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Biomedical subjects

M Engel

Publications and source records attributed to M Engel.

17 recordsLinked to original sources
PubMed1992

Kinetic model of the epidermal growth factor (EGF) receptor tyrosine kinase and a possible mechanism of its activation by EGF.

The tyrosine kinase activity of the epidermal growth factor receptor (EGFR-TK) was determined at varying poly-Glu6Ala3Tyr1 (GAT) or [Val5]-angiotensin II (AT) and constant ATP concentrations and vice versa. With GAT as substrate, double reciprocal plots intersected practically on the abscissa following EGFR-TK pre-activation with EGF, but below the abscissa without EGF pre-activation. The EGFR-TK inhibitors App(NH)p (5'-adenylyl-beta, gamma-imidodiphosphate) and ADP were competitive with ATP and noncompetitive with GAT. Four families of 1/v vs. 1/[ATP] plots, constructed at different fixed concentrations of ADP and a different constant concentration of GAT for each family, yielded Slope1/ATP replots which intersected to the left of the ordinate and below the abscissa. GAT and AT, as cosubstrates, were competitive with each other and noncompetitive with ATP; 1/v vs. 1/[GAT] or 1/[AT] plots were hyperbolic and reached horizontal asymptotes when v was expressed as the rate of common product formation. All data were subjected to computer best-fit analysis by a program written especially for this purpose. We conclude that (i) the EGFR-TK reaction follows a Sequential Bi-Bi Rapid Equilibrium Random mechanism, and (ii) EGF induces conformational changes in the EGFR-TK active center which lead to marked decreases in the apparent dissociation constants of both substrates of the kinase reaction and a concomitant increase in initial velocities and Vmax (apparent).

Carcinoma, Squamous Cell↗
PubMed1992

A novel galactose- and arabinose-specific lectin from the sponge Pellina semitubulosa: isolation, characterization and immunobiological properties.

A new lectin from the sponge Pellina semitubulosa is derived which was extracted and purified to homogeneity. The purified lectin is probably a hexamer of polypeptide chains (each M(r) 34,000) which are covalently linked via disulfide linkages; the isoelectric point is 6.1. The lectin displays the following specificities: D-galactose (50% inhibition of hemagglutination at 0.2 mM) = L-arabinose (0.2 mM) greater than D-fucose (1.5 mM) greater than D-glucose (3.0 mM). It precipitates human erythrocytes (A1, A2, A1B, B, and O) with a titer between 2(8) and 2(11) and erythrocytes from sheep and rabbits with a titer between 2(5) and 2(10). The Pellina lectin displays a strong mitogenic effect on spleen lymphocytes from mice. Immunochemical analyses revealed that both murine T- and B-lymphocytes display a capping of the lectin receptors on their cell surfaces after lectin treatment. Murine macrophages were found to endocytose the lectin. Pellina lectin at concentrations between 0.3 and 10.0 micrograms/ml potently enhances interleukin 1 (IL-1) release from mouse peritoneal macrophages and interleukin 2 (IL-2) production in mixed murine lymphocyte cultures.

Amino Acids↗
PubMed1992

Inadvertent intracranial placement of a Foley catheter. A rare iatrogenic complication of severe frontomaxillary trauma.

Severe comminuted fractures of the facial bones involving the cranial base are often accompanied by heavy bleeding into the nasopharynx. This presents considerable problems in primary care both for the anesthesiologist and the surgeon. Such bleeding can be controlled by Bellocq tamponade or using a Foley inflatable catheter. Skull base fractures may involve the risk of the catheter inadvertently penetrating into the brain. The authors describe a case in which a misguided Foley catheter, which was blindly inserted through the nose in an attempt to tampon the nasopharynx, resulted in fatal cerebral damage.

Adult↗
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↗
PubMed1979

Increased intraventricular pressure without ventriculomegaly in children with shunts: "normal volume" hydrocephalus.

Five patients with shunt-dependent hydrocephalus were observed to have apparently normal ventricular size despite marked increases in ventricular pressure after shunt malfunction. Elastance (dP/dV) was determined in four of these patients by removing increments of cerebrospinal fluid and measuring the resulting pressure. These patients without ventricular enlargement and with markedly increased ventricular pressure had high elastance. This group of patients with "normal volume" hydrocephalus had distal shunt occlusions, in contrast to previously reported patients with cephalic shunt obstructions after ventricular decompression. Initial shunting in early infancy, prolonged shunt dependency, and lack of recent shunt revision were common factors in these patients. Markedly elevated pressure with normal volume is a threatening clinical entity, requiring prompt surgical intervention

Abducens Nerve↗
PubMedDate not supplied

Oral immunisation with killed Haemophilus influenzae for protection against acute bronchitis in chronic obstructive lung disease.

Fifty patients with chronic obstructive lung disease were randomly allocated to three groups, to assess whether an oral vaccine containing non-typable Haemophilus influenzae protected against acute bronchitis. The double-blind prospective study over a three-month winter period included two placebo groups and one test group. Oral immunisation with H influenzae induced a tenfold reduction in the incidence of infection (p less than 0.001). During the subsequent winter, without further immunisation, protection by the vaccine was no longer statistically significant. There was no clear correlation between clinical protection and either carriage of H influenzae or the level of antibody to H influenzae antigen in saliva.

Acute Disease↗