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Biomedical subjects

N Endo

Publications and source records attributed to N Endo.

At least 37 records · Page 2Linked to original sources

[Determinants of occurrence of negative priming for novel shapes with matching paradigm].

We examined the effect of relation between interferences from distractor and inhibitory mechanism on the occurrence of negative priming, by using a matching paradigm. The ease of perceptual target selection was determined by magnitudes of interference. Stereoscopic depth was used to manipulate the relative position of a target, a distractor and a standard figure. When the ease of perceptual target selection was manipulated by separation of the target from the distractor in depth, positive priming occurred. However, the ease of target selection turned out to be unnecessary in the occurrence of priming effects. When the distractor and the standard figure were displayed at the same depth plane, where the distractor was supposed to interfere with the encoding of a standard figure, negative priming occurred consistently regardless of the ease of perceptual target selection. This study suggests that inhibitory mechanism contributes to the suppression of inappropriate processes by distractor, and inhibitory mechanism actively keeps distractors from interfering with standard figures.

Adult↗

[Thoracic kyphotic deformity impairs QOL of osteoporotic patients].

Severe osteoporotic patients likely to have multiple spinal compression fractures, resulting in spinal kyphotic deformity. We compared the QOL of osteoporotic patients between the patients with and without thoracic kyphosis using the questionnaire of the Japanese Bone and Mineral Society for osteoporotic patients (1999 version). The patients with thoracic kyphosis, whose thoracic kyphotic angles were over than 45 degrees, complained low back pain, disturbance of activity of daily living, anxiety about falling, and dissatisfaction with their posture. We have to concern about the QOL and take care of psychological aspects of osteoporotic patients with spinal deformity as well as low back pain.

English Abstract↗

Effects of 6-formylpterin, a xanthine oxidase inhibitor and a superoxide scavenger, on production of nitric oxide in RAW 264.7 macrophages.

As well as superoxide generated from neutrophils, nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) in macrophages plays an important role in inflammation. We previously showed that 6-formylpterin, a xanthine oxidase inhibitor, has a superoxide scavenging activity. In the present study, to elucidate other pharmacological activities of 6-formylpterin, we investigated the effects of 6-formylpterin on production of nitric oxide (NO) in the murine macrophage cell line RAW 264.7 stimulated by lipopolysaccharide (LPS) and interferon-gamma (INF-gamma). 6-Formylpterin suppressed the expression of iNOS, and it also inhibited the catalytic activity of iNOS, which collectively resulted in the inhibition of NO production in the stimulated macrophages. However, 6-formylpterin did not scavenge the released NO from an NO donor, S-nitroso-N-acetylpenicillamine (SNAP). These results indicate that 6-formylpterin inhibits pathological NO generation from macrophages during inflammation, but that it does not disturb the physiological action of NO released from other sources.

Animals↗

Formation of 2'-deoxyoxanosine from 2'-deoxyguanosine and nitrous acid: mechanism and intermediates.

The reaction mechanism for the formation of 2'-deoxy-oxanosine from 2'-deoxyguanosine by nitrous acid was explored using methyl derivatives of guanosine and an isolated intermediate of the reaction. When 1-methylguanosine was incubated with NaNO(2)under acidic conditions, N (5) -methyloxanosine and 1-methylxanthosine were generated, whereas the same treatment of N (2), N (2)-dimethylguanosine generated no product. In a similar experiment without NO(2)(-), participation of a Dimroth rearrangement was ruled out. In the guanosine-HNO(2)reaction system, an intermediate with a half-life of 5.6 min (pH 7.0, 20 degrees C) was isolated and tentatively identified as a diazoate derivative of guanosine. The diazoate intermediate was converted into oxanosine and xanthosine at a molar ratio (oxanosine:xanthosine) of 0.26 at pH 7.0 and 20 degrees C. The ratio was not affected by the incubation pH between 2 and 10, but increased linearly with temperature from 0.22 (0 degrees C) to 0.32 (50 degrees C). The addition of acetone also increased the ratio up to 0.85 (98% acetone). Based on these results, a con-ceivable pathway for the formation of 2'-deoxyoxanosine from 2'-deoxyguanosine by HNO(2)is proposed.

Cations↗

Herbimycin A induces G1 arrest through accumulation of p27(Kip1) in cyclin D1-overexpressing fibroblasts.

The ansamycin antibiotic herbimycin A is a potent tyrosine kinase inhibitor and reduces the growth rate of various types of mammalian cells. When quiescent Rat6 fibroblast cells were treated with herbimycin A, serum-induced expression of cyclin D1 was inhibited, and this was associated with inhibition of G1 phase progression. However, herbimycin A also inhibited serum-induced G1 progression in derivatives of the Rat6 fibroblast cell line that stably overexpress a human cyclin D1 cDNA (R6ccnD1#4 cells), without affecting the expression levels of G1 cyclins. We found that herbimycin A prevented serum-induced downregulation of the cyclin-dependent kinase inhibitor p27(Kip1), thereby leading to inactivation of the protein kinase activity of CDK2. These results suggest that herbimycin A inhibits a tyrosine kinase(s) that plays a role in degradation of the p27(Kop1) protein.

Animals↗

Epidemiology of cervical and trochanteric fractures of the proximal femur in 1994 in Tangshan, China.

The purpose of this study was to determine the incidence of cervical and trochanteric fractures of the proximal femur in 1994 in Tangshan City, China. There are many reports on hip fracture incidence in many countries, suggesting that there are many factors affecting hip fractures. We visited 15 hospitals with an orthopaedic department within Tangshan City, and reviewed the medical records and radiographs of all patients with hip fractures occurring between January 1 and December 31, 1994. The population of Tangshan in 1994 was determined to be 1,454,543 (746,015 males and 708,528 females). The population of those over 65 years of age was 88,490 (41,519 males and 46,971 females), representing 6.08% of the total population. This study detected 184 cervical and trochanteric fractures of the proximal femur in 1994 in Tangshan (127 men and 57 women). The overall incidence or rate of the combined number of cervical and trochanteric fractures was 25 fractures per 100,000 population per year for men and 12 for women. There were a total of 147 cervical fractures (80%) and 37 trochanteric fractures (20%). The incidence of the combined number of cervical and trochanteric fractures in patients over 70 years of age increased to 108 for men and 156 for women. The incidence of hip fractures increased with age in both sex groups, especially in women over 65. Severe trauma fractures happened more often in younger groups, and mainly occurred in men, which may be a result of the particular composition of the population in Tangshan, which is young and male dominated. In addition, because Tangshan is an industrial city, many of its citizens are involved in occupations requiring a high level of physical activity.

Age Distribution↗

Epidemiology of cervical and trochanteric fractures of the proximal femur in 1996 in Kaohsiung City, Taiwan.

The goal of this study was to determine the incidence of cervical and trochanteric fractures of the proximal femur in 1996 in Kaohsiung City, Taiwan. Kaohsiung City is the industrial and commercial center of southern Taiwan, with a population of 1,433,621 in 1996. The number of individuals over 65 years of age accounted for 6.2% of the total population. Data from the archives of reimbursement of the National Health Insurance program were used to investigate the incidence of fractures of the proximal femur. This study detected 580 cervical and trochanteric fractures (40.5 fractures per 100,000 population per year) in 261 males (35.8 fractures per 100,000 men per year) and 319 females (45.3 fractures per 100,000 women per year), with 420 (72%) of these fractures occurring in individuals over 65 years of age. The age-specific incidences of cervical and trochanteric fractures increased exponentially with age in both genders. The overall ratio of cervical to trochanteric fractures was 1:1.04. The mean ages of women with cervical or trochanteric fractures (71.6 and 74.0 years, respectively) were significantly higher than those of males (59.9 and 64.8 years, respectively; P < 0.01). The age-adjusted incidences of fractures of the proximal femur in Kaohsiung City were higher than in other Asian countries, but were lower than in Western countries such as the United States and Norway. The urban lifestyle and low daily calcium intake may be responsible for this increased incidence of proximal femoral fractures in Kaohsiung City.

Adult↗

Spatiotemporal change of rat collagenase (MMP-13) mRNA expression in the development of the rat femoral neck.

The interepiphyseal region between the greater trochanter and the capital femoral epiphysis and the medioproximal portion of the femoral neck exhibit extensive morphological changes during the first 4 weeks after birth in rats. Previous reports show that matrix metalloproteinase-13 (MMP-13, rat collagenase) mRNA is expressed in bone and cartilage during embryonal development and fracture healing. We examined MMP-13 mRNA expression and compared it with the distribution of osteopontin and osteocalcine mRNA in the femoral neck. Moreover, we examined histomorphometric analysis in the femoral neck where the morphology changes rapidly. Histomorphometric analysis of the 4-week-old rat femoral neck showed a high rate of bone formation and resorption in the region where shape changed rapidly. Osteopontin mRNA was expressed diffusely along the endosteum. In contrast, MMP-13 mRNA expression was restricted to the medial endosteal portion near the cartilage-bone interface of the femoral neck in 15- and 28-day-old rats and in the deepest endosteal interepiphyseal region of 15-day-old rats. MMP-13 mRNA-expressing osteoblastic cells were also expressing osteopontin but not osteocalcin mRNA. MMP-13 mRNA-expressing cells differ from tartrate-resistant acid phosphatase (TRAP)-positive cells, and MMP-13 mRNA-positive cells are located adjacent to TRAP-positive cells. The results of the site- and cell-specific expression of MMP-13, taken together with its enzymatic property, suggest that MMP-13 plays an important role in morphological changes in the rat femur, at least during the third and fourth week after birth, and that MMP-13 itself is involved in the interaction between osteoblastic and TRAP-positive cells.

Acid Phosphatase↗

Relief from pain after Bombelli's valgus-extension osteotomy, and effectiveness of the combined shelf operation.

Between 1979 and 1993, we treated 67 hips in 58 patients with severe osteoarthritis caused by congenital dislocation of the hip, employing Bombelli's valgus-extension osteotomy. The mean age of the patients was 43.6 years (range, 23-59 years). The mean follow-up period was 9.7 years (range, 5-16 years). Thirty-three of the 67 joints were followed-up for more than 10 years after the operation. Of the 67 joints, 31 were operated on by Bombelli's valgus-extension osteotomy combined with a shelf operation (combined group), and 36 by Bombelli's valgus-extension osteotomy alone (single group). Clinical evaluation was made according to the Japanese Orthopaedic Association (JOA) hip score system (JOA hip score). In order to assess the effectiveness of this operation in regard to sustained relief from pain after the operation, Kaplan-Meier survivor analysis was performed on the basis of pain score on the JOA hip score. The end-point of the Kaplan-Meier analysis was defined as a score of less than 20 points on the pain score at the time of follow-up or conversion to total hip arthroplasty. In order to analyze the factors that exacerbated pain and to assess the effectiveness of the combined shelf operation, the degree of superior displacement of the femoral head (measured from roentgenograms) after the operation was examined in relation to the pain score. The mean JOA hip score improved, from 56.1+/-11.0 before the operation to 77.0+/-16.1 at the latest follow-up. Kaplan-Meier analysis showed a survival rate of 79.4% 10 years after the operation. Superior displacement of the femoral head had gradually progressed with time after the operation in patients with and without the combined shelf operation. Displacement of the femoral head was positively correlated with the acetabular angle of the weight-bearing surface (WBS angle) (sourcil) preoperation. The mean pain score in the combined group was significantly higher than that in the single group 6 to 9 years after the operation. The results of our assessments led us to conclude that Bombelli's valgus-extention osteotomy is satisfactory as far as clinical and radiological evaluations are concerned, as relief from the pain has continued for more than 10 years after the operation. The combined shelf operation is effective for relieving pain in severe osteoarthritis caused by congenital dislocation of the hip.

Activities of Daily Living↗

Immunohistochemical localization of P-selectin in the glomeruli from forensic autopsies.

The expression of the adhesion molecule P-selectin is known to be up-regulated in several vital organs including the kidney after trauma in experimental animals. We examined the expression of P-selectin in the kidney by immunohistochemistry in 41 forensic autopsies mainly from trauma cases. P-selectin immunoreactivity was present in the glomerular capillary endothelial tufts and cortical interstitial vascular endothelial cells. The P-selectin immunoreactivity in the glomeruli was not co-localized with CD41 (platelet marker) immunoreactivity. The antemortem interval between the onset of injury and death (AMI) was statistically significantly longer in the cases with more P-selectin-positive capillary endothelial tufts in the glomeruli. Our results show that P-selectin immunoreactivity exists in the glomerular capillary endothelial cells rather than platelets. Our results also indicate that the P-selectin expression increases in the glomerular endothelial cells of the human kidney with the longer duration of the state under injury.

Journal Article↗

An immunohistochemical study on cathepsin D in human hippocampus.

Cathepsin D is a lysosomal enzyme involved in neuronal degeneration. In this study, the immunohistochemistry of cathepsin D was studied in hippocampal CA1 neurons that are vulnerable to ischemia, and parahippocampal glial cells. CA1 neurons from the majority of cases showed cathepsin D immunoreactivity in the cytoplasm, whereas shrunk neurons were unstained in only one case. There was no statistically significant correlation between the postmortem interval between death and autopsy, and cathepsin D immunoreactivity in CA1 neurons. These observations indicate that cathepsin D immunoreactivity is not a sensitive marker for neuronal degeneration or postmortem changes. On the other hand, there was a statistically significant correlation between age and cathepsin D immunoreactivity in the cytoplasm of parahippocampal glial cells. This shows that senescence is correlated with cathepsin D expression in humans as has been reported previously in an animal study.

Adolescent↗

Specific loss of chondromodulin-I gene expression in chondrosarcoma and the suppression of tumor angiogenesis and growth by its recombinant protein in vivo.

Chondromodulin-I (ChM-I) was previously identified as an angiogenesis inhibitor in cartilage. Here, we demonstrated that the level of ChM-I transcripts was substantially reduced to 100 or even less in the lower-grade chondrosarcomas, in articular cartilage or other benign cartilage tumors. We implanted human chondrosarcoma OUMS-27 cells into nude mice that reproducibly produced tumors with cartilaginous matrix. Tumor-induced angiogenesis was evident when the tumors were excised 30 days after implantation. However, the local administration of recombinant human ChM-I almost completely blocked vascular invasion and tumor growth in vivo. Moreover, ChM-I also inhibited the growth of HT-29 colon adenocarcinoma in vivo, implying its therapeutic potential for solid tumors.

Animals↗

Five different genes, Eif4a1, Cd68, Supl15h, Sox15 and Fxr2h, are clustered in a 40 kb region of mouse chromosome 11.

We characterized a region of the mouse genome disrupted by integration of a gene trap (GT) vector in ES cells. On 5' rapid amplification of cDNA ends analysis of the fusion transcripts containing the GT vector, we identified the eukaryotic protein synthesis initiation factor 4A1 gene (Eif4a1) as a promoter-trapped gene. Plasmid rescue was used to show that the other end of the integrated vector disrupted the murine homolog of the human fragile X mental retardation syndrome-related protein 2 gene (Fxr2h). Structural analysis of P1 clones, isolated from the wild-type mouse genome by PCR with Eif4a1-specific primers, indicated that the integration of the GT vector was accompanied by the deletion of about 35 kb of genomic DNA and that the disrupted region also included three genes, Cd68, Supl15h and Sox15, the latter two of which are transcribed in opposite directions with overlapping 3' ends. These five different genes at least, Eif4a1, Cd68, Supl15h, Sox15 and Fxr2h, are clustered in a 40 kb region. The chromosomal location of this region was mapped by means of interspecific backcross panel DNAs to the central part of mouse chromosome 11, exhibiting a known region of synteny with human chromosome 17.

Animals↗

Maturational disturbance of chondrocytes in Cbfa1-deficient mice.

Cbfa1, a transcription factor that belongs to the runt-domain gene family, plays an essential role in osteogenesis. Cbfa1-deficient mice completely lacked both intramembranous and endochondral ossification, owing to the maturational arrest of osteoblasts, indicating that Cbfa1 has a fundamental role in osteoblast differentiation. However, Cbfa1 was also expressed in chondrocytes, and its expression was increased according to the maturation of chondrocytes. Terminal hypertrophic chondrocytes expressed Cbfa1 extensively. The significant expression of Cbfa1 in hypertrophic chondrocytes was first detected at embryonic day 13.5 (E13.5), and its expression in hypertrophic chondrocytes was most prominent at E14.5-16.5. In Cbfa1-deficient mice, whose entire skeleton was composed of cartilage, the chondrocyte differentiation was disturbed. Calcification of cartilage occurred in the restricted parts of skeletons, including tibia, fibula, radius, and ulna. Type X collagen, BMP6, and Indian hedgehog were expressed in their hypertrophic chondrocytes. However, osteopontin, bone sialoprotein, and collagenase 3 were not expressed at all, indicating that they are directly regulated by Cbfa1 in the terminal hypertrophic chondrocytes. Chondrocyte differentiation was severely disturbed in the rest of the skeleton. The expression of PTH/PTHrP receptor, Indian hedgehog, type X collagen, and BMP6 was not detected in humerus and femur, indicating that chondrocyte differentiation was blocked before prehypertrophic chondrocytes. These findings demonstrate that Cbfa1 is an important factor for chondrocyte differentiation.

Animals↗

Differential production of MCP-1 and cytokine-induced neutrophil chemoattractant in the ischemic brain after transient focal ischemia in rats.

Chemokines have been shown to play an important role in leukocyte infiltration into ischemic lesions. Recently, the increased expression of monocyte chemoattractant protein-1 (MCP-1) and cytokine-induced neutrophil chemoattractant (CINC) was observed in experimental stroke models where infiltrated leukocytes were supposed to induce tissue injury, however, the protein level and time course of these chemokines have not been fully elucidated. Therefore, we analyzed the time-dependent production of MCP-1 and CINC in the rat brain after transient middle cerebral artery occlusion (MCAO) by means of specific enzyme-linked immunosorbent assay systems. The MCP-1 levels in the ipsilateral hemispheres increased from 6 h, peaked at 2 days, and thereafter gradually decreased. The peak MCP-1 concentration was 89.2+/-28.2 ng/g tissue wet weight (mean +/- SEM, n = 5, 49.3-fold greater than the contralateral value at the same time, P < 0.05), which is supposed to be high enough to exert its biological effects. In contrast, the maximum CINC concentration that corresponded to 2.9+/-0.7 ng/g tissue wet weight (mean +/- SEM, n = 5, 55.0-fold greater than the contralateral value at the same time, P < 0.05), was observed at 6 h. In addition, we confirmed the temporal profile of leukocyte subtypes that infiltrated into the ischemic brain, thus, neutrophil infiltration occurred at early stages (1-3 days), followed by massive infiltration of macrophages at later stages (2-7 days). These studies suggest that MCP-1 in cerebral ischemia actually plays a significant role in the migration of macrophages into the lesion and that the differential temporal production of these chemokines contributes to the regulation of infiltrated leukocyte subtypes.

Animals↗

Immunohistochemical localization of c-fos in the nuclei of the medulla oblongata in relation to asphyxia.

The immediately early gene product c-fos is known to be induced in neurons under noxious stimuli. Therefore, the immunohistochemistry of c-fos expression in human brains might offer information on the localization of stimulated neurons. In this study, the immunohistochemical localization of c-fos was studied in the neurons of the hypoglossal nucleus (XII), the dorsal motor nucleus of the vagal nerve (X), the nucleus solitarius (Sol), the accessory cuneate nucleus (Cun), the spinal trigeminal nucleus (V) and the inferior olive (Oli) of the human medulla oblongata from forensic autopsy cases. The neurons in the X nucleus showed the highest percentage of positive reactions for c-fos, followed in descending order by the Cun, V, Oli, XII and Sol. The c-fos immunoreactivity in the Cun and X was statistically significantly higher than in the Sol, XII and Oli. Although neurons in the Sol are known to be involved in respiration, there was no statistically significant difference in the c-fos immunoreactivity in the neurons in the Sol between asphyxia and non-asphyxia cases. On the other hand, the percentage of neurons positive for the c-fos immunoreactivity was statistically significantly higher in the Oli of asphyxia cases than of non-asphyxia cases. Our results indicate the difference in the immunoreactivity of c-fos among the nuclei of the human medulla oblongata and that the c-fos immunoreactivity in the Oli might assist the diagnosis of asphyxia.

Adolescent↗

Treatment with active vitamin D metabolites and concurrent treatments in the prevention of hip fractures: a retrospective study.

UNLABELLED: The purpose of this study was to determine the effect of treatment with active vitamin D metabolites and other concurrent medication on the prevention of hip fractures in elderly women. We inspected the medical records of the entire female population over 65 years of age on Sado Island, and followed a total of 11,377 women for a 3-year period. Of these, 1208 osteoporotic patients were treated with either 1,25-(OH)2D3 or 1 alpha-(OH)D3. The 765 patients who received the minimum effective dosage for more than 6 months made up the 'treatment group'. Nearly half these patients were also treated with either calcitonin or calcium. The 443 patients who received treatment with active vitamin D metabolites, but at a dosage or for a duration that did not meet the criteria for the treatment group, were deemed the 'ineffective group'. The remaining 10,169 women were the 'non-treatment group'. Fractures in the non-treatment group occurred at a rate of 39.8 fractures/10,000 person-years. The rate in the treatment group was 10.8, which was significantly lower (p = 0.039). Interestingly, the fracture rate after ceasing treatment was 52.1, which was significantly higher (p = 0.002) than the rate in patients receiving treatment. No statistical differences in the fracture rate were found between the ineffective, non-treatment and post-treatment groups. A reduction in the fracture rate was observed only in the treatment subgroup that did not also receive calcitonin (p = 0.042), and not in the subgroup that also received calcitonin therapy (p = 0.333). However, there was no statistical difference in the hip fracture rates between these two subgroups (p = 0.157) and the actual number of fractures was minimal (0 vs 2). Therefore, in this study, the advantage of treatment with active vitamin D alone over combined treatment with calcitonin seems to be marginal. IN CONCLUSION: (1) treatment with active vitamin D metabolites and with combined therapy may be marginally effective in preventing hip fractures, and (2) stopping the treatment clearly increases the risk of hip fractures.

Adjuvants, Immunologic↗

Peripheral quantitative computed tomography of the femoral neck in 60 Japanese women.

Peripheral quantitative computed tomography (pQCT) is able to evaluate trabecular and cortical bone separately, and to determine geometric properties from cross-sectional images for noninvasive assessments of mechanical strength. In order to assess the diagnostic value of pQCT of the femoral neck, 60 healthy women were examined with a new pQCT machine, XCT-3000 (Norland-Stratec, Germany), which is suitable for direct measurement of the hip. The region of interest chosen was the center of the femoral neck. pQCT of the distal radius and dual energy X-ray absorptiometry (DXA) of the lumbar spine and femoral neck were also performed. The study demonstrated that total bone mineral density (BMD) (femoral MD) and trabecular BMD (femoral-TBD) decreased with advancing age. Percent cortical area showed a small but significant decrease with advancing age and % trabecular area increased slightly. Both the endosteal perimeter and the periosteal perimeter were relatively constant with aging. Bone strength index (BSI) and stress-strain index (SSI), which reflect the mechanical strength of bone, declined with advancing age, especially after menopause. Femoral TBD correlated strongly with femoral neck BMD by DXA and L2-L4 BMD by DXA but femoral-CBD did not correlate with femoral neck BMD by DXA. Volumetric BMD of the femoral neck and distal radius were closely correlated. It is concluded that (1) cortical thinning occurs with aging by endocortical resorption and loss of femoral-TBD; (2) loss of femoral-CBD occurred at a slower rate than radial CBD, perhaps due to the weight-bearing effect; (3) biomechanical parameters such as the BSI and SSI may reflect increasing fragility of the femoral neck in pre- and postmenopausal women; (4) pQCT of the femoral neck had diagnostic value at least equivalent to that of DXA or pQCT of the distal radius.

Absorptiometry, Photon↗