Biomedical subjects

Tamio Nakajima

Publications and source records attributed to Tamio Nakajima.

11 recordsLinked to original sources

PubMed2006

Cardiac expression of placental growth factor predicts the improvement of chronic phase left ventricular function in patients with acute myocardial infarction.

OBJECTIVES: Our aim was to investigate cardiac expression of placental growth factor (PlGF) and its clinical significance in patients with acute myocardial infarction (AMI). BACKGROUND: Placental growth factor is known to stimulate wound healing by activating mononuclear cells and inducing angiogenesis. The clinical significance of PlGF in AMI is not yet known. METHODS: Fifty-five AMI patients and 43 control subjects participated in the study. Peripheral blood sampling was performed on days 1, 3, and 7 after AMI. Blood was also sampled from the coronary artery (CAos) and the coronary sinus (CS), before and after acute coronary recanalization. Cardiac expression of PlGF was analyzed in a mouse AMI model. RESULTS: In AMI patients, peripheral plasma PlGF levels on day 3 were significantly higher than in control subjects. Plasma PlGF levels just after recanalization were significantly higher in the CS than the CAos, which indicates cardiac production and release of PlGF. Peripheral plasma levels of PlGF on day 3 were negatively correlated with the acute phase left ventricular ejection fraction (LVEF), positively correlated with both acute phase peak peripheral monocyte counts and chronic phase changes in LVEF. Placental growth factor messenger ribonucleic acid expression was 26.6-fold greater in a mouse AMI model than in sham-operated mice, and PlGF was expressed mainly in endothelial cells within the infarct region. CONCLUSIONS: Placental growth factor is rapidly produced in infarct myocardium, especially by endothelial cells during the acute phase of myocardial infarction. Placental growth factor might be over-expressed to compensate the acute ischemic damage, and appears to then act to improve LVEF during the chronic phase.

Animals↗

PubMed2006

Inhibitory effect of efonidipine on aldosterone synthesis and secretion in human adrenocarcinoma (H295R) cells.

Targeting aldosterone synthesis and/or release represents a potentially useful approach to the prevention of cardiovascular disease. Aldosterone production is stimulated by angiotensin II (Ang II) or extracellular K+ and is mediated mainly by Ca2+ influx into adrenal glomerulosa cells through T-type calcium channels. We therefore examined the effects of efonidipine, a dual T-type/L-type Ca2+ channel blocker, on aldosterone secretion in the H295R human adrenocarcinoma cell line; 100 nmol/L Ang II and 10 mmol/L K+ respectively increased aldosterone secretion from H295R cells 12-fold and 9-fold over baseline. Efonidipine dose-dependently inhibited both Ang II- and K+-induced aldosterone secretion, and nifedipine, an L-type Ca2+ channel blocker, and mibefradil, a relatively selective T-type channel blocker, similarly inhibited Ang II- and K+-induced aldosterone secretion, but were much less potent than efonidipine. Efonidipine also lowered cortisol secretion most potently among these drugs. Notably, efonidipine and mibefradil also significantly suppressed Ang II- and K+-induced mRNA expression of 11-beta-hydroxylase and aldosterone synthase, which catalyze the final two steps in the aldosterone synthesis, whereas nifedipine reduced only K+-induced enzyme expression. These findings suggest that efonidipine acts via T-type Ca2+ channel blockade to significantly reduce aldosterone secretion, and that this effect is mediated, at least in part, by suppression of 11-beta-hydroxylase and aldosterone synthase expression.

Adrenal Gland Neoplasms↗

PubMed2006

Usefulness of 16-slice multislice spiral computed tomography for follow-up study of coronary stent implantation.

BACKGROUND: Although multislice spiral computed tomography (MSCT) is a promising technique for non-invasive coronary angiography, its usefulness in patients with stent implantation remains unclear. The aim of the present study was to compare the usefulness of MSCT with that of invasive coronary angiography for evaluating coronary stent patency. METHODS AND RESULTS: Thirty-one patients were enrolled after coronary stent implantation. Sixteen-slice MSCT scans were performed (39.0+/-21.8 days) before follow-up coronary angiography. After assigning an image score based on luminal visibility (1= poor, 2= fair, 3= good), factors determing image quality were analyzed. Among 42 implanted stents, 33 (78%) were assigned an image score of 3, 2 (5%) a score of 2, and 7 (17%) a score of 1. Image scores among stents with diameters >or=3.5 mm were significantly (p<0.05) higher than among smaller stents (<or=3.0 mm). Stent strut thickness did not affect image quality, but coronary calcification significantly (p<0.01) hampered the image quality. After excluding 7 stents with image scores of 1, the sensitivity, specificity, positive and negative predictive values of MSCT to identify patent stents were 83%, 90%, 63% and 96%, respectively. CONCLUSIONS: MSCT can provide useful and valuable clinical information for assessing stent patency during the follow-up period when patients are treated with relatively large diameter coronary stents.

Aged↗

PubMed2006

Blocking T-type Ca2+ channels with efonidipine decreased plasma aldosterone concentration in healthy volunteers.

Efonidipine can block both L- and T- type Ca2+ channels. In a previous in vitro study, we clarified that efonidipine dramatically suppresses aldosterone secretion from human adrenocortical tumor cells during angiotensin II (Ang II)- and K+-stimulation, whereas nifedipine, a dominant L-type Ca2+ channel antagonist, does not. This study was conducted to assess the in vivo effects of efonidipine and nilvadipine on the plasma aldosterone concentration. Placebo, 40 mg of efonidipine, or 2 mg of nilvadipine was administered to five healthy male volunteers. Hemodynamic parameters (pulse rate [PR] and blood pressure [BP]), plasma concentrations of neurohormonal factors (plasma renin activity, Ang II, aldosterone, and adrenocorticotropic hormone [ACTH]), and serum concentrations of Na+ and K+ were measured before and 6 h after administration of the agents. All three agents had little effect on PR and BP. Efonidipine and nilvadipine significantly increased plasma renin activity and Ang II. Both had little effect on ACTH, Na+, and K+. The plasma aldosterone concentration was significantly decreased after efonidipine treatment (88.3 +/- 21.3 to 81.6 +/- 24.9 pg/ml, p = 0.0407), whereas it was significantly increased after nilvadipine treatment (66.5 +/- 12.2 to 82.17 +/- 16.6 pg/ml, p = 0.0049). Placebo had little effect on neurohormonal factors. Efonidipine decreased plasma aldosterone concentration despite the increase in plasma renin activity and Ang II, suggesting that T-type Ca2+ channels may also play an essential role in the secretion of aldosterone in healthy human volunteers.

Adrenocorticotropic Hormone↗

PubMed2005

Histological observations on the microenvironment of osteolytic bone metastasis by breast carcinoma cell line.

Bone tissue, with its dynamic microenvironment featuring osteoclastic bone resorption, angiogenesis and matrix degradation, appears to facilitate proliferation of tumor cells after the onset of bone metastasis. In this study, we examined metastatic lesions in the femora of BALB/c nu/nu mice two weeks after intracardiac injection with human breast carcinoma MDA-231 cells. Histopathological observations showed the metastatic lesions close to the chondro-osseous junction, and revealed MDA-231 cells loosely intermingled with different cell types such as osteoblasts, fibroblastic stromal cells, osteoclasts and endothelial cells. In the metastatic nest, many tartrate resistant acid phosphatase (TRAPase)-positive osteoclasts accumulated in direct contact with or were close to alkaline phosphatase (ALPase)- or receptor activator of NF-kappaB ligand (RANKL)-positive osteoblastic cells. It seems likely that osteoclastogenesis is mediated through cell-to-cell contacts with ALPase- and RANKL-expressing osteoblastic cells. Formation of many capillaries lacking complete basal membranes and pericytes ratified the results of in situ hybridization, which revealed intense expression of VEGF in tumor nests, and therefore, indicated ongoing tumor-induced angiogenesis. The tumor cells possessed matrix metallo-proteinases (MMPs)-1 and -9, and frequently extended their stout cytoplasmic processes into fragmented fibrillar components of the growth plate cartilage, implicating degradation of cartilaginous matrix. Thus, osteolytic bone metastasis has demonstrated pathological features as tumor-induced angiogenesis and degradation of extracellular matrix, in addition to osteoclastogenesis. This complex interplay between tumor cells and host tissues may enable and nourish the establishment of a microenvironment that facilitates tumor progression.

Animals↗

PubMed2004

Periodontal regeneration of transplanted rat molars after cryopreservation.

The effects of cryopreservation on periodontal regeneration of transplanted rat molars were investigated histologically and histochemically in rats. Bilateral first and second maxillary molars of 4-week-old Wistar rats were gently extracted and transplanted into the abdominal subcutaneous connective tissue immediately or after cryopreservation in liquid nitrogen overnight. Donor teeth were slowly frozen by a rate-controlling freezer (program freezer) using 5% dimethylsulfoxide (DMSO) and 6% hydroxyethyl starch (HES) as cryoprotectants. One-four weeks after transplantation, they were carefully excised with the surrounding tissues. Regeneration of acellular cementum, periodontal ligament, and alveolar bone were observed 2 weeks after immediate transplantation. The pulp was repaired by the ingrowth of granulation tissue from the root apex followed by the formation of calcified tissue. The regenerated periodontal ligament was positive for alkaline phosphatase (ALP). Small or mononuclear tartrate resistant acid phosphatase (TRAP) positive cells were scattered on the newly formed alveolar bone and on the hard tissue in the pulp, but there was no external or internal progressive root resorption at 4 weeks. Cryopreserved teeth had acellular cementum with a rough surface at 1 week, but with the increase of cementoblasts and the appearance of periodontal ligament and alveolar bone, the surface became smooth at 3 weeks. Epithelial rests of Malassez (ERM) also revived. After regeneration of the periodontal tissues at 4 weeks, there was no evidence of root resorption. Although the process proceeded slowly, the cryopreserved teeth showed the periodontal regeneration substantially similar to that of the immediately transplanted teeth without progressive root resorption, indicating that they could be applicable for clinical use.

Alkaline Phosphatase↗

PubMed2003

Ultrastructural and cytobiological studies on possible interactions between PTHrP-secreting tumor cells, stromal cells, and bone cells.

Parathyroid hormone-related peptide (PTHrP) induces pathological bone resorption in an endocrine manner, resulting in hypercalcemia of malignancy. However, the histopathological aspect of the action of PTHrP secreted by tumor cells on bone resorption has not well been documented. Therefore, we studied cell-cell interactions between bone cells, stromal cells, and PTHrP-secreting tumor cells (EC-GI-10) morphologically. Tumor cells injected subcutaneously into the parietal region formed a tumor mass, invading the bone marrow. The tumor mass was surrounded by a membrane structure consisting of stromal cells. These stromal cells were positive for alkaline phosphatase (ALPase). Tartrate-resistant acid phosphatase (TRAPase)-positive osteoclasts were localized close to the ALPase-positive cells, and numerous osteoclasts were observed on the neighboring bone surfaces. PTHrP, vascular endothelial growth factor (VEGF), and matrix metalloproteinase (MMP)-9 were detected in the tumor cells. Using RT-PCR, expression of interleukin (IL)-1Alpha, IL-1Beta, and PTHrP, which are strong bone resorption factors, was detected in the tumor cells. Some ALPase-positive cells localizing on the neighboring bone surfaces and endothelial cells revealed PTH/PTHrP receptor immunoreactivity. Ultrastructurally, numerous blood vessels were observed between the tumor nests and the stromal cells. The nests were surrounded by a basement membrane, but it was discontinuous, therefore permitting direct contact between the tumor cells and the stromal cells. These results indicate that PTHrP secreted by tumor cells appears to stimulate osteoclast differentiation and bone resorption in a paracrine manner through PTH/PTHrP receptor-immunopositive cells. IL-1Alpha, IL-1Beta, VEGF, and MMP-9 may also be involved in facilitating osteoclast formation and the subsequent bone resorption.

Animals↗

PubMed2003

Osteoclast differentiation in ectopic bone formation induced by recombinant human bone morphogenetic protein 2 (rhBMP-2).

Osteoclast differentiation in the process of ectopic bone formation induced by recombinant human bone morphogenetic protein 2 (rhBMP-2) was examined to clarify the relationship between osteoclast development and rhBMP-2-induced bone formation. A combination of rhBMP-2 with a porous microsphere (PMS) and blood clot was implanted subcutaneously on the bilateral chest muscles of rats. Tartrate-resistant acid phosphatase (TRAPase) activity, cathepsin K (cath K), and calcitonin receptor (CTR), as markers of osteoclasts and their precursors, were examined using enzyme and immunohistochemical analysis up to 7 days after implantation. Mononuclear cells positive for TRAPase, cath K, and CTR first appeared on day 3 in connective tissue surrounding the PMS after implantation of rhBMP-2. Simultaneously, alkaline phosphatase activity became detectable in mesenchymal cells in the connective tissue. Electron microscopy demonstrated some mononuclear cells with abundant mitochondria and poorly developed rough endoplasmic reticulum in the proximity of mesenchymal cells. However, there was no evidence of cartilage or bone matrix formation on day 3. Osteoclasts in various stages of development, classified by the pattern of immunoreactivity for cath K, were observed by day 7. The polarized intracellular distribution of cath K was found only in osteoclasts attached to bone matrix. In conclusion, we have demonstrated for the first time the appearance of osteoclast precursors before bone matrix formation induced by rhBMP-2, suggesting that bone matrix is not a prerequisite for osteoclast precursor recruitment. Furthermore, we suggest that differentiation into polarized functional osteoclasts is accomplished when the osteoclasts attach to the bone matrix.

Animals↗

PubMed2003

Bisphosphonate incadronate inhibits maturation of ectopic bone induced by recombinant human bone morphogenetic protein 2.

To determine the effects of a bisphosphonate on the quality of bone morphogenetic protein-(BMP-) induced bone, incadronate was administered to rats in which subcutaneous ectopic bones were induced by recombinant human BMP-2. Incadronate (1 microg/kg/day) was administered to rats carrying the BMP-induced bones three times per week, from the 3rd to 7th week after BMP implantation (incadronate group). Aliquots of phosphate-buffered saline were administered in the same protocol without incadronate to the control group. During the 3rd, 4th, 7th, or 10th week, the BMP-induced bones were removed and observed by contact microradiography (CMR), H&E staining, enzyme histochemistry for tartrate-resistant acid phosphatase (TRAP), and immunohistochemistry for cathepsin K. By 3 weeks when administration of incadronate began, woven bones formed in the periphery of the BMP pellets and osteoclasts were attached to these bones. At 4 weeks, in both the incadronate and control groups, bone formation advanced inward. However, in the incadronate group, poorly calcified areas, corresponding to the remaining BMP pellets, were found in the middle areas of bone formation, whereas osteoclasts decreased when compared with those of the control group. During the 10 weeks, bone marrow was formed and the characteristics of lamellar bones, in which the lacunae of small osteocytes were regularly arranged, were noted in the control group. In contrast, the poorly calcified areas were still present up to 10 weeks in incadronate group in which the osteoclasts were also scarcer than in the control group. These findings suggested that osteoclast-mediated bone resorption was inhibited by incadronate administration, and that immature bones including the BMP pellets remained for a long time, indicating that the process of bone maturation was blocked. The possibility of using incadronate for the purpose of inhibiting osteoclastic bone resorption was confirmed, but further study is needed before clinical application.

Acid Phosphatase↗

PubMed2003

Jaw bone remodeling at the invasion front of gingival squamous cell carcinomas.

BACKGROUND: It is still unknown how jaw bone remodeling occurs at actual invasion sites of oral squamous cell carcinomas. Since there is no other human carcinomas which make a direct invasion of the bone, gingival carcinomas are valuable examples. METHODS: Twelve surgical specimens of gingival squamous cell carcinoma were examined histopathologically and immunohistochemically for remodeling of bone and its surrounding tissue. RESULTS: Three types of bone interfaces with carcinomatous invasion were distinguished. These included areas with bone resorption, smooth bone surface and new bone formation. In the bone-resorption area, numerous osteoclasts were located along the bone surface, which was surrounded by myxoid stroma. The myxoid stroma was characterized by immunopositivity for heparan sulfate proteoglycan (HSPG), abundant vascularity and macrophagic infiltration. In the bone-formation area, rows of osteoblasts were aligned on the bone surface. The stroma around osteoblasts was also HSPG-immunopositive, poor in vascularity but rich in activated fibroblasts. In the smooth-bone area, the stroma showed an organizing phase of granulation tissue with slender fibroblasts and mature collagen fibers but with less vascularity and inflammatory infiltrates. CONCLUSION: The results indicate that the stromal architecture, especially in terms of its inflammatory cellular, vascular and matrix compositions, is strictly regulated in the timing and site of jaw bone remodeling which is causes by carcinomatous invasion.

Antigens, CD↗

PubMed2002

Squamous cell carcinomas of the mandibular alveolus: analysis of prognostic factors.

BACKGROUND: To assess the effect of clinicopathologic factors on local tumor control and survival in patients with mandibular alveolar carcinoma. METHODS: Fifty patients with mandibular alveolar carcinoma treated surgically were included in this study. There were 3 patients with T1, 25 with T2, 5 with T3, and 17 with T4 disease. Clinical evidence of bone invasion was noted in 47 patients. A hemi- or segmental mandibulectomy was performed on 37 patients, whereas 10 patients had a marginal mandibulectomy. The impact of clinicopathologic variables on local tumor control and patient survival was assessed by univariate analysis. Variables included T and N stage, dental extraction, treatment modality, tumor differentiation, nodal status, surgical margin, and bone invasion. RESULTS: Eleven patients (22%) develop recurrent disease, including 8 local recurrences, 1 neck, and 2 distant metastases. Overall, the 5-year actuarial rates of local control and disease-specific survival were 85 and 73%, respectively. Most local recurrences after surgical treatment were caused by inadequate resection margins. When resection margins were negative, the survival and local control rate were significantly better than when there were positive resection margins (survival, 91 vs. 11%; local control, 100 vs. 49%; p < 0.01). Neither T and N stages, clinical stage, tumor differentiation, dental extraction, bone invasion, extent of bone resection, nor treatment modality influenced outcome. CONCLUSIONS: The status of surgical margins was of major importance for the outcome of patients with gingival carcinoma of the mandible.

Adult↗