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Biomedical subjects

Y Sugioka

Publications and source records attributed to Y Sugioka.

At least 55 records · Page 3Linked to original sources

Administration of growth hormone modulates the gene expression of basic fibroblast growth factor in rat costal cartilage, both in vivo and in vitro.

We examined the effect of growth hormone on local growth factor mRNA expression in male Sprague-Dawley rats. Repetitive systemic administration of growth hormone (0.4 IU every 4 h) increased the expression of IGF-I mRNA up to 2.8-fold in costal cartilage tissue compared with controls. Basic FGF (bFGF) mRNA expression gradually increased up to 15.5-fold compared with pre-injection samples, where the mRNA expression was 5.3-times greater than vehicle-injected controls. TGF-beta mRNA showed little changes. Moreover, one microgram/ml of growth hormone enhanced the expression of bFGF mRNA in costal chondrocytes in culture. We conclude that growth hormone increased the local expression of bFGF, as well as that of IGF-I, in cartilage, and suggest that bFGF is directly regulated by growth hormone within a local area.

Animals↗

Three-dimensional MRI reconstructions of musculoskeletal tumors. A preliminary evaluation of 2 cases.

We have developed a new method for three-dimensional (3D) reconstruction of malignant bone and soft-tissue tumors from MRI. Data from transverse images of T2-weighted images were transferred into a personal computer. The contours of tumors, major vessels, major nerves and bones were outlined, whereupon the 3D data were processed into a 3D display, using a solid model. The determination of tumor volume both before and after preoperative adjuvant therapy was quantified. The 3D images allowed a better understanding of the relationship between the tumor and the major vessels and nerves, thereby aiding in preoperative planning. The images also provided a quantitative, reproducible measurement of the effect of adjuvant therapy.

Adolescent↗

Corticosteroid enhances the experimental induction of osteonecrosis in rabbits with Shwartzman reaction.

Bacterial endotoxic reactions can cause osteonecrosis in humans by disseminated intravascular coagulation. The authors first used a combination of the Shwartzman reaction and corticoid injections in rabbits to develop a new animal model of osteonecrosis. This model showed a significantly higher incidence and wider area of osteonecrosis in the femur and humerus than that found in rabbits with either Shwartzman reaction or steroid injection alone. Osteonecrosis was observed in several foci that were distributed from the diaphysis to the epiphysis in both bones. Histologically, the bone marrow cells underwent necrosis, whereas the bone trabeculae demonstrated either empty lacunae or pycnotic nuclei of osteocytes. Exogenous steroids appeared to potentiate the Shwartzman reaction and the magnitude of osteonecrosis, perhaps by increasing endothelial damage and hypercoagulability of those intraosseous and extraosseous vessels that subsequently thrombosed. This model may not only be useful in clarifying the etiology and early pathogenesis of human osteonecrosis after corticoid therapy, but also in designing pharmaceuticals for prevention and early treatment.

Animals↗

The establishment and characterization of a peripheral neuroepithelioma cell line in soft tissue of extremity.

BACKGROUND: The histogenetic and biologic features of peripheral neuroepithelioma (PN) are still a matter of controversy. More detailed analyses might be facilitated by permanent PN cell lines. However, there have been only a few reports on the establishment of a PN cell line. EXPERIMENTAL DESIGN: We established and characterized a PN cell line and further carried out experiments for potentiality of drug-induced neural differentiation. RESULTS: The cultured cells were spindle shaped with slender cytoplasmic processes. The histologic features of transplanted tumors in nude mice were essentially the same as those of the original tumor. Immunohistochemically, the neuroectodermal characteristics of the cell line were demonstrated by positive stain for neuron specific enolase, glial fibrillary acidic protein, S-100 protein, neurofilament, and beta 2-microglobulin. Ultrastructurally, microtubules and dense core granules were observed in the cultured cells. Northern blot analyses revealed that c-myc was overexpressed in the cell line, whereas N-myc was not. The cell line showed neural differentiation after treatment with cAMP elevating reagents and nerve growth factor (NGF). The synergistic effects of cAMP analog and NGF on the neurite outgrowth were also observed. Furthermore, a cAMP-dependent protein kinase (PKA) inhibitor strongly blocked the action of cAMP analog, although it was not able to inhibit the same action of NGF. These findings suggested that the neurite outgrowth induced by the cAMP analog requires activation of PKA, whereas the same actions of NGF do not mediate such a pathway involving PKA activation. CONCLUSIONS: This is, to our knowledge, the first NGF responsive cell line derived from PN. This cell line might be valuable for further investigations of signal transduction pathways induced by cAMP analogs and NGF, for more precise analyses of the biological characteristics of PN, and finally, for the identification of differences between PN and several related tumors.

Adult↗

[Clinical usefulness of dipyridamole loading 99mTc-tetrofosmin myocardial scintigraphy].

This study performed to establish the most suitable method in one-day protocol and to evaluate clinical usefulness of 99mTc-tetrofosmin myocardial scintigraphy after dipyridamole infusion. Image quality and liver overlapping of the myocardial SPECT were evaluated in 107 patients with old myocardial infarction (42 cases), angina pectoris (53 cases) and others (12 cases). Left ventricular wall motion and coronary artery stenosis were compared to myocardial uptake score in 55 patients who received cardiac catheterization. The suitable image quality was acquired in early SPECT images using 259 MBq of 99mTc-tetrofosmin. The overlapping between inferior wall and liver uptake was able to minimize over 45 minutes interval from injection of 99mTc-tetrofosmin to data acquisition. The segments of normal wall motion had no perfusion defect of the myocardial SPECT in all cases (100% (148/148)). The segments of abnormal wall motion had decreased myocardial uptake of the myocardial SPECT (77% (24/31)). The agreement between coronary artery stenosis and decreased myocardial uptake was 96% (24/25) in right coronary artery, 87% (26/30) in left anterior descending coronary artery and 83% (19/23) in left circumflex coronary artery. These data suggests that image quality of dipyridamole loading 99mTc-tetrofosmin myocardial scintigraphy. Myocardial perfusion in the 99mTc-tetrofosmin myocardial scintigraphy is good correlation to both left ventricular wall motion and coronary artery stenosis.

Adult↗

Exacerbation of established collagen-induced arthritis in mice treated with an anti-T cell receptor antibody.

OBJECTIVE: To investigate the effect of T cell depletion on established collagen-induced arthritis (CIA) in mice, using monoclonal antibodies (MAb) to T cell receptor alpha/beta (TCR alpha/beta). In addition, experiments using anti-CD3 MAb were performed for comparison. METHODS: CIA was induced in male DBA/1 mice by immunizing them twice with bovine type II collagen (CII). The arthritis score and anti-CII antibody titers were examined serially. Proportions of T cells were determined by fluorescence-activated cell sorter (FACS) analysis on spleen cells or peripheral blood cells. RESULTS: When anti-TCR alpha/beta MAb was injected on the day of CII priming, no arthritis was detected in association with depressed anti-CII antibody titers. Unexpectedly, however, when MAb was given after arthritis was established, a rapid exacerbation of arthritis was observed, which resulted in ankylosis of most joints. Anti-CII antibody titers were not affected. The addition of anti-TCR gamma/delta MAb had no effect on the augmented arthritis. T cell depletion by anti-CD3 MAb during established CIA also caused an enhancement of arthritis, which was, however, weak and only transient. FACS analysis revealed that the early improvement of arthritis after the transient augmentation seen in the mice treated with anti-CD3 MAb paralleled the early recovery of alpha/beta T cells in the periphery. CONCLUSION: The present results support the concept that alpha/beta T cells, in general, may play a regulatory role in the clinical course of murine CIA after disease onset. Therefore, caution is recommended when using intensive T cell-targeted therapy in patients with rheumatoid arthritis.

Animals↗

Evaluation of carcinogenicity and chronic toxicity associated with orthopedic implants in mice.

The carcinogenicity and chronic toxicity of 316L stainless steel, nickel, Ti-6A1-4V, hydroxyapatite (HA)-coated Ti-6A1-4V, aluminum oxide containing yttrium oxide, and zirconium oxide containing yttrium oxide were evaluated by implanting solid rods of each material in the thigh muscle of C57BL/6N mice for 24 months. Nickel alloy showed high carcinogenic and toxic potencies, whereas other materials showed no evidence of them. Tumors retaining nickel alloys were malignant fibrous histiocytoma or fibrosarcoma. In some cases, lymphomata that seemed to develop spontaneously were found around the implants because lymphocytes were known to accumulate in chronic inflammatory lesions, and this phenomenon also might be applied to lymphoma.

Alloys↗

Legg-Calvé-Perthes' disease in the Russell-Silver syndrome. A report of two cases and a review of the literature.

Perthes' disease was seen in two boys, aged 6 1/2, with the Russell-Silver Syndrome. Both presented with groin or thigh pain in their shortened side together with a progressive limp. They were treated conservatively, and when reviewed 6 1/2 years after diagnosis the lesions of the hip had improved clinically and radiographically. The leg length discrepancy did not increase.

Abnormalities, Multiple↗

In vitro assay of the invasive potential of malignant bone and soft tissue tumours through basement membranes.

We have used reconstituted basement membrane molecules which have formed into barriers in order to investigate the invasive potential of malignant bone and soft tissue tumour cells in vitro. A number of cell lines established from human malignant tumours demonstrated a high degree of invasiveness, although fibroblasts showed no ability to penetrate the basement membrane barrier. H-ras oncogene transfected cells into the fibroblasts were much more invasive than the parent lines. Primary cultures of malignant tumour cells demonstrated invasiveness, while those of nonmetastatic cells and fibroblasts did not. The binding of tumour cells to laminin in the basement membranes was found to induce secretion of collagenase and motility which are crucial factors for invasion. A synthetic peptide, Tyr-Ile-Gly-Ser-Arg, was able to suppress the invasiveness of HT1080 human fibrosarcoma cells, and also reduced lung colonisation in vitro. The results suggest that the in vitro assay was useful, firstly to determine the invasive potential, secondly to investigate the mechanism of invasion, and finally to development treatment against invasion and metastases.

Basement Membrane↗

Remodelling of bone around hydroxyapatite and titanium in experimental osteoporosis.

The affinity of the tibia bone for cylinders of hydroxyapatite (HA) and Ti-6Al-4V was investigated in three experimental animal models: intact rat tibiae, ovariectomized rat tibiae and ovariectomized plus neurectomized rat tibiae. The affinity index (the length of bone directly apposed to the implant/the total length of the bone-implant interface x 100%) was calculated. In intact and ovariectomized tibiae, no significant difference existed between the affinity index of HA and Ti-6Al-4V. In ovariectomized plus neurectomized tibiae, the affinity index of HA was greater than for Ti-6Al-4V from 8 to 24 wk after implantation (8 wk, P < 0.05; 12 wk, P < 0.005; 24 wk, P < 0.05). The affinity index of Ti-6Al-4V in normal tibiae was greater than that in ovariectomized or ovariectomized plus neurectomized tibiae. There was no significant difference of the affinity index of HA between normal, ovariectomized or ovariectomized plus neurectomized tibiae. Osteoporotic bone demonstrated a greater affinity to HA than Ti-6Al-4V in an experimental animal model.

Animals↗

Effect of surface roughness of hydroxyapatite-coated titanium on the bone-implant interface shear strength.

We have investigated the bone-implant interface shear strength of hydroxyapatite (HA)-coated Ti-6Al-4V (HA-coating A) (roughness average, Ra = 3.4 +/- 0.5 microns) and HA-coated Ti-6Al-4V with a rougher surface (HA-coating B) (Ra = 8.4 +/- 1.8 microns). There was no significant difference between HA-coating A and HA-coating B implants with respect to the bone-implant interface shear strength as determined in push-out tests using the transcortical model in adult dogs. The bone-implant interface shear strength of bead-coated porous Ti-6Al-4V was significantly greater than that of both HA-coating A and HA-coating B implants. The failure site, as determined by scanning electron microscopy, was the coating-substrate interface, not the coating-bone interface. This indicates a need to protect the HA coating from the direct shear forces. HA coating enhances early bone growth into the porous surface of the implant. Long-term fixation should depend on bone anchoring to this porous surface. Hydroxyapatite coatings must be developed which do not obstruct the pores of the surface of the implant.

Analysis of Variance↗

Spontaneous hemarthrosis of the knee in the elderly: etiology and treatment.

The etiology of spontaneous hemarthrosis of the knee in elderly patients with osteoarthritis is still unknown. This report discusses six cases, one that was managed with conservative measures and five in which arthroscopic evaluation and treatment were performed. These patients were elderly individuals whose chief complaint was knee pain and swelling about the joint, without an obvious history of trauma. Each of the five operative patients underwent arthroscopic surgery after repeated hemorrhage into the joint that did not respond to serial aspirations of large amounts of blood and immobilization, using a knee immobilizer. The roentgenograms of each involved knee demonstrated lateral compartment osteoarthritis. Arthroscopic examination revealed a degenerative flap tear of the posterior horn of the lateral meniscus in the five operative cases. These patients underwent arthroscopic resection of the injured lateral meniscus and did not experience a recurrence of the hemarthrosis. The origin of the bleeding was most likely from the peripheral arteries of the posterior horn of the lateral meniscus.

Aged↗

High-density proteoglycan induces specific suppression of adjuvant-induced arthritis in rats.

In vitro data support the view that T cells in adjuvant-induced arthritis (AIA) respond to the proteoglycan (PG) component of articular cartilage; however, an in vivo role for PG in AIA has yet to be shown. To do so, we examined the effects of pretreatment with bovine cartilage high density PG (HDPG) on AIA induced by heat-killed Mycobacterium butyricum in Lewis rats. Purified bovine cartilage HDPG emulsified in Freund's incomplete adjuvant (FIA) was injected intradermally into rats 7 days before challenge with Myco. butyricum. The severity of arthritis was significantly suppressed in rats pretreated with as little as 0.75 mg of HDPG, and the arthritis was completely suppressed in rats pretreated with 3.0 mg of HDPG. This suppression was specific, as the same treatment did not protect against type II collagen-induced arthritis. Suppression of AIA is primarily a property of the HDPG, as suppression of the arthritis was significantly less with pretreatment with 3.0 mg of middle density fractions of PG, and no suppression was observed with pretreatment with the lowest density fraction of PG. Thus we report that pretreatment with cartilage HDPG, but not lower density PG, can induce specific suppression of AIA. These in vivo results support the view that immunity to cartilage HDPG plays a major role in the pathogenesis of AIA, and can induce specific tolerance to this type of arthritis.

Animals↗

Autologous blood transfusion with recombinant erythropoietin treatment. 22 arthroplasties for rheumatoid arthritis.

12 anemic and 10 non-anemic patients with rheumatoid arthritis were treated with recombinant human erythropoietin (rHuEPO) before arthroplasty. The patients received 400-800 units/kg of rHuEPO subcutaneously once a week. Autologous blood was collected after the hemoglobin concentration was increased by 5 percent or more. All but one of the patients responded to the treatment. They were given 1-3 units of autologous blood, and underwent the operation without homologous blood transfusion. The mean duration of the treatment was 1 month. In 1 patient with severe anemia, additional transfusion with 2 units of blood was necessary during the operation. In all patients, there was a tendency for the hemoglobin response ratio to rHuEPO to correlate negatively with the initial CRP levels. The treatment did not affect the patients' clinical rheumatologic condition and there were no adverse effects. These results demonstrated that the treatment with subcutaneous rHuEPO is both effective and non-toxic and can therefore eliminate the need for homologous blood transfusion in anemic patients undergoing arthroplasty for rheumatoid arthritis.

Adult↗

Ethylene oxide sterilization of bone grafts. Residual gas concentration and fibroblast toxicity.

We examined the concentration of ethylene oxide in bone allografts after gas sterilization. Chips of the human femoral head were investigated. Residual gas concentration was determined by gas chromatography after the bone chips had been subjected to defatting and freeze-drying, followed by ethylene oxide gas sterilization. Bones were prepared in various ways in an attempt to reduce the concentration of residual ethylene oxide. The concentration was higher when gas sterilization was performed before freeze-drying than when it was done afterwards. An experiment performed with fibroblasts showed the high toxicity of residual ethylene oxide in bone chips, even when the concentration was very low. The growth of fibroblast was reduced more in medium which had been shaken with bones sterilized with ethylene oxide before freeze-drying than in medium which had been shaken with bones sterilized after freeze-drying. The higher residual ethylene oxide concentrations resulted in a decrease in fibroblastic culture activity. Our experiment showed the importance of reducing the residual ethylene oxide gas concentration. Defatting and freeze-drying result in lower residual ethylene oxide concentrations.

Bone Transplantation↗

[Assessment of myocardial contraction and relaxation with 99mTc-tetrofosmin multi-gated myocardial SPECT].

Myocardial relaxation at the diastolic phase was not evaluated by multi-gated myocardial SPECT, although myocardial contraction at the systolic phase was studied by percent wall thickening and Bull's eye methods. We make out a myocardial volume curve and report to evaluate the myocardial relaxation using multi-gated myocardial SPECT. The study population consisted of 3 normal human subjects (3 male, 32-37 years old), 10 idiopathic cardiomyopathy, 10 coronary artery disease and 1 hypertensive heart disease combined with aortic regurgitation. All cases were injected 555 MBq of 99mTc-tetrofosmin (Amersham Healthcare Corporation) intravenously at rest. A triple detector gamma-camera (GCA-9300A, Toshiba Medical, Japan) and a data processing computer (GMS-5500A, Toshiba Medical, Japan) were used in this study. A cardiac cycle (R-R interval) was divided by 16 frames (50-80 msec per 1 frame). Eight myocardial volume curves were calculated at the anterior wall, apex and inferior wall of the vertical long axis view and were calculated at the septal wall, apex and lateral wall of the horizontal long axis view, respectively. The patterns of the myocardial volume curves were classified into 5 patterns (Normal pattern (N), Delayed Contraction pattern (DC), Delayed Relaxation pattern (DR), Mixed pattern (M) and Normal pattern with Decreased amplitude (ND)). Myocardial uptake was evaluated visually of grading into severe hypertrophy (5), hypertrophy (4), normal (3), mild hypoperfusion (2), hypoperfusion (1) and perfusion defect (0). We compared patterns of the myocardial volume curves to myocardial uptake in the same segments. It was possible to detect myocardial edge of the total 16 frames with 50-60% threshold in the normal volunteer and in patients with hypertrophic cardiomyopathy and to make a myocardial volume curve. The region of the severe myocardial perfusion defect could be detected with 20% threshold in patients with old myocardial infarction. In comparison with myocardial volume curves and myocardial uptake, 74.6% in the N pattern had a normal uptake (3), 66.7% in the ND pattern had a normal uptake (3), 61.5% in the DC pattern had a hypoperfusion segment (0, 1 or fill-in to normal uptake), 44.4% in the DR pattern had a hypertrophic segment (4, 5 or fill-in to increased uptake). The pattern of myocardial volume curve indicates myocardial contractility and relaxation in each myocardial segment.

Adult↗