of conjugates of this double-chain bis-cystinyl hinge-peptide were prepared i) by linking its C-termini to [NIe15]-human-little-gastrin-[2,17] and ii) by elongating the resulting hinge-peptide/[NIe15]-little-gastrin-[2-17] conjugate at the two N-termini with the human big-gastrin sequence 1-14 to produce the big-gastrin-[1-14]/hinge-peptide/little-gastrin-[2-17] conjugate. For the synthesis of these peptide structures both the route via the preformed double-chain bis-cystinyl peptide and the route via suitably protected monomeric bis-cysteinyl peptides were used. For the latter approach advantage was taken of the previous observation about the preferred oxidation of the bis-cysteinyl hinge-peptide 225-232 to the dimer in parallel alignment. Both synthetic routes led to identical products. Immunization experiments in guinea pigs with the synthetic hybrids led to surprisingly strong immune responses with anti-little-gastrin antibody titers comparable to those induced by the iso-1-cytochrome c/little-gastrin-[2-17] conjugate as carrier-hapten system. These findings show that the two gastrin constructs are fully competent immunogens. Additionally, the gastrin receptor-like specificity of the antibodies indicates that both the synthetic hybrids and the cytochrome c conjugate allow for expression of a little-gastrin-specific conformational epitope similar to the bioactive structure of this hormone. The usefulness of such synthetic hybrids is further confirmed by the observation that the bivalent immunogen, containing both the little-gastrin 2-17 and the big-gastrin 1-14 sequence, is capable of inducing an immune response against both antigenic sequences, although with different efficiency. These results fully confirm our expectations.

Amino Acid Sequence↗
PubMed1991

[Preliminary experience with achieving immune tolerance in patients with hemophilia A and circulating factor VIII inhibitor].

The appearance of antibodies to factor VIII is a serious complication in the treatment of haemophilia A. A protocol is presented aiming at suppression of the anticoagulant using continued treatment with factor VIII (25 u/kg b.w. twice weekly). Ten patients with previous maximal factor VIII antibody titre from 7 to 2900 Bethesda units were treated. So far the inhibitor was eradicated in 3 cases treated continuously for from 5 to 20 months. In two of these three cases successful surgical procedures were performed without anamnestic response.

Adolescent↗
PubMed1991

Fully synthetic immunogens. Part II. Studies on parallel dimerization of the human IgG1 hinge-fragment 225-232 with N- or C-terminal gastrin related extensions.

The bis-cysteinyl hinge-fragment 225-232 of human IgG1 has been extended at the N- or C-terminus with Nle15-desamido-human-little-gastrin-[5-17] and Nle15-human-little-gastrin-[5-17]-NH2, respectively. Thermodynamically controlled air oxidation of the resulting bis-cysteinyl-peptides led to the predominant formation of the corresponding dimers in parallel alignment despite the incorporation of the immunoglobulin-unrelated gastrin-sequences. These surprising results confirm the high degree of structural information inherent in the hinge-sequence and its intrinsic tendency to fold into the correct structure in terms of cysteine pairings. This protein subdomain-the hinge-peptide-is therefore well suited as core molecule for the design of fully synthetic immunogens with multiple attachment of antigenic determinants.

Amino Acid Sequence↗
PubMed1990

A human cellular sequence implicated in trk oncogene activation is DNA damage inducible.

Xeroderma pigmentosum cells, which are deficient in the repair of UV light-induced DNA damage, have been used to clone DNA-damage-inducible transcripts in human cells. The cDNA clone designated pC-5 hybridizes on RNA gel blots to a 1-kilobase transcript, which is moderately abundant in nontreated cells and whose synthesis is enhanced in human cells following UV irradiation or treatment with several other DNA-damaging agents. UV-enhanced transcription of C-5 RNA is transient and occurs at lower fluences and to a greater extent in DNA-repair-deficient than in DNA-repair-proficient cells. Southern blot analysis indicates that the C-5 gene belongs to a multigene family. A cDNA clone containing the complete coding sequence of C-5 was isolated. Sequence analysis revealed that it is homologous to a human cellular sequence encoding the amino-terminal activating sequence of the trk-2h chimeric oncogene [Kozma, S. C., Redmond, S. M. S., Xiao-Chang, F., Saurer, S. M., Groner, B. & Hynes, N. E. (1988) EMBO J. 7, 147-154]. The presence of DNA-damage-responsive sequences at the 5' end of a chimeric oncogene could result in enhanced expression of the oncogene in response to carcinogens.

Amino Acid Sequence↗
PubMed1990

[The improvement of the tolerance of the kidney for ischemia with the prostacyclin analog iloprost].

Operative trauma, ischemia, release of catecholamines and thermal stimuli in consequence of harvesting, preservation and transplantation deteriorate the renal capillary circulation. By crossing of tolerance limits arises an irreversible transplant damage. The conditions of our examinations were placed in this field. By pre- and postischemic application of Iloprost was demonstrable an improvement of the ischemic tolerance of the kidney. Correction of renal hemodynamics, antiplatelet action and cytoprotection are the reasons of the protective influence of Iloprost in our opinion.

Acute Kidney Injury↗
PubMed1990

Side products in the synthesis of secretin.

Analytical studies on side products in the synthesis of secretin led to the discovery of a further side reaction, involving conversion of the carboxamide function of glutamine to glutamic acid gamma-methyl ester. The chemical structure of the side products was determined by NMR spectroscopy upon their tryptic digestion and isolation of the modified secretin fragments. Possible pathways for the observed side reaction are discussed.

Amino Acids↗
PubMed1989

[Health requirements of sauna facilities in East Germany].

There was a considerable increase in sauna attendance in the GDR in recent years. For excluding the risk of an infection transfer when attenting the sauna it is necessary to pay particular hygienic attention to this special type of sports and recreational facilities. The special hygienic requirements to the staff and sauna users are explained. The tasks and responsibilities of the state sanitary inspection when opening and controlling public saunas are described.

Communicable Disease Control↗
PubMed1987

Hazards of thrombolytic therapy in deep vein thrombosis.

From 1965 to 1985, 64 deep vein thrombosis (DVT) patients were treated with streptokinase (SK). In 26 cases 'high-dose SK' (IV 100,000 units/h for 4 days) was used and in 38 patients a 'low-dose SK' regime (IV 250,000 units every 12 h for 4 days) was employed. The clinical signs of DVT subsided in 78 per cent of treated patients within 30 days of completing SK treatment. A repeat phlebography was performed immediately after SK therapy in 29 patients (45 per cent) and a total recanalization or partial thrombolysis was achieved in 80 per cent of the studied cases. In 15 patients minor and major haemorrhagic complications occurred. There were five fatalities, all in the high-dose SK group (three intracranial haemorrhages and two major bleeds). Three patients developed pulmonary embolism and none of them died. The post-treatment clinical and phlebographic evaluation did not reveal any significant difference between the two methods of SK administration, but more haemorrhagic complications (P less than 0.02, chi=5.50825) occurred in the high-dose SK patients. This report emphasizes the risk of bleeding complications during thrombolytic therapy. If SK is to be used, therefore, careful selection of patients and meticulous monitoring are mandatory.

Adolescent↗