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Biomedical subjects

D Simmons

Publications and source records attributed to D Simmons.

At least 19 recordsLinked to original sources
PubMed1998

Does the "Thunderbirds syndrome" still exist.

Rationing of resources within both the private and public health care systems is a fact of life. The Thunderbirds TV series encapsulated an idealistic philosophy that life should be saved independent of the pecuniary cost. Doctors, in particular, are trapped between their role as advocates for the patient within the "Thunderbirds" philosophy and as citizens with a responsibility to use resources wisely. This dichotomy is challenged by point of care rationing, which can conflict with clinical responsibilities, undermines the patient-doctor relationship and is often undertaken in a clandestine manner. This form of controlling health costs is difficult to justify from an ethical perspective, particularly when other forms of health care rationing and expenditure are frequently modulated by political expediency and inadequate economic modelling. Indeed, focusing on improving quality and disease prevention, rather than reducing marginal costs can often control the long-term growth in health expenditure. Doctors have a responsibility to ensure that rationing decisions are made but these should be made as part of a transparent, evidence-based and democratic process away from the point of care. While the resources to implement the "Thunderbirds Syndrome" have never been available, the philosophy must remain at the heart of patient-doctor relationship.

Cost Control↗
PubMed1998

Junctional adhesion molecule, a novel member of the immunoglobulin superfamily that distributes at intercellular junctions and modulates monocyte transmigration.

Tight junctions are the most apical components of endothelial and epithelial intercellular cleft. In the endothelium these structures play an important role in the control of paracellular permeability to circulating cells and solutes. The only known integral membrane protein localized at sites of membrane-membrane interaction of tight junctions is occludin, which is linked inside the cells to a complex network of cytoskeletal and signaling proteins. We report here the identification of a novel protein (junctional adhesion molecule [JAM]) that is selectively concentrated at intercellular junctions of endothelial and epithelial cells of different origins. Confocal and immunoelectron microscopy shows that JAM codistributes with tight junction components at the apical region of the intercellular cleft. A cDNA clone encoding JAM defines a novel immunoglobulin gene superfamily member that consists of two V-type Ig domains. An mAb directed to JAM (BV11) was found to inhibit spontaneous and chemokine-induced monocyte transmigration through an endothelial cell monolayer in vitro. Systemic treatment of mice with BV11 mAb blocked monocyte infiltration upon chemokine administration in subcutaneous air pouches. Thus, JAM is a new component of endothelial and epithelial junctions that play a role in regulating monocyte transmigration.

Amino Acid Sequence↗
PubMed1998

A pilot urban church-based programme to reduce risk factors for diabetes among Western Samoans in New Zealand.

We have assessed the impact of a 2-year pilot church-base diabetes risk reduction programme on major lifestyle predictors of future Type 2 diabetes mellitus: exercise and weight control in a prospective non-randomized controlled study of a modular lifestyle and diabetes awareness intervention programme using a community development model. The study involved two complete church congregations from an ethnic group at high risk of diabetes (Western Samoans) (intervention church n = 78; control church n = 144). Weight remained stable (0+/-4.8 kg) in the intervention church but increased by 3.1+/-9.8 kg in the control church (p = 0.05). In the intervention church, there was an associated reduction in waist circumference (-4+/-10 cm vs +2+/-7 cm in control, p < 0.001), an increase in diabetes knowledge (46+/-26% vs 4+/-17% in control, p < 0.001) and an increase in the proportion exercising regularly (+22% vs -8% in control, p < 0.05). Consumption of key fatty foods was also reduced in the intervention church. We conclude that diabetes risk reduction programmes based upon lifestyle change, diabetes awareness, and empowerment of high risk communities can significantly reduce risk factors for future Type 2 diabetes.

Adult↗
PubMed1998

Personal barriers to diabetes care: lessons from a multi-ethnic community in New Zealand.

The aim of this study was to identify and quantify barriers to diabetes care perceived by diabetic subjects from a multiethnic, urban community (mainly New Zealand Europeans, Maori, and Pacific Islanders). A qualitative survey including 57 diabetic subjects and health care providers from a diverse range of backgrounds was followed by a cross-sectional household survey. Barriers to care were quantified among 1862 (2.1%) diabetic residents of a total surveyed population of 90477. Thirty barriers to care categories were generated incorporating patient beliefs, internal and external physical barriers, educational, psycho-social and psychological barriers. In spite of major difference in culture, acculturation, and socio-economic status, the top 10 barriers were similar between the ethnic groups. The most important barriers were perceiving that the benefits of self-care were outweighed by the disadvantages (20% Europeans, 20% Maori, 29% Pacific Islanders, 16% others, p<0.001), lack of community-based services (13% Europeans, 27% Maori, 25% Pacific Islanders, 11% others, p<0.001) and the limited range of services available (15% Europeans, 22% Maori, 20% Pacific Islanders, 14% others, p<0.05). It is postulated that definition of these barriers, with subsequent, systematic action to reduce their impact, in both patients and populations could result in an improvement in diabetes outcomes.

Attitude to Health↗
PubMed1998

Early childhood growth in ethnic groups predisposed to NIDDM: a prospective study.

Evidence is accumulating to suggest that the intrauterine environment may not only influence fetal growth and anthropometric indices at birth but also contribute to susceptibility to adult onset diseases such as non-insulin-dependent diabetes (NIDDM). We have followed up 77 out of 123 (65%) children at age 2 years 8 months derived from a population at high risk of NIDDM who were initially studied throughout pregnancy and birth to determine whether their weight, height, and measures of adiposity were predicted by maternal size, glycaemic control during pregnancy, or ethnicity. Adiposity was correlated with maternal pre-pregnancy weight and maternal serum triglyceride concentration. In contrast to the data gathered at birth, ethnic group did not predict any anthropometric variable except that South Asian children demonstrated faster weight gain in infancy compared to Polynesian or European subgroups.

Adult↗
PubMed1998

Cloning, characterization, and tissue expression pattern of mouse tuftelin cDNA.

Tuftelin is a protein that has been suggested to function during enamel crystal nucleation. Published sequences for bovine tuftelin cDNA and genomic clones proposed different reading frames that radically affected the derived amino acid sequence of the tuftelin carboxyl-terminus. We have isolated and characterized a full-length mouse cDNA clone and a partial porcine cDNA clone that include the region of the proposed frame-shift. The mouse tuftelin clone is 2572 nucleotides in length, exclusive of the poly(A+) tail. Translation from the 5'-most ATG yields a protein of 390 amino acids with an isotope-averaged molecular mass of 44.6 kDa and an isoelectric point of 5.9. Comparison of the bovine, mouse, and porcine cDNAs supports the revised bovine tuftelin amino acid sequence and suggests that the bovine tuftelin translation initiation codon be re-assigned to a more 5' ATG. Re-assigning the translation initiation codon lengthens the tuftelin protein by 52 amino acids, 51 of which are identical between bovine and mouse. At the carboxyl-terminus, the revised bovine and the mouse sequences match at 39 of the final 42 amino acid positions, compared with 2 identities with the originally published bovine reading frame. Northern blot analysis reveals that tuftelin is not ameloblast-specific but is expressed in multiple tissues, including kidney, lung, liver, and testis. Two tuftelin RNA messages, of 2.6 and 3.2 kb, were detected. DNA sequence characterization of an RT-PCR amplification product confirmed expression of tuftelin in kidney, and identified an alternatively spliced mouse tuftelin mRNA lacking exon 2.

Amino Acid Sequence↗
PubMed1998

Identification of a novel isoform of mouse dentin matrix protein 1: spatial expression in mineralized tissues.

Dentin matrix protein 1 (Dmp1) is an acidic phosphoprotein first identified by cDNA cloning from a rat tooth library. Northern blot hybridization of a variety of tissues detected Dmp1 mRNAs only in odontoblasts, suggesting that this protein was odontoblast specific. In situ hybridization studies showed expression of Dmp1 in odontoblasts with transient expression in secretory ameloblasts. The purpose of this study was to isolate and characterize a mouse Dmp1 cDNA and determine its spatial expression pattern related to other mineralizing tissues. A mouse molar cDNA library was screened with a 32P-labeled Dmp1 polymerase chain reaction amplification product in order to isolate a full-length clone. DNA sequence analysis of the largest mouse Dmp1 cDNA (2802 base pairs [bp]) revealed an open reading frame of 1509 nucleotides encoding a 503 amino acid protein with a single polyadenylation signal. Comparison with rat and bovine Dmp1 sequence showed high homology and the identification of a 45 bp (15 amino acid) insert, representing an alternative spliced mRNA. This 45 bp segment was shown to represent a small exon by DNA analysis of a mouse genomic Dmp1 clone. In situ hybridization studies revealed a much broader Dmp1 tissue expression pattern than previously reported. Dmp1 transcripts were detected in the odontoblast and ameloblasts, osteoblasts, and cementoblasts. Our data indicate that Dmp1 is alternatively spliced, and the primary full-length transcript contains a 45 bp insert which is encoded by a small exon. Therefore, Dmp1 is not a tooth-specific protein but rather is expressed in a number of mineralizing tissues including enamel, bone, and cementum.

Ameloblasts↗
PubMed1997

Perceptions of diabetes among rural Maori elders and spokespersons.

AIMS: To assess knowledge and opinions of diabetes among rural Maori elders and spokespersons. METHODS: Interviews were conducted in rural South Auckland. Subjects were identified through their affiliation with one marae (meeting house), residence near the marae and being recognised locally as either male (kaumatua) or female (kuia) elders or spokespersons. The main researcher was a kuia chosen by and from within the local community. Interviews were conducted with 43/44 (98%) subjects identified. RESULTS: While specific diabetes knowledge was low, diabetes was seen, along with cancer, as one of the two major health issues for Maori. Results need to be understood in the context of the holistic understanding of health by Maori. CONCLUSION: The recognition of diabetes as a major health problem was accompanied by a call for diabetes education in a form that will generate interest and participation by Maori. It is timely for the introduction of marae based diabetes awareness and sustained exercise programmes as part of a diabetes prevention and control strategy among Maori communities where diabetes risk is high.

Aged↗
PubMed1997

TLiSA1 (PTA1) activation antigen implicated in T cell differentiation and platelet activation is a member of the immunoglobulin superfamily exhibiting distinctive regulation of expression.

T lineage-specific activation antigen 1 (TLiSA1) antigen was initially described as a T lineage-specific activation antigen involved in the differentiation of human cytotoxic T cells. Subsequently, the antigen was identified on platelets and was shown to be involved in platelet activation, hence it was renamed platelet and T cell antigen 1 (PTA1), although identity between the two antigens was not established. In the present study we have cloned the cDNA encoding TLiSA1 from Jurkat cells and show it to be a novel member of the immunoglobulin superfamily with the unusual structure of two V domains only. Identity between TLiSA1 and platelet PTA1 is established by immunological criteria, by internal peptide sequences obtained from the purified platelet glycoprotein and by sequencing the platelet transcript after reverse transcriptase-polymerase chain reaction. In Jurkat cells, TLiSA1/PTA1 mRNA and surface protein expression is greatly stimulated by treatment of the cells with phorbol ester, but the T cell proliferative signal of phorbol ester and ionophore combined greatly reduces or abrogates this response, and this suppressive effect of the ionophore is not reversed by incorporating FK506 to inhibit calcineurin. Together with the known signaling role of PTA1, these data substantiate the notion that this molecule is implicated in T cell differentiation, perhaps by engagement of an adhesive ligand.

Amino Acid Sequence↗
PubMed1997

Elucidation of the sequence and the genomic organization of the human dentin matrix acidic phosphoprotein 1 (DMP1) gene: exclusion of the locus from a causative role in the pathogenesis of dentinogenesis imperfecta type II.

The dentin matrix acidic phosphoprotein 1 (DMP1) gene has been mapped to human chromosome 4q21 and shown to exhibit no recombination with the autosomal dominant disorder of dentin formation, dentinogenesis imperfecta type II. In the current study, sequencing of DMP1 cDNA and genomic clones has indicated that the human gene contains an open reading frame of 1539 bp, which predicts a highly acidic, serine-rich protein of 513 amino acids. Comparison of the human DMP1-coding sequence with that of the rat, mouse, and cow indicated that the predicted protein contains a conserved hydrophobic signal peptide sequence and an Arg-Gly-Asp cell attachment sequence. The gene is encoded by six exons, the splicing phase of which is type 0, the first exon containing solely 5' untranslated sequence. Sequencing of each of the coding exons in individuals affected by dentinogenesis imperfecta type II failed to reveal any disease-specific mutations, suggesting that mutations in DMP1 are not causative of this condition at least in the two families examined in this study.

Amino Acid Sequence↗
PubMed1997

Ameloblastin gene (AMBN) maps within the critical region for autosomal dominant amelogenesis imperfecta at chromosome 4q21.

Amelogenesis imperfecta (AI) is a broad group of hereditary enamel defects that is characterized by a high degree of clinical diversity. Recently, the local hypoplastic form of autosomal dominant AI (AIH2) has been mapped to human chromosome 4q in a 17.6-cM region. This locus has been further refined to a 4-Mb interval between D4S2421 and Albumin. Recently, a cDNA clone for an enamel matrix protein, ameloblastin (AMBN), has been isolated. In this report, we have isolated a PAC human genomic clone containing the human AMBN gene. The AMBN was mapped by two color fluorescence in situ hybridization using two P1 genomic clones for sequence tagged site (STS) markers, D4S400 and D4S409, which flank the critical AIH2 region. Our results place AMBN at 4q21 between D4S409 (4q13) and D4S400 (4q21). Furthermore, the AMBN PAC genomic clone was shown to contain three STS markers, D4S2604, D4S2670, and D4S2609, which are contained within the critical region defined by six Swedish families with AIH2. AMBN is therefore a strong candidate gene for AIH2.

Amelogenesis Imperfecta↗