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Biomedical subjects

J R Webb

Publications and source records attributed to J R Webb.

33 records · Page 2Linked to original sources
PubMed1988

Isolation and characterization of a cDNA clone encoding the 19 kDa protein of signal recognition particle (SRP): expression and binding to 7SL RNA.

Signal recognition particle (SRP) consists of a 7SL RNA molecule and 6 protein subunits. We have isolated and characterized cDNA clones from human liver which encode the 19kDa protein subunit (SRP19). This subunit binds to the RNA directly and mediates binding of a second polypeptide, the 54kDa subunit which is involved in signal sequence recognition. Amino acid sequences deduced from the human cDNA sequence were identical to amino acid sequences of tryptic peptides from canine pancreatic SRP19. In vitro transcription and translation of the human cDNA resulted in a protein product the same size as canine SRP19 which could be immunoprecipitated by an antiserum raised against canine SRP19. SRP19 synthesized in a cell-free system specifically bound to 7SL RNA. The sequence of SRP19 is discussed with respect to its binding to 7SL RNA.

Amino Acid Sequence↗
PubMed1987

Secretion in yeast: structural features influencing the post-translational translocation of prepro-alpha-factor in vitro.

In vitro, efficient translocation and glycosylation of the precursor of yeast alpha-factor can take place post-translationally. This property of prepro-alpha-factor appears to be unique as it could not be extended to other yeast protein precursors such as preinvertase or preprocarboxypeptidase Y. In order to determine if specific domains of prepro-alpha-factor were involved in post-translational translocation, we carried out a series of experiments in which major domains were either deleted or fused onto reporter proteins. Fusion of various domains of prepro-alpha-factor onto the reporter protein alpha-globin did not allow post-translational translocation to occur in the yeast in vitro system. Prepro-alpha-factor retained its ability to be post-translationally translocated when parts or all of the pro region were deleted. Removal of the C-terminal repeats containing mature alpha-factor had the most profound influence as post-translational translocation decreased in proportion to the number of repeats deleted. Taken together, these results suggest that efficient post-translational translocation requires a signal sequence and the four C-terminal repeats. There does not however, appear to be specific information contained within the C-terminus, as their presence in fusion did not enable the post-translational translocation of reporter proteins. Lastly, the ability to post-translationally translocate radiochemically pure prepro-alpha-factor that had been isolated by immuno-affinity chromatography required the addition of a yeast lysate fraction. Moreover, post-translational translocation is a function of the microsomal membrane of yeast microsomes and not of a factor peculiar to the yeast lysate, as reticulocyte lysate supported this as well.

Glycosylation↗
PubMed1987

Serum alpha-thiol protease inhibitor concentrations in health and disease.

Serum alpha-thiol protease inhibitor (alpha-TPI) concentration was assayed by radial immunodiffusion in normal subjects, pregnant women, and in a wide variety of diseases. The normal concentration (448 (SD 75) mg/l) increased significantly (p less than 0.001) in pregnancy to 575 (89) mg/l, and in prostatic cancer treated by oestrogens to 666 (87) mg/l. Inconsistent changes were observed in inflammatory and malignant disease and in liver disease. A temporary pronounced fall of alpha-TPI was seen after burn injury, and a sustained fall after bone marrow transplantation. Crossed immunoelectrophoresis showed that the serum alpha-TPI occurred in two forms, with alpha 2 and alpha 1 electrophoretic mobilities. A heavy demand on this antiprotease may result in suppression of the alpha 1 form.

Blood Proteins↗
PubMed1986

Dose response of patients to oral corticosteroid treatment during exacerbations of asthma.

Ten patients with asthma were treated with different doses of oral corticosteroids during three separate exacerbations. Prednisolone was given in doses of 0.2, 0.4, and 0.6 mg/kg body weight daily for two weeks in a double blind randomised order (equivalent to 14, 28, and 42 mg of prednisolone daily in a person weighing 70 kg). Patients developing an exacerbation recorded peak expiratory flow rate twice daily for two days before starting and two weeks during treatment. A dose response was shown that was significant for the difference between the peak flows, low dose less than medium dose (p less than 0.005), medium dose less than high dose (p less than 0.001) at the end of treatment. These results confirm the value of treatment with oral corticosteroids in exacerbations of asthma not requiring admission to hospital and indicate that a short high dose course of corticosteroids should consist of a minimum dose of 0.6 ng prednisolone/kg body weight for a period up to two weeks.

Adult↗
PubMed1985

Chromatographic study of the interrelationships of immunoglobulin A and alpha 1-microglobulin in myelomatosis.

The binding of alpha 1-microglobulin (alpha 1-m) to serum immunoglobulin A (IgA) myeloma proteins have been examined by analytical and preparative Superose high-performance gel chromatography. Enzyme immunoassays showed that in the serum alpha 1-m was bound to monomeric IgA, but not to the polymeric IgA, and was also present in a free form. The IgA-alpha 1-m complexes involved covalent and non-covalent bonds. Considerable variation in the ratio of bound to unbound forms of alpha 1-m was observed that appears to be a result of variation of the IgA alpha heavy chains. Reduction of monomeric IgA produced alpha 1-m-heavy chain complexes, free alpha 1-m, light and alpha heavy chains, and traces of alpha 1-m attached to IgA that was resistant to reduction.

Alpha-Globulins↗
PubMed1985

Fast protein liquid chromatography scale-up procedures for the preparation of low-molecular-weight proteins from urine.

A system for the rapid isolation of low molecular weight proteins from urine has been devised, and illustrated by alpha 1-microglobulin, beta 2-microglobulin, retinol binding protein, lysozyme and monoclonal light chains. Urine proteins from patients with tubular dysfunction were concentrated, either by ultrafiltration or ammonium sulphate precipitation. This was followed by gel chromatography on Sephadex G-50. The appropriate fractions were then separated by chromatography on Pharmacia monobead columns. A Mono Q strong anion exchanger was used for beta 2-microglobulin, retinol binding protein, alpha 1-microglobulin and free monoclonal light chains. Lysozyme was separated on a Mono S cation exchanger. The chromatography was first optimized on HR 5/5 columns and then scaled up to HR 16/10 columns.

Alpha-Globulins↗
PubMed1983

Premedication for fibreoptic bronchoscopy.

A randomised, double-blind trial of atropine, atropine plus papaveretum, and atropine plus diazepam given intramuscularly as premedication for fibreoptic bronchoscopy in 60 patients showed no difference between the three regimens as assessed by bronchoscopist or patient. Bronchoscopists frequently attributed a sedative action to atropine alone and their assessment of tolerance and sedation was more optimistic than that of the patients. In a second study comparing intravenous diazepam (10 mg) with saline, after prior intramuscular atropine (0.6 mg), both the bronchoscopists and the patients noted a significant sedative effect of diazepam, and coughing was reduced by diazepam.

Atropine↗
PubMedDate not supplied

Feasibility of human trials to assess developmental immunotoxicity, and some comparison with data on New World monkeys.

Procedures to reveal 'immunotoxic' potentials of chemicals in animal experiments (mostly in rodents) have been recommended, but the selection of test systems is rather arbitrary. The predictive power of extrapolations to the possible situation in humans is unknown because human studies to confirm or to reject clues from animal data are largely lacking. End points selected in animal studies and those expected to be relevant in humans are not identical. Results of animal experiments are based on doses, generally ignoring the important species differences in pharmacokinetics. This unfavorable situation is especially pronounced when attempting to evaluate 'environmental chemicals'. Because much more information is available on many medicinal drugs, exposures can be defined and pharmacokinetic data are available or obtainable. The situation is even more complicated when attempting to assess possible adverse effects on the developing immune system: in addition to the problems mentioned, numerous different developmental periods with varying susceptibilities must be considered, and species differences in the immune response are superimposed with large differences in pre-, early post-, and later postnatal development. Simultaneously, the kinetic variables are continuously changing with time (with additional variability among species). Different results, even between rats and mice, are bound to occur. Extrapolation to the situation possibly relevant for human exposure will be almost impossible, especially from rodent data. The majority of such effects induced peri- or early postnatally may be expected to be reversible. It must also be assessed whether qualitatively different adverse effects are likely to be induced during 'development', which cannot be revealed (accepting quantitative differences) by more easily performed tests on the adult organism. Considering the intrinsic difficulties, the most promising approach would be to directly obtain data from human trials. This is feasible for medicinal drugs. Alternatively, data on nonhuman primates, the species phylogenetically closest to man, may provide useful information. The status quo for such a strategy and the possible pitfalls are discussed in this overview.

Adult↗