The purpose of this study was to investigate the effects of oral care using simple tools and methods on the cleanliness of the oral cavity in the elderly. Enrolled were 84 elderly subjects with a mean (± S.D) age of 85.1±7.0 years in a nursing home. They were given tongue and oral mucosa cleaning (the oral care) after lunch every day or every other day for two consecutive weeks by the authors. The effect of the oral care was studied in terms of Candida scores in tongue coating, concentration of volatile sulfur compounds (VSC) which are the main causative substance of bad breath, and change in tongue coating scores. The above parameters were measured five times; just before the oral care program, weekly during, and at the end of the oral care program. The groups of patients, who were given the oral care, especially the group of patients cared with sponge brushes every day, showed a significant reduction in Candida scores but not in VSC concentration and tongue coating scores. The present method of oral care proved effective in cleaning the tongue and oral mucosa, and the Candida scores appeared to be a reliable indicator for evaluation. It is suggested that this way of oral care is simple, easy and useful not only for the elderly at a nursing home but for the house-bound elder people who will rapidly increase in the near future in Japan.

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Nucleosome (NS)-reactive autoantibodies appear to be involved in the pathogenesis of systemic lupus erythematosus (SLE), but the mechanisms responsible for their production remain elusive. To study whether antibodies specific to NS are present prior to anti-double-stranded (ds) DNA antibodies in lupus mice, ELISA was carried out using the plates which had been confirmed to be coated with comparable amounts of oligo-NS and dsDNA. IgG antibodies reactive with NS or dsDNA were both detected as early as 6 weeks and 10 weeks of age in MRL/lpr and MRL/+ mice, respectively. Their titers increased with age. The specificity of dsDNA binding activity in these young mice was confirmed by the finding that their sera reacted not only with mammalian dsDNA but also with dsDNA from different sources including synthetic polynucleotides. On the other hand, NS binding activity in young mice could be ascribed to cross-reactivity of the antidsDNA antibodies, because it was completely inhibited by free dsDNA. A role for NS or chromatin in triggering the production of anti-dsDNA antibodies has recently been suggested, but the present results argue that, at least in these strains of mice, antibodies specifically recognizing conformational epitopes on NS are not produced before those specific to dsDNA.

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Neuronal loss is frequently found in brains of patients with human immunodeficiency virus (HIV)-encephalopathy. Extensive apoptosis of neurons is probably involved in the development of HIV-encephalopathy. The present study was designed to investigate the mechanism of neuronal apoptosis. For this purpose, we examined autopsy brains of two patients with HIV-encephalopathy. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells and active forms of caspase-3- and -8-positive cells, including neurons, were found in the perivascular regions of the brains. In these regions, TNF-related apoptosis-inducing ligand (TRAIL)⁺ macrophages were also observed. We also examined brains of HIV-1-infected mouse model inoculated with human cells. In these brains, TUNEL⁺ neurons were also found in the perivascular region, the site where infiltrated HIV-1- infected and TRAIL-expressing macrophages were observed. Using an in vitro-culture system, we also demonstrated that the HIV-1-infected monocyte-derived macrophages preferentially expressed TRAIL and that the addition of HIV-1- infected macrophages or human TRAIL-overexpressing mouse cells to cultured mouse primary neurons/glia resulted in neuronal apoptosis. Our results suggest the involvement of TRAIL expressed on HIV-1-infected macrophages in the induction of neuronal apoptosis in infected brain.

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We report here that human B cells produce thymus and activation-regulated chemokine (TARC/CCL17) and macrophage derived chemokine (MDC/CCL22) if stimulated with anti- CD40 and IL-4. The production was determined by both protein and mRNA level using specific ELISA and semi-quantitative RT-PCR methods. Since the ligand of the TARC and MDC is CCR4, which is specifically expressed on Th2 type T cells, the production of these CC chemokines is likely to play important roles in the T cell and B cell interaction. Consistent with this, ovalbumin (OVA) specific IgE levels, which reflect the T-B cell interaction, are significantly correlated with the amounts of TARC and MDC in sera. Furthermore, we found that TARC and MDC levels are significantly increased in the sera obtained from patients with atopic dermatitis, and that the amounts are correlated with the severity of atopic dermatitis. Since CD40 ligand and IL-4 are produced by activated T helper cells, these results indicate that TARC and MDC produced by B cells play important roles in the production of antigen specific IgE by the T-B cell interaction and in the pathogenesis of allergic disease.

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Exposing neonatal rats with the synthetic estrogen, diethylstilbestrol (DES), induces morphological and functional abnormalities in the adult ovary. We examined the events that lead to this condition using female rats that were exposed to DES for the first five days after birth. The expression of steroidogenic acute regulatory protein (StAR) and cholesterol side-chain cleavage cytochrome P450 (P450scc), which are both required for steroidogenesis in the theca/interstitial region was markedly reduced. The expression of Müllerian inhibiting substance (MIS) was transiently increased in small growing follicles in the ovary of DES-treated rats at postnatal day 7 (P7), and the expression profile in the ovary differed between DES- and vehicle oil-treated rats at P14 and P21. The expression of the transcription factor, steroidogenic factor-1 (SF-1), reduced in theca/interstitial cells, but increased in granulosa cells of primary follicles. These results indicate that altered steroidogenesis and MIS production are mechanisms through which DES induces abnormal ovarian development, and support the notion that androgens and MIS are both critical factors in regulating early ovarian differentiation.

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Thirteen Japanese patients with hyper-IgM syndrome but normal CD40 ligand were characterized. All patients had mutations in AID (activationinduced cytidine deaminase) gene. Five of them had a missense mutation of Arg112His. In all patients, serum IgG, IgA and IgE levels were undetectable, B cells failed to produce detectable amounts of IgE even if cultured them with anti- CD40 and IL-4. Somatic hypermutation (SHM) was also impaired in their peripheral blood B cells. These results suggest that Arg112 is the hot spot of AID mutation and demonstrate that AID plays indispensable roles in class switch recombination (CSR) and somatic hypermutation (SHM) in human B cells. In addition, serum IgM levels in the patients have been continuously high even after proper intravenous immunogloburin infusion (IVIG) and without infection, indicate that AID has the function to induce spontaneous IgM production in B cells.

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The purpose of this study was to examine how the periodontal sensory inputs of working-side maxillary posterior teeth affect nonworking-side anterior temporalis activities at the starting jaw position of the slow-closing phase in mastication. Six subjects with normal occlusion were asked to bite an incisal block to maintain the initial jaw position of the slow-closing phase and to generate jawclosing muscle activities. Bipolar needle electrodes were inserted into the nonworking-side anterior temporalis to record spike discharges from a single motor unit. To stimulate the periodontal mechanoreceptors, mechanical stimulations were applied to the working-side maxillary first molar, first and second premolar in buccopalatal, palato-buccal, and apical directions. Meanwhile, we examined changes in the discharge frequency of the motor unit activities of the nonworking-side anterior temporalis. We found that the palato-buccal stimulation to the workingside maxillary first molar and the apical stimulation to each working-side maxillary posterior tooth significantly increased the nonworking-side anterior temporalis activities; however, palato-buccal and bucco-palatal stimulations applied to the first and second premolar didn’t. Thus, differential responses of the nonworking-side anterior temporalis are found by the working-side maxillary first molar and premolar stimulations. These findings may be due to some differences in function between molar and premolar.

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Interocclusal recording for removable partial denture in bilateral mandibular distal extension were evaluated for the differences of the interocclusal recording material utilized during different impression techniques. The purpose of this study is to develop interocclusal recording utilizing occlusion rims with high accuracy. The intraoral model with urethane rubber mucosa with 3 metallic spheres as measuring points was utilized. With the applied pressure (functional) and minimum pressure (anatomical) impression techniques, working casts were fabricated. Interocclusal recording was registered with the occlusion rim on the intraoral model unto the articulator by applying the interocclusal materials; paraffin wax (PW), ALUWAX (AW), impression paste (IP) and Exabite II (EB). Analyses were conducted with the three-dimensional analyzer and calculated for the amount of vertical and antero-posterior displacement between the intraoral model and the working cast. The results were that PW had the greatest displacement, especially with the functional impression technique, while AW had minimum displacement especially in the posterior direction. With the functional impression technique utilizing AW was revealed to minimize the amount of interocclusal displacement.

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Background: Expanding cells ex vivo is an important step in tissue engineering and the culture medium is usually supplemented with bovine serum. When a patient receives bone marrow stromal cells (BMSCs) grown in a medium containing bovine serum, infection of bovine diseases and/or the patient’s unfavorable immune reaction to bovine proteins are of concern. To overcome these problems, we examined whether a patient’s autologous serum could support the growth and differentiation of his/her BMSCs. Methods: Bone marrow was collected from the iliac by aspiration and cultured in a medium supplemented with 10% autologous serum or 10% fetal bovine serum (FBS). Number and area of the colonies of fibroblast-like cells (colony-forming unit fibroblast, CFU-f) were measured 8 days after the cell inoculation (day 8). Number and area of the alkaline phosphatase (ALP) positive colonies were measured on day 10. On day 40, the cultures were stained with alizarin red S. RNA was prepared from the culture on day 20, and the mRNA expression of osteoblastic genes was examined by reverse transcription polymerase chain reaction (RT-PCR) analysis. Results: BMSCs, which were cultured in the medium supplemented with autologous serum, produced CFU-f, ALP-positive area and mineralized nodules, which is comparable to the BMSCs in the culture supplemented with FBS. The mRNA expressions of osteopontin, parathyroid hormone receptor, osteocalcin, and bone sialoprotein were detected in the culture supplemented with autologous serum. Conclusions: A patient’s autologous serum could expand BMSCs without losing their potentiality for osteoblastic differentiation. Patients' autologous serum could be efficient to expand BMSCs and to be utilized safely for bone regeneration therapy.

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The purpose of this study was to investigate whether lidocaine could be transported through excised rat skin in vitro using alternating current (AC). In addition, the relationships between factors such as voltage and frequency, and transported lidocaine concentration were studied using the in vitro model. A pair of platinum plate electrodes was installed at opposite ends of two cylindrical glass cells in parallel to the full-thickness rat skin. The donor compartment was filled with 10 % lidocaine hydrochloride, and the receptor compartment with Ringer solution. A sinusoidal wave was applied between the electrodes at 5 kinds of constant voltages at 1 kHz and at 4 kinds of frequencies at 20 volts. Our experimental system was successfully used to quantify the concentration of transported lidocaine induced by AC application. The applied sinusoidal waves evoked the transport of lidocaine through the rat skin at every voltage and frequency protocol. Our results suggest that the applied electric voltage and frequency affect the movement of the lidocaine ions. We conclude that the transdermal delivery of lidocaine by AC iontophoresis has a possibility to use for local anesthesia and the pain management of the skin.

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Endochondral bone formation observed at the mandibular condyle is regulated by various growth factors including insulin-like growth factor- I (IGF-I). In this paper, we describe a method for the local administration of IGF-I to the bilateral mandibular articular cavities of 3- and 12-week-old rats, and the effects of IGF-I on endochondral bone formation by histomorphometric techniques. In 3-week-old IGF-I-treated rats, three days after administration, an increase in bone tissue was found in the area of the subchondral cancellous bone layer. In 12-week-old IGF-I-treated rats, three days after administration, an increase in the thickness of the condylar cartilage and a decrease in bone tissue were observed in the area of the subchondral cancellous bone layer. This study revealed that the local administration of IGF-I on mandibular condyle caused different histological changes between growth and maturation periods. These results indicated that the effects of IGF-I on endochondral bone formation in the mandibular condyle were age-dependent.

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To reveal roles of neurotrophic factors in plastic changes of the primary afferent neurons following nerve injury, we investigated expression of glial cell line-derived neurotrophic factor (GDNF) as well as nerve growth factor (NGF) in a neuropathic pain model of the rat. The rats exhibited hyperalgesia and allodynia on the injured left side for at least 2 weeks after chronic constrictive injury to the sciatic nerve. Accompanied by the behavioral changes, expression of GDNF decreased in the dorsal root ganglia (DRGs) and the sciatic nerve on the injured side on the fourteenth day after the surgery. In contrast, the amount of NGF in DRGs was unchanged in spite of disturbance of NGF transport in the nerve. The present results suggest that decreased expression of GDNF takes some part in development and/or maintenance of neuropathic pain.

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Rats were subjected to unpredictable chronic stress (UCS), which was composed of 3 cycles of 7 kinds of stress for 21 days. Rats given UCS exhibited a depressive state in behavioral tests such as emergence tests and forced swim tests. Administration of cyclosporine-A (CsA), an immunosuppressive drug, gave rise to antidepressant effect in rats under the UCS, but not in stress-free rats. In other words, CsA shortened both the latency time in emergence tests and the immobility time in forced swim tests in rats given UCS. Analysis of brain tissue by HPLC revealed that CsA caused a significant increase in NE, 5-HT and 5-HIAA levels in the cortex of UCS treated rats, but treatment with either UCS or CsA alone resulted in the opposite effect. Comparing the data of monoamines and their metabolites in the brain, cascades may be different between CsA and imipramine, although both of them showed antidepressive effect in behavioral tests.

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It has been suggested that oral care is essential for improving the quality of life (QOL). The aim of oral care involves not only maintenance of oral health but also enhancement of mastication and appetite by means of improving taste sensitivity. There are, however, few studies that have investigated the effect of oral care on taste sensitivity. In the present study, we focused on tongue brushing among oral care and examined the changes in taste sensitivities by mild tongue brushing in the nursed elderly. Ninety subjects, over 64 years old with ability to communicate, were divided into 2 groups, one was the cared group (subject's tongue was brushed) and the other was the control group (not brushed but rinsed). The thresholds for four primary tastes such as saltiness, sourness, sweetness and bitterness were measured before and after treatments using the whole mouth method. The mean recognition thresholds for salty and sour tastes significantly decreased after tongue brushing in the cared group, while those for all four tastes were not changed after mouth rinsing in the control group. The present result suggests that mild tongue brushing may enhance taste sensitivity of saltiness and sourness in the nursed elderly.

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In order to investigate the morphological characteristics of Japanese patients with obstructive sleep apnea (OSA) and basis for selection of an oral appliance (OA) therapy, the craniofacial skeleton, soft tissue and upper airway were analyzed on lateral cephalograms from 103 patients with OSA and 98 control subjects. At first, the 103 OSA patients were divided into two groups according to their body mass index (BMI). The results were the following: Micrognathia was a major risk factor of Japanese OSA patients instead of obesity; the narrowing in the hypopharynx was observed due to the inferiorlocated hyoid bone, especially in the obese group, an enlarged tongue and sticking of fatty-tissue to upper airway wall were observed in addition. Secondly, the 103 OSA patients were treated by OA, and were classified according to the reduction ratio of AHI (rAHI) again. The results suggested that the patients group which showed rAHI ≧50 % had a balanced relationship between the maxilla and mandible. These findings proved that the morphological characteristics specific to Japanese patients with OSA and patients who were allowed to accept the OA therapy were exist.

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The pharmacological actions of bisphosphonates are due to the inhibitory effects on bone resorption, but little is known about the bisphosphonate action on bone formation. The purpose of this study is to elucidate the actions of bisphosphonates, clodronate, on bone formation in the experimental in vivo and in vitro rat models. The bone mineral density (BMD) was decreased in the rats fed a low-calcium diet (0.05% Ca) for 6 days compared with the rats fed a normal-calcium diet (0.5% Ca). The decrease in BMD was suppressed in the 2 mgP/day and the 4 mgP/day clodronate administrations. Bone formation rate (BFR) in rats fed a low-calcium diet was significantly increased compared with the rats fed a normal-calcium diet, and the 2 mgP clodronate administration further increased the BFR. In the cultured rat bone marrow cells, the area of mineralized nodules was significantly increased at 10^-7 and 10^-6 M clodronate, but high concentration of clodronate decreased the area. From these results, it is concluded that clodronate stimulates bone formation when the drug was given to a rat with a relatively lower dose that is sufficient to prevent bone resorption and that this effect may be due to the stimulatory effect on the differentiation process of osteoblasts.

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Synovial chondromatosis of the temporomandibular joint is a rare disease, and extra-articular synovial condromatosis of the temporomandibular joint is even rarer. A review of the English literature from 1980 to 2000 has revealed 51 cases of synovial chondromatosis affecting the temporomandibular joint. We report a case of extra-articular synovial condromatosis, for which we carried out a long-term follow-up of the postoperative course using diagnostic images.

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