Reduced oxidative function in gingival crevicular neutrophils in periodontal disease.

Measurable amounts of viable and functional polymorphonuclear neutrophils (PMNs) are recovered from pooled washings of the gingival crevice of healthy individuals. In the present study, we have assessed the ability of the PMNs removed from single healthy or diseased pocket sites to mount an oxidative burst when challenged with phorbol myristate acetate (PMA) and compared these activities with each other and with those obtained with autologous peripheral-blood PMNs. The oxidative burst after PMA stimulation was evaluated by using methods developed for the flow cytometer. The results showed that the PMNs collected from untreated disease sites were minimally responsive to PMA when compared with peripheral-blood PMNs collected at the same time from the same individual. Thus, whereas the peripheral-blood PMNs exhibited significantly lower resting oxidative product formation and a 500% increase when stimulated with PMA, all gingival-crevicular PMNs exhibited significantly higher resting formation of oxidized products but only a 150% increase after PMA stimulation. PMNs obtained from a consistently healthy site had significantly higher resting production of oxidized products and were able to mount the greatest absolute increase in oxidized products after PMA stimulation when compared with PMNs collected from diseases sites. Mechanical debridement of these diseased sites, which both reduced the bacterial numbers and restored clinical health, resulted in the recovery of gingival-crevicular PMNs that exhibited an oxidative burst more typical of that observed in PMNs obtained from healthy gingival sites and from the peripheral blood. This suggested that the PMNs collected from the diseased sites either had been exhausted by the large numbers of bacteria present in these sites or had been specifically inhibited by these bacteria.     

Multiple interactions between murine cytomegalovirus and lymphoid cells in vitro.

Spleen cultures from various strains of mice were infected in vitro with murine cytomegalovirus (MCMV). Infectious centres were established in a small proportion (not greater than 1%) of the cells. Virus could be rescued from these cells by co-cultivation with syngeneic or allogeneic fibroblasts, but the frequency of rescue could not be altered by incubation with cyclic nucleotide analogues, iododeoxyuridine, cortisol, or allogeneic spleen cells. In addition a smaller fraction of the cell population, possibly a sub-population of the infectious centres, replicated virus spontaneously. The presence of mitogens did not affect these interactions qualitatively or quantitatively. A third response to infection was an inhibition in DNA synthesis, which was suffered by unstimulated cultures and by cells transformed by concanavalin A and bacterial lipopolysaccharides, although overall cell viability was maintained. This response was also mediated by u.v.-inactivated virus.     

The problem of host DNA synthesis in murine cytomegalovirus-infected cells

Murine cytomegalovirus (MCMV) infection in mouse fibroblasts resulted in an early inhibition in thymidine incorporation into cell DNA. In contrast [32P]phosphate incorporation was only slightly inhibited, while the incorporation of deoxycytidine, deoxyadenosine, and deoxyguanosine continued unabated. The limiting factor in thymidine incorporation was a decrease in uptake by the infected cells. Uptake of the other nucleosides, however, was either normal or enhanced. Nuclear monolayers, derived from infected cells, incorporated thymidine triphosphate into cell DNA at the same rate as nuclei of uninfected cells. Measurement of total DNA content of the cells revealed no difference between infected and control cultures. Thus MCMV neither inhibits nor stimulates cellular DNA synthesis.     

Investigation and comparison of some models for removing ocular artefacts from EEG signals

An investigation of ocular artefacts (OAs) in the human electroencephalogram (EEG) to quantify the effectiveness of OA removal and to find the most effective model for removing OAs online is described. In Part 1, the models used in the investigation are described and the data analysed. The analysis showed that the ‘true’ EEG exhibited a high degree of serial correlation and so the ordinary least-squares (OLS) method employed to remove OA was inefficient. Efficient alternative methods based on autoregressive models of the ‘true’ EEG are discussed. It is also shown that the EOGs are linearly dependent making some of them redundant. In Part 2, the models are compared.     

Identification of a frequent variant in ALG6, the cause of Congenital Disorder of Glycosylation-Ic

Congenital Disorder of Glycosylation (CDG) type Ic is caused by mutations in ALG6. This gene encodes an alpha1,3 glucosyltransferase used for synthesis of the lipid linked oligosaccharide (LLO) precursor of the protein N-glycosylation pathway. CDG-Ic patients have moderate to severe psychomotor retardation, seizures, hypotonia, strabismus, and feeding difficulties. We previously identified a typical patient with a heterozygous point mutation, c.391T>C (p.Tyr131His) in ALG6. Using complementation analysis of ALG6-deficient yeast, we show that this alteration is as severe as the most common disease-causing mutation, c998C>T (p. Ala333Val), which occurs in over half of all known CDG-Ic patients. The frequency of c.391T>C (p.Tyr131His) in the US population, is 0.0214, suggesting that homozygotes would occur at a rate of& tilde;1:2,200. We identified one patient with typical CDG-Ic symptoms and a homozygous p.Tyr131His alteration in ALG6. However, in contrast to most CDG patients, her LLO and plasma transferrin glycosylation appeared normal. Thus, it is unclear whether c.391T>C causes CDG-Ic or contributes to the symptoms. Genotyping additional patients with CDG-like symptoms will be required to resolve this issue.     

Diabetic vascular disease: it's all the RAGE

The major consequence of long-term diabetes is the increased incidence of disease of the vasculature. Of the underlying mechanisms leading to disease, the accumulation of advanced glycation end products (AGEs), resulting from the associated hyperglycemia, is the most convincing. Interaction of AGEs with their receptor, RAGE, activates numerous signaling pathways leading to activation of proinflammatory and procoagulatory genes. Studies in rodent models of macro- and microvascular disease have demonstrated that blockade of RAGE can prevent development of disease. These observations highlight RAGE as a therapeutic target for treatment of diabetic vascular disease.     

Investigation and comparison of some models for removing ocular artefacts from EEG signals

An investigation of ocular artefacts (OAs) in the human electroencephalogram (EEG) to quantify the effectiveness of OA removal, and to find the most effective model for removing OAs online is described. It was found unnecessary to use the vertical and horizontal EOGs of both eyes, although more than one EOG signal is required for adequate OA removal. The model using the vertical right EOG and the two horizontal EOGs was the best overall, but in most cases the use of only the vertical and horizontal right EOGs was sufficient. OAs were not completely removed by any of the models investigated, suggesting that more complex models are necessary.     

Comparison of serologic screening tests for brucellosis.

The slide agglutination test (SAT), microagglutination test (MAT), and card agglutination test (CAT) were compared with each other, using the tube agglutination test (TAT) as the standard method, by two reference laboratories to determine effectiveness as screening tests for human brucellosis. TAT titers of 1,253 sera tested in both laboratories were compared. In one laboratory, 1,270 sera were tested by the TAT and SAT, while the other laboratory tested 1,261 sera by both methods. Of these sera, 1,155 were tested in one laboratory by the CAT and 187 sera were tested by the MAT. Compared with that of the TAT (greater than or equal to 160 positive), the sensitivities were 97 to 100% (SAT), 90% (CAT), and 88% (MAT). The specificities were 88 to 89% (SAT), 98% (CAT), and 88% (MAT). For populations with a low prevalence of disease, increased specificity offers higher predictive value, so the CAT and MAT are preferable for screening purposes and the choice between tests depends on the number and frequency of tests performed. All sera reactive in the CAT and MAT should be retested with the TAT.