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Biomedical subjects

A Yamaguchi

Publications and source records attributed to A Yamaguchi.

At least 145 records · Page 8Linked to original sources

Using the spleen for time-delay correction of the input function in measuring hepatic blood flow with oxygen-15 water by dynamic PET.

By the spleen, we calculated a time-delay correction of the input function for quantitation of hepatic blood flow with oxygen-15 water and dynamic positron emission tomography. The time delay (deltat) between the sample site and the spleen was calculated based on nonlinear multiple regression analysis when splenic blood flow was determined. Then hepatic blood flow was quantified by a method using the input function and incorporating deltat, which was assumed to be equal to the time delay between the sample site and the liver. Then hepatic arterial and portal blood flows were estimated separately as well as the delay time for passage within the organs of the portal circulation. The mean coefficient of variation and the mean sum of squares of errors decreased to about 70% when total hepatic blood flow was calculated from the results for regions of interest in three slices of the same liver segment. We concluded that using the spleen for time-delay correction of the input function for measuring hepatic blood flow by this method gave satisfactory results.

Adult↗

Thirty-six cases of obturator hernia: does computed tomography contribute to postoperative outcome?

Obturator hernia is relatively rare and occurs mostly in elderly, thin, multiparous women. Recent reports have highlighted the importance of pelvic computed tomography (CT) for the preoperative diagnosis. Thirty-six patients with an obturator hernia operated in our hospital were divided retrospectively into two groups (group A: 18 operations from 1973 to 1986, before we used CT; group B: 18 CT cases from 1987 to 1995). Preoperative diagnoses, operative procedures, and postoperative course were reviewed. No statistically significant differences were found between groups A and B in terms of patient characteristics. Rates of accurate preoperative diagnoses were significantly higher in group B: 39% (7/18) in group A and 78% (14/18) in group B (p = 0.018). The intraoperative findings, occurrence of postoperative complications, and overall mortality rates were similar between the two groups. There were four postoperative deaths (mortality rate 11%). Three of four patients who died had panperitonitis because of small bowel perforation. The correct preoperative diagnosis of obturator hernia was facilitated by CT of the pelvis, but it has no impact on patient outcome. Early diagnosis and surgical intervention are essential for this rare entity.

Aged↗

Expression of bone matrix proteins, osteonectin and osteopontin, in salivary pleomorphic adenomas.

Osteonectin (OSN) is a glycoprotein involved in the early steps of the mineralization of skeletal tissue, while osteopontin (OPN) is a protein involved in normal and pathological calcifications. OSN and OPN are non-collageneous bone matrix proteins expressed by some epithelial tumor cells in exceptional cases. We immunohistochemically investigated the presence and the distribution of OSN and OPN in 43 pleomorphic adenomas to elucidate the production of their molecules by modified myoepithelial cells. In normal salivary glands, OSN was immunolocalized in the striated ducts, while OPN was not expressed. In pleomorphic adenomas, the inner layer of tubulo-glandular structures and modified myoepithelial cells in the myxoid areas showed moderate positivity for OSN (83.7%). OSN was expressed in all of the lacuna cells in the chondroid areas. OPN was strongly expressed in the stroma of the myxoid and hyaline areas of the pleomorphic adenomas (65.1%), but there was no expression of OPN in the chondroid area. All cases of pleomorphic adenomas expressed type IV collagen. These findings suggested that OSN was related to the production of the type IV collagen by modified myoepithelial cells, whereas OPN was involved in the stromal formation of myxoid or hyaline tissues in pleomorphic adenomas. In summary, pleomorphic adenomas expressed the bone matrix proteins OSN and OPN.

Adenoma, Pleomorphic↗

Clinical features and management of oral and maxillofacial tumors in children.

OBJECTIVE: To clarify the characteristics of oral and maxillofacial tumors in children, we carried out a clinical study of such tumors and reviewed the relevant procedures for treatment. Study design. Medical records of 105 patients less than 15 years of age who were treated for oral and maxillofacial tumors during the 20 years between 1976 and 1997 were retrieved and analyzed. RESULTS: Of the 105 cases, 102 (97.1%) involved tumors that were benign; only 3 patients (2.9%) had tumors that were malignant. With regard to benign soft tissue tumor, the most common type was hemangioma (25/69; 36.2%), the second most common type was papilloma (19/69; 27.5%), and the most common site was the tongue. With regard to bone tumor, the most common type was odontoma (14/33; 42.4%), the second most common type was ameloblastoma (11/33; 33.3%), and the most common site was the mandible. Most of the odontogenic tumors (25/28; 89.3%) developed in patients more than 6 years of age; these tumors may develop after dental crown formation. In each case of benign soft tissue tumor, resection was performed; 4 of these tumors (2 hemangiomas, 1 lymphangioma, and 1 papilloma) recurred, but after re-resection recurrence has not been found for more than 4 years. In the cases of benign jawbone tumor, resection and enucleation were the procedures principally performed; 3 ameloblastomas recurred after enucleation, but after relatively wide resection for these recurrent tumors there has been no recurrence for more than 17 years. With regard to the ameloblastomas, enucleation with preservation of the periosteum was effective and bone regeneration occurred rapidly. CONCLUSIONS: Most oral and maxillofacial tumors in children are benign. In any case of such benign tumor, including ameloblastoma, minimal surgical treatment should be the procedure of first choice.

Adolescent↗

Bone reactions to titanium screw implants in ovariectomized animals.

OBJECTIVE: The purpose of this study was to investigate the reactions of bone tissue after the placement of implants into the tibiae of osteopenic model rats. STUDY DESIGN: Commercially pure titanium screw implants were placed in the bilateral proximal tibial metaphyses 168 days after ovariectomy had been performed on 12-week-old female Wistar rats. For control purposes, implants were similarly placed in sham-ovariectomy rats. The healing process was examined histologically by means of undecalcified sections at various intervals from 7 to 168 days after implantation. Through use of an automated imaging analytic system, changes in relative bone mass and implant-bone contact were histomorphometrically evaluated. RESULTS: In the cortical bone area, only a slight difference in bone contact was noted with the implant until 28 days after implantation. However, ovariectomy significantly affected bone contact at 56 days after implantation. The rate of bone contact in the cancellous bone area and the relative bone mass around the implant were significantly lower in the test group than in the control group. CONCLUSIONS: It is considered that a decrease in bone mass causes a reduction in the contact area between implant and bone and may also cause a reduction in the supporting ability of the implant because of thinning of the surrounding bone tissue.

Animals↗

Bone reactions around hydroxyapatite-coated implants in ovariectomized rats.

OBJECTIVE: The purpose of this study was to investigate bone reaction after implantation in an estrogen-deficient state by examining the changes in bone reactions within tissue surrounding implants in ovariectomized rats. STUDY DESIGN: Ninety-six 12-week-old female Wistar rats were used in the study; they were divided into 2 groups, an ovariectomized group and a sham-operated group. Hydroxyapatite-coated implants were placed in the proximal metaphyses of the tibiae 21 days after surgery. The tibiae were examined histologically by undecalcified sections at various intervals from 7 to 168 days after surgery. RESULTS: In the cortical bone area of the ovariectomized rats, the procedure did not induce any apparent changes in bone volume around the implant or in bone contact with the implant in comparison with the sham-operated rats. In contrast, both bone volume around the implant and contact of the implant with new bone were significantly decreased in the cancellous bone area in the ovariectomized rats in comparison with the sham-operated rats. CONCLUSIONS: Ovariectomy did not seriously affect bone healing after the placement of implants in cortical bone areas, but it reduced the bone contact ratio and the bone in the cancellous bone area.

Acid Phosphatase↗

Effects of bone morphogenetic protein-2 and transforming growth factor-beta1 on gene expression of decorin and biglycan by cultured osteoblastic cells.

The influence of bone morphogenetic protein-2 (BMP-2) and transforming growth factor beta (TGF-beta) on the expression of small proteoglycans, decorin and biglycan was investigated in a clonal rat osteoblastic cell line, ROS-C26 (C26) cells, which is a potential osteoblast precursor cell line and capable of differentiating into mature osteoblasts after treatment with recombinant BMP-2 (rhBMP-2). Following the culture of C26 cells for 3, 6, and 9 days in the presence or absence of rhBMP-2, alkaline phosphatase activity increased in the rhBMP-2 treated cells in direct proportion to their differentiation into more mature osteoblastic cells, whereas decorin mRNA decreased in the cells, when compared to control cells without rhBMP-2 treatment. These results were evident 6 days after treatment. However, rhBMP-2 treatment had no effect on biglycan mRNA expression in the cells. Subsequently, after removal of rhBMP-2 from the culture media, the cells were further cultured for 24 h with graded concentrations of TGF-beta1 (0, 0.1, 1.0, 5.0, and 10 ng/ml). TGF-beta1 decreased decorin mRNA expression in the cells dose dependently, but did not affect their biglycan mRNA expression. Furthermore, either removal of rhBMP-2 from the culture media or addition of TGF-beta1 significantly decreased alkaline phosphatase activity of rhBMP-2-induced cells. These results indicate that osteoblastic differentiation is accompanied by increased alkaline phosphatase activity and decreased expression of decorin mRNA, but continuous expression of biglycan mRNA. Both rhBMP-2 and TGF-beta1 inhibit decorin mRNA expression in osteoblasts at varying stages of differentiation, but their effects on biglycan mRNA expression and alkaline phosphatase are different.

Alkaline Phosphatase↗

Pilot study of screening for Wilson disease using dried blood spots obtained from children seen at outpatient clinics.

Wilson disease (WD) is an autosomal recessive disorder of copper accumulation leading to liver and/or brain damage. In this paper, we describe the results of a pilot study of screening for WD using ceruloplasmin determinations in dried blood samples. Specimens were collected from children aged 1 to 6 years who were seen at local paediatric outpatient clinics in the Miyagi Prefecture. We measured ceruloplasmin (CP) concentrations in 2789 children using an enzyme-linked immunosorbent assay. The mean value was 12.4 +/- 3.95 mg/dl blood. Among these children, we identified two (case 1, male, 2 years old; case 2, female, 3 years old) with markedly reduced CP concentrations. Apart from low serum copper concentrations, their biochemical findings were almost normal, as were growth and development. To confirm the diagnosis, we analysed the WD gene and detected A803T/2871delC mutations in case 1 and R778L/G1035V mutations in case 2. We conclude that these children were presymptomatic WD patients. The CP level in dried blood samples from children aged 1 to 6 years appears to be a reliable marker for early detection of WD.

Ceruloplasmin↗

Immunohistochemical localization of the bone morphogenetic protein-6 in salivary pleomorphic adenomas.

Salivary pleomorphic adenomas are often associated with chondroid tissue formation. We have found that bone morphogenetic proteins (BMP), especially BMP-2, may play an important role in ectopic chondrogenesis in this tumor. Bone morphogenetic protein-6 was reported to be related to the osteogenic metastasis of prostatic carcinomas. The relationship between BMP-6 expression and chondroid tissue formation is investigated. Twenty-three pleomorphic adenomas were examined immunohistochemically. The overexpression of BMP-6 was observed in 10 pleomorphic adenomas of the major salivary glands (43. 5%), and no evidence of BMP-6 expression in any of the nine pleomorphic adenomas of the palate. Bone morphogenetic protein-6 was immunolocalized in the lacuna cells of the chondroid tissue, in which type II collagen was localized. Bone morphogenetic protein-6 was expressed in inner ductal cells of the tubulo-glandular structures in the pleomorphic adenomas. This finding indicates that BMP-6 may be associated with the differentiation of inner ductal cells. Bone morphogenetic protein-6 was expressed weakly in neoplastic myoepithelial cells in the myxoid areas, which may be related to the production of extracellular matrices. Bone morphogenetic protein-6 has a role in chondroid formation, and also tubulo-glandular differentiation in pleomorphic adenomas. In conclusion, a large portion of pleomorphic adenomas of the salivary gland origin, but not of palate origin, was shown to overexpress BMP-6 protein.

Adenoma, Pleomorphic↗

A novel presenilin-2 splice variant in human Alzheimer's disease brain tissue.

Mutations in the presenilin-1 (PS-1) and presenilin-2 (PS-2) genes account for the majority of cases of early-onset familial Alzheimer's disease (AD). Alternative splicing forms of the PS-1 and PS-2 gene products have previously been reported in fibroblast and brain tissue from both familial and sporadic AD patients, as well as from normal tissues and cell lines. We demonstrate here unusual alternative splicing of the PS-2 gene that leads to the generation of mRNA lacking exon 5 in human brain tissue. This product was more frequently detected in brain tissue from sporadic AD patients (70.0%; 21 of 30) than from normal age-matched controls (17.6%; three of 17). In cultured neuroblastoma cells, this splice variant was generated in hypoxia but not under other forms of cellular stress. Hypoxia-mediated induction of this splice variant was blocked by pretreatment of neuroblastoma cells with the protein synthesis inhibitor cycloheximide or antioxidants such as N-acetylcysteine and diphenyl iodonium, suggesting that hypoxia-mediated oxidant stress might, at least in part, underlie the alternative splicing of PS-2 mRNA through de novo protein synthesis. Furthermore, the stable transfectants of this splice variant produced the N-terminal part of PS-2 protein (15 kDa) and were more susceptible to cellular stresses than control transfectants. These results suggest the possibility that altered presenilin gene products in stress conditions may also participate in the pathogenesis of AD.

Aged↗

Errors in the spleen-blood partition coefficient for water in C15O2 steady-state PET.

The aim of this study was to clarify if the value of 0.93, determined for patients with normal livers, is useful as a pathological spleen-blood partition coefficient for water when the splenic blood flow is quantified by the C15O2 steady-state method. A steady-state PET scan with continuous inhalation of C15O2 and a dynamic PET scan with a H(2)15O bolus injection were performed. From 157 patients, 392 slices were chosen as having planes that encompassed the spleen and provided regions of interest with full signal imaging. A comparison of the results of the steady-state and dynamic methods was performed. When 0.93 was adopted as the spleen-blood partition coefficient for water, an error of about 25% was seen in the splenic blood flow of patients with cirrhosis. When measuring splenic blood flow, the H(2)15O dynamic method is necessary. However, a rough estimate of splenic blood flow is possible by the C15O2 PET steady-state method, if this error is known.

Adult↗

Effect of prostaglandin E2 on recombinant human bone morphogenetic protein-2-stimulated osteoblastic differentiation in human periodontal ligament cells.

Recombinant human (rh) bone morphogenetic protein-2 (BMP-2) stimulates osteoblastic differentiation in cells isolated from human periodontal ligament (HPLC), and this action of rhBMP-2 may be modulated by prostaglandins (PGs), which are local regulatory factors in the bone metabolism. In the present study, we investigated the effect of prostaglandin E2 (PGE2) on rhBMP-2-stimulated osteoblastic differentiation in cultured HPLC. rhBMP-2 (500 ng/ml)-stimulated alkaline phosphatase (ALPase) activity was enhanced by simultaneous treatment with low concentrations (10(-10)-10(-8) M) of PGE2, whereas a high concentration (10(-6) M) of PGE2 suppressed it. rhBMP-2 did not induce cyclo-oxygenase-2 (COX-2) mRNA expression or subsequent PGE2 production, whereas it remarkably suppressed rhIL-1 beta-induced COX-2 mRNA expression and PGE2 production. The rhBMP-2 action on osteoblastic differentiation in HPLC was also enhanced by co-treatment with 0.25 to 25 ng/ml of rh interleukin-1 beta (IL-1 beta). The ALPase activity stimulated by simultaneous treatment with rhBMP-2 and rhIL-1 beta was partially inhibited by addition of 10(-6) M of indomethacin, which completely inhibited rhIL-1 beta-induced PGE2 production. These results reveal that PGE2 at different concentrations exerts a biphasic effect on BMP-2-stimulated osteoblastic differentiation in HPLC, BMP-2 inhibits IL-1 beta-induced PGE2 production through suppressing COX-2 expression, and the BMP-2-stimulated osteoblastic differentiation may be enhanced by the endogenous PGE2 induced by BMP-2 and IL-1 beta. These suggest that BMP-2 action on osteoblastic differentiation in HPLC may be modulated by PGE2 in autocrine and paracrine fashions.

Adult↗

Characterization of osteoblastic differentiation of stromal cell line ST2 that is induced by ascorbic acid.

The stromal cell line ST2, derived from mouse bone marrow, differentiated into osteoblast-like cells in response to ascorbic acid. Ascorbic acid induced alkaline phosphatase (ALPase) activity, the expression of mRNAs for proteins that are markers of osteoblastic differentiation, the deposition of calcium, and the formation of mineralized nodules by ST2 cells. We investigated the mechanism whereby ascorbic acid induced the differentiation of ST2 cells. Inhibitors of the formation of collagen triple helices completely blocked the effects of ascorbic acid on ST2 cells, an indication that matrix formation by type I collagen is essential for the induction of osteoblastic differentiation of ST2 cells by ascorbic acid. We furthermore examined the effects of bone morphogenetic proteins (BMPs) on the differentiation of ST2 cells induced by ascorbic acid. Ascorbic acid had no effect on the expression of mRNAs for BMP-4 and the BMP receptors. However, a soluble form of BMP receptor IA inhibited the induction of ALPase activity by ascorbic acid. These results suggest that ascorbic acid might promote the differentiation of ST2 cells into osteoblast-like cells by inducing the formation of a matrix of type I collagen, with subsequent activation of the signaling pathways that involve BMPs.

Alkaline Phosphatase↗

Expression of DCC protein in colorectal tumors and its relationship to tumor progression and metastasis.

A loss of heterozygosity (LOH) at the DCC gene locus was detected in colorectal tumors, and this LOH might be related to metastasis. The aim of this study was to determine DCC protein expression in colorectal cancer and to evaluate its prognostic value. Allelic loss of the DCC locus was observed in 16 of the 23 patients (66.7%). In all 16 patients with LOH, DCC expression was decreased in the cancer tissue compared with the adjacent normal mucosa. All 23 colorectal tumors had decreased expression of this protein relative to the adjacent normal colonic mucosa in Western blot analysis. The levels of DCC protein were significantly lower in cancer tissues than in adenoma tissues. Decreased DCC protein expression was also observed by immunohistochemistry in the colorectal cancer cases. There were significant correlations between DCC protein expression and histologic type, venous invasion, and hematogenous metastasis. Patients with DCC-protein-negative tumors had a greater relative risk of recurrence compared with those whose tumors were DCC protein-positive. The 5-year survival rate was 91.0% in patients with DCC-protein-positive tumors, and 58.8% in those with DCC-protein-negative tumors; these differences between the two groups of patients were significant (p < 0.01). In multivariate analysis using the Cox regression model, DCC protein expression emerged as an independent prognostic indicator. These findings suggested that a decrease in DCC expression may have an important role in the progression of colorectal cancers and may be a biologic marker of prognostic significance.

Adenoma↗

Efficacy of continuous hyperthermic peritoneal perfusion for the prophylaxis and treatment of peritoneal metastasis of advanced gastric cancer: evaluation by multivariate regression analysis.

Thirty-two patients with advanced gastric cancer underwent continuous hyperthermic peritoneal perfusion (CHPP) combined with surgery: to prevent peritoneal recurrence in 15 patients without peritoneal metastasis (prophylactic CHPP) and to treat 17 patients with peritoneal metastases (therapeutic CHPP). The postoperative outcome was compared with that of control patients treated with surgery alone. Peritoneal recurrence was less frequent (26%) and the 5-year survival rate was significantly higher (39%) in the patients with prophylactic CHPP than in 40 control patients (42 and 17%, respectively). The patients with therapeutic CHPP showed significantly better median survival than did 20 control patients (11 vs. 6 months). Cox multivariate regression analysis revealed that CHPP was an independent prognostic factor in the prophylactic study (hazard ratio = 0.3965), and that the independent prognostic factor in the therapeutic study was not CHPP but complete resection of the peritoneal metastasis. Thus, CHPP has no marked benefit for established peritoneal metastasis. CHPP for the prevention of peritoneal recurrence may have a beneficial effect on long-term survival, but a prospective randomized trial is needed to clarify its prognostic value.

Adult↗

Recombinant human bone morphogenetic protein-2 stimulates osteoblastic differentiation in cells isolated from human periodontal ligament.

Periodontal ligament cells may play an important role in the successful regeneration of the periodontium. We investigated the effects of recombinant human bone morphogenetic protein-2 (rhBMP-2), one of the most potent growth factors that stimulates osteoblast differentiation and bone formation, on cell growth and osteoblastic differentiation in human periodontal ligament cells (HPLC) isolated from four adult patients. rhBMP-2 induced no significant changes in cell growth in any of the HPLCs. rhBMP-2 at concentrations over 50 ng/mL significantly stimulated alkaline phosphatase (ALPase) activity and parathyroid hormone (PTH)-dependent 3', 5'-cyclic adenosine monophosphate accumulation, which are early markers of osteoblast differentiation, in the HPLCs. rhBMP-2 (500 ng/mL) also slightly enhanced the level of PTH/PTH-related peptide receptor mRNA expression in these cells. While interleukin-1 beta enhanced ALPase activity stimulated with rhBMP-2, tumor necrosis factor-alpha inhibited the rhBMP-2-stimulated activity. Interleukin-6 induced no significant changes in ALPase activity stimulated with rhBMP-2. Although HPLCs, whether treated with rhBMP-2 or not, could not produce measurable amounts of osteocalcin, which is a marker of more mature osteoblasts, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] induced osteocalcin mRNA expression and protein synthesis in these cells. rhBMP-2 inhibited 1,25(OH)2D3-induced osteocalcin synthesis in HPLCs at both the mRNA and protein levels. These results suggest that rhBMP-2 provides an anabolic effect on periodontal regeneration by stimulation of osteoblastic differentiation in human periodontal ligament cells, and that this stimulatory effect is differentially modulated by inflammatory cytokines during the course of periodontal regeneration.

Adolescent↗