Toshitaka Koga

Relationship between Upper Body Obesity and Periodontitis

Upper body obesity, related to visceral fat accumulation, is known to increase the risk of various adult diseases, especially type 2 diabetes and cardiovascular disease. This study was conducted to clarify the relationship between upper body obesity and periodontitis. We studied 643 apparently healthy, dentulous Japanese adults who attended programs at Fukuoka Health Promotion Center. Waist-hip ratio, body-mass index (BMI), and body fat were significant risk indicators for periodontitis after adjustment for known risk factors (p < 0.002). Subjects were divided into four BMI (or body fat) categories. In only the subjects with high waist-hip ratio, higher categories of BMI (or body fat) significantly increased the adjusted risk of periodontitis, compared with subjects with low waist-hip ratios and the lowest category of BMI (or body fat). The reported relationship between cardiovascular disease and periodontitis should be reconsidered, since abdominal adiposity or visceral fat can be related to both diseases.

Influence of Dentition Status on Physical Disability, Mental Impairment, and Mortality in Institutionalized Elderly People

The loss of teeth is known to influence the mastication of foods and nutritional status. Therefore, we hypothesize that poor dentition status can impair the systemic health of the aged. To clarify the influence of dentition status on deterioration in physical ability, mental impairment, and mortality, we conducted a six-year prospective cohort study of the institutionalized elderly living in 29 of the 30 institutions for the elderly in Kitakyushu, Japan. Bivariate analysis revealed that worse dentition status at baseline led to significantly worse physical and mental impairment, and higher mortality. In a multiple logistic regression analysis, the physical ability of edentulous subjects without dentures significantly deteriorated compared with that of dentate subjects with 20 or more teeth. The six-year mortality rate of the edentulous subjects without dentures was significantly higher than that of the subjects with 20 or more teeth. Poorer dentition status, especially edentulousness without dentures, may therefore be related to deterioration in the systemic health of the aged.

The Severity of Periodontal Disease is Associated with the Development of Glucose Intolerance in Non-diabetics: The Hisayama Study

Inflammation is hypothesized to play a significant role in the development of type 2 diabetes; however, reports on clinical inflammatory conditions are limited. Studies have suggested that periodontitis affects glucose control in diabetics. This community-based study examined the relationship between periodontitis and glucose tolerance status, including changes in status. The relationship between periodontal condition and the results of a 75-g oral glucose tolerance test was examined in 961 adults in 1998. Deep pockets (mean pocket depth > 2.0 mm) were significantly associated with impaired glucose tolerance and with diabetes as compared with shallow pockets (< 1.3 mm). In the subgroup with normal glucose tolerance 10 years previously, subjects who subsequently developed impaired glucose tolerance were significantly more likely to have deep pockets. Deep pockets were closely related to current glucose tolerance status and the development of glucose intolerance.

Depression of T-cell Epitope Generation by Stabilizing Hen Lysozyme

Conformational stability of proteins is an important factor that determines their resistance/susceptibility to proteolytic digestion. Intracellular proteolysis is the key step in antigen presentation events for protein antigens; hence, it is likely that increasing protein stability reduces the antigenicity of proteins. We prepared three hen egg white lysozyme derivatives possessing different stabilities by chemical modification to clarify the relationship between conformational stability and the antigenicity of the protein. One of the derivatives was conformationally unstabilized by removing one intramolecular disulfide bond, whereas the two others were stabilized by the addition of an intramolecular cross-link. The antigenicity of these derivatives was evaluated using hen egg white lysozyme-specific T-cell hybridoma cells and a B-lymphoma cell line, A20, as antigen-presenting cells. With an increase in conformational stability, the T-cell response decreased. However, the reduction was not derived from the inefficiency of internalization to A20 cells nor the alteration of antigenicity by chemical modifications. Moreover, from analyses of their susceptibility to proteolysis and the kinetics of presentation of the T-cell epitope, it was confirmed that increasing protein stability led to the depression of T-cell epitope generation by increasing resistance to proteolysis. These results have an important implication in devising a new strategy for manipulating T-cell response by the stability of protein antigen.

Guest-induced conformational change in a flexible host: mono-altro-β-cyclodextrin †

Mono-altro--cyclodextrin 1 ,a -cyclodextrin with one of the seven glucose units being configurationally changed to an altrose, is shown to be a flexible host undergoing a distinct conformational change within its altropyranose geometry upon intracavity inclusion of adamantanecarboxylate, thus representing an induced-fit model of binding rather than one following the rigid lock-and-key type pattern.

Inhibition of macrophage migration by synthetic muramyl dipeptide.

Abstract N-acetylmuramyl-L-alanyl-D-isoglutamine, a synthetic compound which is known to have a minimal effective structure for an adjuvant activity of cell wall peptidoglycans, was found to inhibit the migration of normal macrophages. It was shown that the inhibition was neither due to cytotoxic or agglutinating effect of the muramyl dipeptide on macrophages nor due to lymphokine production uopn stimulation of lymphocytes by the muramyl dipeptide.

Dual Regulatory Effects of Interferon-α, -β, and -γ on Interleukin-8 Gene Expression by Human Gingival Fibroblasts in Culture upon Stimulation with Lipopolysaccharide from Prevotella intermedia, Interleukin-1α, or Tumor Necrosis Factor-α

In a previous study, we demonstrated that the amount of interleukin (IL)-8 mRNA expressed by human gingival fibroblasts stimulated with lipopolysaccharide (LPS) from Prevotella intermedia ATCC 25611 is increased by pre-treatment with beta or gamma interferon (IFN-β or --y). In the present study, we identified the regulatory effects of these IFNs on IL-8 mRNA expression and IL-8 production by human gingival fibroblasts. Priming with IFN-alpha (a), -β, or --y upregulated the IL-8 mRNA expression in response to P. intermedia LPS, whereas co-stimulation with these IFNs reduced the amount of mRNA expressed by the cells. The regulation of IL-8 mRNA expression induced by recombinant human tumor necrosis factor-a (rHuTNF-a) or rHuIL-1α was similar to that induced by LPS. The IL-8 mRNA expression in response to P. intermedia LPS was enhanced by IFN-γ independently of de novo protein synthesis, and was regulated, at least in part, at the transcriptional level. The IL-8 mRNA accumulation in response to P. intermedia LPS was inhibited by tosylphenyl-alanyl chloromethyl-ketone, an inhibitor of NF-KB activation, although the NF-KB activation itself was not altered by IFN-γ. These findings suggest that IFNs might be capable of both enhancing and inhibiting inflammatory responses in periodontal tissues through the dual regulation of IL-8 production by gingival fibroblasts in response to bacterial components and cytokines.

Inositol 1, 4, 5-trisphosphate affinity chromatography

Inositol 1,4,5-trisphosphate (IP3) affinity columns were made by coupling IP3 analogs to a supporting matrix. Sepharose 4B. IP3 5-phosphatase activity. IP3 3-kinase activity and IP3 binding activity from rat brain were absorbed on the IP3 columns. and were eluted by increasing KC1 concentration. This purification procedure increased the specific activities of these parameters 5-200-fold. Thus Sepharose 4B immobilized IP3 analogs can specifically interact with IP3-binding proteins, demonstrating that IP3 affinity columns are a good method for purifying such proteins. Furthermore, our results suggest that IP3 analogs can be linked to other molecules to make useful derivatives without loss of their biological activities.

Augmentation of the proliferative response of thymocytes to phytohemagglutinin by the muramyl dipeptide

A synthetic N-acetylmuramyl-L-alanyl-D-isoglutamine or muramyl dipeptide (MDP) and adjuvant-active analogs, but not lipopolysaccharide (LPS), exhibited the augmenting effect on the proliferative response of thymocytes to phytohemagglutinin (PHA). MDP also had a comitogenic effect on PHA-stimulated T lymphocytes. It was shown that the thymocyte-stimulating effect of MDP is not through the production of the monikines by MDP-stimulated macrophages and that MDP has a direct action on lymphocytes.

Guest-induced conformational change of β-cyclodextrin capped with an environmentally sensitive chromophore

Abstract A capped cyclodextrin, 6-deoxy-6-( p -hydroxy- m -nitrophenacylthio)-β-cyclodextrin, was prepared in order to detect any conformational change of the host upon the guest binding. The association constant between the cyclodextrin and 1-adamantanecarboxylate, cyclohexanecarboxylate, p -methylbenzoate, 3,3-dimethylbutyrate, or 2,2-dimethylpropionate was enhanced 20, 5.3, 3.7, 2.3, or 2.0 times, respectively, by chromophore capping. The changes in the electronic, NMR, and circular dichroism spectra as well as p K a of this cyclodextrin upon binding of the guest strongly indicate a conformational change around the chromophoric moiety of the cyclodextrin.