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Biomedical subjects

N Endo

Publications and source records attributed to N Endo.

At least 55 records · Page 3Linked to original sources
PubMed1999

Local effects of transforming growth factor-beta1 on rat calvaria: changes depending on the dose and the injection site.

Transforming growth factor-beta1 (TGF-beta1) has opposite effects on osteoblastic cells in vitro, namely an inhibitory or stimulatory effect on cell differentiation. Because these effects are dependent on TGF-beta1 concentration or culture condition, we investigated whether the in vivo effects of TGF-beta1 on bone formation in infant rat calvaria were affected by the dose or the injection site. Human platelet-derived TGF-beta1 was injected subcutaneously onto the periosteal surface of parietal bone of 4-week-old rats at doses of 5 or 20ng/100microl per animal for 14 days, and the local effect on bone formation was examined by bone histomorphometry. TGF-beta1 treatment for 7 days decreased the mineral apposition rate, bone formation rate, and elongated mineralization lag time at the injection site. This change became more prominent when treatment continued for 14 days. These changes were restricted to the TGF-beta1-exposed area. Multiple subcutaneous injections of a relatively high dose (200ng/100microl per animal) of TGF-beta1 induced woven bone formation, in addition to marked inhibition of bone formation rate and prolongation of mineralization lag time. On the other hand, direct exposure of TGF-beta1 in the subperiosteal layer induced woven bone with periosteal cell proliferation even at a single injection of a low dose (5 or 50ng/25 microl) of TGF-beta1. In conclusion, the in vivo effects of TGF-beta1 on bone formation varied depending on its concentration and injection site. Also, subcutaneous injection of relatively low doses of TGF-beta1 inhibited local lamellar bone formation.

Animals↗
PubMed1999

Number of osteoprogenitor cells in human bone marrow markedly decreases after skeletal maturation.

Pluripotent mesenchymal stem cells in bone marrow differentiate to osteoblast progenitor cells. When the bone marrow cells are cultured in vitro, they form colony-forming units-fibroblastic (CFU-Fs) with exhibiting osteoblastic features such as expression of alkaline phosphatase (ALP) and formation of calcified nodules ex vivo. This article describes the effect of growth, maturation, and aging of the skeleton on human CFU-Fs harvested from human iliac bone marrow. Human bone marrow cells were harvested from the ilia of 49 women, and were cultured ex vivo for examination. The 49 subjects ranged in age from 4 to 88 years and were without metabolic bone disease. These aspirated bone marrow cells from human ilium exhibited osteoblastic phenotype such as alkaline phosphatase (ALP) activity, expression of osteocalcin (OSC) and parathyroid hormone-receptor (PTH-R) mRNA, and the formation of calcified nodules in vitro. The number of ALP-positive CFU-Fs and the ALP activity were quantified. The highest levels of ALP-positive CFU-Fs were observed in the young group, particularly in those under 10 years of age. The levels of ALP-positive CFU-Fs declined sharply after 10 years of age; those above 20 years of age exhibited a lower number of ALP-positive CFU-Fs, with a gradual decline with increasing age. These results indicate that change in the number of ALP-positive CFU-Fs may be associated with skeletal growth and maturation. The results also show that osteoblastic features such as ALP activity and capability of formation of calcification nodules were maintained even in the older subjects. These findings suggest that decreased activity of bone formation in the aged subjects could be, in part, caused by the decreased number of osteoprogenitor cells differentiating into osteoblasts because the number of ALP-positive CFU-Fs was one of the indices exhibiting bone-forming activity in the human marrow stromal cells.

Adolescent↗
PubMed1999

Increase in the incidence of cervical and trochanteric fractures of the proximal femur in Niigata Prefecture, Japan.

This study aimed to determine the incidence of cervical and trochanteric fractures of the proximal femur in 1994 in Niigata Prefecture, Japan, and to compare this incidence with those previously reported in Niigata in 1985, 1987, and 1989. We visited all hospitals within Niigata Prefecture having an orthopedic department and reviewed the medical records and radiographs of all patients who sustained such fractures in 1994. The population of Niigata Prefecture was determined in 1994 to be 2,483,879 (1,205,151 males and 1,278,728 females). The population over 65 years of age was 428,795 (172,788 males and 256,007 females), representing 17.3% of the total population. In 1994, there were 1,468 cervical or trochanteric fractures in 378 males and 1,090 females, with a male-to-female ratio of 1:2.9. The incidence of these fractures in persons over 65 years of age was 304 fractures per 100,000 population per year. Of 528 cervical and 940 trochanteric fractures, the latter accounted for 64% of the total number. The age-specific incidence of the fractures in Niigata exhibited an exponential increase with age, similar to those reported in Sweden and the United States. However, the incidence was lower than in those countries. When comparing the number of cervical and trochanteric fractures in 1994 with the numbers reported in 1985, 1987, and 1989, it is evident that the overall number and incidence of these fractures has been increasing over this period. Even if the difference of the age-specific population among these years is adjusted, the fractures have been increasing.

Adolescent↗
PubMed1999

Microstructure of the trabecula and cortex of iliac bone in primary hyperparathyroidism patients determined using histomorphometry and node-strut analysis.

The purpose of this study was to use histomorphometry to compare the microstructure of trabecular and cortical bone in patients with primary hyperparathyroidism (PH) with that seen in osteoporosis. Histomorphometric and node-strut analyses of iliac bones were performed on 11 female patients with PH (61.3 +/- 8.0 years old) and 61 age-matched female patients with involutional osteoporosis (OP) (63.6 +/- 5.6 years old). Cancellous bone volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), and wall thickness (W.Th) were not significantly different in these two groups. The bone formation rate (BFR) tended to be higher in the PH group than in the OP group. The number of nodes (N.Nd/TV) and node-to-node strut length (Nd.Nd/TV) were significantly higher in the PH group than in the OP group. The number of termini (N.Tm/TV) and terminus-to-terminus strut length/total strut length (Tm.Tm/TSL) were significantly lower in the PH group; cortical porosity was significantly higher in the PH group than in the OP group. No correlation was found between age and N.Nd in the PH group, but there was a negative correlation between age and N.Nd in the OP group. Our results show that trabecular connectivity was maintained while cortical porosity deteriorated in patients with PH compared with OP. These results suggest that there are microstructural differences between PH and OP in cancellous and cortical bone that result from the bone remodeling sequence in humans.

Aged↗
PubMed1999

Arthrodesis of the hip joint using an external fixator.

Arthrodesis of the hip has been plagued by high rates of nonunion, and by complications associated with prolonged cast immobilization. To prevent these problems, we devised a procedure for hip arthrodesis using an external fixator in combination with internal fixation at the fusion site. We have treated nine patients with this technique. All of the arthrodeses were solidly united without wound infections at the most recent follow-up. Patients were able to leave their hospital bed and walk on the affected limb with a cane shortly after surgery. This was possible because the external fixator was low in profile, as it was applied from the anterosuperior iliac spine to the femoral shaft, and provided rigid stabilization of the arthrodesis. The technique resulted in a reduction in the period of bed rest, immediate postoperative mobilization, shorter periods of hospitalization, no limitation in the range of knee and ankle motion, improvement in the patient's ability to carry out the personal hygiene, and fewer complications.

Activities of Daily Living↗
PubMed1999

Immunohistochemical localization of heat shock protein 70 in the human medulla oblongata in forensic autopsies.

Heat shock protein 70 (hsp70) can be induced under various stresses in experimental animals. We investigated hsp70 immunoreactivity in the human medulla oblongata in forensic autopsies. Hsp70 immunoreactivity was observed in the cytoplasm of some neurons in the hypoglossal nucleus (XII), the dorsal motor nucleus of the vagal nerve (X), the lateral cuneate nucleus (Cun), and the inferior olive (Oli). Neurons with positive hsp70 immunoreactivity were statistically significantly fewer in the Oli than in the XII, X, and Cun. There was no statistically significant correlation between the AMI (the antemortem interval between the onset of injury and death) or PMI (the postmortem interval between death and autopsy), and the percentage of positive cytoplasmic hsp70 immunoreactivity in any of the nuclei studied. Age had a statistically significant negative correlation with the percentage of positive hsp70 immunoreactivity in the Oli. The percentages of positive hsp70 immunoreactivity in the XII and Cun were statistically significantly lower in burn cases than in other cases. Therefore, the induction of hsp70 immunoreactivity in the medulla oblongata may not reflect the duration of stress in the AMI, but may reflect the regional (nuclei) and conditional (burns) differences in autopsy specimens.

Journal Article↗
PubMed1999

Expression of metalloproteinase-13 (Collagenase-3) is induced during fracture healing in mice.

In fracture healing, a large amount of cartilage is formed, then rapidly replaced by osseous tissue. This process requires the transition of extracellular matrix component from type II to type I collagen. We investigated the expression of matrix metalloproteinase-13 (MMP-13), which has a high potential to cleave type II as well as type I collagen, during fracture repair in mouse ribs. In situ hybridization demonstrated that MMP-13 mRNA was present throughout the healing process. It was detected in the cells of the periosteum at day 1. As fracture callus grew, strong MMP-13 mRNA signals were detected in cells of the cartilaginous callus. In the reparative and remodeling phases, both hypertrophic chondrocytes and immature osteoblastic cells in the fracture callus expressed MMP-13 mRNA strongly. These cells were located adjacent to tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts at the sites of cartilage/bone transition. In osteoclasts, MMP-13 expression was not detected. The level of MMP-13 mRNA peaked at day 14 postfracture by northern blotting. Immunohistochemical staining showed that MMP-13 was detected primarily in hypertrophic chondrocytes. These results indicate that MMP-13 is induced during fracture healing. The site- and cell-specific expression of MMP-13 and its enzymatic property suggest that MMP-13 initiates the degradation of cartilage matrix, resulting in resorption and remodeling of the callus. In conclusion, MMP-13 plays an important role in the healing process of fractured bone in mice.

Acid Phosphatase↗
PubMed1999

Three-dimensional microstructural analysis of human trabecular bone in relation to its mechanical properties.

The purpose of this preliminary study is to explore the relationship between elastic modulus, bone mineral density (BMD), and trabecular microstructure in three dimensions. Twenty cubes of trabecular bone were processed from two lumbar vertebrae obtained from one individual. The BMD of each cube was measured by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography. Each cube was serially scanned by microcomputed tomography to produce three-dimensional data sets. By analyzing these data sets, three-dimensional trabecular microstructural indices of connectivity density and fractal dimension were calculated as well as histomorphometric parameters. The cubes were tested mechanically in a nondestructive manner for measurement of their elastic modulus. This preliminary study showed that: (1) bone mass index is correlated with mechanical properties, with coefficients of correlation ranging from 0.552 to 0.601; and (2) when controlling for BMD, no association could be detected between measures of structural complexity (connectivity density and fractal dimension) and elastic modulus in the craniocaudal direction of human vertebral bodies.

Biomechanical Phenomena↗
PubMed1999

Molecular cloning of human chondromodulin-I, a cartilage-derived growth modulating factor, and its expression in Chinese hamster ovary cells.

Bovine chondromodulin-I (ChM-I) purified from fetal cartilage stimulated the matrix synthesis of chondrocytes, and inhibited the growth of vascular endothelial cells in vitro. The human counterpart of this bovine growth regulating factor has not been identified. We report here the cloning of human ChM-I precursor cDNA and its functional expression in Chinese hamster ovary (CHO) cells. We first identified a genomic DNA fragment which encoded the N-terminus of the ChM-I precursor, and then isolated human ChM-I cDNA from chondrosarcoma tissue by PCR. The deduced amino acid sequence revealed that mature human ChM-I consists of 120 amino acids. In total, 16 amino acid residues were substituted in the human sequence, compared to the bovine counterpart. Almost of all the substitutions were found in the N-terminal hydrophilic domain. In the C-terminal hydrophobic domain (from Phe42 to Val120), the amino acid sequence was identical except for Tyr90, indicating a functional significance of the domain. Northern blotting and in situ hybridization indicated a specific expression of ChM-I mRNA in cartilage. We also successfully determined the cartilage-specific localization of ChM-I protein, using a specific antibody against recombinant human ChM-I. Multiple transfection of the precursor cDNA into CHO cells enabled us to isolate the mature form of human ChM-I from the culture supernatant. Purified recombinant human ChM-I stimulated proteoglycan synthesis in cultured chondrocytes. In contrast, it inhibited the tube morphogenesis of cultured vascular endothelial cells in vitro and angiogenesis in chick chorioallantoic membrane in vivo.

Amino Acid Sequence↗
PubMed1999

Origin of histiocyte-like cells and multinucleated giant cells in malignant fibrous histiocytoma: neoplastic or reactive?

The origin of histiocyte-like cells in malignant fibrous histiocytoma (MFH) remains controversial. To determine whether histiocyte-like cells and multinucleated giant cells show reactive or neoplastic proliferation, we transplanted human storiform-pleomorphic MFH to nude mice and investigated the origin of histiocyte-like cells using the DNA in situ hybridization (ISH) system. In addition, we analyzed the mRNA expression of mouse c-fms and human colony stimulating factor-1 (CSF-1); immunohistochemical expression of markers detectable in cells of monocyte/macrophage lineage. The DNA ISH revealed neoplastic proliferation of fibroblastic cells and bizarre multinucleated giant cells of human origin. Monocyte/macrophage lineage cells were seen in parental tumors, whereas they did not participate in neoplastic proliferation in transplanted tumors. The parental tumors expressed human CSF-1 mRNA and the histiocyte-like cells in transplanted tumors expressed 'mouse' c-fms mRNA. These results suggest that MFH induce infiltration of monocyte/macrophage and CSF-1 is one of the mediators involved in this phenomenon, because the human CSF-1 can act as a ligand to the mouse c-fms. Histiocyte-like cells in MFH should be considered as a reactive monocyte/macrophage lineage rather than as an element of neoplasm.

Aged↗
PubMed1999

Physical and psychological improvements after phase II cardiac rehabilitation in patients with myocardial infarction.

We have designed a new 4-week hospitalized phase II cardiac rehabilitation program. The purpose of the present study is to clarify whether the physical and psychological status of patients with myocardial infarction (MI) improves after participation in our program. Twenty-nine patients (27 males, two females) with acute MI who enrolled in the 4-week hospitalized phase II rehabilitation program were assessed. All patients enrolled in this study had received coronary interventions. The rehabilitation consisted of exercise training, education and counseling. We evaluated the physical and psychological status of the patients before and just after the program, and at a 6-month follow up. The physical status was assessed by exercise tolerance measured by the peak oxygen consumption and anaerobic threshold, frequency of exercise, and serum concentrations of triglyceride, total cholesterol, high-density lipoprotein-cholesterol, and low-density lipoprotein-cholesterol. The psychological status was assessed by the Spielberger state-trait anxiety inventory questionnaire (STAI) and the self-rating questionnaire for depression (SRQ-D). Thirty-four patients (27 men, seven women) with MI who did not participate in our rehabilitation program served as a control group. After participation in our rehabilitation program, exercise tolerance and the serum lipid profiles of the patients were improved compared with those before rehabilitation. These parameters had improved significantly 6 months after rehabilitation. The STAI anxiety score was improved significantly and the SRQ-D depression score tended to be improved just after the rehabilitation program. Regular physical activity was continued even 6 months after the completion of the program. Our hospitalized phase II cardiac rehabilitation program improved the management of cardiac risk factors and the psychological status in patients with MI. This comprehensive program may contribute to the secondary prevention of MI as well as the recovery of physical and psychological activities.

Adult↗
PubMed1999

[Soluble proteins from Staphylococcus aureus can change expression of CD11b and CD62L, but not H2O2 production by human blood granulocytes].

We examined the production of CD11b, CD62L and H2O2 by human peripheral blood granulocytes after treatment with soluble proteins prepared from five different pressure-disrupted strains of Staphylococcus aureus (SaSP) by flow cytometory. Peripheral blood was treated with final SaSP concentrations of 0.05, 0.5 and 5.0 micrograms for 20 min at 37 degrees C. The ratio of CD11b positive granulocytes did not increase at concentrations from 0.05 to 5.0 micrograms, but fluorescence intensity showed about two and three-fold increase, respectively, at concentrations of 0.5 and 5.0 micrograms, in comparison with that of control cells. The ratio CD62L positive cells decreased as follows: 0.5 microgram, 53.8% and 5.0 micrograms, 19.0%, respectively, whereas the control value was 79.8%. Fluorescence intensity also decreased as follows: 0.5 microgram, 10.4 and 5.0 micrograms, 9.2, respectively, whereas the control value was 46.8. Slight induction of H2O2 was found at 5.0 micrograms concentration only. In addition, SaSP treatment granulocytes that stimulated with PMA (1 ng) increased H2O2 production. Thus, SaSP has no beneficial effect against H2O2 production by granulocytes. All of the SaSP preparations indicated similar results for the production of CD11b, CD62L and H2O2 by granulocytes. SaSP effects activation of granulocytes, and the activation may occur independently of protein kinase C.

Bacterial Proteins↗
PubMed1999

[Effect of complement on the production of tumor necrosis factor alpha by human leukocytes with culture supernatants of clinical isolates of Staphylococcus aureus].

Induction of tumor necrosis factor alpha (TNF-alpha) of human leukocytes by overnight culture supernatants of Staphylococcus aureus (S. aureus) (CS) (4 strains) and then the effect of the complement on production of TNF alpha by the treated cells were examined. One-tenth diluted solution of CS was added to Heparinized blood and was incubated for 6 hrs at 37 C in a 5% CO-air humidified incubator. TNF alpha level in the plasma was measured by ELISA. The level in the plasma was different in different CS. The induction of TNF alpha was not found in EDTA-added blood but was found in the EGTA-added them treated with CS, though different levels were showed. Western blotting assay of these plasma samples without EDTA-added blood found the presence of both C5a and C3a. Neither C5a and C3a was found in Heparinized blood treated with a relative concentration to TSST-1, enterotoxin C and alpha (alpha) homolysin contained in CS. Mixture of these toxins induced only 1/6.5 of the TNF alpha amount obtained with the CS. Human leukocytes isolated by Mono.-Poly. resolving solution were cultured with CS in RPMI 1640 medium with or without 10% fresh or heated serum. Production of TNF alpha by the isolated leukocytes was not found under the condition of serum free. But it was found in the presence of fresh serum and also in the presence of heated serum. The addition of CS to RPMI 1640 containing heated serum did not occur naturally in the production of C5a. These results suggest that there is a difference in TNF alpha inductivility to human leukocytes in each strain and that other bacterial components without TSST-1, SEC and alpha-hemolysin are more important to induce TNF alpha. Serum may be necessary to produce TNF alpha by CS-treated cells as a source of factor(s) to interact with bacterial components rather than a source of complement.

Cells, Cultured↗
PubMed1998

Effects of human PTH(1-34) and bisphosphonate on the osteopenic rat model.

It has been demonstrated that the intermittent administration of human parathyroid hormone (hPTH) is beneficial for restoration of bone mass in osteoporotic patients. The mechanisms of anabolic effects of hPTH have been determined by ovariectomized rat models and other larger remodeling animals. However, treatment with hPTH may increase the cancellous bone mass at the expense of cortical bone mass and cessation of the treatment results in rapid bone loss. Efforts have been made to maintain newly formed bone mass after withdrawal of the hPTH treatment. These issues are not well understood. In this article, the authors would like to represent previous studies of their own and others concerning these issues.

Animals↗
PubMed1998

L-selectin-specific autoantibodies in murine lupus: possible involvement in abnormal homing and polarization of CD4+ T cell subsets.

One notable functional abnormality in murine and human systemic lupus erythematosus (SLE) is the defect in the production of IL-2 in association with the deficit in naive CD4+ T cells. The mechanism is unknown, but one idea is that naturally occurring autoantibodies with specificities to the naive CD4+ T cell subpopulation are related to this event. We selected hybridoma monoclonal autoantibodies from SLE-prone (New Zealand Black (NZB) x New Zealand White (NZW))F1 mice that reacted with restricted populations of CD4+ T cells. One of these, H32, was specific for L-selectin, as determined by 1) distribution of Ag H32 on lymphoid cells similar to Mel-14, an epitope of L-selectin; 2) shedding of 80-kDa molecules with epitope H32 from the surface of lymph node cells coincidentally with Mel-14, when stimulated with phorbol ester; 3) cross-inhibitory activities on Ag binding between H32 and Mel-14; and 4) reactivity of H32 with recombinant mouse L-selectin. Pretreatment of 51Cr-labeled lymphocytes from BALB/c mice with H32 significantly inhibited their homing to lymph nodes in vivo. The BALB/c splenic H32+ CD4+ T cell subset produced few cytokines except IL-2, thus corresponding to naive ThP-type cells. This subset was markedly selectively depleted in aged (NZB x NZW)F1 mice. There was an age-associated increase in frequencies and titers of anti-L-selectin autoantibodies in sera from (NZB x NZW)F1 mice. Thus, abnormalities of naive CD4+ T cell subset, including IL-2 production in subjects with SLE, are at least partly attributed to the generation of autoantibodies to L-selectin.

Aging↗
PubMed1998

Neuroprotective effects of pterin-6-aldehyde in gerbil global brain ischemia: comparison with those of alpha-phenyl-N-tert-butyl nitrone.

The superoxide (O2.-) scavenging activity and the neuroprotective effects of pterin-6-aldehyde (P6A), a xanthine oxidase inhibitor, were examined and compared with those of alpha-phenyl-N-tert-butyl nitrone (PBN), a spin trapping agent. The scavenging activity of P6A was more potent than that of PBN by 150-fold in neutrophil/phorbol myristate acetate O2.- generating system. P6A attenuated the neuronal damage with a much smaller dose and a greater efficiency than PBN in global brain ischemia in gerbils. These findings suggest that P6A is a more potent neuroprotective agent than PBN and has possible therapeutic effects against various diseases in which O2.- is involved.

Animals↗
PubMed1998

Origin of bone-forming cells in human osteosarcomas transplanted into nude mice--which cells produce bone, human or mouse?

Osteosarcomas are malignant tumours producing osteoid and/or bone. It is difficult to distinguish tumour bone formation from reactive, based on their morphological features alone. The objective of this study was two-fold: to clarify the origins of bone-forming cells in human osteosarcoma transplanted into nude mice; and to examine the role of bone morphogenetic proteins (BMPs) in the tumour-induced osteogenesis. DNA in situ hybridization was carried out with digoxigenin (DIG) polymerase chain reaction (PCR) labelled DNA probes for human-specific 'Alu' and mouse-specific 'mouse L1 (m-L1)' genes. Human osteosarcoma cells, established cell lines of NOS-1, NOS-2, and HuO9, were transplanted separately into nude mice. Bone-forming cells of the bone in the NOS-1 or NOS-2 tumours were positive for Alu, while they were negative for m-L1. The cells lining the surface of trabeculae in the HuO9 tumour were positive for Alu, but a few of them were also positive for m-L1. The m-L1-positive cells expressed mouse osteocalcin and type 1 collagen mRNAs. These facts suggest that the mouse cells were involved in osteoid synthesis of the HuO9 tumour. The NOS-1 or NOS-2 tumours expressed human BMP 2-7 mRNAs, whereas the HuO9 tumour expressed human BMPs 2, 4, 5, and 7. The osteogenetic potential of the tumours may depend on the expression patterns of BMPs. These results demonstrate two distinct types of bone formation, by tumour cells and by an admixture of tumour and non-tumour cells. The present study showed that the HuO9 tumour produces chimeric bone formation. This is the first report to demonstrate the relationships between tumour cells and non-tumour cells in bone formation, using genetic markers.

Alkaline Phosphatase↗