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R Aitken

Publications and source records attributed to R Aitken.

At least 19 recordsLinked to original sources
PubMed2003

Low but detectable serum thyroid-stimulating hormone concentrations in ambulant subjects not receiving thyroxine.

BACKGROUND: In laboratories employing 'front-line' sensitive thyroid-stimulating hormone (TSH) measurement, it is generally accepted that a fully suppressed serum TSH concentration (third-generation assay) alongside normal serum concentrations of free thyroid hormones indicates subclinical hyperthyroidism. However, other explanations are often provided for low but detectable serum TSH concentrations, such as drug effects or non-thyroidal illness. METHODS: We investigated 25 consecutive ambulant individuals, identified over an 18-month period as having low but not fully suppressed TSH concentrations (third-generation assay; sensitivity 0.003 mIU/L) with additional free thyroxine (T(4)), free tri-iodothyronine (T(3)) and thyroid microsomal antibody estimations and thyroid isotope scanning (technetium). RESULTS: Concentrations of serum hormones (median, inter-quartile range) were: TSH, 0.23, 0.17-0.26 mIU/L (reference range 0.34-5.6 mIU/L); free T(4), 14.6, 10.6- 17.6 pmol/L (reference range 10-25 pmol/L); free T(3), 6.1, 5.7-6.6 pmol/L (reference range 4.5-7.5 pmol/L). Thyroid antibodies were negative in all but one individual. On isotope scanning, nine individuals had hot nodules and ten individuals had multinodular goitres (MNG). Of the six with normal scans, ultrasound scanning showed a definite MNG (n = 1) and early MNG (n = 2). CONCLUSIONS: A low but detectable serum TSH concentration, obtained using a third-generation assay, found in an ambulant individual, is frequently a pointer to underlying thyroid disease.

Adult↗
PubMed2001

Nutrient partitioning during adolescent pregnancy.

Human adolescent mothers have an increased risk of delivering low birth weight and premature infants with high mortality rates within the first year of life. Studies using a highly controlled adolescent sheep paradigm demonstrate that, in young growing females, the hierarchy of nutrient partitioning during pregnancy is altered to promote growth of the maternal body at the expense of the gradually evolving nutrient requirements of the gravid uterus and mammary gland. Thus, overnourishing adolescent dams throughout pregnancy results in a major restriction in placental mass, and leads to a significant decrease in birth weight relative to adolescent dams receiving a moderate nutrient intake. High maternal intakes are also associated with increased rates of spontaneous abortion in late gestation and, for ewes delivering live young, with a reduction in the duration of gestation and in the quality and quantity of colostrum accumulated prenatally. As the adolescent dams are of equivalent age at the time of conception, these studies indicate that nutritional status during pregnancy rather than biological immaturity predisposes the rapidly growing adolescents to adverse pregnancy outcome. Nutrient partitioning between the maternal body and gravid uterus is putatively orchestrated by a number of endocrine hormones and, in this review, the roles of both maternal and placental hormones in the regulation of placental and fetal growth in this intriguing adolescent paradigm are discussed. Impaired placental growth, particularly of the fetal component of the placenta, is the primary constraint to fetal growth during late gestation in the overnourished dams and nutritional switch-over studies indicate that high nutrient intakes during the second two-thirds of pregnancy are most detrimental to pregnancy outcome. In addition, it may be possible to alter the nutrient transport function of the growth-restricted placenta in that the imposition of a catabolic phase during the final third of pregnancy in previously rapidly growing dams results in a modest increase in lamb birth weight.

Adolescent↗
PubMed1999

Structure and diversification of the bovine immunoglobulin repertoire.

Our understanding of the basis to immunoglobulin formation in cattle has benefited substantially from the application of molecular biology over the past decade. It is now established that both the lambda light chain and heavy chain repertoires are founded upon the frequent expression of single gene families and subgroups of segments which are of conserved sequence. It is likely that a functional kappa locus exists in the bovine genome but this isotype comprises as few as 5% of bovine light chains. Similarly, alternative but non-expressed V(H) gene families are present posing intriguing but unresolved questions about the regulation of immunoglobulin synthesis. The heavy chain frequently bears a third complementarity-determining region which is atypically long but the processes which expand this region of the reading frame and its contribution to the interaction with antigen remain matters of speculation. Opportunities exist to map the major immunoglobulin loci and to define the membership and sequence diversity of the gene families which dominate each repertoire. However, it is already evident that cattle cannot generate significant diversity from rearrangement and junctional imprecision alone. Elucidation of the mechanism(s), dynamics and tissue distribution of immunoglobulin diversification in cattle, thus, remain key challenges in this branch of veterinary immunology.

Animals↗
PubMed1999

Generation of native bovine mAbs by phage display.

Modeling of disease pathogenesis and immunity often is carried out in large animals that are natural targets for pathogens of human or economic relevance. Although murine mAbs are a valuable tool in identifying certain host/pathogen interactions, progress in comparative immunology would be enhanced by the use of mAbs isolated from the host species. Such antibodies would reflect an authentic host immune response to infection or vaccination, and as they are host derived, would allow the application of in vivo experiments that previously have been unrealizable in large animals because of induction of an antispecies immune response. The advent of antibody phage display technology provides a way of producing host-derived mAbs in animals where the molecular genetics of Ig formation are known. Exploiting recent advances in the molecular immunology of cattle, we report here the design of an optimized phage display vector, pComBov, for the construction of combinatorial libraries of bovine Ig antigen-binding fragments (Fab) of native sequence. By using this system, we initially have generated and characterized a panel of bovine mAbs against a model antigen glutathione S-transferase. The isolated mAbs showed features typical of bovine Igs and recognized glutathione S-transferase with high specificity in ELISA and by Western blotting. The pComBov expression system can be readily adapted for the preparation of libraries from related ruminant species and advances the use of monoclonal reagents derived in this way for comparative studies in animals of economic importance.

Amino Acid Sequence↗
PubMed1999

Primary and secondary structure of the small-subunit ribosomal RNA of the naked, marine amoeba Vannella anglica: phylogenetic implications.

The primary and secondary structure of the small-subunit ribosomal RNA (ssrRNA) gene from the naked, marine amoeba, Vannella anglica (subclass Gymnamoebia), was determined. The ssrRNA is 1962 nucleotides in length, with a low G+C content of 37.1%. The ssrRNA is composed of several uncommon secondary structure features including helix E8-1, which may be a useful target for rRNA probes for the direct identification of isolates in mixed culture. Phylogenetic analysis of sequence data showed that V. anglica branched prior to the rapid diversification of the eukaryotes. It did not associate with the other naked, lobose amoebae represented by Acanthamoeba and Hartmannella, indicating that Vannella represents a separate amoeboid lineage and the subclass Gymnamoebia is polyphyletic.

Amino Acid Sequence↗
PubMed1997

Bovine IgG repertoire is dominated by a single diversified VH gene family.

Using methods based upon the PCR, we have analyzed sequences that encode the V domain of bovine Ig heavy chain. Pairwise comparison indicates that the heavy chain repertoire in cattle is dominated by a single VH gene family that is homologous to human VHII. The third complementarity-determining region (CDR3) is particularly variable and 60% of the sequences encode a CDR3 in excess of 21 amino acids. Southern blots, single-stranded conformation polymorphism analysis, and sequencing of segments from the germline indicate that the dominant VHII gene family is of small size, comprising as few as 10 unique members, and carries a very low level of diversity in CDRs 1 and 2. Comparison of germline VH sequences with those gathered from adult bovine splenic cDNA demonstrates a pattern of nucleotide substitution that is consistent with diversification through somatic hypermutation.

Animals↗
PubMed1997

A collaborative European study of personal inhalable aerosol sampler performance.

Following the adoption of new international sampling conventions for inhalable, thoracic and respirable aerosol fractions, a working group of Comité Européen de Normalisation (CEN) drafted a standard for the performance of workplace aerosol sampling instruments. The present study was set up to verify the experimental, statistical and mathematical procedures recommended in the draft performance standard and to check that they could be applied to inhalable aerosol samplers. This was achieved by applying the tests to eight types of personal inhalable aerosol sampler commonly used for workplace monitoring throughout Europe. The study led to recommendations for revising the CEN draft standard, in order to simplify the tests and reduce their cost. However, some further work will be needed to develop simpler test facilities and methods. Several of the samplers tested were found to perform adequately with respect to the inhalable sampling convention, at least over a limited range of typical workplace conditions. In general the samplers were found to perform best in low external wind speeds, which are the test conditions thought to be closest to those normally found in indoor workplaces. The practical implementation of the CEN aerosol sampling conventions requires decisions on which sampling instruments to use, estimation of the likely impact that changing sampling methods could have on apparent exposures, and adjustment where necessary of exposure limit values. The sampler performance data obtained in this project were affected by large experimental errors, but are nevertheless a useful input to decisions on how to incorporate the CEN inhalable sampling convention into regulation, guidance and occupational hygiene practice.

Europe↗
PubMed1995

PCR strategies for isolation of the 5' end of an immunoglobulin-encoding bovine cDNA.

We have employed two in vitro amplification strategies in our attempts to characterise the variable region of bovine immunoglobulin heavy chains (VH). Products derived by 5' RACE (rapid amplification of cDNA ends) spanned the coding sequence, but diversity in the complementarity determining regions was highly restricted, indicating that a limited subset of the heavy-chain repertoire had been recovered. In contrast, unique, full-length VH determinants were obtained with ease by an inverse application of the polymerase chain reaction. The strength of this approach is considerable: it is straightforward to perform, requiring none of the tailing procedures inherent to RACE strategies, yet it enables the rapid isolation of uncharacterized regions of genes for which limited sequence data are available. Our findings suggest strongly that the heavy-chain repertoire of cattle is highly dependent upon a very limited number of germline VH and JH (joining region) gene families.

Animals↗
PubMed1995

Molecular characterization of bovine V lambda regions.

Using an inverse PCR technique with primers directed against constant region sequences, 18 V lambda regions have been isolated at random from bovine splenic cDNA for detailed analysis. On the basis of protein sequences in FR1 and their homologies to the human lambda chains NEWM and MCG, the bovine determinants can be separated into two families that have been designated V lambda 1 (94% of all clones isolated) and V lambda 2 (6% of all clones isolated). Scrutiny of the nucleotide sequences has allowed subdivision of the dominant family into V lambda 1a, V lambda 1b and V lambda 1c groupings, which represent 29, 65, and 6% of all V lambda 1 clones respectively. It appears that the size of CDR1 is V lambda group-specific--the region comprises 14 amino acids in V lambda 1a determinants and 13 residues in V lambda 1b and V lambda 1c,--whereas with a single exception, seven amino acids make up CDR2. The size of CDR3 is variable, ranging from 10 to 15 amino acids in length. Conservation of those nucleotide sequences that encode the signal peptide and FR3 has enabled us to amplify and characterize 14 V lambda 1 genes from kidney genomic DNA. Interestingly, half of the germline sequences were not represented in the data gathered from splenic cDNA, while the remaining genes could be identified as members of the V lambda 1a and V lambda 1b groups. The findings indicate that the V lambda 1 family dominates the expressed bovine light chain repertoire but that a large proportion of the germline segments from which this repertoire is derived may be nonfunctional.

Amino Acid Sequence↗
PubMed1994

Vectors to facilitate the creation of translational fusions to the maltose-binding protein of Escherichia coli.

A set of vectors has been constructed to facilitate the fusion of heterologous sequences to the C terminus of the maltose-binding protein (MBP) of Escherichia coli. The plasmids carry a cloning region comprising two blunt cloning sites, a BamHI site and multiple stop codons, and this has been placed in each reading frame so that translational fusions to MBP can be generated and manipulated with ease. To demonstrate the utility of this system, recombinant proteins have been engineered in which staphylococcal enterotoxin A has been fused to MBP.

ATP-Binding Cassette Transporters↗
PubMed1994

The Rapunzel syndrome. Report of a case and review of the literature.

The Rapunzel Syndrome, a rare manifestation of trichobezoar, occurs when bolus gastrointestinal obstruction is produced by an unusual trichobezoar with a long tail that extends to or beyond the ileocaecal valve. A five-year-old Jamaican girl presented with this abnormality and was found at laparotomy also to have an ileo-ileal intussusception. For the Rapunzel Syndrome, we recommend bezoar extraction at laparotomy via multiple enterotomies. In addition, psychiatric evaluation and therapy is essential due to the commonly associated finding of underlying emotional stress.

Bezoars↗
PubMed1993

Recombinant enterotoxins as vaccines against Escherichia coli-mediated diarrhoea.

A fusion protein, comprising the B subunit of the heat-labile enterotoxin and a portion of the precursor to the heat-stable enterotoxin of Escherichia coli, has been created by recombinant genetic techniques. It is exported successfully to the bacterial periplasm and assembles into pentamers which retain the ability to bind to GM1 ganglioside. Native toxin epitopes are displayed and the molecule can be easily purified from periplasmic extracts of cells expressing the gene fusion. Although the protein carries the natural sequence of the heat-stable enterotoxin, it is greatly attenuated in toxicity. Systemic immunization of mice or oral administration of the fusion elicits antibody responses against both classes of E. coli enterotoxin.

Administration, Oral↗
PubMed1992

Development of an immunoassay using recombinant maltose-binding protein-STa fusions for quantitating antibody responses against STa, the heat-stable enterotoxin of Escherichia coli.

A set of fusion proteins containing heat-stable enterotoxin (STa) and maltose-binding protein were engineered. These molecules were readily purified and used as solid-phase antigens in an enzyme-linked immunosorbent assay to monitor anti-STa responses in mice immunized with a recombinant vaccine composed of STa and the B subunit of heat-labile enterotoxin.

ATP-Binding Cassette Transporters↗
PubMed1989

The growth and development of Schistosoma mansoni in mice exposed to sublethal doses of radiation.

The maturation of Schistosoma mansoni was studied in mice exposed to various sublethal doses of radiation. Although the treatment of mice with 500 rads of radiation prior to infection did not alter parasite maturation, doses in excess of 500 rads led to a reduction in worm burden. This could not be attributed to a delay in the arrival of parasites in the hepatic portal system. Worms developing in mice treated with 800 rads commenced egg-laying about 1 wk later than worms in intact mice, and the rate of egg deposition appeared to be lower in irradiated hosts. The data demonstrate that exposure of C57BL/6 mice to doses of radiation in excess of 500 rads impairs their ability to carry infections of S. mansoni. The findings do not support the hypothesis that primary worm burdens in the mouse are controlled by a host immune response.

Animals↗