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Biomedical subjects

H Norimatsu

Publications and source records attributed to H Norimatsu.

At least 37 records · Page 2Linked to original sources

Enhanced expression of catalytic subunit isoform PP1 gamma 1 of protein phosphatase type 1 associated with malignancy of osteogenic tumor.

The expressions of the three catalytic subunits of protein phosphatase (PP) type 1 and 2A, PP1 alpha, PP1 gamma 1, and PP2AC, were examined in 14 cases of three types of osteogenic tumor using immunohistochemical analysis. The percentage of tumor cells stained positively with antiserum against PP1 catalytic subunit-isoform PP1 gamma 1 was significantly higher in malignant osteogenic tumors than in benign osteogenic tumors. Furthermore, malignant osteogenic tumor showed markedly high S-phase fraction in the cell cycle of tumor cells, as compared to benign osteogenic tumors. These results suggest that PP1 gamma 1 is involved in the accelerated growth of malignant cells in osteogenic tumors.

Adolescent↗

A histomorphometric study on effects of single and concurrent intermittent administration of human PTH (1-34) and bisphosphonate cimadronate on tibial metaphysis in ovariectomized rats.

This study compared the single administration of hPTH(1-34), bisphosphonate cimadronate (YM-175), and concurrent therapy of these two for restoration of lost bone mass in ovariectomized (OVX) rats. Animals were untreated for 4 weeks after surgery, and then injected s.c. with vehicle (OVX+V), hPTH(1-34) (30 micrograms/kg) (OVX+P), YM-175 (5 micrograms/kg) (OVX+Y), or a combination of these two (OVX+P+Y), 3 days a week, for 8 weeks, and sacrificed. Their proximal tibia were processed undecalcified for quantitative bone histomorphometry. Although OVX+Y showed a reduction of bone turnover compared to OVX+V, it failed to restore lost bone mass in OVX rats. In contrast, OVX+P exhibited a stimulation of bone formation and restored cancellous osteopenia due to OVX. OVX+P+Y also resulted a recovery of osteopenia, however, stimulation of bone formation by PTH was suppressed by YM-175.

Animals↗

Enhanced expression of catalytic subunits of protein phosphatase type 1 and high S-phase fraction in liposarcoma.

The expression of the three catalytic subunits of protein phosphatase (PP) type 1 and 2A, PP1 alpha, PP1 gamma 1, and PP2AC, was examined in 8 cases of lipoma as a benign tumor and 4 cases of liposarcoma as a malignant tumor using immunohistochemical analysis. Both types of of tumor cells stained positively with antisera against PP1 catalytic subunit isoforms PP1 alpha and PP1 gamma 1 were significantly higher in liposarcoma than in lipoma. Furthermore, liposarcoma showed a markedly high S-phase fraction in the cell cycle of tumor cells, as compared with lipoma. These results suggest that PP1 is involved in the accelerated growth of malignant cells in liposarcoma.

Adult↗

Enhanced expression of catalytic subunit isoform PP1 gamma 1 of protein phosphatase type 1 in malignant fibrous histiocytoma.

The expression of the three catalytic subunits of protein phosphatase (PP) type 1 and 2A, PP1 alpha, PP1 gamma 1, and PP2AC, was examined in malignant fibrous histiocytoma using immunohistochemical analysis. The percentage of cells stained positively with antiserum against PP1 catalytic subunit isoform PP1 gamma 1 was significantly higher in tumorous region than in non-tumorous region of malignant fibrous histiocytoma. Furthermore, tumorous region showed markedly high S-phase fraction in the cell cycle, as compared to non-tumorous region. These results suggest that PP1 gamma 1 is involved in the accelerated growth of tumor cells in malignant fibrous histiocytoma.

Adult↗

[Burst fracture: osteoporotic vertebral compression fracture associated with paraplegia].

It is rare that vertebral compression fracture of senile osteoporosis causes paraplegia. This article reviews 164 cases reported in Japan since 1974. These fractures were characterized as follows: 1) paraplegia occurred in elderly females (average 69.3 years old) with severe osteoporosis, 2) traumatic histories were revealed in 52%, 3) 91% of the fractures were classified into burst type, 4) location was in the thoracolumber region (80.5%), 5) average onset of paraplegia was 5.7 months after fracture. One hundred and twenty nine cases were surgically treated either by anterior vertebral fusion or by posterior instrumentation and 35 cases were conservatively treated. Surgical cases showed better recovery of walking ability than conservative cases.

Aged↗

[A pharmacokinetic study on high-dose methotrexate administration--the effects of volume changes of parenteral solutions on the elimination rate].

Methotrexate (MTX) serum concentrations were measured in 7 cases (2 patients) in which a high-dose administration of MTX with citrovorum factor rescue for osteogenic sarcoma were performed for repressing activity in the original lesion and satellite micrometastasis. In the pharmacokinetic analysis, the changes of MTX serum concentrations were explained by a 2-compartment open model under the assumption that the elimination rate was proportional to both of volume of parenteral solution and the amount of water intake. It was suggested that MTX serum concentration could be controlled by adjusting the volumes of parenteral solutions. MTX amount in the peripheral compartment was found about ten times larger than that in the central compartment after about 40 h of administration. It is considered that an early increase in the volumes of parenteral solutions is effective to keep the safety level of MTX serum concentration, and continuous infusion is important for avoiding the severe side effects caused by delayed elimination of MTX.

Bone Neoplasms↗

Roles of various growth factors in growth of human osteosarcoma cells which can grow in protein-free medium.

The human osteosarcoma cell line (OST-1-PF) can grow in protein-free Coon's modified Ham's F12 medium. Growth of the cells in protein-free medium was partially density-dependent and partially depressed by medium change. An extract and conditioned medium of OST-1-PF cells contained high mitogenic activity for BALB/c3T3 cells. The growth factor in the cells was purified and identified as a basic fibroblast growth factor (bFGF)--like factor on the basis of its elution profile on heparin-affinity chromatography and the result of immunoblotting. An unidentified factor in a conditioned medium eliciting most of the DNA synthesis-stimulating activity showed a weak affinity for heparin. Various additions, including serum and growth factors, stimulated the growth of OST-1-PF cells in protein-free medium. Of these factors, epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), acidic fibroblast growth factor (aFGF) and bFGF were the most potent mitogens. High-affinity receptors of EGF and FGF were found on the surface of these cells. These results indicate that autonomous growth of OST-1-PF cells in protein-free medium is mainly controlled by an intracellular mechanism.

Cell Division↗

A comparison of hip fracture incidence among native Japanese, Japanese Americans, and American Caucasians.

Hip fracture incidence rates among men and women of Japanese ancestry living on Oahu, Hawaii, from 1979 to 1981 were compared with rates for Japanese living on Okinawa, Japan, from 1984 to 1985. Both rates were further compared with those for various American Caucasian populations, including that of Rochester, Minnesota, from 1978 to 1982. Age-specific and cumulative (age 50-84 years) hip fracture rates among persons of Japanese ancestry were approximately half that of Caucasians for both sexes. Although diet and other cultural attributes of the Oahu group have become more westernized than the Okinawan population, there were no detectable differences in hip fracture rates between Oahu and Okinawa Japanese. Additional studies are needed to determine whether the observed differences in fracture rates between Caucasians and Japanese might be related to differences in bone mass, body size, frequency of falls, or other factors.

Adult↗

Bone mineral density of the spine and proximal femur in normal and osteoporotic subjects in Japan.

Bone mineral density (BMD) of the spine and proximal femur in Japanese men and women was investigated with dual photon absorptiometry, using gadolinium-153. Peak bone mass of the spine (L2-4) was 1.20 g/cm2 in women which was lower than that of men by 4.7%, whereas BMD of the femoral neck was 0.91 g/cm2 in women and lower than in men by 13.3%. Bone loss was faster in postmenopausal women than in men of the corresponding age, and the regressions of BMD on age were 6.7-times higher at L2-4 and 5.1-times higher at the femoral neck than in men. Such rates of loss became slower both in the lumbar spine and proximal femur in women after 70 years of age, but the density at the proximal femur kept decreasing in men after 70 years of age. Fracture thresholds of each region were evaluated at the 90th percentile for BMD of L2-4 in patients with vertebral crush fractures and for BMD of the proximal femur in patients with hip fractures. The fracture threshold was 0.97 g/cm2 at the spine and 0.67 g/cm2 at the femoral neck in women. BMD values at the spine and proximal femur in normal Japanese men and women appear to be lower than those in white American control population.

Adult↗

Changes in calcium phosphate on bone surfaces and in lining cells after the administration of parathyroid hormone or calcitonin.

Small doses of parathyroid hormone and calcitonin were injected into thyroparathyroidectomized newborn rats to investigate the histological and chemical changes in bone surfaces and in mitochondrial granules of bone lining cells. Nondecalcified tissue specimens were observed under transmission electron microscope, electron probe X-ray microanalyzer, and microdiffraction after "freeze substitution" preparation of tibia shafts. Amorphous calcium phosphate, which appears as clusters and globules by this "freeze substitution" preparation, appears on the bone surfaces in a short time after the administration of a small dose of calcitonin. The Ca:PO4 ratio in the mitochondria of bone lining cells rises slightly with a small dose of parathyroid hormone and is reduced with a small dose of calcitonin. These data support the postulate that both parathyroid hormone and calcitonin act directly on bone lining cells in the process of influencing calcium concentrations of blood and temporarily storing calcium at bone surfaces.

Animals↗

Evidence for an important physiological role for calcitonin.

We propose that calcitonin, secreted in response to the intake of food, aids in routing calcium, obtained by intestinal absorption, into bone fluid. Here calcium is temporarily stored in combination with phosphate for return to the extracellular fluid (blood) during intervals between oral intakes of calcium. The net result is a conservation of calcium postprandially and a decrease in parathyroid hormone-induced bone destruction during subsequent fasting periods. Evidence for this postulate is provided in the following six sequential steps from the time a calcium-containing meal is consumed until that portion of calcium stored in bone fluid is utilized during fasting periods to aid in plasma calcium maintenance. (i) Calcitonin secretion is stimulated by feeding and subsequent digestive processes. (ii) Postprandial secretion of calcitonin restricts the efflux of calcium from bone fluid to blood, thereby maintaining parathyroid hormone (PTH) secretion. (iii) In thyroid-intact individuals, both PTH and calcitonin are secreted postprandially and act in concert on calcium homeostasis. (iv) Calcitonin actively moves phosphate into bone and prevents its loss from bone fluid to blood. (v) Postprandial storage of calcium with phosphate occurs in bone fluid of thyroid-intact individuals. (vi) This labile storage form of calcium is the first to be utilized during fasting periods. In the absence of partial disruption of this storage mechanism, rapid development of pathological bone conditions would not be expected because PTH action permits the extended utilization of bone calcium for plasma calcium control. However, augmentation of osteopenic conditions could be expected if long-term low calcium intake were accompanied by a malfunction of this calcitonin-induced system for calcium storage.

Animals↗