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It has not yet been clarified how sex hormones affect craniofacial bone development immediately after birth. The purpose of this study was to examine the effects of sex hormone deficiency on craniofacial bone development immediately after birth, in terms of the internal structure of the mandible in newborn mice with orchiectomy (ORX) and ovariectomy (OVX). ORX, OVX and a sham-operation were performed on 40 five-day-old C57BL/6J mice. Eight weeks after surgery, each mandible was subjected to histomorphometric analysis of trabecular (Tr) and cortical (Ct) bone mineral density (BMD) by peripheral quantitative computed tomography (pQCT). In the experimental groups, a significant reduction in BMD was found in comparison with the control groups. In histomorphometric analysis, the number of tartrate-resistant acid phosphatase (TRAP)-positive cells in the condyle and the thickness of the condylar cartilage layer was significantly greater in the experimental mice than in the controls. Trabecular bone volume of the condyle measured on azocarmine-aniline blue (AZAN) sections was significantly less in the experimental mice than in the controls. These results indicate that mandibular growth is inhibited by sex hormone disturbances and the relevant internal structures changed. The findings show that sex hormones are one of the key determinants of mandibular growth and development immediately after birth.

It is well-known that sex hormones influence bone metabolism. However, it remains unclear as to how sex hormones affect bone growth in newborn mice. In this study, we performed orchiectomy (ORX) and ovariectomy (OVX) on newborn mice, and examined the effects on craniofacial growth morphometrically. ORX and OVX were performed on five-day-old C57BL/6J mice. Four weeks after surgery, lateral cephalograms were taken of all of the mice, with the use of a rat and mouse cephalometer. Cephalometric analysis of the craniofacial skeleton was performed by means of a personal computer. Inhibition of craniofacial growth was found in the experimental groups but not in the sham-operated groups. In the nasomaxillary bone and mandible, the amount of growth was significantly reduced. These results suggest that craniofacial growth is inhibited by sex hormone disturbances not only in puberty but also immediately after birth.

Formation of senile plaques (SPs) by amyloid beta (Abeta) protein is a neuropathological change which characterizes Alzheimer's disease (AD), and Abeta deposition and neuron loss are essential for the pathological cascade of the disease. Although the mechanism of Abeta deposition remains unclear, it has been suggested that clearance of Abeta protein may be impaired in the AD brain. Previous studies demonstrated that microglia were able to remove Abeta by releasing a metalloprotease or by phagocytosis, suggesting that microglia may play an important role in preventing Abeta deposition in the central nervous system (CNS). On the other hand, it was reported that the number of microglia was reduced in osteopetrotic (op/op) toothless mice resulting from the lack of functional macrophage colony-stimulating factor (M-CSF). The present study was thus designed to examine the Abeta deposition and the number of hippocampal neurons in the brain of op/op mice. A number of fibrillar plaques were detected in the cerebral cortex, hippocampus, amygdala and hypothalamus in op/op mice, however, no quantitative evidence of Abeta deposition was observed in normal mice. Moreover, the total number of pyramidal cells in the hippocampal CA1, and CA3 regions was significantly reduced in op/op mice when compared to the controls. These results demonstrate that Abeta deposition influence neuron loss and it may be suspected that expression of SPs may be in part regulated by microglia under physiological conditions.

Vascular endothelial growth factor (VEGF) has an ability to induce functional osteoclasts as well as neovascularization. We recently reported that the number of osteoclasts was enhanced by the injection of recombinant human VEGF (rhVEGF) with the application of mechanical force for experimental tooth movement. In this study, the expression of VEGF was detected in osteoblasts on the tension side of the alveolar bone. Moreover, the rate of tooth movement was significantly increased in the rhVEGF injection groups compared with the controls. These results suggested that VEGF, highly expressed by mechanical stimuli, enhances the number of osteoclasts as a paracrine factor, and that the amount of tooth movement is accelerated by both endogenous VEGF and injected rhVEGF.

It is well accepted that mechanical loading inhibits bone resorption and increases in vivo bone formation. It is also known that cyclic mechanical loading, in particular, can enhance bone formation significantly. These findings suggest a significant role for mechanical stimuli in bone remodelling mediated by various local growth factors including insulin-like growth factor-I (IGF-I). Earlier studies showed that the nasal bone length and premaxillary bone width were significantly greater in mice fed a solid diet rather than a granulated diet, and that these dimensions increased significantly in a solid-diet group treated with IGF-I. The present study sought to examine the effect of IGF-I on the expression of osteoclasts and osteoblasts in the nasopremaxillary suture subjected to different masticatory loadings. For the solid-diet groups, the numbers of tartrate-resistant acid phosphatase (TRAP)-positive osteoclastic cells and osteoblasts were significantly greater in the group injected with IGF-I than in the animals injected with physiological saline. In the groups fed a granulated diet, no significant differences in the numbers of TRAP-positive osteoclastic cells and osteoblasts were found over the entire experimental period between mice injected with either IGF-I or physiological saline. It is shown that IGF-I significantly induces the expression of osteoclasts and osteoblasts and the subsequent bone remodelling, and that the effect may be additive as compared to that of mechanical masticatory loading, which seems to be more important in bone remodelling in terms of the numbers of osteoclasts and osteoblasts.

Alendronate, one of the bisphosphonates, is known to have an inhibitory effect on bone resorption. The purpose of study was to investigate the effects of alendronate on ectopic bone graft resorption and to determine the optimal dose in the mouse. In control group, segments of chopped tarsal bone were immersed in saline solution and auto-grafted. In experimental groups, the same bone segments were immersed in alendronate ranging in concentration from 10 - 4 to 10 - 6 M prior to transplantation. The grafted bone in the control group disappeared due to resorption by osteoclasts within 5 weeks. In the experimental groups, the area of bone tissue decreased by only 20-40% at 5 weeks post-operatively. The transplanted bone volume in alendronate-treated groups exhibited a tendency of dose-dependent increase, being highest in the 10 - 4 M group. The number of osteoclasts was significantly less in the alendronate-treated groups than in the controls. These results suggested that the alendronate inhibits resorption of ectopic bone graft at a concentration of 10 - 4 to 10 - 6 M.

It is well accepted that reduced masticatory function resulted from a soft diet with low physical consistency causes morphologic and histologic alterations in the craniofacial skeleton in growing animals. It is also assumed that these alterations are associated with reduced proliferative activity of osteoblasts on the bone surface, indicating a significant role of mechanical stimuli mediated by various local growth factors such as insulin-like growth factor-I (IGF-I) and parathyroid hormone (PTH). A previous study demonstrated that PTH accelerated the effect of IGF-I on bone formation. This study was thus conducted to examine the effect of PTH on the induction of osteoclasts and osteoblasts and the subsequent nasopremaxillary growth under different mechanical loading conditions from mastication. In animals treated with PTH, the nasal bone length increased significantly in the solid-diet group. No significant differences in these dimensions were found between the solid-diet mice injected with physiological saline and the granulated-diet group injected with PTH. It is shown that PTH induces nasal and premaxillary growth, and the effects may be exerted if mechanical loading from mastication is sufficient. It is also demonstrated that the effects of PTH are more potent in the osteogenic activity than in the osteoclastic one, in terms of more significant expression of osteoblasts than osteoclasts.

Osteopetrotic (op/op) mice have a prominent deficiency of osteoclasts caused by the absence of functional macrophage colony-stimulating factor (M-CSF). In the present study, we examined bone formation of the mandibular condyle after consecutive injections of M-CSF using 5 days-old mutant mice. In the M-CSF injected op/op mice, bone resorption on the inner surface of the mandibular ramus was noted at 10 days after birth, normally five days after the start of M-CSF injections, while there was no signs for bone resorption in untreated op/op mice of the some age. This activity increased with the progress in bone marrow cavity formation on postnatal day 15 and there after. In untreated op/op mice the condylar heads were still composed of cartilage tissue at even 25 days after birth. The op/op mice treated by M-CSF may provide us with new knowledge not only about the role of M-CSF in osteoclast differentiation in the mandible but also about the correlations in bone remodeling and morphology of the mandibular condyle and ramus.

The time-dependent effects of daily dosing of IGF-I (1.21 mg/g) on the linear growth of the femur were investigated in mice. The femoral length and volume and the number of osteoclasts were significantly greater after IGF-I injection as compared to the non-injected control, suggesting that the IGF-I imbalance might cause a quick turnover cycle of the bone resulting in the altered femoral modeling.

It is well known that the size of the condyle is different between males and females in humans. It has also been documented that ovariectomy (OVX) and orchiectomy (ORX) influence the remodeling of the condylar head in experimental animals. However, influences of sex hormones on the condyle in terms of its breadth have not been examined. With these considerations, this study was designed to examine the breadth of the mandibular condyle in OVX and ORX mice by histomorphometry 8 weeks after surgery. In the OVX mice, the condylar breadth was significantly larger than in the controls, while no significant differences in the breadth were found between the ORX mice and the controls. The thickness of the condylar cartilage layers exhibited similar findings to the breadth of the condyle. On the contrary, the trabecular bone volume was significantly smaller in the OVX and ORX mice than in the corresponding controls, and the difference was more substantial in female mice than in the males. These findings emphasize that a reduction of sex hormone levels, induced by OVX and ORX, significantly influences condylar morphogenesis.

Ovariectomy (OVX) and orchiectomy (ORX) are well known to increase bone turnover, however, the osteogenic effects are not fully understood. In this study, influences of sex hormone secretion cessation was examined for both sexes and different bones in terms of the change in the number of osteoblasts regarded as an index of bone formation. Male and female mice underwent ORX and OVX at 8 weeks old, respectively. In each of the experimental and control groups, mice were sacrificed 4 weeks after the surgery for OVX and ORX. The experimental mice exhibited an increase in the number of the osteoblasts in the condylar head, significantly different from the controls. Furthermore, in the experiment groups, the number of osteoblasts exhibited a more remarkable increase in the condyle than in the femora. This finding suggests that bone formation is accelerated by the reduction of sex hormone levels and the decrease in the trabecular bone volume is different between bones according to the degree of the enhanced bone formation or osteogenic activity.

The deposition of amyloid beta (Abeta) protein is a neuropathological change that characterizes Alzheimer's disease. Animals with the osteopetrosis (op/op) mutation suffer from a general skeletal sclerosis, a significantly reduced number of macrophages and osteoclasts in various tissues, and have no systemic macrophage colony stimulating factor (M-CSF). This study examined the effect that M-CSF injections had on Abeta deposition and microglial cell distribution in the brains of normal and op/op mice. Abeta-positive plaques were detected in the cerebral cortex of op/op mice, but not in normal mice. M-CSF reduced the numbers of Abeta-positive plaques in op/op mice. The microglial cell population was reduced in op/op mice compared with normal mice, and M-CSF increased the numbers to 65.8% of that observed in normal mice. Our results suggest that a clearer understanding of the role that microglial cells play in Abeta deposition may help determine the mechanisms involved in the pathogenesis of Alzheimer's disease.

We report the case of a girl aged 10 years whose alveolar bony defect was closed with a polytetrafluoroethylene membrane, which was incorporated in bone after 4 months. We suggest that the principle of guided bone regeneration can be used to repair cleft defects provided that the mucoperiosteal flaps are handled carefully and that good anti-infective measures are taken to prevent early exposure and microbial contamination of the membrane barrier.

Alendronate, one of the bisphosphonates, is known to have an inhibitory effect on bone resorption. The purpose of this study was to investigate the effects of alendronate on ectopic bone graft resorption and to determine the optimal dose in the mouse. The grafted bone in the control group disappeared due to resorption by osteoclasts within 5 weeks. In the experimental groups, the area of bone tissue decreased by only 20-40% at 5 weeks post-operatively. At 8 and 9 weeks after surgery, the decreased area of bone structure was significantly less in all the 10(-4) M injected alendronate-immersed groups than in the 10(-4) M non-injected alendronate-immersed. At 9 weeks after surgery, the number of osteoclasts were significantly less in the 10(-4) M injected alendronate-treated groups than in the 10(-4) M non-injected alendronate-treated groups. These results suggest that alendronate inhibits resorption of ectopic bone graft at concentrations of 10(-4) and 10(-6) M.

For orthodontic tooth movement, remodeling of the alveolar bone is maintained by a repeated process of bone resorption and new bone formation, controlled, respectively, by osteoclasts and osteoblasts. Recently, we have found that recombinant human vascular endothelial growth factor (rhVEGF) acts as a macrophage colony-stimulating factor in osteoclast induction in osteopetrotic (op/op) mice. The purpose of this study was to investigate whether rhVEGF stimulates osteoclast differentiation during experimental tooth movement. Purified rhVEGF was injected once into the buccal gingival groove around the incisors. An experimental appliance with a helical loop was bonded onto the upper incisors, and an initial force of 1.0 g was applied for three days. The number of osteoclasts appearing in the periodontal ligament space on the pressure side of the alveolar bone was increased markedly. These results suggest that local administration of rhVEGF enhances the number of osteoclasts, and may increase the rate of orthodontic tooth movement. Abbreviations: recombinant human vascular endothelial growth factor (rhVEGF), macrophage colony-stimulating factor (M-CSF), osteopetrotic mice (op/op mice), fms-like tyrosine kinase (Flt-1), periodontal ligament (PDL), phosphate-buffered saline (PBS), tartrate-resistant acid phosphatase (TRAP), and analysis of variance (ANOVA).

This study was carried out to determine the effect of food texture on the response to trauma of the temporomandibular joint in mice. Animals were fed either a solid or granular diet after weaning. At 8 weeks old, condylar hypermobility was induced by forcing the mouth wide open ten times under ether anaesthesia. This procedure was repeated 10 times once daily for 10 consecutive days. The temporomandibular joint tissues were observed microscopically on day 0 and then 2 days, 5 days, 2 weeks, 3 weeks and 5 weeks after the last forced opening. Eighteen male mice were used in total, three for each timepoint. A proliferation in synovial surface cells and an increased number of capillaries were seen at day 2 in the mice fed a granular diet, but not in those fed a solid diet. Multiple cell layers of the synovial membrane, dilated capillaries and fibrin deposits were expanded further between day 2 and week 5 in the mice fed a granular diet, but not until day 5 to week 5 in the mice that had been fed a solid diet. At week 3, the mice fed a granular diet showed erosion of the anterior articular disc. This was observed in both dietary groups at week 5. This study suggests that, in advanced countries, people who habitually eat easily chewable food should be advised that such practice may lead to a decline in the resistance to trauma of the masticatory system.

It is well accepted that reduced masticatory function induced by a diet with soft physical consistency causes alterations in the craniofacial morphology in growing animals. It is assumed that these alterations are associated with reduced proliferative activity of osteoblasts on the bone surface, indicating a significant role for mechanical stimuli mediated by various local growth factors including insulin-like growth factor-I (IGF-I). Here, the effects of IGF-I on the linear growth of nasal and premaxillary bones subjected to different masticatory loadings were examined. The length of the nasal bone and the width of the premaxilla were measured. These dimensions were significantly greater in mice fed a solid diet than in mice fed a granulated diet. In animals treated with IGF-I, the nasal bone length and premaxillary width increased significantly in a subgroup receiving a solid diet, but these changes were not found in a similar group fed a granulated diet. No statistically significant differences in these dimensions were found between solid-diet mice injected with saline and granulated-diet group injected with IGF-I. It is concluded that IGF-I induces nasal and premaxillary growth, and that its effect is enhanced or accelerated by increased mechanical masticatory loading.

昭和53年春,大垣市近郊の神戸町の中学生を中心に106名の急性肝炎が発生した.大垣市民病院の入院患者のうち,9名の糞便からA型肝炎ウイルスが検出され,A型肝炎と診断され,50名が入院,56名が外来で治療をうけた.診断面を中心に検討するため,初診後数日間の自,他覚症状,血液検査成績を,黄疸群,亜黄疸群,無黄疸群に分けて検討した.自覚症状として発熱,全身倦怠,食思不振がかなり高率にまた,悪心,嘔吐,腹痛もみられた.肝腫大は72%にみられ,何れも黄疸群に著明であった.白血球減少は67%にみられ,19%に異型リンパ球がみられた.TTT, IgMの上昇は61, 71%の高率にみられALP, LAP,γ-GTPは,それぞれ75%, 100%, 87%にみられた.S-GPTの著増した群にγ-GTPの上昇が多くみられた.S-GPTは急激に高値を呈したが,1,000U以上のものは黄疸例に多くみられた.血中アンモニアは全例が上昇しHPT, TTの異常は黄疸例に多くみられた.