Response of resting human peripheral blood natural killer cells to interleukin 2.

The present study shows that recombinant interleukin 2 (IL-2) purified to homogeneity induces a rapid and potent enhancement of spontaneous cytotoxicity of human peripheral blood lymphocytes. The cells mediating cytotoxicity after 18-h treatment with IL-2 have surface markers of natural killer (NK) cells and are generated from the peripheral blood subset containing spontaneous cytotoxic cells. A parallel production of gamma interferon (IFN-gamma) is induced by recombinant IL-2 (rIL-2), and NK cells appear to be the major producer cells, whereas T cells are unable to produce IFN-gamma under these experimental conditions. However, the kinetics of the enhancement of cytotoxicity are faster than those of IFN-gamma production, and monoclonal anti-IFN-gamma antibodies do not suppress this effect, making it unlikely that the IFN-gamma produced is responsible for the enhancement. The enhancement of NK cell activity induced by rIL-2 precedes any proliferative response of the lymphocytes, which is instead observed in longer-term cultures of both NK and T cells.

Quality assessment of clinical practice guidelines used in oral and maxillofacial surgery.

An assessment of the quality of oral and maxillofacial surgery clinical practice guidelines is lacking. The aim of this investigation was to assess the quality of guidelines using the RIGHT (Reporting Items for practice Guidelines in HealThcare) checklist. The primary outcome was to assess the score (quality) of guidelines based on the RIGHT checklist and to identify predictors (region, type, single or multi-centre, and speciality/non-speciality) influencing the quality score. In this review, following a search of electronic databases and national society websites, a total of 25 guidelines were independently assessed by two assessors against the 22-item RIGHT checklist. Inter-assessor reliability was assessed. Deficiencies in the reporting of items relating to limitations, funding, declaration and management of interests, healthcare questions, and quality assurance were evident. The median overall score for the guidelines was 28 (range 14-66). Guidelines produced by multiple centres (ß=57.15, 95% confidence interval -26.62 to 87.68, P= 0.001, multivariate analysis) and non-speciality societies (ß=20, 95% confidence interval -0.03 to 40.03, P=0.05, univariate analysis) tended to have higher quality scores. Overall, the quality of clinical practice guidelines used in oral and maxillofacial surgery was deemed suboptimal. If clinical practice guidelines are to be used in making treatment decisions for patients, clinicians should be aware of their possible limitations.

Human IL-3 and GM-CSF act synergistically in stimulating hematopoiesis in primates.

Interleukin-3 (IL-3) is a member of a family of growth factors, each of which supports the proliferation and development of hematopoietic precursors in culture. Although the biologic effects of the different hematopoietic growth factors have been well documented in different culture systems, it has only recently become possible to study the activities of these molecules in vivo. In comparison with the later acting hematopoietic growth factors granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor, IL-3 elicited a delayed and relatively modest leukocytosis when continuously infused intravenously in primates. The IL-3 infusion, however, greatly potentiated the responsiveness of the animal to subsequent administration of a low dose of GM-CSF. These results suggest that IL-3 expands an early cell population in vivo that subsequently requires the action of a later acting factor such as GM-CSF to complete its development. Optimal stimulation of hematopoiesis may be achieved with combinations of hematopoietic growth factors.

Information for oral and maxillofacial patients: can it be improved?

The aim and objective of this study was to evaluate the quality and readability of leaflet and online Oral and Maxillofacial Surgery patient information leaflets (PILs). The quality, readability and grade level of each PIL was assessed using the DISCERN, Flesch Reading Ease and Flesh-Kincaid Grade Level instruments respectively. In total, 140 patient information leaflets were assessed. For both leaflet and online PILs, many items of the DISCERN instrument were deemed of low quality and poorly reported. The median overall quality score was 30.2. Variation in the quality and readability scores between leaflet and online PILs and those produced by various societies was evident. Overall, PILs were deemed to be of moderate quality. Online PILs were of lower quality, more difficult to read and aimed at a higher reading age level.

National clinical guidelines for the management of unerupted maxillary incisors in children.

This article summarises recently updated guidelines produced by the Clinical Governance Directorate of the British Orthodontic Society through the Clinical Standards Committee of the Faculty of Dental Surgery, Royal College of Surgeons of England (FDSRCS) on the management of unerupted maxillary incisor teeth in children. The maxillary incisor teeth usually erupt in the early mixed dentition but eruption disturbances can occur and are often attributable to local factors. A failure of eruption will affect the developing occlusion and potentially influence psychological development of the child. The general principles of management for delayed eruption or impaction of these teeth is to ensure that adequate space exists in the dental arch and to remove any obstruction to eruption. Consideration should also be given to further promoting eruption through surgical exposure of the incisor, with or without subsequent orthodontic traction. A number of factors influence the decision-making process, including patient age, medical history, potential compliance, aetiology and position of the unerupted incisor. Treatment planning should be complemented by careful clinical assessment and the use of appropriate special investigations. To optimise the treatment outcome a multidisciplinary specialist approach is recommended.

Intraoral Spitz naevus: a case report.

Intraoral occurrences of Spitz naevus are very rare, there being only one previously documented case in the literature. Here is reported a case of a young male who presented with a pigmented lesion of the upper labial mucosa which had the clinical appearance of a simple naevus. Excision biopsy confirmed this to be a Spitz naevus. This lesion shares histopathological similarities with malignant melanoma. Spitz naevus is a benign lesion, but malignant transformation has been reported and close monitoring is recommended.

Crystal structures of substrate binding to Bacillus subtilis holo-(acyl carrier protein) synthase reveal a novel trimeric arrangement of molecules resulting in three active sites.

BACKGROUND: Holo-(acyl carrier protein) synthase (AcpS), a member of the phosphopantetheinyl transferase superfamily, plays a crucial role in the functional activation of acyl carrier protein (ACP) in the fatty acid biosynthesis pathway. AcpS catalyzes the attachment of the 4'-phosphopantetheinyl moiety of coenzyme A (CoA) to the sidechain of a conserved serine residue on apo-ACP. RESULTS: We describe here the first crystal structure of a type II ACP from Bacillus subtilis in complex with its activator AcpS at 2.3 A. We also have determined the structures of AcpS alone (at 1.8 A) and AcpS in complex with CoA (at 1.5 A). These structures reveal that AcpS exists as a trimer. A catalytic center is located at each of the solvent-exposed interfaces between AcpS molecules. Site-directed mutagenesis studies confirm the importance of trimer formation in AcpS activity. CONCLUSIONS: The active site in AcpS is only formed when two AcpS molecules dimerize. The addition of a third molecule allows for the formation of two additional active sites and also permits a large hydrophobic surface from each molecule of AcpS to be buried in the trimer. The mutations Ile5-->Arg, Gln113-->Glu and Gln113-->Arg show that AcpS is inactive when unable to form a trimer. The co-crystal structures of AcpS-CoA and AcpS-ACP allow us to propose a catalytic mechanism for this class of 4'-phosphopantetheinyl transferases.

Arteriovenous malformation of the mandible--a case report.

Both arteriovenous malformations (AVMs) and solitary bone cysts of the mandible are uncommon lesions. The latter can be considered fairly innocuous but AVMs require careful management. The following is a description of a case where an arteriovenous malformation of the mandible presented with mental nerve paraesthesia. However, radiographically the features appeared to be consistent with a solitary bone cyst. It is important for clinicians in both a primary and secondary care setting to be aware that this type of lesion can have life threatening complications.

A survey of undergraduate orthodontic teaching and factors affecting pursuit of postgraduate training.

Background Undergraduate orthodontic teaching has been focused on developing an understanding of occlusal development in an effort to equip practitioners to make appropriate referrals for specialist-delivered care. However, there is a growing interest among general dentists in delivering more specialised treatments, including short-term orthodontic alignment. This study aimed to assess the levels of knowledge of occlusal problems among final year undergraduate dental students, as well as their interest in various orthodontics techniques and training.Methods A 36-item electronic questionnaire was sent to all final year undergraduate students in four dental institutes in the UK (Barts and the London, Kings College London, Cardiff and Dundee). The questionnaire explored satisfaction with undergraduate orthodontic teaching; students' perception of knowledge, based on General Dental Council learning outcomes; perceptions of the need for specialist involvement in the management of dental problems; interest in further training in orthodontics; and potential barriers to undertaking specialist training.Results The overall response rate was 66% (239/362). The majority of students (84.1%) were aware of GDC guidance in terms of undergraduate teaching. Students reported a preference for case-based and practical teaching sessions in orthodontics, with less interest in lectures or problem-based learning approaches. A high percentage were interested in further teaching in interceptive orthodontics (60.3%) and fixed appliance therapy (55.7%). Further training including specialist orthodontic training (36.4%), Invisalign (59%) and Six Month Smiles (41%) courses appealed to undergraduates. Levels of student debt, course fees and geographical issues were seen as potential barriers to formal, specialist training pathways.Conclusions Satisfaction with undergraduate orthodontic teaching is high and interest in further training, including specialist training pathways, continues to be high. While short-term orthodontics is not taught at undergraduate level, there appears to be an appetite to undertake alternatives to conventional orthodontics among dental students.

Characterization of an RNase H deficient mutant of human immunodeficiency virus-1 reverse transcriptase having an aspartate to asparagine change at position 498.

It has been proposed that Asp-443, Glu-478, and Asp-498 are important in RNase H mediated catalysis by human immunodeficiency virus-1 reverse transcriptase (Davies J.F., Hostomska, Z. Hostomsky, Z., Jordan, S.R. and Matthews, D.A. (1991) Science 251, 88-95; Mizrahi, V., Usdin, M.T., Harington, A. and Dudding, L.R. (1990) Nucleic Acids Res. 18, 5359-5363). Single point mutations at either position 443 (Mizrahi, V., Usdin, M.T., Harington, A. and Dudding, L.R. (1990) Nucleic Acids Res. 18, 5359-5363) or 478 (Schatz, O., Cromme, F.V., Grüninger-Leitch, F. and Le Grice, S.F.J. (1989) FEBS Lett. 257, 311-314) severely inhibit RNase H activity but have only small effects on polymerase activity. We show here that a single mutation at position 498 of Asp to Asn (mutant D498N) results in a stable enzyme with a 20-fold reduction in the ratio of RNase H to polymerase activity. The mutant and wild type enzymes were equally processive, paused in the same locations, and extended primers at the same rate during DNA synthesis on a heteropolymeric RNA template. The rate of elongation on the homopolymeric template poly(rA) was also the same. The results indicate that the mutation does not affect normally measured catalytic parameters of the polymerase function of the enzyme. D498N catalyzed strand transfer synthesis on homopolymeric, but not heteropolymeric templates, indicating that RNase H activity is not required for the former activity, but is for the latter.

A comparison of two different techniques for early correction of Class III malocclusion.

OBJECTIVE: To compare the effectiveness of Reverse Twin-Block therapy (RTB) and protraction face mask treatment (PFM) with respect to an untreated control in the correction of developing Class III malocclusion. MATERIALS AND METHODS: A retrospective comparative study of subjects treated cases with either PFM (n  =  9) or RTB (n  =  13) and untreated matched controls (n  =  10) was performed. Both the PFM and control group samples were derived from a previously conducted clinical trial, and the RTB group was formed of consecutively treated cases. The main outcome variables assessed were skeletal and dental changes. Lateral cephalograms were taken at the start and end of treatment or during the observation period. Analysis of variance was used to compare changes in cephalometric variables arising during the study period in the lateral group. Linear regression analysis and an unpaired t-test were used to determine the impacts of treatment duration and gender, respectively. RESULTS: Significantly greater skeletal changes arose with PFM therapy than with RTB therapy or in the control group (SNA, SNB, and ANB; P < .001). The dentoalveolar effects of RTB therapy exceeded those of PFM treatment, with significantly more maxillary incisor proclination (P < .001) and mandibular incisor retroclination (P < .006) arising with treatment. CONCLUSIONS: Both appliances are capable of correction of Class III dental relationships; however, the relative skeletal and dental contributions differ. Skeletal effects, chiefly anterior maxillary translation, predominated with PFM therapy. The RTB appliance induced Class III correction, primarily as a result of dentoalveolar effects.

Bullying in schoolchildren - its relationship to dental appearance and psychosocial implications: an update for GDPs.

Bullying in school-aged children is a global phenomenon. The effects of bullying can be both short- and long-term, resulting in both physiological and psychological symptoms. It is likely that dental care professionals will encounter children who are subjected to bullying. The aim of this narrative review is to discuss the incidence of bullying, the types of bullying, the effects of bullying and the interventions aimed at combating bullying in schoolchildren. The role of dentofacial aesthetics and the relationship of bullying and the presence of a malocclusion are also discussed.

Bacteriorhodopsin precursor. Characterization and its integration into the purple membrane.

Halobacterium halobium spheroplasts synthesize and accumulate a bacteriorhodopsin precursor. By labeling of the precursor with [35S]Met and [3H]Leu followed by Edman degradation, we have confirmed the previous conclusion from the DNA sequencing that the precursor contains 13 additional amino acids at the NH2 terminus of bacteriorhodopsin. Although not processed in the spheroplasts, it integrates into the purple membrane in the correctly folded conformation. This was shown by the mode of cleavage by a number of proteolytic enzymes, the site of attachment of retinal, and the formation of oligomers on reaction with bifunctional cross-linking reagents. In all these respects, the behavior of the precursor was identical with that of native mature bacteriorhodopsin in the purple membrane. Finally, the precursor was not processed to bacteriorhodopsin even when the spheroplasts were subsequently allowed to revert to rod-shaped cells. This suggests that either the processing of the precursor is cotranslational or that the NH2 terminus of the precursor becomes inaccessible to the processing enzyme in the spheroplasts following integration into the membrane.

5-Aminolevulinic acid dehydratase: alkylation of an essential thiol in the bovine-liver enzyme by active-site-directed reagents.

1. 5-Aminolevulinic acid dehydratase from bovine liver has been shown to be inactivated by 5-halolevulinic acids and 3-halolevulinic acids. 2. The substrate, 5-aminolevulinic acid, protects the enzyme from modification by 5-halolevulinic acids. 3. Using tritiated chlorolevulinic acids, it was shown that four of the subunits in the octameric enzyme are preferentially modified. 4. The susceptible enzyme group modified is an --SH group of a reactive cysteine at or near the active site. 5. Oxidized enzyme is not affected by either 5-chlorolevulinic acid or 3-chlorolevulinic acid. 6. Evidence is presented which suggests that 5-chlorolevulinic acid is acting as an active-site-directed reagent.