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Biomedical subjects

D M Martin

Publications and source records attributed to D M Martin.

At least 19 recordsLinked to original sources

Gene expression of the insulin-like growth factors and their receptors in cultured human retinal pigment epithelial cells.

Insulin-like growth factors I and II (IGF I and II) are polypeptides with both growth-promoting and insulin-like metabolic effects. Immunoreactive IGF I is present in the retina and both IGF I and II are present in vitreal fluid. The type I and type II IGF receptors are also localized within the neural retina. The presence of IGFs and IGF receptors within the eye suggests a possible growth-promoting effect of IGFs on ocular tissues. IGF may enter the eye from the blood or, alternatively, arise from an ocular cell type which synthesizes and secretes IGF. IGF I and II mRNA synthesis in scleral cells and IGF I synthesis in rat retina suggests endogenous IGF production in the eye. We hypothesized that IGFs and IGF receptors are synthesized by one ocular cell type, the retinal pigment-epithelium (RPE). As a first step in studying IGF production by the RPE, we analyzed expression of the IGF and IGF receptor genes by cultured human RPE cells. Using Northern analysis, RNase protection and reverse-transcriptase polymerase chain reaction (RT-PCR), we found that cultured RPE cells synthesize mRNA for IGF I and the type I and type II IGF receptors.

Base Sequence

Gene expression of the insulin-like growth factors and their receptors in human neuroblastoma cell lines.

Insulin-like growth factors (IGF) I and II are polypeptides with both growth-promoting and insulin-like metabolic effects. The developmentally specific expression of IGF I and II in the nervous system implies a role for these growth factors in neuronal growth and differentiation. In the present study, we analyzed IGF and IGF receptor mRNA transcripts from two related human neuroblastoma cell lines, SH-SY5Y and SK-N-SH. These cell lines provide a good in vitro model of neuronal development. Northern analysis of total RNA from each cell line revealed three IGF II mRNA transcripts (6.0, 4.8, and 1.8 kb), and one mRNA transcript each for the type I (11.0 kb) and type II (9.4 kb) IGF receptors. The size distribution of these multiple transcripts is similar to that found during normal human fetal development. These results establish both cell lines as good in vitro models for investigating the mechanisms which underly IGF gene expression during nervous system development.

Cell Differentiation

Nuclear magnetic resonance studies of the snake toxin echistatin. 1H resonance assignments and secondary structure.

The 1H-NMR spectrum of the snake toxin echistatin has been assigned using homonuclear two-dimensional methods. Consideration of the NOE patterns, coupling constants and putative hydrogen bonds enabled two regular features of secondary structure to be deduced: a beta-sheet/turn between residues 8 and 13 and a small anti-parallel beta-sheet and bulge linking residues 16-20 with residues 30-33. The recognition region of the protein containing the residues RGD lies in a loop joining the two strands of the beta-sheet. The beta-bulge and the loop containing the RGD sequence undergo pH-dependent conformational interconversion, modulated by the side chain of Asp29.

Amino Acid Sequence

Fluorescence and kinetic properties of Ru(III) (NH3)5 modified transferrin.

Diferric transferrin was modified using aquopentaammine ruthenium(II), a reagent for surface-accessible uncoordinated histidines. Introduction of the cationic Ru(III) (NH3)3 + 5 group on the imidazole of only 5.5 of the 17 uncoordinated histidines enhances the rates of pyrophosphate-assisted iron removal from the N-terminal and C-terminal binding sites by 16- and 2-fold, respectively. This differential effect on the kinetics of the two sites may partially explain why in the native protein the N-terminal site is more labile than the C-terminal site in acidic solutions where histidine residues become positively charged through protonation. The distance between the metal site and nearby uncoordinated histidines was estimated from fluorescence energy transfer measurements using Tb (III) as the donor and pentaammine ruthenium(III)-labeled imidazole of histidine as the acceptor chromophore. A Tsou Chen-Lu statistical analysis of the fluorescence quenching data suggest that two residues in each lobe of the protein are involved in quenching the fluorescence. By using estimates for the index of refraction and the quantum yield and assuming the energy transfer follows parallel first-order kinetics, an upper limit for the donor-acceptor distance of about 1.4 nm was obtained, assuming two uncoordinated histidine residues equidistant from the metal. His-207 and His-242 in the N-terminal lobe of transferrin and His-535 and His-577 in the C-terminal lobe are within this distance, based on information from the lactoferrin crystal structure. It is postulated that His-207 in the N-terminal lobe and His-535 in the C-terminal lobe are the uncoordinated residues that, when protonated or modified with Ru(III) (NH3)3 + 5, lead to accelerated loss of iron from the two binding sites of the protein.

Binding Sites

Specialization in endodontics.

The dental profession within the UK is currently reviewing the desirability of recognition of practice-based specialties and the establishment of specialist registers in various disciplines, including endodontics. In order to merit consideration for specialty status, in any discipline there must be an increase in the level of theoretical knowledge, and in the range and complexity of clinical procedures beyond the basic level of training. There must be an identified public need extending beyond the provisions of the general dental services for the particular skills of the practice-based specialist, who would also complement the consultant services, which have a limited capacity to provide the level of treatment demanded. Acceptance of the principle of specialist practice implies a belief that this will enhance the development of the profession, improve academic and clinical standards and provide a higher-quality and more widely available service to the public. The case for the specialist endodontist is argued, as is the importance of establishing appropriate academic and clinical training programmes to equip individuals with the requisite knowledge and skills. Academic institutions must develop imaginative and innovative courses to provide such education within the profession.

Education, Dental, Graduate

Predictability of radiographic diagnosis of variations in root canal anatomy in mandibular incisor and premolar teeth.

Four hundred and fifty-five extracted mandibular incisor and 340 extracted mandibular premolar teeth were radiographed to assess the incidence of twin canals as visualized on radiographs taken in the mesio-distal direction. The ability to detect the presence of these twin canals by viewing radiographs taken in the standard bucco-lingual direction was then assessed. Using the guideline that 'disappearance or narrowing infers division' when viewing these radiographs resulted in a failure to diagnose one-third of the twin canals.

Bicuspid

In vitro marginal microleakage associated with five dentine bonding systems and associated composite restorations.

Fifty sound premolar teeth, extracted for orthodontic purposes and stored at room temperature in physiological saline since extraction, were prepared with a standardized minimal two-surface Class II cavity. The teeth were then ascribed randomly to five groups, each of ten teeth. Each of four groups was restored using a different dentine bonding system and the associated posterior composite resin according to the manufacturer's instructions. The fifth group was restored with Superbond C & B dentine bonding system and Occlusin composite. After immersion in de-ionized water for at least 7 days, the teeth were sealed with nail varnish to within 1 mm of the margin of the restoration. The teeth were then immersed in 5 per cent buffered Eosin for 48 h. Following mesiodistal sectioning the sections were photographed and subjected to image analysis to establish the length of dye penetration at the tooth/restoration interface and the amount of dye penetration into the crown dentine. Tripton/Occlusin and XR Bond/Herculite XR groups showed a significantly (P less than 0.05) smaller amount of leakage than Gluma/Lumifor or Scotchbond 2/P50 combinations when assessed as a percentage of the tooth/restoration interface exhibiting leakage. When the percentage of crown dentine showing dye penetration was considered, the Tripton/Occlusin group showed less leakage than the other material combinations. It is concluded that Tripton, when used with the recommended composite, will allow significantly less microleakage than Gluma/Lumifor, Scotchbond 2/P50 or Superbond C & B/Occlusin combinations and a similar amount to XR Bond/Herculite XR in vitro.

Acid Etching, Dental

Beta-endorphin decline in late luteal phase dysphoric disorder.

The beta-endorphin hypothesis of late luteal phase dysphoric disorder (premenstrual syndrome or L2D2) was tested. Twenty-two PMS patients were compared to twenty-two controls. Levels of beta-endorphin, ACTH, FSH, LH, cortisol, prolactin and TRH were measured on the first and twentieth days after menses. PMS subjects exhibited a significantly greater drop in the opiate, beta-endorphin, (p less than .001) than controls. No relationship or significant e was seen with the other hormones/transmitters tested. The symptoms of PMS may be due to noradrenergic rebound following beta-endorphin decline. Symptomatic and pharmacological morphine withdrawal and manic phase of bipolar disorder are discussed as possible models for L2D2.

Adult

The effect of thyroxine, 3, 5-dimethyl-3'isopropyl-L-thyronine and iodized oil on fetal brain development in the iodine-deficient sheep.

Studies have been carried out to investigate the role of maternal and fetal thyroid function in the effects of iodine deficiency on fetal brain development in sheep. Iodine deficiency was established with an especially prepared low-iodine diet of maize and pea pollard. The iodine-deficient sheep were mated and the end of the second trimester of pregnancy (100 days gestation) were divided into groups which received either a sc injection of T4 or 3,5-dimethyl-3-isopropyl-L-thyromine or an injection of iodized oil. AT 140 days gestation (10 days prior to parturition) comparison of the fetuses delivered by hysterotomy revealed that the retarded fetal brain development observed in iodine deficiency was greatly improved by T4 and by iodized oil. However, T4 and iodized oil failed to correct the reduction in the number and the increase in the length of synaptic appositions which were observed in the fetal cerebral cortex after iodine deficiency. In addition, the histological appearance of the fetal thyroid gland and the levels of plasma thyroid hormones were restored to normal. The administration of 3,5-dimethyl-3'-isopropyl-L-thyronine had no effect on the retarded fetal brain and body development of the iodine-deficient fetuses. The lack of response may be due to the ability of 3,5-dimethyl-3'-isopropyl-L-thyronine to cross the ovine placenta as no reduction in the abnormally elevated fetal plasma TSH observed in spite of a fall in maternal plasma TSH and apparent restoration of maternal thyroid function.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Heavy cocaine use by adolescents.

Adolescents are susceptible to becoming cocaine users. Twenty-eight teenagers in a drug rehabilitation program were identified as heavy cocaine users and questioned about their experiences. They reported family conflict leading to running away (86%), school drop-out (24%) and delinquent behaviors such as stealing (96%) and vandalism (57%). Cocaine use started at 14 years for 21%, with progression from onset to at least weekly use within eight weeks (54%). Side effects included sleep disturbance (18%) and tolerance to cocaine (25%). Withdrawal was characterized by cocaine craving up to one month later (93%). The majority (96%) were polydrug abusers. Possible causes of teen substance abuse are discussed, and the importance of prevention is emphasized.

Adolescent

Vanadium.

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Animals

Impaired reception of nonverbal cues in women with premenstrual tension syndrome.

The ability to perceive nonverbal facial cues was tested in 30 White, middle-class females. Pre- and post-menses responses of 15 subjects diagnosed as having Premenstrual Tension Syndrome (PMS) were compared to the responses of age-matched controls. Each subject was asked to interpret videotaped facial cues of individuals engaged in a gambling task. Interpretive ability fluctuated during the menstrual cycle and was significantly impaired during the premenstrual phase.

Adult

A method for the study of internal spaces in hard tissue matrices by SEM, with special reference to dentine.

Infiltration of a porous hard tissue with methyl methacrylate, followed by dissolution of the tissue provides a three-dimensional methacrylate cast of spaces within the tissue. Examination of such a cast by scanning electron microscopy provides information on the nature and extent of the pore system to a degree that cannot readily be visualized by the direct examination of fractured surfaces. The findings described concern human dentine but the technique may have a wider application in studies on the internal structure of other hard tissues.

Dental Enamel Permeability