The aims of this study were to explore women's perceptions and experiences of being pregnant and having pre-existing type 1 diabetes mellitus, and to assess their physical, social, psychological, emotional and educational needs during their transition to motherhood.The qualitative design incorporated a purposive sample of seven women in their first pregnancy, who participated in one-to-one interviews with a researcher at 15-20 and 32-36 weeks gestation, and at 6-8 weeks post-partum.Qualitative analysis identified seven key themes from the data including: knowledge; physical and psychological impact; control and trust; catalyst to action; organisation of care and communication; attendance and intervention; expectations and systems.This study has shown that most women with diabetes who become pregnant are resigned to the fact that their pregnancy is considered high risk, and are willing to play their part to achieve a positive pregnancy outcome. However, they would also like to 'do the normal pregnant bit as well', 'normalise it and make it a nice experience' and make it feel 'less fragmented'. This woman-centred experience of pregnancy care, in women with type 1 diabetes mellitus, may motivate health professionals to revise their approach to care, prompt them to utilise the skills of each individual member of the multidisciplinary team to its full strength and potential, and assist in the provision of a positive, balanced and more holistic approach to care, specific to this client group.
Cloned cDNA templates of thyroid peroxidase (TPO) have been used in conjunction with the polymerase chain reaction (PCR) to express selected segments of the thyroid microsomal/peroxidase antigen (TMA/TPO) as recombinant protein in E. coli. Six small, different recombinant fragments averaging 120 amino acid residues and one large fragment (269 amino acids) of TPO which together encompass 80% of the extracellular region of the molecule have been produced and autoantibody (aAb) binding sites analysed by immunoblotting. A minimum of six independent, sequential antigenic determinants have been localized on the recombinant proteins and these map to the amino terminal, the central core region and the carboxyl terminal of the TPO molecule. More accurately, the six antigenic sites reside on overlapping recombinant TPO preparations termed R1a + R1b (residues 1 to 160) R1c (residues 145 to 250), R2b (residues 457 to 589), R3a (residues 577-677), R3b (residues 657-767) and R3c (residues 737-845). The large fragment of TPO termed R3 (residues 577-845) encompassing R3a, R3b and R3c also reacts with the aAbs. Different sera from patients with autoimmune thyroid disease contain antibodies to TMA/TPO which differ in their fine specificity. The use of recombinant molecular biological techniques together with PCR to prepare small segments of a large autoantigen as recombinant protein will now allow studies to progress on autoepitope mapping of the precise amino acid sequences of the TPO molecule with the use of synthetic peptides.
Five separate monoclonal antibodies (MoAbs) to human thyroid peroxidase (hTPO) were raised by immunising Balb/c mice with hTPO purified from detergent solubilised thyroid microsomes by high performance liquid chromatography (HPLC). The epitope specificities of these MoAbs were determined by assessing their ability to bind to purified recombinant fusion protein fragments of human TPO (TPO(r)) generated in E. coli. A total of seven small overlapping fragments (averaging 104 amino acid residues) of hTPO, encompassing over 90% of the extracellular region of the molecule, were generated as glutathione S-transferase (GST) fusion proteins. The sequential epitopes on TPO(r) recognised by these MoAbs were analysed by both immunoblotting and enzyme linked immunosorbent assay (ELISA). Two different MoAbs (A4 and A5) recognised sequential epitopes within the TPO(r) preparation termed R1a + b (residues 1-160) and more specifically, in the case of MoAb A4, within the subfragment R1b (residues 70-160). The inability of the other MoAbs (A1-A3) to recognise recombinant fragments, suggests they either recognise conformational determinants on the TPO molecule or epitopes that are present on the small regions of the TPO molecule which have not been expressed as recombinant proteins.
This study demonstrates a very high prevalence of autoimmune thyroid disease in Familial Alzheimer's Disease kindreds and suggests that a genetic factor contributing towards the development of autoimmune thyroid disease may be located on chromosome 21 within close proximity to the Familial Alzheimer's Disease gene.
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