The effect on the composition of subgingival plaque of a simplified oral hygiene system including pulsating jet subgingival irrigation

The aim of this study was to investigate the effect on subgingival plaque of a simplified oral hygiene regime consisting of instruction in Bass brushing without stress on interdental cleaning, scaling and root planing, in combination with subgingival pulsated jet irrigation with dilute solutions of chlorhexidine, metronidazole or placebos. Twenty-five patients, 14 women and 11 men, each with periodontal pockets ≥ 4 mm, participated in a randomized, double-blind, placebo-controlled study. The patients were assigned to 4 groups: 2 test groups (0.02% chlorhexidine and 0.05% metronidazole) and 2 placebo groups (0.01% quinine sulphate and 0.09% sodium chloride). Subgingival plaque samples were obtained from at least 4 sites in each subject on days 0 (prior to scaling and root planing), 7, 28, 56 and 84. Subgingival irrigation was terminated on d 28. Darkfield microscopy was used to assess the effects of treatment on the subgingival microflora by observing 4 morphologic groups: cocci, motile organisms, spirochetes and others (i.e. non-motile rods and filaments). All the groups showed marked beneficial changes at the end of the 28-d irrigation period, with increases in cocci and decreases in motile forms and spirochetes to less than baseline values. These beneficial effects were maintained for at least 8 weeks after irrigation was stopped. Metronidazole was more effective in reducing motile forms, but the reduction was not significant at d 84. It was concluded that pulsating monojet subgingival irrigation as part of a simplified oral hygiene program, with or without an active antimicrobial agent at low concentration, is effective in reducing the motile and spirochete portions of the subgingival microflora. These effects might be enhanced and prolonged if suitable antimicrobial solutions of higher concentration were used.     

Novel human autoantibodies to phosphoepitopes on mitotic chromosomal autoantigens (MCAs).

BACKGROUND: Human autoantibodies to proteins of the mitotic apparatus have demonstrated clinical utility and usefulness as molecular probes for identification and characterization of novel autoantigens, as exemplified by autoantibodies to centromere proteins. In contrast, there have been very few reports of autoantibodies with reactivity to antigens located along mitotic chromosome arms, but not in interphase nuclei. The purpose of this study was to identify and characterize autoantibodies with reactivity to mitotic chromosomal antigens (MCAs) located exclusively on mitotic chromosome arms, and to determine if patients with these autoantibodies have common clinical features. METHODS: Routine immunofluorescence screening of serum samples referred for antinuclear antibody investigation over a 10-year period was used to identify autoantibodies to MCAs. MCAs were identified by exclusive immunofluorescence staining of mitotic chromosome arms with no staining of interphase nuclei. MCA-reactive sera were further characterized for patterns of staining on mitotic chromosome arms and sensitivities to chemical and enzymatic treatments, and for one of these sera, its ability to abrogate progression through mitosis when microinjected into cells. RESULTS: Of 60,000 sera screened for antinuclear antibodies by immunofluorescence, we identified three IgG autoantibodies reacting exclusively to MCAs. The anti-MCA autoantibodies did not react with condensed chromatin in spermatozoa or in apoptotic HeLa cells. Reactivity of all three sera was abrogated by treatment with protease, but not RNase, indicating that the MCAs are protein in nature and do not contain RNA epitopes. The three anti-MCA antibodies seem to react to three different antigens because they gave different patterns of staining of chromosome arms, reacted with chromosomes in different stages of mitosis, and displayed different sensitivities to treatment with DNase 1, salt, and phosphatases. Phosphatase treatment suggests that MCA1 and MCA2 contain serine/threonine phosphoepitope(s) and MCA3 tyrosine phosphoepitope(s). Loss of MCA2 reactivity to DNase 1 treatment and its retention after salt extraction suggests that it is a chromosomal scaffold protein. Sensitivity of all three MCAs to acid suggests that they are histone-like or histone-associated proteins. CONCLUSIONS: We report the identification of three novel MCA-reactive sera. Patient diagnoses included discoid lupus erythematosus, chronic lymphocytic leukemia, Sj?gren's syndrome, and polymyalgia rheumatica. The reactivity of anti-MCA antibodies with phosphoepitopes is likely to explain restriction of immunofluorescence staining to chromosome arms during mitosis. Microinjection of MCA1-reactive antibodies led to metaphase arrest, without any change in morphology of the mitotic spindle or metaphase chromosomes suggesting that MCA1 may have a role in sister chromatid separation.     

Retinal vascular biomarkers for early detection and monitoring of Alzheimer's disease

The earliest detectable change in Alzheimer''s disease (AD) is the buildup of amyloid plaque in the brain. Early detection of AD, prior to irreversible neurological damage, is important for the efficacy of current interventions as well as for the development of new treatments. Although PiB-PET imaging and CSF amyloid are the gold standards for early AD diagnosis, there are practical limitations for population screening. AD-related pathology occurs primarily in the brain, but some of the hallmarks of the disease have also been shown to occur in other tissues, including the retina, which is more accessible for imaging. Retinal vascular changes and degeneration have previously been reported in AD using optical coherence tomography and laser Doppler techniques. This report presents results from analysis of retinal photographs from AD and healthy control participants from the Australian Imaging, Biomarkers and Lifestyle (AIBL) Flagship Study of Ageing. This is the first study to investigate retinal blood vessel changes with respect to amyloid plaque burden in the brain. We demonstrate relationships between retinal vascular parameters, neocortical brain amyloid plaque burden and AD. A number of RVPs were found to be different in AD. Two of these RVPs, venular branching asymmetry factor and arteriolar length-to-diameter ratio, were also higher in healthy individuals with high plaque burden (P=0.01 and P=0.02 respectively, after false discovery rate adjustment). Retinal photographic analysis shows potential as an adjunct for early detection of AD or monitoring of AD-progression or response to treatments.     

Spectrum of FDG uptake in large (>10 cm) esophageal leiomyomas

Esophageal leiomyomas are rare benign tumors that can be treated successfully with limited surgical resection. It is occasionally important to distinguish leiomyomas from more aggressive submucosal esophageal tumors, most notably gastrointestinal stromal tumors (GISTs). GISTs have a worse prognosis, particularly when they are large (>10 cm). Increased uptake of ¹⁸F-fluorodeoxyglucose on positron emission tomography (PET) scans is common in GISTs, potentially allowing PET scanning to differentiate between GIST and benign esophageal tumors. Three patients presented with large (>10 cm) esophageal masses of ranging PET avidity [maximum standardized uptake value (SUVmax) of 1.3–10.1]. All were treated surgically and histologically confirmed to be esophageal leiomyomas. Unfortunately, the wide range of PET uptake precludes PET scanning from differentiating large leiomyomas from more aggressive lesions.     

Differing HLA types influence inhibitory receptor signalling in CMV-specific CD8 T cells

The dysregulated immune response to CMV constitutes a major force driving T cell immunosenescence and growing evidence suggests that it is not a benign virus in old age. We show here that the PD-1/L pathway defines a reversible defect in CMV specific CD8⁺ T cell proliferative responses in both young and old individuals. More specifically, highly differentiated CD45RA⁺CD27⁻ CMV-specific CD8⁺ T cells exhibit a proliferative deficit compared their central and effector memory counterparts, which is reversed following PD-L blockade. However, we also report that HLA-B^∗07/TPR specific CD8⁺ T cells express higher levels of PD-1 than HLA-A^∗02/NLV specific cells and HLA-A^∗02 individuals show a higher proliferative response to PD-L blockade, than HLA-B^∗07 individuals, which we postulate may be due to the differing functional avidities for these two CMV-specific CD8⁺ T cells populations. Nevertheless data presented here demonstrate that CMV-specific CD8⁺ T cells can be functionally enhanced by perturbation of the PD-1/L signalling pathway, whose manipulation may provide a therapeutic modality to combat age-associated immune decline.