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Biomedical subjects

M Engel

Publications and source records attributed to M Engel.

At least 73 records · Page 4Linked to original sources
PubMed1991

Designed coiled-coil proteins: synthesis and spectroscopy of two 78-residue alpha-helical dimers.

Receptor-adhesive modular proteins are nongenetic proteins designed to contain ligand, spacer, coil, and linker modules and to interact strongly with integrins or other types of cell-surface receptors. We have designed, chemically synthesized, and characterized a 39-residue peptide chain having a 6-residue ligand module (Gly-Arg-Gly-Asp-Ser-Pro-) for adherence to Arg-Gly-Asp-binding integrin receptors, a 3-residue spacer module (-Gly-Tyr-Gly-) for flexibility, and a 30-residue coil module [-(Arg-Ile-Glu-Ala-Ile-Glu-Ala) 4-Arg-Cys-NH2] containing four 7-residue repeats for dimerization. This chain was designed to form a 78-residue noncovalent dimer (P39) by folding the coils of two chains into an alpha-helical coiled coil through hydrophobic interaction of eight pairs of Ile residues. Air oxidation of P39 gave P78, a 78-residue covalent dimer having a disulfide bridge linking its C termini. Raman spectroscopy indicated that both synthetic proteins have high alpha-helical content. Ultraviolet circular dichroic spectroscopy indicated that both dimers contain stable alpha-helical coiled coils. Its C-terminal disulfide bridge renders P78 significantly more stable than P39 to thermal denaturation or denaturation by urea. The coiled coil of P39 was 30% unfolded near 55 degrees C and half-unfolded in 8 M urea, while that of P78 was 30% unfolded only near 85 degrees C. These studies have demonstrated the feasibility of using these ligand, spacer, and coil modules to construct the designed coiled-coil proteins P39 and P78, a stage in the nanometric engineering of receptor-adhesive modular proteins.

Amino Acid Sequence↗
PubMed1991

High-level secretion of biologically active aprotinin from the yeast Pichia pastoris.

A synthetic gene encoding aprotinin (bovine pancreatic trypsin inhibitor) was fused to the Saccharomyces cerevisiae prepro alpha mating factor leader sequence at the dibasic amino acid processing site. Pichia pastoris strains were developed to express one or multiple copies of a methanol-inducible expression cassette containing the gene fusion. P. pastoris containing a single copy of the vector secreted approximately 150 mg/l of immunoreactive protein. A construct bearing five copies of the expression cassette secreted 930 mg/l of aprotinin. The purified aprotinin molecule was equipotent with the native molecule in a trypsin inhibition assay. Protein sequence analysis showed that the alpha factor-aprotinin fusion was not processed at the basic amino acid residues Lys-Arg. Instead, recombinant aprotinin had additional N-terminal amino acids derived from prepro alpha factor. The N-terminal extension was variably 11 or 4 amino acids. Inclusion of the spacer DNA sequence encoding Glu and Ala between aprotinin and the Lys-Arg processing site led to the secretion of a biologically active aprotinin containing only a Glu-Ala N-terminal extension.

Amino Acid Sequence↗
PubMed1990

Connective tissue disease in southeast Georgia. A community based study of immunogenetic markers and autoantibodies.

HLA antigens, C4 allotypes and T cell antigen receptor (TcR)beta DNA polymorphisms were determined in a community based study of connective tissue diseases (CTD). HLA-B8, DR3 and C4A null phenotypes occurred frequently in Caucasian patients with CTD, especially those with systemic lupus erythematosus (SLE), but were also more commonly found among healthy white controls of this southeast Georgia community. TcR beta gene polymorphisms also showed differential segregation patterns between patients with SLE and scleroderma. High frequencies of ANA and anti-ssDNA antibodies occurred among apparently healthy family members and local controls. Genetic factors predisposing to CTD in a community setting appear to be similar to those reported from referral centers.

Alleles↗
PubMed1989

Vaccination and eradication programme against Aujeszky's disease in Sweden, based on a gI ELISA test.

A killed gI-negative vaccine combined with a gI enzyme-linked immunosorbent assay (ELISA) test was used for the first time in Sweden in an attempt to eradicate Aujeszky's disease from a weaner pig producing herd. The herd had experienced three severe outbreaks of the disease during a 10 year period and at the start of the programme 96 per cent of the herd's 104 breeding animals were seropositive to the Aujeszky's virus. In addition, there was serological evidence of active virus circulation among younger animals. During the programme, all breeding animals were vaccinated every sixth month and replacement animals were tested free of disease and vaccinated before entry into the herd. When the originally seropositive animals had been rotated out of the herd, all breeding animals and a sample of weaner pigs were tested twice at six weeks' interval. No seroconversions to gI had taken place and the herd was declared Aujeszky's disease-free, 22 months after the start of the programme.

Animals↗
PubMed1989

[The central nervous system arousing effects of ketamine are decreased by addition of midazolam. A post-anesthesia study of patients following maxillary surgery with spontaneous respiration].

The present study was done in order to investigate the central nervous activity in patients (n = 15) after maxillo-facial surgery, 5 and 90 minutes post ketamine-midazolam-anesthesia. The combination of a benzodiazepine with ketamine was thought to be beneficial to reduce the usual excitatory effects after ketamine postoperatively. In order to demonstrate these benefits EEG-power spectra as well somatosensory-evoked potentials were derived (Neurotrac). Additionally, the central nervous effects were correlated with blood pressure changes. 5 minutes post ketamine-midazolam-anesthesia EEG-power spectra showed a marked depression in the alpha, theta and delta power band when compared to the control-awake situation. However, power in the beta domain (13-30 Hz) was significantly elevated. 90 minutes post anesthesia the high power values returned back to control. In no instance were there any signs of theta-paroxysms which can be taken as an index for central excitation. In the evoked potential a significant increase in amplitude of the early N20 and late N50 peak was evident. This correlated with an increase in systolic blood pressure. 90 minutes post anesthesia only the late N50 peak still remained elevated suggesting some residual excitatory effects in the thalamo-cortical projection area to be present. The latter may reflect an increase in activity in the associative cortical areas of the cerebral cortex. In general however, the additional administration of midazolam resulted in a marked reduction in excitatory central nervous effects when compared to the well known excitation after sole ketamine injection. Thus, the beneficial venture of the two separate classes of anesthetics is advocated for clinical practice.

Adolescent↗
PubMed1988

The pharmacokinetics of melphalan during intermittent therapy of multiple myeloma.

During intermittent melphalan-prednisone therapy the area under the plasma concentration-time curve of melphalan increased by an average of 45% after oral or intravenous administration of the drug in myeloma patients during the initial three courses at six-week intervals. The rise in melphalan plasma concentrations could not be referred to an alteration in melphalan elimination, metabolism, erythrocyte/plasma partition ratio, or protein binding. A possible explanation could be that covalent binding sites of melphalan were successively saturated during intermittent treatment, resulting in higher drug concentrations during successive courses of therapy.

Administration, Oral↗
PubMed1988

Drawing ability in four young children with congenital unilateral brain lesions.

The drawings of four 5-yr-old children, two with left and two right hemisphere congenital brain injury, were compared with those of 20 normal 3.5-5 yr-olds. Two types of drawings were evaluated: copied geometric forms and free drawings. The children with left hemisphere injury showed normal development in both copying and free drawing. The children with right hemisphere injury were developmentally impaired in the copying task. In addition, their free drawings lacked configurational coherence; they included the elements of the figures but failed to arrange them in spatially organized ways. This failure to organize spatially elements is consistent with the descriptions of spatial cognitive disorders found in the drawings of adults with right parietal brain lesions.

Brain↗
PubMed1986

Bereitschaftspotential preceding speech after holding breath.

Cerebral potentials prior to speaking were recorded in 36 healthy righthanded subjects. Subjects began holding breath at irregular intervals prior to the voluntary onset of speech. This was done in order to avoid respiration-related potential shifts. The Bereitschaftspotential (BP) or readiness potential started already 2 s prior to the onset of speaking and was present over either hemisphere. During the last 100 to 200 ms of preparation period, the BP became significantly lateralized towards the left hemisphere. The close temporal relation to speech onset characterized this hemispheric lateralization to be an indicator of the final motor mechanisms for speech. Still, the BP was a bilateral phenomenon, i.e. it was also present over the right hemisphere, indicating involvement of the non-dominant hemisphere as well. The data are compatible with the view of an early bihemispheric motor preparation for speech followed by a late left hemisphere preponderance as the final common pathway.

Adult↗