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Biomedical subjects

J R Sandy

Publications and source records attributed to J R Sandy.

At least 73 records · Page 4Linked to original sources
PubMed1996

TGF-beta isoforms fail to modulate inositol phosphates and cAMP in normal and tumour-derived human oral keratinocytes.

This study examined inositol phosphate and cAMP regulation by TGF-beta 1, -beta 2 and -beta 3 in normal and tumour-derived human oral keratinocytes. Previous findings indicated that the cell lines expressed TGF-beta cell surface receptors and had a range of response to exogenous TGF-beta 1, -beta 2 and -beta 3 from being refractory to the ligand to marked inhibition. Basal levels of inositol phosphates broadly reflected the differentiation status of the cells as demonstrated by involucrin expression, but did not correlate with responsiveness to TGF-beta 1, as measured previously by thymidine incorporation. Treatment of cells with bradykinin or serum caused up-regulation of inositol phosphate levels; by contrast, TGF-beta 1, -beta 2 and -beta 3 failed to modulate inositol phosphates. In two tumour-derived cell lines, the TGF-beta isoforms had no effect on cAMP levels, despite a significant increase in cAMP using a potent agonist of adenylate cyclase (forskolin). Furthermore, the cAMP analogue, dibutyryl cAMP, failed to mimic the inhibitory or refractory responses of TGF-beta in these cells lines. The results demonstrate that in normal and tumour-derived human oral keratinocytes, TGF-beta signal transduction is not mediated by inositol phosphates or cAMP.

Bradykinin↗
PubMed1996

The surgical care of cleft lip and palate patients in England and Wales.

The results of a postal survey in 1992 of surgeons in England and Wales undertaking primary repairs for babies born with cleft lip and palate are presented. 64 plastic surgeons undertaking primary cleft repairs were identified. The majority of cleft surgeons were low volume operators undertaking 10 or less lip repairs annually. Low volume operators were less likely to attend joint disciplinary clinics than high volume operators and those that did attended clinics with fewer specialities represented. None of the low volume operators collected standardised records for their patients. The recommendations of the Royal College of Surgeons of England for centralisation of cleft care in England and Wales on a regional basis and a minimum case-load per surgeon of 30 new cases per year are discussed.

Child, Preschool↗
PubMed1996

Consultant orthodontic services for cleft patients in England and Wales.

A postal questionnaire survey of consultant orthodontists in England and Wales was undertaken as part of a national audit of the care of children born with cleft lip/and or cleft palate. A 100% response rate was achieved. The majority of respondents stated that they provide orthodontic treatment for cleft patients but only 78% of these attend multi-disciplinary cleft clinics. Consultant orthodontists provide treatment not only in the form of appliances for patients born with clefts but are also involved in the counselling of parents and coordination of regional data bases. Only 24% of hospital orthodontists are involved in the provision of presurgical appliances for cleft babies on a regular basis. The lack of rationalisation of orthodontic services and a low uptake of standardised record keeping protocols for cleft patients by consultant orthodontists gives cause for concern.

Child↗
PubMed1996

Periodontal and microbiological changes associated with the placement of orthodontic appliances. A review.

This review examines specific aspects of orthodontic treatment and periodontal health, namely the effects of orthodontic banded attachments on periodontal disease and more specifically the microflora found around the gingival margins. This review highlights critical developments in orthodontic techniques and microbiological advances which have helped clarify the interrelationships between orthodontic appliances and periodontal disease. Suggestions as to how these may be modified are made, as well as targeting specific areas for research.

Bacteria↗
PubMed1996

Minimum standards for the management of cleft lip and palate: efforts to close the audit loop. Royal College of Surgeons of England.

Intercentre audit in the late 1980s revealed poorer outcomes for facial growth for British patients with cleft lip and palate than equivalent patients in northern Europe. A subsequent survey of the surgical practices in England and Wales, under the auspices of the Surgical Audit and Epidemiology Unit, revealed the widespread involvement of low-volume operators in cleft care, a tendency for low-volume operators to have an incomplete network of associated professionals, and non-standardised record keeping protocols. Recommendations for minimum standards of care for children born with cleft lip and palate were produced by a multidisciplinary steering group. A further investigation is planned to determine their validity and to provide a baseline for future audit cycles.

Cleft Lip↗
PubMed1995

Effects of transforming growth factor beta-1 on growth-regulatory genes in tumour-derived human oral keratinocytes.

This study examined the effect of transforming growth factor beta-1 (TGF-beta 1) on c-myc, RB1, junB and p53 expression together with pRb phosphorylation, in carcinoma-derived and normal human oral keratinocytes with a range of inhibitory responses to this ligand. Amplification of c-myc was observed in eight of eight tumour-derived cell lines and resulted in corresponding mRNA expression. The down-regulation of c-myc expression by TGF-beta 1 predominantly reflected growth inhibition by TGF-beta 1, but in two of eight tumour-derived cell lines which were partially responsive to TGF-beta 1 c-myc expression was unaltered by this ligand. While RB1 mRNA levels were unaltered by TGF-beta 1, the ligand caused the accumulation of the underphosphorylated form of the Rb protein in all cells irrespective of TGF-beta 1-induced growth arrest. junB expression was up-regulated by TGF-beta 1 in cells with a range of growth inhibitory responses. All cells contained mutant p53. TGF-beta 1 did not affect p53 mRNA expression in both tumour-derived and normal keratinocytes and there was no alteration in p53 protein levels in keratinocytes expressing stable p53 protein following TGF-beta 1 treatment. The data indicate that TGF-beta-induced growth control can exist independently of the presence of mutant p53 and the control of Rb phosphorylation and c-myc down-regulation. It may be that TGF-beta growth inhibition occurs via multiple mechanisms and that the loss of one pathway during tumour progression does not necessarily result in the abrogation of TGF-beta-induced growth control.

Carcinoma, Squamous Cell↗
PubMed1995

Fronto-sternal traction: an adjunct to orthognathic surgery.

A case is reported in which an unexpected occlusal result arose following bimaxillary osteotomy for correction of a skeletal Class III discrepancy. In order to correct the occlusion, the mandible was protracted independently of the recently plated maxilla, by means of a fronto-sternal traction device.

Adult↗
PubMed1995

Adult orthodontics--a review.

The increased demand for orthodontic treatment by adults suggests a review of the literature might be timely. In this review we explore whether the increased in demand is real and matched by need. We also examine the reasons for treatment being sought and special considerations which are important during orthodontic treatment. Finally, we compare the orthodontic experience of adults and adolescents. We conclude that adults seeking treatment can be excellent patients with high motivation and co-operation. The limitations of orthodontic treatment must be explained at the beginning of treatment since adult expectations of orthodontics can be very high.

Adolescent↗
PubMed1995

Multidisciplinary approach to obstructive sleep apnoea: a case report.

Obstructive sleep apnoea is a well recognized clinical problem. This paper presents a case in which a joint orthodontic and surgical approach was used to diagnose and treat a patient suffering from this condition. Initially these cases could be treated with a conservative approach, which has a potential role in establishing a diagnosis.

Adult↗
PubMed1995

Should second molars be extracted?

The effect of removal of the first premolar on the facial profile is controversial, and some orthodontists prefer to extract the second permanent molar as an alternative. However, this procedure is not widely practised in spite of the many advantages claimed for it. The arguments for and against the technique are described here. Practising orthodontists should take all these arguments into account when planning treatment.

Decision Making↗
PubMed1994

Standards of orthodontic treatment in cases treated by undergraduate students at Bristol Dental Hospital from 1982 to 1992.

Recent changes in the teaching of orthodontics to undergraduates and postgraduates at Bristol Dental School led us to examine treatment results achieved by undergraduates over a 10-year period. In a sample of 225 orthodontic cases (mean pre-treatment age 12.5 years) which presented for the final BDS examination there was good evidence that students were achieving acceptable treatment results before 1988. The mean percentage reduction of PAR scores for the period 1982-1987 was 64%. In contrast, in the more recent period 1988-1992, the mean percentage reduction of the PAR scores achieved by the students was 47%. This statistically significant reduction appeared to correlate with changes in teaching staffing levels since other factors such as age, type of malocclusion, appliance type or initial PAR scores were not significantly different in any of the years examined.

Adolescent↗
PubMed1994

TGF-beta receptor regulation mediates the response to exogenous ligand but is independent of the degree of cellular differentiation in human oral keratinocytes.

This study examined the expression of TGF-beta cell-surface receptors, the response to exogenous TGF-beta 1 and the autocrine production of TGF-beta in normal and squamous cell carcinoma-derived human oral keratinocytes with variable degrees of cellular differentiation. TGF-beta receptor expression, the response to exogenous ligand and the autocrine production of TGF-beta appeared unrelated to cellular differentiation. Cells expressed variable proportions of type-I, -II and -III TGF-beta receptors. The expression of type-III receptors correlated inversely with the expression of type-I receptors, but there was no relationship between type-II and either type-I or type-III TGF-beta receptors. Normal cells and the majority (7 of 8) of tumour-derived keratinocytes were inhibited by exogenous TGF-beta 1 and the degree of inhibition correlated with the expression of type-I, but not type-II or type-III, TGF-beta receptors. One tumour-derived cell line was refractory to exogenous TGF-beta 1 although it expressed all 3 receptor types. Endogenous TGF-beta was produced by both normal and tumour-derived keratinocytes and correlated inversely to the expression of type-I, but not type-II, TGF-beta receptors. Further, cells that produced more autocrine TGF-beta had a diminished response to exogenous TGF-beta 1. The data indicate a complex interaction between the expression of TGF-beta cell-surface receptors, endogenous ligand production and the cellular response to exogenous TGF-beta 1.

3T3 Cells↗
PubMed1993

Pertussis toxin-sensitive activation of phospholipase A2 can be resolved from phosphoinositidase C in primary cultures of mouse osteoblasts using indomethacin.

Recent work has established that various bone-resorbing hormones are able to activate phosphoinositide metabolism as well as eicosanoid production in osteoblast-like cells, although the relationship between these pathways is unclear. We used pertussis toxin and indomethacin to inhibit the stimulation of [3H]arachidonic acid release and [3H]phosphoinositide turnover caused by treating primary cultures of mouse osteoblasts with fetal calf serum. We found (1) that pertussis toxin and indomethacin each inhibited both pathways and (2) that although pertussis toxin inhibited [3H]arachidonic acid release to a greater extent than indomethacin, [3H]inositol phosphate accumulation was inhibited rather more effectively by indomethacin. These data suggest that whereas ligands in fetal calf serum activate [3H]arachidonic acid release largely directly via the action of a pertussis-sensitive G protein, activation of phosphoinositidase C is indirect, being substantially dependent upon eicosanoid production. These experiments suggest that serial activation of phospholipase A2 and phosphoinositidase C may occur in osteoblasts and that only the former enzyme is regulated by a pertussis toxin-sensitive G protein.

Adenosine Diphosphate Ribose↗
PubMed1993

Recent advances in understanding mechanically induced bone remodeling and their relevance to orthodontic theory and practice.

This review highlights recent developments in bone cell biology, evaluates previous research, and offers future direction toward improving our understanding of events that mediate orthodontic tooth movement. The in vivo and in vitro models that have been developed to examine the responses of connective tissues and how they have contributed to our understanding of the mechanisms involved in mechanically induced bone remodeling are discussed in detail. Osteoblasts are now recognized as the cells that control both the resorptive and the formative phases of the remodeling cycle, and receptor studies have shown them to be the target cells for resorptive agents in bone. The osteoblast is perceived as a pivotal cell, controlling many of the responses of bone to stimulation with hormones and mechanical forces. It is apparent that not all the cellular responses induced by mechanically deformed tissues can be explained by the current paradigm emphasizing the importance of prostaglandin production and cAMP elevation; the mobilization of membrane phospholipids giving rise to inositol phosphates offers an alternative second messenger pathway. It is also argued from circumstantial evidence that changes in cell shape produce a range of effects mediated by membrane integral proteins (integrins) and the cytoskeleton, which may be important in transducing mechanical deformation into a meaningful biologic response.

Animals↗
PubMed1993

DNA changes in mechanically deformed osteoblasts: a new hypothesis.

The available evidence strongly implicates the osteoblast as the key regulator of bone remodelling activity. Since orthodontic tooth movement is a potent inducer of such activity it is relevant to study the effect of mechanical forces on this cell population. The development of a model for mechanically deforming monolayer cultures of cells is described. The effect of mechanical forces on osteoblast-like cells was examined by a number of parameters. Changes in DNA synthesis seen in short-term experiments were at variance with previous published data. The data derived from longer term experiments was in close agreement with in vivo models; intermittent forces producing an increase in DNA synthesis when compared to static or continuous forces. These changes are discussed in relation to current perspectives of second messenger activation by mechanical strain. Prostaglandins did not appear to mediate these events. There was also no evidence that synthesis of the cytokine, interleukin-1 (IL-1), or the metalloproteinase, collagenase was altered by mechanical forces.

Cells, Cultured↗