Biomedical subjects

N Miyakoshi

Publications and source records attributed to N Miyakoshi.

At least 37 records · Page 2Linked to original sources

PubMed2000

Development and evaluation of C-telopeptide enzyme-linked immunoassay for measurement of bone resorption in mouse serum.

The mouse is increasingly being used as an animal model for the study of skeletal phenotypes in humans, mainly because of the ease of genetic manipulation. Biochemical markers of bone metabolism provide a valuable parameter for the assessment of skeletal metabolism. In the mouse model, assays for bone formation have been available for a long time; however, little is known about bone resorption markers. The present study describes the development of a serum C-telopeptide enzyme-linked immunoassay (ELISA), which measures degradation products of type I collagen that are generated by osteoclastic bone resorption. The C-telopeptide ELISA uses affinity-purified antibodies generated against human sequence DFSFLPQPPQEKAHDGGR. The epitope involves an amino acid sequence, which is identical in the mouse and human C-terminal peptide of type I collagen (alpha1 chain). Sensitivity of the ELISA used was <0.1 ng/mL. The average intra- (n = 10) and interassay (n = 8) coefficient of variation for two controls was <12%. The average dilution and spike recovery rates were 98% and 97%, respectively. Application of the ELISA to measure C-telopeptide in 3-4-week postovariectomized (ovx) C57BL/6J (B6) mice (n = 9 or 10) showed a 45% higher C-telopeptide concentration than the sham-operated mice. Treatment of ovx mice with estradiol (400 microg/kg body weight) or alendronate (1.0 mg/kg body weight) resulted in a 20%-50% decrease in C-telopeptide levels compared to the vehicle-treated ovx group. In addition, B6 mice fed a calcium-deficient diet (0.01% calcium) showed a 50% higher C-telopeptide concentration compared to the B6 mice receiving a normal diet (0.6% calcium). In conclusion, the C-telopeptide ELISA exhibited acceptable analytical performance and sufficient discriminatory power to show expected directional changes in the rate of bone resorption following ovariectomy, ovx plus estradiol or alendronate treatment, and administration of a calcium-deficient diet. Therefore, the ELISA developed in this study could be used for measuring bone resorption in the mouse model.

Alendronate↗

PubMed1999

Anterior decompression with single segmental spinal interbody fusion for lumbar burst fracture.

STUDY DESIGN: The clinical and radiologic records for seven patients with lumbar burst fracture who underwent anterior decompression with single segmental interbody fusion were reviewed. OBJECTIVE: To determine the clinical results obtained with this method and its influence on the intervertebral disc degeneration inferior to the fusion. SUMMARY OF BACKGROUND DATA: Some patients with Denis' type B fracture can tolerate one-segment anterior fusion. However, there is no reliable information in the literature regarding the juxtafusional disc degeneration after one-segment fusion. METHODS: Seven patients with type B lumbar burst fractures, including four with cleavage fracture of the lower endplate, underwent anterior single segmental fusion; three patients underwent surgery with no instrumentation, and four underwent surgery with Kaneda instrumentation. The mean follow-up period lasted 85 months. The kyphosis angle and inferior intervertebral disc height adjacent to the fusion were measured before and after surgery. Pain and working status were evaluated using the scales proposed by Denis et al. RESULTS: Significant correction loss was obtained 1 year after surgery in the patients in whom no instrumentation was used (7.3 +/- 0.6 degrees), compared with the correction loss in patients whose surgery included the use of instrumentation (0.3 +/- 0.5 degree; P = 0.00001). No further correction losses were seen in either group at the final follow-up examination. No marked reduction in disc height was observed in any patient, including the four patients with cleavage fracture of the lower endplate. All patients returned to their previous occupation; five patients were rated as P1 (no pain) and W1 (returned to heavy labor), and two patients were rated as P2 (minimal pain) and W2 (return to heavy labor with lifting restrictions) at the final follow-up examination. CONCLUSIONS: There was slight correction loss within 1 year when no instrumentation was used, but this deformity did not affect the clinical results. The results provided no evidence that cleavage fracture of the lower endplate accelerates degeneration of the adjacent intervertebral disc.

Adolescent↗

PubMed1999

Histomorphometric evaluation of the effects of ovariectomy on bone turnover in rat caudal vertebrae.

The purpose of this study was to learn whether caudal vertebrae can be used to evaluate the effects of ovariectomy (OVX) in rats. Seven-month-old female Wistar rats were divided into two groups: the OVX group and the untreated control group. All rats were killed at 8 weeks and their 4th lumbar (L4), 1st caudal (C1), 3rd caudal (C3), and 5th caudal (C5) vertebrae were processed undecalcified and sectioned with Villanueva bone stain for quantitative bone histomorphometry. Both length of vertebral bodies and the cancellous tissue area in C1 were similar in size to L4 but significantly bigger than C3 and C5. Within the groups, cancellous bone volume (BV/TV) and trabecular thickness in both groups gradually increased in caudal vertebrae in relation to the distal direction. Between the groups, OVX rats exhibited a significantly lower BV/TV relative to control rats at L4 and C1, however, no significant difference were seen at C3 and C5. Bone formation-related parameters such as osteoid and mineralizing surface, and eroded surface were higher in the OVX group than in the control group in caudal as well as in lumbar vertebrae. By quantitative analysis of bone marrow composition, yellow marrow volume in C3 and C5 was significantly higher than that in L4 and C1, in both groups. Our results suggest that C1 is similar to L4 in size, bone turnover, and bone marrow composition. However, further experiments are needed to evaluate the possibility that C1 vertebra could be used as an alternative site for histomorphometric evaluation of bone changes in OVX rats.

Animals↗

PubMed1999

Trabecular remodeling processes in the ovariectomized rat: modified node-strut analysis.

The purpose of this study was to evaluate the trabecular bone remodeling processes in ovariectomized rats, focusing on diminishing trabecular connectivity. We used modified node-strut analysis defining three areas in the trabecular surfaces for the three-dimensional understanding of trabecular resorption derived from two-dimensional conventional sections, in addition to conventional bone histomorphometry and node-strut analysis. Seven-month-old female Wistar rats were used and treated with bilateral ovariectomy (ovx) and sham operation. Six rats in each group were examined at 4 and 8 weeks. We prepared undecalcified sections from the left tibiae with Villanueva bone and Goldner stains. We divided the trabecular bone surfaces (BS) into three areas: node (Nd), terminus (Tm), and strut (St), and measured the bone resorption and formation parameters, including eroded surface (ES), osteoclast surface (Oc.S), osteoid surface (OS), and double-labeled surface (dLS) in each defined area. In conventional bone histomorphometry, the ovx group showed high turnover osteopenia compared with the sham operation group. In node-strut analysis, the ovx group showed significantly lower values for node-related parameters than did the sham operation group. In the modified node-strut analysis, bone resorption parameters in the ovx group showed significantly higher values, particularly for strut and terminus-eroded surfaces (StES/BS, TmES/BS), and for each area of osteoclast surface (NdOc.S/BS, TmOc.S/BS, and StOc.S/BS) compared with the sham operation group. Bone formation parameters in the ovx group also showed significantly higher values, particularly for strut and terminus osteoid surfaces (TmOS/BS, StOS/BS), and for each area of double-labeled surface (NddLS/BS, TmdLS/BS, and StdLS/BS) compared with the sham operation group at 4 weeks. At 8 weeks, each area of bone formation parameter in the ovx group showed significantly higher values than that in the sham operation group. These results suggest that in the ovx group, the trabecular plates became perforated and the perforative cavities progressively enlarged, and/or the edges of plates were eroded regardless of elevated bone formation, resulting in diminished trabecular connectivity, and the node area might not be influenced relatively by bone remodeling in the early resorption.

Animals↗

PubMed1999

Effects of recombinant insulin-like growth factor-binding protein-4 on bone formation parameters in mice.

Insulin-like growth factor (IGF)-binding protein-4 (IGFBP-4), one of the most abundant IGFBPs produced by bone cells, is a potent inhibitor of IGF actions in vitro. To evaluate the modulation of IGF actions on bone formation in vivo by IGFBP-4, we produced intact and fragment (50- to 100-fold reduced IGF affinity) forms of BP-4 and examined their local and systemic effects using biochemical markers. Local administration of IGF-I over the right parietal bone significantly increased bone extract alkaline phosphatase activity; this was completely blocked by an equimolar dose of intact IGFBP-4, but not IGFBP-4 fragment. A single sc administration of IGF-I (2 microg/g BW) significantly increased bone formation markers in both serum and skeletal extracts; surprisingly, so did intact IGFBP-4, but not fragment IGFBP-4. Subcutaneous administration of an equimolar dose of IGFBP-4 along with IGF-I did not significantly block the IGF-I effect. Administration of intact IGFBP-4 significantly increased the serum 50-kDa IGF pool and decreased the 150-kDa IGF pool without significantly changing total IGF-I. We postulate that the increase in the 50-kDa IGF pool might enhance IGFs bioavailability via a mechanism involving IGFBP-4-specific protease. This study demonstrates for the first time that a single local administration of IGFBP-4 inhibits IGF-I-induced increases in bone formation, whereas systemic administration of IGFBP-4 alone increases serum levels of bone formation markers.

Alkaline Phosphatase↗

PubMed1996

Spinal subdural hematoma.

We report the case of a 68-year-old patient with a traumatic spinal subdural hematoma. MRI demonstrated an area of abnormal intensity and a black line in the inner part of the intradural space. We anticipate that MRI will help to make one more confident in the preoperative diagnosis of spinal subdural hematoma. The symptoms completely disappeared immediately after the operation. Spinal subdural hematoma requires immediate surgical evacuation. The prognosis for functional recovery is good if the condition is appropriately diagnosed and treated before development of irreversible paralysis. We recommend MRI to make an early diagnosis and early evacuation of spinal subdural hematoma.

Aged↗

PubMed1994

Case report 858: Postradiation osteosarcoma of the patella.

A case of postradiation osteosarcoma of the patella in a 54-year-old man was presented. The lesion in the patella was diffuse and highly sclerotic, and was partially radiolucent in radiographs. The whole patella was removed by Miyakawa's method. Diagnostic criteria, clinical features, and radiographic findings of postradiation sarcoma were described. The rarity of osteosarcoma of the patella was emphasized.

Bone Neoplasms↗

PubMed1989

Preliminary dose finding study for subacute toxicological study of pravastatin sodium in monkeys.

Pravastatin sodium was orally administered to cynomolgus monkeys at dosage levels of 50, 200 and 800 mg/kg/day for 7 successive days. Excretion of diarrhea and/or loose stool were observed in the more than 50 mg/kg dose group, but the changes are quite mild. Animals of the 800 mg/kg dose group showed vomiting, diarrhea and/or excretion of soft stool and reduction of cholesterol content in serum. In conclusion, it is estimated that the no effective level is less than 200 mg/kg because no abnormalities were observed except for only very slight excretions of diarrhea and/or loose stool, and that the effective dose is 800 mg/kg in which vomiting was observed.

Administration, Oral↗

PubMed1989

Subacute toxicological study in monkeys treated orally with pravastatin sodium for 5 weeks.

Pravastatin sodium was administered orally to cynomolgus monkeys at dosage levels of 50, 100, 200 and 400 mg/kg/day for 5 successive weeks. Five animals of 200 mg/kg and 400 mg/kg dose groups were sacrificed during the study period, because these animals deteriorated in general condition and/or showed remarkable changes in serum biochemical examination. Pathological examination revealed hepatic and/or renal disturbance in these animals. These changes are thought to be the cause of deterioration of general condition or changes in serum biochemical examination. All other animals were terminated at the end of the study period. In the animals of the 100 mg/kg dose group, only one animal showed hepatic and renal disorder similar in nature to the changes in the animals sacrificed during the study period. No animals in the 50 mg/kg dose group showed toxic findings in any examination.

Administration, Oral↗

PubMed1989

Long term oral administration study of pravastatin sodium to beagles for 104 weeks.

Pravastatin sodium was successively given for 104 weeks to beagles orally at doses of 5 and 25 mg/kg/day. A decrease in serum cholesterol levels was observed at week 4 and thereafter. No other abnormal findings were obtained in any animals in general conditions, hematological and biochemical examination, various function tests, and pathological examinations. The no-effect dose level in beagles receiving pravastatin sodium orally for 104 weeks is toxicologically estimated to be more than 25 mg/kg/day.

Animals↗

PubMed1980

Autoradiographic studies on distribution of L-3,4-dihydroxyphenylalanine (L-DOPA)-14C and L-5-hydroxytryptophan (L-5-HTP)-14C in the cat brain.

The distribution and metabolism of L-DOPA-14C and L-5-HTP-14C in the cat brain were examined by means of autoradiography and chromatography. The results revealed that an appreciable amount of radioactivity in the gray matter, but not the white, and that the localization of radioactivity of L-DOPA and L-5-HTP significantly differed. After L-DOPA-14C administration, a high accumulation was found in the caudate nucleus, putamen and pallidum. With L-5-HTP-14C administration, high radioactivity was observed in the hypothalamus, raphe nucleus, substantia nigra, inferior olivalis and caudate nucleus. An analysis of the main metabolites of both amino acids in various regions of the brain was also made. When L-DOPA was given, a high concentration of dopamine was detected in the caudate nucleus, followed by the hypothalamus. In the case of L-5-HTP, a high concentration of serotonin was detected in the hypothalamus and the medulla oblongata. These results suggest that amines derived from exogenously administered L-DOPA and L-5-HTP accumulate in the brain regions known as the corresponding amine rich regions, under physiological conditions.

5-Hydroxytryptophan↗

PubMed1977