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Biomedical subjects

B Walker

Publications and source records attributed to B Walker.

At least 235 records · Page 13Linked to original sources

Protecting our children.

American society will face major economic and social difficulties in the years to come if we do not address the serious threat to our prosperity posed by the growing numbers of young people who lack the education to function in a highly technical world. The author identifies some of the circumstances and behaviors that place children at risk of academic failure, including poverty, teenage pregnancy, drug abuse, unstable families, and suicide. Failure of the education, health, and social service systems set up to deal with these risk factors is also identified as part of the problem. The author offers four proposals for restructuring failing systems to provide our youth with the support they need to mature, learn, and develop.

Adolescent↗

Synthesis of lysine-containing sulphonium salts and their properties as proteinase inhibitors.

Some sulphonium salts derived from lysine were synthesized with the general structure R-Lys-CH2S+-(alkyl)2. They were examined as inhibitors of the cysteine proteinase clostripain, which has a preference for cleaving peptide bonds at the carboxy group of basic amino acids, and of a number of trypsin-related serine proteinases. Clostripain was irreversibly inactivated by all reagents examined, but in the case of the serine proteinases, depending on the reagent structure, irreversible and reversible inhibitions were observed. These were kinetically characterized.

Cysteine Endopeptidases↗

A soluble CD4 protein selectively inhibits HIV replication and syncytium formation.

The CD4 (T4) molecule is expressed on a subset of T lymphocytes involved in class II MHC recognition, and is probably the physiological receptor for one or more monomorphic regions of class II MHC (refs 1-3). CD4 also functions as a receptor for the human immunodeficiency virus (HIV) exterior envelope glycoprotein (gp120) (refs 4-9), being essential for virus entry into the host cell and for membrane fusion, which contributes to cell-to-cell transmission of the virus and to its cytopathic effects. We have used a baculovirus expression system to generate mg quantities of a hydrophilic extracellular segment of CD4. Concentrations of soluble CD4 in the nanomolar range, like certain anti-CD4 monoclonal antibodies, inhibit syncytium formation and HIV infection by binding gp120-expressing cells. Perhaps more importantly, class II specific T-cell interactions are uninhibited by soluble CD4 protein, whereas they are virtually abrogated by equivalent amounts of anti-T4 antibody. This may reflect substantial differences in CD4 affinity for gp120 and class II MHC.

Animals↗

Sonographic estimation of fetal weight and Doppler analysis of umbilical artery velocimetry in the prediction of intrauterine growth retardation: a prospective study.

A prospective study was undertaken to examine whether Doppler velocimetry studies of the umbilical artery give a better or an earlier prediction of intrauterine growth retardation (IUGR) than do sonographic estimation of fetal weight. A total of 385 examinations were performed between 30 and 42 weeks of gestation on 168 patients who were at risk for IUGR. Forty-two (25%) of the patients delivered an infant with a birth weight below the tenth percentile. Although sensitivity was lower for the systolic to diastolic ratio (55%) of the umbilical artery than for the sonographic estimation of fetal weight (76%), the umbilical artery studies had a higher specificity (92% versus 80%) and predictive value of a positive test (73% versus 58%) when the last study to delivery interval was within 2 weeks. Furthermore, among 21 IUGR pregnancies with serial studies, the umbilical systolic to diastolic ratio was abnormal at a significantly earlier gestational age than when the sonographic estimate of fetal weight identified growth retardation. These findings indicate that sonographic biometry is a more sensitive technique for identifying IUGR but that the umbilical artery waveforms are a valuable adjunct for improving the diagnostic accuracy for the prenatal detection of IUGR. These data also provide suggestive evidence that umbilical artery velocimetry may be predictive of IUGR at an earlier gestational age than sonographic estimation of fetal weight.

Adult↗

Purification and properties of Drosophila heat shock activator protein.

Drosophila heat shock activator protein, a rare transacting factor which is induced upon heat shock to bind specifically to the heat shock regulatory sequence in vivo, has been purified from shocked cells to more than 95 percent homogeneity by sequence-specific duplex oligonucleotide affinity chromatography. The purified protein has a relative molecular mass of 110 kilodaltons, binds to the regulatory sequence with great affinity and specificity, and strongly stimulates transcription of the Drosophila hsp70 gene. Studies with this regulatory protein should lead to an understanding of the biochemical pathway underlying the heat shock phenomenon.

Animals↗

An improved spectrophotometric assay for leucine aminopeptidase.

A sensitive assay to determine the activity of leucine aminopeptidase (EC 3.4.11.1), using L-leucine thiobenzyl ester as substrate, was developed. Hydrolysis of the ester by leucine aminopeptidase can be monitored in the presence of 5,5-dithiobis-(2-nitrobenzoic acid) by continuous spectrophotometric measurement at 412 nm. Comparison with some amide substrates showed that the thiol ester provides a much more sensitive assay, its specificity constant (Vmax./Km) being some 3000-fold higher than that of leucine p-nitroanilide.

Animals↗

Prenatal sonographic assessment of the fetal thorax: normal values.

Fetal thoracic circumference and thoracic length measurements were obtained by ultrasonographic examination on 576 women between 16 and 40 weeks gestation. Nomograms for thoracic circumference and thoracic length with respect to gestational age were developed. Growth of both thoracic parameters was observed to be linear throughout gestation. In normal pregnancy the ratios of thoracic circumference to abdominal circumference and thoracic length to humerus length remained virtually constant at 0.89 and 0.93, respectively.

Adolescent↗

Alpha-acetoxy derivatives of methyl-2-oxopropylnitrosamine: synthesis, hydrolysis rate and bacterial mutagenicity.

N-Methyl-N-2-oxopropylnitrosamine (MOP) induces pancreatic tumors in hamsters. As models for the putative proximate carcinogenic alpha-hydroxy derivatives, we studied N-acetoxymethyl-N-2-oxopropylnitrosamine (AMOP) and N-methyl-N-(1-acetoxy-2-oxopropyl)nitrosamine (MAOP). AMOP was synthesized from aminoacetone by the method of Roller et al. [1975), Tetrahedron Lett., 25, 2065-2068) and MAOP was synthesized by acetoxylation of MOP with lead tetraacetate. The half-lives of AMOP, MAOP and acetoxymethylmethylnitrosamine (ADMN) in aqueous buffer decreased as the pH rose from 5 to 9, with values at pH 5 of 2.8 X 10(4) min for AMOP, 3.2 X 10(3) min for ADMN, and 23 min for MAOP. Mutagenicity was examined in Salmonella typhimurium TA1535, using a pre-incubation at pH 5 without microsomal activation. The mutagenic potency, expressed as revertants/mumole, was 56 for AMOP, 150 for ADMN, and 4.5 X 10(4) for MAOP. Hence, hydrolysis rates at pH 5 were probably important in determining the relative mutagenicity.

Chemical Phenomena↗

Use of the objective structured clinical examination for assessment of vocational trainees for general practice.

General practice training schemes currently have no structured methods of assessment and most rely on a variety of subjective ratings of performance. In West Cumbria the ;objective structured clinical examination' has been used to assess training performance in areas covered by small group teaching during the preceding terms. Consultation skills, interpretation of clinical data and a number of aspects of practice management were tested. The examination was conducted in the local postgraduate centre and assessed 20 trainees. Each trainee received feedback of his performance on each problem set and also an overall comparison with his peers.This method of assessment appeared to be well received by trainees and was practicable within the limited resources available. In addition, the variety of problems set allowed for a broad range of trainees' performances to be assessed.

Education, Medical, Graduate↗

The synthesis of peptidylfluoromethanes and their properties as inhibitors of serine proteinases and cysteine proteinases.

A synthesis of peptidylfluoromethanes is described that utilizes the conversion of phthaloyl amino acids into their fluoromethane derivatives. These can be deblocked and elongated. The inactivation of chymotrypsin by Cbz-Phe-CH2F (benzyloxycarbonylphenylalanylfluoromethane) was found to be considerably slower than that of the analogous chloromethane. The fluoromethane analogue inactivates chymotrypsin with an overall rate constant that is 2% of that observed for the inactivation of the enzyme with the chloromethane. However, the result is the same. The reagent complexes in a substrate-like manner, with Ki = 1.4 X 10(-4) M, and alkylates the active-centre histidine residue. Cbz-Phe-Phe-CH2F and Cbz-Phe-Ala-CH2F were investigated as inactivators of the cysteine proteinase cathepsin B. The difference in reactivity between fluoromethyl ketones and chloromethyl ketones is less pronounced in the case of the cysteine proteinase than for the serine proteinase. Covalent bond formation takes place in this case also, as demonstrated by the use of a radiolabelled reagent.

Cathepsin B↗