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Biomedical subjects

A Whyte

Publications and source records attributed to A Whyte.

At least 55 records · Page 3Linked to original sources

Complications and cardiovascular risk factors in insulin-dependent diabetes--findings in an Irish clinic and in other European centres.

The Eurodiab Insulin Dependent Diabetes (IDDM) Complications Study was a cross-sectional investigation of a stratified random sample of IDDM patients attending 31 clinics in 16 European countries. We compared the findings in the only participating Irish centre (Cork Regional Hospital) with those of the study group as a whole. There were fewer episodes of ketosis but severe hypoglycaemia occurred more frequently in Cork patients, when compared to the full study group. There were no significant differences in the prevalence of background retinopathy, proliferative retinopathy, microalbuminuria, macroalbuminuria or peripheral neuropathy, when the two groups were compared. However, autonomic neuropathy was significantly less common in Cork. The prevalence of cardiovascular disease was slightly lower than the Eurodiab average in Cork patients, and cardiovascular risk factors were more favourable. Waist-hip ratio and total plasma cholesterol were significantly lower than in the full study group. The prevalence of hypertension was similar, but there were fewer smokers in Cork than in most other centres.

Adult↗

Infiltrating gamma delta T-cells and selectin endothelial ligands in the cutaneous phytohaemagglutinin-induced inflammatory reaction.

The 24 h phytohaemagglutinin-induced skin inflammatory site (intradermal and subcutaneous) was studied in inbred MHC-homozygous (SLAb/b) pigs and it was found, by immunohistology, that the predominant lymphocytes in the infiltrate are CD2-CD4-CD8-sIg-T-cells, the Null/gamma delta T-cell family, identified using the monoclonal antibodies (mAbs) MAC320 and MAC319 (which recognises a subset of MAC320+ cells). A large percentage of the infiltrating cells expressed the gamma delta T-cell receptor phenotype identified by binding of the mAb 86D. Fewer CD2+, CD8+ and CD4+ cells were present and surface immunoglobulin positive (sIg+) cells were virtually absent in the infiltrate. Areas of lymphocytic infiltration were associated with endothelial activation as determined by expression of the E-selectin and a ligand for the L-selectin.

Animals↗

Phylogenetic analysis of the rpoB gene from the plastid-like DNA of Plasmodium falciparum.

Malaria and other Apicomplexan parasites harbour two extrachromosomal DNAs. One is mitochondrial and the other is a 35-kb circle with some plastid-like features but whose provenance and function is unknown. In addition to genes for rRNAs, tRNAs and ribosomal proteins, the 35-kb circular DNA of Plasmodium falciparum carries an rpoBC operon which encodes subunits of a eubacteria-like RNA polymerase. The phylogenetic analysis of the complete rpoB sequence presented here supports our inference that the 35-kb circle is the remnant of a plastid genome.

Amino Acid Sequence↗

Beckwith-Wiedemann syndrome: antenatal diagnosis.

The Beckwith-Wiedemann syndrome is an unusual complex with variable features. The major findings include abdominal wall defects, macroglossia and visceromegaly. These features should be amenable to antenatal ultrasound detection. Only a few such cases have been reported to date. Antenatal diagnosis allows optimum perinatal care. Hypoglycaemia in the neonatal period is common in these babies and requires early detection and appropriate management to prevent long-term intellectual complications. We present a case where the diagnosis was suggested prior to delivery.

Adult↗

Distribution of saccharides in pig lymph-node high-endothelial venules and associated lymphocytes visualized using fluorescent lectins and confocal microscopy.

The distribution of saccharides in pig lymph nodes, particularly on high-endothelial venule (HEV) endothelium and on lymphocytes in these vessels, was studied by examining the binding of fluorescent conjugates of 18 different lectins. Eight of the lectins, particularly with glycan specificity restricted to mannose and polyacetyllactosamine determinants, were found to bind with a high affinity to these structures. Competitive inhibition experiments revealed that polylactosamine-containing glycans were present on endothelia and lymphocytes using lectins from Lycopersicon esculentum and Solanum tuberosum, the latter lectin reacting with lymphocytes only when apparently adherent to the luminal endothelium. The The absence on pig endothelium of the Ulex europaeus binding, shown by human endothelia due to the presence of certain fucose epitopes, was confirmed. Pig lymph-node endothelium, however, bound the fucose-specific lectin of Tetragonolobus purpureas, indicating the presence of fucose on pig endothelia in a different conformation to that seen on human endothelia. The results suggested that pig lymph-node HEV endothelium expressed a core fucosylated tri- or tetra-antennary complex glycan with polylactosamine extensions and expressing an Ley determinant.

Animals↗

Proto-oncogene erbA expression and increased abundance of progesterone receptors in the mouse uterus after passive immunisation against progesterone before implantation.

Passive immunisation with a monoclonal anti-progesterone antibody (DB3) prevents pregnancy in the mouse, and antibody is localised in the endometrium before the onset of implantation. BALB/c female mice were injected intraperitoneally with 9 nmol of DB3 (a dose known to cause 100% infertility) 32 h post coitum, and the uterus was removed at various times after injection. Using a monoclonal anti-progesterone receptor antibody (PR6), expression of progesterone receptors was found to be abundant in uterine tissue of DB3-treated mice; this was associated with substantial progesterone receptor mRNA levels and with maximum localisation of DB3 antibody as detected by anti-idiotype antibody. Control animals treated with an equal amount of the mouse myeloma protein P3 showed very low levels of progesterone receptor in the uterus. DB3 treatment also affected uterine expression of the proto-oncogene erbA product (which shows primary sequence homology with the progesterone receptor) as revealed by specific antiserum to the ERBA protein and by in situ hybridisation with a cDNA probe to v-erbA. Time-course studies indicated that the erbA gene was expressed at a high level before progesterone receptor expression increased, that its expression was dependent on the presence of the embryo and that erbA expression persisted longer in DB3-treated females. The observations suggest that anti-progesterone immunisation has a direct effect within the uterus, involving persistence of proto-oncogene erbA expression (which itself may represent an early maternal response to pregnancy) and increased progesterone receptor levels resulting from an unopposed oestrogen effect derived from local ligand withdrawal.

Amino Acid Sequence↗

Biotinylated anti-progesterone monoclonal antibodies specifically target the uterine epithelium and block implantation in the mouse.

Post-coital administration of a mouse monoclonal antibody (mAb) against progesterone (DB3; IgG1) prevents pregnancy in several species. Our previous studies in mice have shown that passively transferred DB3 specifically targets the uterus before the expected time of implantation, probably through progesterone-binding sites. DB3 and two other anti-progesterone mAbs, i.e. 11/34 (IgG1) and 11/64 (IgM), were biotinylated and 9 nmol of each (a dose known to reduce pregnancy rate by greater than 80% with unconjugated mAbs) was injected into BALB/c female mice 32 h post coitum (p.c.). The biotin-mAb complexes were highly effective in blocking pregnancy (83-100%) compared with control animals that had received the biotinylated MOPC21 myeloma protein P3 (IgG1). Using the streptavidin-FITC (fluorescein isothiocyanate) reporter complex or second-stage anti-biotin-FITC antibodies, biotinylated conjugates of DB3, 11/34 and 11/64 were specifically localized on the uterine luminal epithelium at 68 h p.c. (i.e. 36 h after i.p. injection). Neither P3-biotin-treated pregnant mice nor biotinylated anti-progesterone mAb-treated pseudopregnant females showed a positive reaction. In addition, the localization of biotin-conjugated anti-progesterone mAbs could be blocked by absorption of the antibodies with free progesterone or progesterone conjugates prior to injection. These results show that localization to the uterine epithelium occurs with different anti-progesterone mAbs, and that this phenomenon is probably associated with progesterone-binding sites on the luminal epithelium.

Animals↗

Antibodies, implantation and embryo survival.

The diverse strategies adopted among species for the maintenance of luteal function converge to meet the indispensable requirement for this hormone particularly at the time of onset of implantation. What has emerged from immunization studies is the difference that exists between various species in the effects of progesterone depletion. The findings affirm the uterus as a primary site of progesterone action in the preimplantation period of gestation in the mouse, whereas in the hamster the positive feedback by progesterone on pituitary luteotrophin secretion is important in maintaining luteal function and hormone secretion at a level necessary for uterine preparation. The impact of progesterone in the rat seems to be established within 48 h after fertilization, whereas in the ferret the hormone's action ensures a suitable uterine environment in which the early embryo can flourish. Its effects in early pregnancy in the marmoset are ambiguous from the present studies unless it emerges that target organ responses are tuned to low concentrations of active steroid. However, the discoveries in mice of a conserved family of immunoglobulin genes used exclusively by immunogenic forms of progesterone conjugated to proteins to stimulate antibody production, and of antibody binding to the uterine epithelium, reveal systems potentially inimical for embryo survival. The endometrial expression of the proto-oncogene erb-A at a time when the embryo has not yet arrived in the uterus, and of antibody-binding to the uterine epithelium, are early maternal responses whose significance require closer examination. The present findings support the hypothesis that the primary site of action of progesterone during the preimplantation period differs between species, and that it is not only the mother that recognizes, but the embryo that initiates early changes before the onset of implantation 'in the bed of soil that nourishes it', a symbiosis that may yet prove to be a common feature of the adoption of viviparity as a preferred mode of reproduction.

Animals↗

Lymphomatoid granulomatosis.

A case of lymphomatoid granulomatosis is presented demonstrating the most common chest radiograph findings as well as some infrequent but recognized associations. The clinical presentation and pathogenesis are discussed. The difficulty in radiological diagnosis is highlighted.

Female↗

Increased levels of prolactin during, but not after, the immunisation with rat collagen II enhances the course of arthritis in DBA/1 mice.

In addition to its well known effects on reproductive organs and lactation the pituitary hormone prolactin (PRL) also influences immune functions. The present investigation was performed in order to clarify the regulatory role of prolactin in autoimmune disease by using the collagen II arthritis model. Groups of virgin female DBA/1 mice were subjected to different short-term treatment protocols (5-10 days) with rat PRL and the drugs bromocriptine (inhibits prolactin secretion) and haloperidol (enhances prolactin secretion). Treatments were performed at different stages of disease development, and effects on clinical scores, anti-collagen II antibody titres as well as agalactosyl IgG levels were recorded. The effects of the treatment protocols on serum PRL levels were assessed by using a radioimmunoassay (RIA) system. Although the accumulated results of the present study indicate that PRL does not fulfil a major role in the regulation of collagen II arthritis, some interesting observations were made. High levels of PRL (PRL injections) made the arthritis worse only if treatment was performed during the induction stage of the disease. Bromocriptine treatment during the immunisation period did not significantly affect the course of arthritis, but treatment at later stages tended to cause exacerbation (significant at the onset period only). These results indicate that PRL has different effects during early and late stages of the development of collagen II-induced arthritis.

Animals↗

Changes in IgG glycoform levels are associated with remission of arthritis during pregnancy.

It was found that the percentage of IgG-associated agalactosyl N-linked oligosaccharides (G0) falls during normal human pregnancy and rises to values higher than before conception following delivery (n = 10, 39-55 days after delivery). Serial bleeds from a normal pregnant woman showed a fall in the percentage G0 during gestation and a rapid rise post-partum. A similar study on a pregnant arthritic woman with a pathologically elevated percentage G0 also showed a fall in percentage G0 during pregnancy and a rapid rise post-partum. The changes in IgG glycosylation in the pregnant arthritic woman occurred simultaneously with the pregnancy-induced remission and post-partum recurrence of disease. A further seven pregnant women with rheumatoid arthritis were studied and analysis of their G0 values pre- and post-partum confirmed the result. In a further series of experiments using an animal model of rheumatoid arthritis, DBA/1 mice with collagen-induced arthritis were found to have elevated G0 levels compared with control mice. The percentage G0 was found to fall simultaneously with pregnancy-induced remission to the same value as non-arthritic pregnant mice. Post-partum recurrence of arthritis in these mice was also accompanied by a simultaneous and rapid rise in percentage G0. Pseudopregnancy did not result in a change in the percentage G0, confirming the effect of true pregnancy. Since the proportion of agalactosyl IgG is abnormally high in the serum of patients with rheumatoid arthritis these changes in IgG glycoform levels, or the factors which control them, may be related to the mechanisms underlying remission of arthritis in humans during pregnancy.

Acetylglucosamine↗

Maintained pregnancy levels of oestrogen afford complete protection from post-partum exacerbation of collagen-induced arthritis.

Pregnancy is known to influence the course of rheumatoid arthritis (RA) in women, as well as type II collagen-induced arthritis (CIA) in DBA/1 mice. A characteristic feature is the remission during gestation and the exacerbation of the diseases during the post-partum period. In the case of CIA in DBA 1 mice, two hormonal changes have been assumed to be critical for the induction of the post-partum flare: (i) the fall in steroid hormone levels from those present during pregnancy; and (ii) surges of prolactin (PRL) release at and after delivery. Our results show that treatment with oestradiol during a short period immediately after parturition protects the mouse from a post-partum flare of the disease, and that treatment with bromocriptine, a drug known to inhibit the endogenous PRL release, has a significant though less marked effect. Studies of lactating (i.e. animals with physiological stimulation of endogenous PRL release) and non-lactating arthritic mice revealed no clear-cut differences, indicating that PRL is of minor importance for the induction of the post-partum flare. Some steroids other than oestradiol, which may be implicated in the exacerbation of arthritis, namely progesterone and hydrocortisone, had no clinical effect. Analyses of agalactosyl IgG levels in mice with CIA, and anti-collagen II antibodies in sera collected at the end of the experiments revealed no significant differences between the oestradiol and the control groups. The successful oestradiol treatment of the mice indicates that the drop in endogenous oestradiol levels prior to delivery ends the oestrogen-mediated protection against arthritis during pregnancy.

Animals↗

Characterization of the synthetic capacities of isolated placental binucleate cells from sheep and goats.

Sheep and goat binucleate cells (BNC) play a central role in placental growth and development. This study reports a simple method for isolating 60-70% pure populations of BNC of high viability. After incubation of the isolated BNC with a brief pulse of 14C-leucine or 3H-fucose or 3H-galactose, electron microscope autoradiography showed that label was eventually incorporated into the characteristic BNC granules via the Golgi body. Fucose and galactose initially showed a much higher Golgi body label than leucine, which was at first predominantly localised in the endoplasmic reticulum. 35S-methionine incorporation by BNC suspensions was extensive enough to allow an immunoprecipitation investigation which demonstrated that the protein hormone ovine placental lactogen and the SBU-3 antigen were synthesised de novo. Previous studies with isolated BNC have shown a remarkable range of substances to be released into the incubation medium but not necessarily synthesised during the incubation. The results demonstrate unequivocally that isolated BNC's are capable of total synthesis in vitro of two of the proteins that these same cells are known to secrete in vivo.

Animals↗