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D Simmons

Publications and source records attributed to D Simmons.

At least 91 records · Page 5Linked to original sources

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↗

Identification and characterization of a cDNA for mouse ameloblastin.

Ameloblastin was first identified as one of the most abundant novel transcripts from a random screening of a rat incisor cDNA library. In situ hybridization experiments have shown ameloblastin expression to be specific to ameloblasts, with highest levels in secretory and maturation stage ameloblasts and cells of the epithelial root sheath. Ameloblastin has been identified as a candidate gene for the local hypoplastic form of autosomal dominant amelogenesis imperfecta, by virtue of it's location within the critical disease locus. The purpose of this study was to isolate a full length mouse ameloblastin cDNA and determine its temporal expression pattern during odontogenesis. A newborn mouse molar cDNA library was screened using a rat ameloblastin cDNA probe. Positive clones were confirmed by PCR analysis with ameloblastin-specific primers, and their size determined with vector-specific primers. Phage clones were rescued to phagemid using Exassist helper phage and the nucleotide sequence determined. We report here the identification of two clones, exhibiting alternative splicing of the putative open reading frame, and use of multiple polyadenylation signals. Nucleotide sequence analysis indicated a high degree of similarity to rat ameloblastin, rat amelin 1 and 2 and porcine sheathlin. Reverse transcriptase-PCR analysis using mouse first and second mandibular molar mRNA indicated initial expression at E-14. This is one day after the initial expression of tuftelin (E-13) and one day prior to that of amelogenin (E-15).

Amino Acid Sequence↗

Developmental regulation of dentin sialophosphoprotein during ameloblast differentiation: a potential enamel matrix nucleator.

The two major dentin matrix proteins, dentin sialoprotein and dentin phosphoprotein have been shown to be expressed as a single large transcript termed dentin sialophosphoprotein (DSPP). These non-collagenous matrix proteins, identified biochemically by their unique physical-chemical properties, are specific cleavage products of a large parent acidic phosphorylated protein (pI 4.0). Previous studies have shown expression of dentin sialoprotein at the protein level by ameloblasts. The purpose of this study was to determine the temporal-spatial pattern of DSPP expression during amelogenesis. In situ hybridization and immunohistochemistry were performed on sections of developing mouse molars. These data were correlated with RT-PCR analysis of in vitro enamel organ epithelium monolayer cell cultures enriched for ameloblasts. Our data indicates initial expression of the DSPP transcripts and protein during early ameloblast differentiation prior to the secretory phase when the majority of the enamel matrix is formed. Ameloblasts appear to tightly down-regulate DSPP transcription as enamel matrix formation is up-regulated. These data demonstrate DSPP expression during amelogenesis is under highly controlled developmental regulation. Therefore, DSPP may have a primary role in the initial mineralization events of both enamel and dentin, acting as a potential nucleator of hydroxyapatite crystal formation.

Ameloblasts↗

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↗

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↗

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↗

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↗

The Diabetes Care Support Service for general practitioners in Auckland.

AIMS: Diabetic complications can often be prevented by timely detection and intervention. Optimising diabetes care requires effective monitoring of risk factors at both practice and district level. We describe a novel method which combines district monitoring of diabetes with enhanced diabetes care by individual general practitioners. METHODS: All general practitioners in south and west Auckland (n = 291) were invited to join the Diabetes Care Support Service (DCSS). This involved the identification of all diabetic patients within the practice and the completion of an audit from with key measures of diabetes and its care. RESULTS: Audit was completed for 217 (75%) of general practitioners and 4611 diabetic patients: 39% of general practitioners completed their own audit. The proportion of completed patient assessments ranged between 35% (foot pulses) and 89% (blood pressure). The process was found to be helpful by 88% of general practitioners (who commented). CONCLUSION: The DCSS is a seamless, service-orientated approach to the delivery of diabetes care by primary and secondary services and is likely to improve care district-wide and identify the need for further interventions. Subsequent audit passes will allow the demonstration and monitoring of any changes that occur, as well as the demonstration of its feasibility and acceptability on an ongoing basis.

Blood Pressure↗

Dentin phosphoprotein and dentin sialoprotein are cleavage products expressed from a single transcript coded by a gene on human chromosome 4. Dentin phosphoprotein DNA sequence determination.

Dentin is the major mineralized extracellular matrix of the tooth. The organic components of dentin consist of type I collagen (90%) with 10% noncollagenous proteins, which are also components of bone. Two dentin proteins, dentin sialoprotein and dentin phosphoprotein, have been shown to be tooth-specific being expressed mostly by odontoblast cells. In this study, we screened a mouse molar tooth library for dentin sialoprotein and dentin phosphoprotein cDNA clones. Analysis of the clones resulted in characterization of a 4420-nucleotide cDNA that contained a 940-amino acid open reading frame. The signal peptide and NH2-terminal sequence was 75% homologous to the cDNA sequence of rat dentin sialoprotein. The continued open reading frame, however, contained a RGD sequence followed by a region of repeated aspartic acid and serine residues. This portion of the protein codes for amino acid sequence consistent with that of dentin phosphoprotein. The noncoding region contains three potential polyadenylation signals, two of which were shown to be utilized. Northern blot analysis indicated the presence of two major transcripts of 4.4 and 2.2 kilobases in odontoblasts. Chromosomal mapping localized the gene to human chromosome 4. These data suggest that the previously identified dentin extracellular matrix proteins, dentin sialoprotein and dentin phosphoprotein, are expressed as a single cDNA transcript coding for a protein that is specifically cleaved into two smaller polypeptides with unique physical-chemical characteristics. Therefore, we propose that the gene be named dentin sialophosphoprotein. The location of the human dentin sialophosphoprotein gene on chromosome 4 suggests that this gene may be a strong candidate gene for the genetic disease dentinogenesis imperfecta type II.

Amino Acid Sequence↗

Association between neonatal blood pressure and umbilical cord insulin concentration.

The aetiology of the metabolic syndrome remains unknown. This study investigated whether two components of this syndrome, higher blood pressure and higher plasma insulin concentrations, are related at birth. Neonates in the study were from 23 European, 25 Maori, 22 South Asian, and 25 Pacific Islands women having normal singleton pregnancies as well as 6 Maori, 5 Indian, and 19 Pacific Islands women with gestational diabetes (diagnosed by a 3 h 100 g oral glucose tolerance test at 28-32 weeks). Additional fasting glucose and fructosamine concentrations were measured at 36-38 weeks. Umbilical cord blood was taken for insulin, C-peptide, fructosamine and insulin-like growth factor I. Neonatal anthropometry and blood pressure were measured 24 h after delivery. Compared with those with a lower systolic blood pressure (SBP), neonates with a higher SBP had higher umbilical cord insulin (45.6 (39.6-52.8) vs 63.0 (54.6-72.6) pM, p < 0.01), C-peptide (0.22 (0.20-0.25) vs 0.28 (0.26-0.30) nmol l-1, p < 0.001) and fructosamine concentrations, higher maternal fructosamine concentrations and heavier placentas. These data suggest that neonatal hyperinsulinaemia, possibly driven by minor elevations in maternal glycaemia, may be linked to a higher neonatal SBP.

Asia↗

Community-based approaches for the primary prevention of non-insulin-dependent diabetes mellitus.

The prevalence of non-insulin-dependent (Type 2) diabetes mellitus (NIDDM) is increasing worldwide. Although recent studies suggest that primary prevention of NIDDM is possible, strategies for controlling the NIDDM pandemic remain under development. Successful interventions to date have mainly relied upon the control of obesity and increased exercise, although pharmacological agents are being studied. While a mixture of both high risk and population-based approaches is likely to be required, the former will not prevent new high risk cases developing. Unfortunately, the success in the primary prevention of cardiovascular disease through risk factor reduction has not controlled obesity, the most important risk factor for NIDDM. New strategies are currently being developed and focus upon changes in the food supply of whole populations and a community development approach to altering attitudes to food and exercise. As these interventions are in the early stages of their development, formative, process, and quantitative evaluation remain essential components of any community-based programme aimed at the primary prevention of NIDDM.

Community Health Services↗

Influence of maternal insulin treatment on the infants of women with gestational diabetes.

The criteria for the diagnosis and management of diabetes in pregnancy are currently based upon maternal, neonatal, and obstetric outcomes. We have investigated the long-term impact of antenatal insulin therapy on adiposity of the offspring. A cohort of offspring from 20/35 women with past gestational diabetes, who had been biochemically and anthropometrically characterized at birth, were followed up after 2 years 8 months (standard deviation 1 month). Measures of growth and adiposity were taken. In comparison with offspring of women treated with diet alone, offspring of women treated with insulin therapy had less subscapular fat (median (interquartile range): 7.9 (7.0-9.4) vs 5.9 (5.4-7.9) mm) and less biceps fat (6.3 (6.0-9.0) vs 5.1 (4.3-6.6) mm). This was in spite of the insulin-treated mothers being more obese, older, and more hyperglycaemic than those who received diet alone. In conclusion, insulin therapy in gestational diabetes may reduce the incidence of obesity in the offspring of women with gestational diabetes and this should now be tested by a larger, randomized controlled trial.

Anthropometry↗

Health care costs of obesity in New Zealand.

OBJECTIVE: To estimate the costs of health care that are attributable to obesity in New Zealand. METHODS: The 1991 health care costs of non-insulin dependent diabetes, coronary heart disease, hypertension, gallstone disease, post-menopausal breast cancer and colon cancer were estimated and multiplied by the population attributable factor for obesity for each condition. The relative risk estimates were taken from the literature, the obesity prevalence from a 1990 New Zealand survey, and the costs and volumes of services were taken from a variety of sources and covered hospital (inpatient and outpatient) services, general practitioner consultations, pharmaceuticals, laboratory tests and ambulance services. Calculations were conservative and net of goods and services tax. RESULTS: A conservative estimate of the health care costs attributable to obesity for the six conditions was NZ$135 million. This represents about 2.5% of total health care costs which is similar to analyses from other countries. CONCLUSIONS: The health care costs of obesity as estimated are considerable. However, the total cost of overfatness to the New Zealand population is far greater than this because lesser degrees of overfatness, the health care costs of other obesity-related conditions such as arthritis, the costs to individuals of weight-loss programs and the indirect and intangible costs were not included in the analysis. A substantial and wide-ranging public health effort is needed to turn around the increasing prevalence and costs of obesity.

Adult↗

Dietary practices among Europeans and different South Asian groups in Coventry.

The dietary customs of people of South Asian origin living in Britain are important determinants of health but have been relatively little studied. As part of the Coventry study of diabetes carried out in the Foleshill ward of the city, subjects undergoing oral glucose tolerance tests provided information on this aspect of lifestyle. A questionnaire was completed by all of the last 612 subjects undergoing testing. These included 304 of European origin, 118 Punjabi Sikhs, seventy-six Pakistani/Punjabi Moslems, twenty-eight Gujerati Moslems, twenty-five Punjabi Hindus and forty-seven Gujerati Hindus. There were no discernible differences in the dietary customs of those with normal glucose tolerance, impaired glucose tolerance and newly diagnosed diabetes. Subjects of South Asian origin ate significantly fewer meals per day than European subjects. Evening meal times were 2-3 h later among South Asians. Europeans ate less fruit but more vegetables and more brown rice than South Asians. Gujeratis ate more rice, fried snacks and white flour. Moslems were least likely to be vegetarians, to drink alcohol and to use home-made ghee and yoghurt, and Punjabi Sikhs and Hindus ate dhal more frequently than Pakistani Moslems, Gujerati Moslems or Hindus. Most South Asians ate Indian sweets and 'Western' snacks.

Adult↗