Biomedical subjects
Publications and source records attributed to Naoto Endo.
Intermittent administration of low dose PTH has strong anabolic effect on bone by enhancing bone formation, resulting in increase of mechanical strength. Although newly formed bone with less mineralization and increased cortical porosity induced by high bone turnover may have adverse effect on bone strength, PTH is expected to be a new drug for the treatment of osteoporosis.
Osteoporosis is characterized by fragile bone with decreased bone mass, resulting in fractures of vertebra, hip, distal radius and proximal humerus. Spinal deformities caused by multiple compression fractures and walking disability after hip fracture induce decreased QOL and limited ADL in elderly patients with osteoporosis. The goal of treatment for patients with osteoporosis is to improve ADL and QOL.
Preaxial polydactyly (PPD) is a common limb malformation in human. A number of polydactylous mouse mutants indicate that misexpression of Shh is a common requirement for generating extra digits. Here we identify a translocation breakpoint in a PPD patient and a transgenic insertion site in the polydactylous mouse mutant sasquatch (Ssq). The genetic lesions in both lie within the same respective intron of the LMBR1/Lmbr1 gene, which resides approximately 1 Mb away from Shh. Genetic analysis of Ssq reveals that the Lmbr1 gene is incidental to the phenotype and that the mutation directly interrupts a cis-acting regulator of Shh. This regulator is most likely the target for generating PPD mutations in human.
OBJECTIVE: To examine the effects of the lipid-lowering agent fenofibrate on experimental AA amyloidosis and on serum amyloid A (SAA) levels. METHODS: Fenofibrate was administered orally in a mouse model of amyloidosis, which is induced by injections of amyloid-enhancing factor and Freund's complete adjuvant. Fenofibrate was given for 3 weeks, including a 1-week course before induction of amyloidosis. Splenic amyloid deposits were evaluated histologically, and SAA levels were measured. RESULTS: Fenofibrate inhibited the formation of splenic amyloid deposits and suppressed the elevation of SAA levels. CONCLUSION; Fenofibrate inhibits experimental amyloidosis by reducing levels of the precursor SAA.
Prominent osteoconductive activity and the biodegradable nature of beta tricalcium phosphate (beta-TCP) for bone grafts in animal experiments has been reported. A new type of beta-TCP has been manufactured at extraordinarily high purity and has been available as potent bone grafting substitute for clinical use. The histological features of grafted beta-TCP in human bone have been analyzed. A 33-year-old female with a bone tumor of the proximal femur underwent curettage and beta-TCP graft under the diagnosis of probable benign fibrous dysplasia. Four weeks later, the proximal femur, including the grafted beta-TCP was resected because of the final diagnosis of the curettaged materials was osteosarcoma. The resected specimen revealed abundant direct new bone apposition on beta-TCP. There was no cartilaginous tissue or enchondral ossification. Bone formation was more prominent in the periphery of the grafted area than in the center. There was a considerable number of osteoclast-like giant cells surrounding the beta-TCP. This case illustrated that highly purified beta-TCP had prominent osteoconductive activity and biodegradable nature in human bone.
The growth plate is a specialized structure that is responsible for longitudinal bone growth (LGR). Growth plate organization is altered with loading in rats. Parathyroid hormone (PTH) is known to induce mitogenic effect on chondrocytes in vitro. Type I PTH/PTH related peptide (rP) receptor is expressed in growth plate cartilage in rats. We therefore investigated the effect of PTH administration on the organization and longitudinal growth rate of the growth plate in rats. We also investigated the effect of PTH on the changes induced by unloading in the organization and growth of the growth plate. Thirty 6-week-old and 30 15-week-old male Sprague-Dawley rats were randomly assigned to five groups (n = 6 per group), i.e., basal controls, control (i.e., normally loaded), PTH-treated control (i.e., PTH-treated under normal loading), unloaded, and PTH-treated under unloading. PTH-treated animals received human PTH (1-34) at a dose of 80 microg/kg per day five times per week for 3 weeks, for the duration of unloading. In young loaded rats treated with the systemic administration of PTH, growth plate thickness, chondrocyte number, and LGR were increased in the proximal tibiae compared with findings in young loaded rats without PTH administration. Hindlimb unloading induced a reduction in growth plate thickness, chondrocyte number, and LGR. In young rats, systemic administration of PTH partly prevented these changes induced by unloading. These preventive effects of PTH were observed only in young rats; not in adult rats. These results show that the systemic administration of PTH stimulates longitudinal bone growth, and diminishes the reduction in growth plate growth induced by unloading in young rats.
The purpose of this study was to determine the incidence of cervical and trochanteric fractures of the proximal femur in 1999 in Niigata Prefecture, Japan, and to compare this incidence with those previously reported in Niigata in 1985, 1987, 1989, and 1994. The authors visited all hospitals within Niigata Prefecture having an orthopedic department and reviewed the medical records and radiographs of all patients who sustained such fractures in 1999. The population of Niigata Prefecture was determined in 1999 to be 2 486 999 (1 208 195 males and 1 278 804 females). The population over 65 years of age was 515 290 (210 564 males and 304 726 females), representing 20.7% of the total population. In 1999, there were 1697 cervical or trochanteric fractures, in 400 males and 1297 females, with a male-to-female ratio of 1 : 3.2. The incidence of these fractures in persons over 65 years of age was 308.7 fractures per 100 000 per year. This incidence increased from 1985 to 1989 and from 1989 to 1994, but after that, the rate of increase in incidence from 1994 to 1999 slowed down slightly. This suggests that the prevention of fractures in the elderly population in Niigata Prefecture influenced the lower ratio.
It is important to assess QOL in the patients with osteoporosis. Osteoporosis results in fractures of vertebrae and hips, consequently inducing spinal deformity and limited walking ability. These indicate that osteoporosis decreased QOL. The goal of the treatment for osteoporosis is to improve bone fragility as well as to maintain QOL. QOL questionnaire could be widely used.
This study was undertaken to determine whether or not nitric oxide metabolites (NO(2)(-) plus NO(3)(-): NOx levels) in cerebrospinal fluid (CSF) would be predictors of treatment outcome in patients with degenerative lumbar diseases (DLD) including lumbar disc herniation (LDH) and lumbar spinal canal stenosis (LCS). The NOx levels in CSF were measured using an NO analyzer based on the Griess method. Six healthy volunteers and 18 patients with painless diseases were included in the control group. The pre- and postoperative NOx levels in 25 DLD patients, who underwent herniotomy for LDH (17 patients) or selective decompression for LCS (eight patients), were analyzed. The postoperative follow-up periods were approximately 8 months. Nineteen of 25 DLD patients, whose preoperative NOx levels were two standard deviations higher than the mean NOx levels of an age-matched control group, were included in an NO elevated (NOE) group. Among the 25 DLD patients, the preoperative NOx levels in six patients (young LDH group) were within the normal range. The pain-related Japanese Orthopaedic Association score and the Hirabayashi recovery rate were respectively used to evaluate the pain severity and the degree of pain relief. The preoperative and changes of postoperative NOx levels in the NOE group were negatively correlated with the Hirabayashi recovery rate. Normal postoperative NOx levels and excellent pain relief were achieved in young DLD patients. In conclusion, the preoperative and changes in postoperative NOx levels are quantitative predictors of postoperative pain relief in DLD patients.
BACKGROUND: Activating Gs a mutations have been identified in most instances of fibrous dysplasia (FD). This mutation leads to consistently elevated intracellular cyclic adenosine monophosphate (cAMP) levels, with various biological consequences. The development of secondary sarcoma in FD is a rare but well-established phenomenon. This finding raised the possibility that a common gene mutation exists in these tumors. MATERIALS AND METHODS: The expression of the Gs a mutation was examined in 16 cell lines and 173 musculoskeletal tumor tissues, including 13 cases of FD, via RT-PCR and sequence analysis. RESULTS: No expression of a Gs a mutation was detected in any cell line or clinical tissue sample, excluding FD tissues. Direct sequence analysis demonstrated results identical to those of RT-PCR. CONCLUSION: Activating Gs a mutation rarely occurs in musculoskeletal tumors other than FD. The occurrence of most sarcomas displays no correlation with Gs a mutations.