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Biomedical subjects

R Todd

Publications and source records attributed to R Todd.

At least 55 records · Page 3Linked to original sources

Sequential cytogenetic alterations in hamster oral keratinocytes during DMBA-induced oral carcinogenesis.

Using the hamster cheek pouch oral cancer model, we have performed a comprehensive analysis of the cytogenetic changes in hamster oral keratinocytes during 7,12-dimethylbenz[a]anthracene (DMBA)-induced carcinogenesis. Tumour induction in the hamster cheek pouch required repeated application of the carcinogen for 14 weeks. We have found that this hamster oral cancer model to be suitable for cytogenetic studies. Unlike human oral cancers where chromosome breaks have been shown, this is only infrequently observed in DMBA-treated hamster oral keratinocytes. Of importance is the finding that at the beginning of the second week of DMBA treatment, there is a significant increase of karyotypes demonstrating tetraploid or near-tetraploidy. We propose that the significant increase in hamster oral keratinocytes exhibiting tetraploidy be further evaluated as a marker of premalignancy/malignancy.

9,10-Dimethyl-1,2-benzanthracene↗

A survey of the training, practice and dental health knowledge of traditional dentists practising in Phnom Penh, Cambodia.

Interviews with 50 traditional dentists practising in Phnom Penh, Cambodia showed that the majority had been trained as an apprentice of either their father or a relative. The most frequently undertaken treatment procedures were tooth coloured fillings, and cast, preformed metal or acrylic crowns and bridges. Knowledge of dental pathology was poor. With the recommencement of dental training in the University of Phnom Penh restriction on the training and practice of traditional dentists needs to be considered, together with the possible retraining of these practitioners as dental technicians.

Adult↗

Utilisation of dental services in Cambodia and the role of traditional dentists.

Cambodia has a small, but growing number of qualified dentists, as well as about 300 traditional dentists. This study describes the current level of utilisation of dental services in Cambodia in Phnom Penh and in 6 provincial areas. 548 adults aged 35-45 and 60-80 years of age were interviewed concerning previous dental attendance, type of service used and preference for qualified or traditional practitioner services. Only 38 per cent had ever had dental treatment, with 87 per cent of attenders last visiting the dentist because of toothache. Although 34 per cent of attenders received their last course of treatment from a traditional dentist, 77 per cent of all subjects said they would prefer to visit a qualified dentist if they had the choice. The role of traditional practitioners may therefore diminish as numbers of qualified dentists increase.

Adult↗

Identification of rabbit eosinophils and heterophils in cutaneous healing wounds.

The study of wound healing has traditionally used the rabbit as an experimental model. We have recently localized the production of the multifunctional cytokine, TGF-alpha, to eosinophils in rabbit skin wounds. It was evident that during the process of TGF-alpha localization, the distinction between the two granulocytic cell types, eosinophils and heterophils, was impossible by conventional histochemical techniques. This paper describes a rapid method to distinguish these two granulocytes by virtue of their endogenous peroxidases and differential resistance to blockade by inhibitors. In sections that have been blocked by hydrogen peroxide, the peroxidase substrate 3,3'-diaminobenzidine, together with nickel chloride (DAB-Ni), preferentially stained the cytoplasm of rabbit eosinophils while sparing those of heterophils. This selective DAB staining of rabbit eosinophil peroxidase in H2O2-blocked rabbit wounds was verified at the ultrastructural level by electron microscopy. We applied this technique to quantify eosinophil and heterophil infiltration into the 21-day rabbit cutaneous healing wound model. Heterophils were found infiltrated into all three layers of the wound (clot > granulation > base), but eventually all disappeared by day 21. As with the heterophils, eosinophils which had infiltrated into the clot and base of the wound had disappeared by day 21. Unlike the heterophils, eosinophils in the granulation layer of the wound continued to increase up to day 21. The continually increased and sustained presence of the eosinophils together with their demonstrated production of TGF-alpha, in the granulation layer of the healing would suggests that these cells play an important role in the organizational aspects of healing wounds.

3,3'-Diaminobenzidine↗

Sequential expression of transforming growth factors alpha and beta 1 by eosinophils during cutaneous wound healing in the hamster.

Transforming growth factor-alpha (TGF-alpha) and TGF-beta 1 have been proposed as important regulators of processes critical to successful wound healing. Although various cells present in wounds represent potential sources of either TGF-alpha and/or TGF-beta, including macrophages, neutrophils, keratinocytes, fibroblasts, and endothelial cells, we recently identified eosinophils as an additional potential source of these cytokines. We therefore used in situ hybridization and immunohistochemistry to determine whether eosinophils represent significant sources of TGF-alpha and/or TGF-beta 1 in skin wounds in the hamster. We found that these wounds developed a prominent infiltration of eosinophils, and that eosinophils were a cellular source of both TGF-alpha and TGF-beta 1 mRNAs. TGF-alpha and TGF-beta 1 proteins were detectable both within eosinophils and extracellularly. Moreover, there was a sequential pattern of TGF-alpha and TGF-beta 1 expression by infiltrating eosinophils, with the onset of eosinophil-associated TGF-alpha expression preceding that of TGF-beta 1. This sequential pattern of TGF expression suggests that eosinophils may help to regulate critical biological processes during wound healing.

Amino Acid Sequence↗

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Arteriovenous Malformations↗

Chiral copper-chelate complexes alter selectivities in metal affinity protein partitioning.

Proteins can be distinguished by exploiting complementarity between a histidine's microenvironment and a metal-chelate ligand in metal-affinity separations. The partitioning behavior of three myoglobins was investigated in aqueous two-phase polyethylene glycol-dextran systems containing polyethylene glycol derivatized with Cu(II) complexes of the L- and D-isomers of methionine and aspartate. TSK chromatographic supports derivatized with the methionine complexes were used to study retention of these proteins in metal-affinity chromatography. In the partitioning studies, the amino acid metal chelates exhibit selectivities for the myoglobins that are different from that of Cu(II)-iminodiacetate. Significant differences in selectivity based on the chiral nature of the amino acid complexes were also observed. The chromatographic selectivities of the chelating ligands exhibit little variation, however, suggesting that interactions occurring in solution but not on a surface play an important role in protein binding to the Cu(II)-amino acid-PEG complexes. In solution, the Cu(II)-amino acid complexes are sensitive probes of the microenvironments of surface histidines. The choice of the metal chelate affinity ligand offers a powerful means by which the selectivity of metal-affinity separations can be altered.

Animals↗

Cellular sources of transforming growth factor-alpha in human oral cancer.

Aberrant expression of TGF-alpha is associated with human malignant oral epithelium. Experiments were initiated to determine the cellular sources of transforming growth factor-alpha (TGF-alpha) in human oral cancer. Ten freshly resected human oral cancers and four specimens of normal human oral epithelium were studied by in situ hybridization and immunohistochemistry. Tissues were probed with 35S-labeled sense and antisense riboprobes to (i) human TGF-alpha (hTGF-alpha), (ii) human epidermal growth factor receptor (EGFR) to determine the distribution of TGF-alpha responsive cells, and (iii) histone H3 to examine TGF-alpha and/or EGFR's possible contribution to altered proliferation in transformed epithelium. Results of our experiments showed that TGF-alpha mRNA could be detected in normal and transformed human oral epithelium. More surprising, we have identified the major source of TGF-alpha mRNA to be the infiltrating eosinophils. A monoclonal antibody to the mature human TGF-alpha peptide stained similar areas in normal and malignant specimens. Eosinophils associated with tumors exhibited positive cytoplasmic immunostaining for TGF-alpha protein. Labeling of EGFR mRNA in human oral epithelium demonstrated uniform labeling of basal layers in normal, hyperplastic, and mildly dysplastic epithelium. In severely dysplastic epithelium and carcinomas (particularly moderate to poorly differentiated types), cellular levels of EGFR mRNA were significantly higher. The profile of altered cellular levels of EGFR mRNA correlated well with the profile of altered proliferation as indicated by H3 mRNA labeling. We hypothesize that the overproduction of EGFR mRNA in tumor epithelium--together with the localized delivery of high amounts of TGF-alpha by eosinophils at tumor-developing sites--is responsible for the increased proliferation of the tumor epithelium.

Antibodies, Monoclonal↗

Dental caries and dental attendance patterns in Vietnamese children aged 11-12 years resident in three inner London boroughs, UK.

Ninety-one Vietnamese children aged 11-12 years were examined in schools in Lambeth, Lewisham and Southwark. Their dental caries prevalence and attendance for dental care were compared with 464 Caucasians, Negroes and Asians. Vietnamese children had a greater caries experience than all except Asians. Although most caries was treated, over a third of Vietnamese children were symptomatic attenders.

Asian People↗

The eosinophil as a cellular source of transforming growth factor alpha in healing cutaneous wounds.

Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) are known to promote the healing of epithelial wounds. Eosinophils are present in healing wounds and have recently been shown to be capable of producing TGF-alpha. This investigation was done to determine if eosinophils infiltrated into healing wounds are capable of expressing this cytokine. Using the rabbit cutaneous open wound model, the study found that the eosinophil is one of the predominant cell types in the healing wound, beginning from the seventh day and thereafter. Most surprisingly, the majority of the eosinophils present in the healing wound were found to contain TGF-alpha mRNA and protein by in situ hybridization and immunohistochemistry. Thus it is proposed that the delivery of TGF-alpha by eosinophils to epithelial wound healing sites represents a normal body mechanism whereby this multifunctional cytokine can accelerate the wound healing process.

Animals↗

Dental caries prevalence in Vietnamese children and teenagers in three London boroughs.

Over one quarter of the 20,000 Vietnamese refugees resident in Britain live in the London boroughs of Lambeth, Lewisham and Southwark. Examination of 268 Vietnamese children showed a high caries rate in deciduous teeth and a low rate in permanent teeth. Five-year-olds had a mean dmft of 8.3 and none were caries free. The mean dmft was significantly related to the length of time the children had lived in Britain. Factors affecting the severity of dental caries in young Vietnamese children are discussed. Interviews with parents indicated that bottle feeding habits were being adopted for their children born in the UK. The results are compared with studies on Vietnamese refugees in other countries.

Adolescent↗

A randomized evaluation of smoking cessation interventions for pregnant women at a WIC clinic.

Pregnant smokers attending a local health department WIC clinic were randomly assigned to one of two self-help smoking cessation programs or usual care. The multiple component program resulted in larger quit rates than usual care during the last month of pregnancy (11 percent vs 3 percent) and postpartum (7 percent vs 0 percent). Achieving quit rates in WIC similar to those in studies conducted at prenatal care settings, suggests that smoking cessation programs for low-income pregnant WIC clients are feasible.

Adult↗

TGF-alpha and EGF-receptor mRNAs in human oral cancers.

Transforming growth factor alpha (TGF-alpha) and epidermal growth factor receptor (EGFR) have been shown to be present in most squamous cell carcinomas. Using the Syrian hamster oral cancer model, we have recently demonstrated the consistent presence of TGF-alpha and EGFR mRNAs in chemically transformed hamster oral keratinocytes. We now present evidence that in human oral cancer (in vivo and in vitro), TGF-alpha and EGFR mRNAs can also be consistently detected. No TGF-alpha mRNA can be detected in normal human oral epithelium by Northern blot analysis. These findings reinforce the use of the hamster cheek pouch as an experimental model for the study of oral cancer development, at least in reference to the possible participation of TGF-alpha in the malignant transformation process.

Animals↗