Biomedical subjects

T Myles

Publications and source records attributed to T Myles.

22 records · Page 2Linked to original sources

PubMed1990

Albumin Redhill (-1 Arg, 320 Ala----Thr): a glycoprotein variant of human serum albumin whose precursor has an aberrant signal peptidase cleavage site.

Albumin Redhill is an electrophoretically slow genetic variant of human serum albumin that does not bind 63Ni2+ and has a molecular mass 2.5 kDa higher than normal albumin. Its inability to bind Ni2+ was explained by the finding of an additional residue of Arg at position -1. This did not explain the molecular basis of the genetic variation (since proalbumin contains adjacent Arg residues at -1 and -2) or the increase in apparent molecular mass. Fractionation of tryptic digests on concanavalin A-Sepharose followed by peptide mapping of the bound and unbound fractions and sequence analysis of the glycopeptides identified a mutation of 320 Ala----Thr. This introduces an Asn-Tyr-Thr oligosaccharide attachment sequence centered on Asn-318 and explains the increase in molecular mass. This, however, did not satisfactorily explain the presence of the additional Arg residue at position -1. DNA sequencing of polymerase chain reaction-amplified genomic DNA encoding the prepro sequence of albumin indicated an additional mutation of -2 Arg----Cys. This introduces a prepro sequence, Met-Lys-Trp-Val-Thr-Phe-Ile-Ser-Leu-Leu-Phe-Leu-Phe-Ser-Ser-Ala-Tyr- Ser-Arg-Gly-Val-Phe-Cys-Arg (cf.-Tyr-Ser-Arg-Gly-Val-Phe-Arg-Arg- in normal human pre-proalbumin). We propose that the new Phe-Cys-Arg sequence in the propeptide is an aberrant signal peptidase cleavage site and that the signal peptidase cleaves the propeptide of albumin Redhill in the lumen of the endoplasmic reticulum before it reaches the Golgi vesicles, the site of the diarginyl-specific proalbumin convertase.

Alanine↗

PubMed1990

Hypermutability of CpG dinucleotides in the propeptide-encoding sequence of the human albumin gene.

An electrophoretically slow albumin variant was detected with a phenotype frequency of about 1:1000 in Sweden and was also found in a family of Scottish descent from Kaikoura, New Zealand, and in five families in Tradate, Italy. Structural study established that the major variant component was arginyl-albumin, in which arginine at the -1 position of the propeptide is still attached to the processed albumin. A minor component with the amino-terminal sequence of proalbumin was also present as 3-6% of the total albumin. After amplification of the gene segment encoding the prepro sequence of albumin, specific hybridization of DNA to an oligonucleotide probe encoding cysteine at position -2 indicated the mutation of arginine at the -2 position to cysteine (-2 Arg----Cys). This produced the propeptide sequence Arg-Gly-Val-Phe-Cys-Arg. This was confirmed by sequence analysis after pyridylethylation of the cysteine. This mutation produces an alternate signal peptidase cleavage site in the variant proalbumin precursor of arginyl-albumin giving rise to two possible products, arginyl-albumin and the variant proalbumin. Another plasma from Bremen had an alloalbumin with a previously described substitution (1 Asp----Val), which also affects propeptide cleavage. Hypermutability of two CpG dinucleotides in the codons for the diarginyl sequence may account for the frequency of mutations in the propeptide. Mutation at these two sites results in a series of recurrent proalbumin variants that have arisen independently in diverse populations.

Amino Acid Sequence↗

PubMed1984

Management of acute subdural hematomas from aneurysmal rupture.

Subdural hematomas (SDH) from ruptured aneurysm (RA) are much less common than intracerebral (ICH) hematomas or subarachnoid (SAH) or intraventricular hemorrhage (IVH). With computerized tomography, preoperative diagnosis is now made more often. The authors have collected 18 such cases from a review of 897 cases of RA admitted to eleven medical centers in 1980 and 1981. Nine (50%) of these patients died prior to discharge from hospital. Four (22%) had surgery and died postoperatively and 9 (50%) were operated upon and survived. Thirteen (72%) of the patients showed anisocoria, decreased consciousness and unilateral weakness prior to surgery. Eight (89%) of the fatalities had shown preoperative herniation as opposed to only 5 (56%) of the survivors. The overall incidence of delayed ischemia due to vasospasm was 11% (2 cases). Those who died had greater midline shift and larger SDH on the admission CT scan. Sixteen (89%) of these patients were female. Thirteen (72%) had ruptured aneurysms on the internal carotid artery. All of these hematomas were unilateral and uniformly hyperdense, and the convexity hematomas were crescentic in shape. Seventeen (94%) had evidence of blood in locations other than the subdural space. If the patient is potentially salvageable and has a midline shift, the SDH should probably be evacuated immediately and the aneurysm clipped at the same operation since the development of a tentorial herniation has such an adverse effect on outcome.

Acute Disease↗

PubMedDate not supplied

Chorioamnionitis does not affect fetal urine production in patients with premature rupture of membranes.

The objective of this study was to evaluate fetal urine production rate in patients with premature rupture of membranes in the presence or absence of chorioamnionitis and to determine its clinical usefulness. Fetal urine production was evaluated in 30 women between 24 and 39 weeks' gestational age with ruptured membranes. Fetal bladder measurements were determined every 3-5 min for 30-90 min. Chorioamnionitis was defined by both clinical criteria and histological examination of the placenta. The last determination of fetal urine production rate prior to delivery was compared in patients with and without histologic and/or clinical chorioamnionitis. Fetal urine production rate was corrected for gestational age using birth weight prior to analysis. A total of 96 assessments of fetal urine production were performed (range 1-16 per patient). Twelve subjects (40%) had no evidence of chorioamnionitis (group 1), 10 (33%) had histologic chorioamnionitis alone (group 2), and eight (27%) had both clinical and histologic chorioamnionitis (group 3). The mean (+/- SD) urine production rates in these groups were 9.43 +/- 3.15 ml/kg/hr, 10.65 +/- 3.43 ml/kg/hr, and 9.97 +/- 2.81 ml/kg/hr, respectively. The difference in fetal urine production rate between the three groups was not statistically significant. A power analysis revealed that individual group sizes were adequate to document a 50% increase in fetal urine production rate with a type II error of < 10%. There were no documented cases of fetal infection based on neonatal cultures. The presence of histologic or clinical chorioamnionitis does not significantly affect fetal urine production in patients with premature rupture of membranes. The prospective assessment of fetal urine production rate does not appear to be clinically useful as an early indicator of chorioamnionitis.

Chorioamnionitis↗