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Biomedical subjects

K Ono

Publications and source records attributed to K Ono.

At least 613 records · Page 34Linked to original sources

Prognostication of osteonecrosis of the femoral head in patients with systemic lupus erythematosus by magnetic resonance imaging.

To detect and prognosticate osteonecrosis of the femoral head in the preradiographic stage, 60 patients with systemic lupus erythematosus who had normal hip radiology were followed prospectively for a mean period of 5 years (range, 3-7 years) using magnetic resonance imaging (MRI). The first MRI scans showed a low intensity band in the femoral head of normal fat intensity on T1 weighted images in 16 hips of 9 patients. The MRI findings were used to classify the lesions into three categories. Type A (six hips): the lesions occupied the medial one third or less of the weight bearing portion. Type B (two hips): the lesions occupied the medial two thirds or less of the weight bearing portion. Type C (eight hips): the lesions occupied more than the medial two thirds of the weight bearing portion. At the final followup, all of the Type A and one of the Type B hips were classified as being in Stage 1, and one Type B and two Type C hips had progressed to Stage 2. The MRI appearance of six Type C hips had changed from a band to an inhomogeneous pattern with the femoral head progressing to collapse on radiographs 2-5 years after the diagnosis of systemic lupus erythematosus. The remaining hips, which had been classified as normal at the first MRI, maintained a normal appearance, except for one hip that developed a Type A lesion. The presence of a low intensity band on T1 weighted images was an early specific finding of osteonecrosis of the femoral head, and extensive lesions demarcated by band images signified a poorer prognosis in systemic lupus erythematosus patients. If no MRI abnormalities appeared after 1 year of the startup treatment for systemic lupus erythematosus, there was little risk of femoral head collapse based on the subsequent clinical course of the patients followed in the current study.

Adolescent↗

Ectopic ossification associated with osteoid osteoma in the acetabulum. A case report.

Ectopic bone formation was associated with osteoid osteoma in the anterior rim of the acetabulum. A factor, which has been speculated to be secreted from the nidus and is responsible for increased osteoblastic activity, also seemed to have the capacity to stimulate young mesenchymal cells to differentiate into an osteogenic pathway. A case of a 35-year-old woman with osteoid osteoma, which caused ectopic ossification adjacent to the nidus, is presented.

Acetabulum↗

Transfilter bone induction by Chinese hamster ovary (CHO) cells transfected by DNA encoding bone morphogenetic protein-4.

This study was undertaken to identify the factor responsible for classical transfilter bone induction by a murine osteosarcoma. Chinese hamster ovary (CHO) cells were transfected with the complementary DNA (cDNA) for bone morphogenetic protein-4 (BMP-4) that was purified from a murine (Dunn) osteosarcoma. Diffusion chambers were filled with the cells expressing the gene for BMP-4 and implanted subcutaneously into the flanks of ICR strain nude mice. Ectopic transfilter bone formation was seen consistently on the outer surfaces of the cellulose acetate membranes of chambers containing transfected cells at three weeks after implantation. Bone was not observed on chambers loaded with nontransfected CHO cells. The transfected CHO cells were inoculated into nude mice to form tumors, which were then homogenized, defatted, and bioassayed also in the ICR, nu/nu mice. The cell-free implants consistently elicited new bone and marrow within three weeks, whereas the control implants consisting of nontransfected tumor were not osteoinductive. These experimental results suggest that BMP-4 is one of the molecules responsible for the transfilter bone induction by vital Dunn osteosarcoma cells reported by Heiple and for the ectopic bone induction after implantation of devitalized, freeze-dried Dunn osteosarcoma tissue described originally by Amitani.

Animals↗

Estimation of the initial slope of the cell survival curve after irradiation from micronucleus frequency in cytokinesis-blocked cells.

We have already reported that the alpha/beta ratio of the cell survival curve could be estimated from the micronucleus frequency in cytokinesis-blocked cells treated with cytochalasin-B after irradiation. In this paper, we investigate the direct relationship between the alpha value and the appearance of micronuclei. Cells of the SCCVII, RIF-1, EMT6, V-79, CHO, HeLa and human esophageal cancer cell lines were used for the study. Low-dose-rate irradiation was used to determine the alpha component of the relationship between dose and micronucleus frequency according to the linear-quadratic (LQ) model. A reduction of the dose rate from 3.09 to 0.0142 Gy/min correspondingly decreased the micronucleus frequency; however, the fraction of binucleate cells without micronuclei was not affected in SCCVII and RIF-1 cells. When this fraction was defined as the normal nuclear division fraction, it decreased exponentially as a function of radiation dose. Then dose vs normal nuclear division fraction (NNDF) was fitted as follows: -ln NNDF = aD + C, where D is radiation dose in grays and C is constant. The slope of the dose vs normal nuclear division fraction was not affected by dose rate. The correlation was also explored between the slope (a) and the alpha value of the cell survival curve determined by the colony formation assay in cells of eight cell lines. These two values showed extremely high agreement: alpha = 1.01 a + 0.00795 (r = 0.99, P < 0.01). This assay was applied to estimate the alpha value of the cell survival curve of human esophageal cancer cell lines established from surgical specimens.

Animals↗

Prognostication of nontraumatic avascular necrosis of the femoral head. Significance of location and size of the necrotic lesion.

After reviewing the radiographs of 149 hips with nontraumatic avascular necrosis of the femoral head (ANFH), a method for evaluating the prognosis in patients with ANFH in its early stages was devised. The evaluation was made primarily by classifying the radiographic features of each involved femoral head according to the location and size of its necrotic lesion. In a group of 120 hips, massive collapse occurred without exception in cases where both of the following criteria were true. First, in a standing position, the necrotic lesion involved more than the medial one third of the weight-bearing surface from the anteroposterior view. Second, from the lateral view, the lesion occupied more than 43% of the total area of the femoral head. However, in 29 hips, the extent and size of necrosis was less than the above, and no massive collapse occurred during the follow-up period of three to 15 years (average, 5.2 years). In these 29 hips, function was preserved. These data suggest that hips with a high risk for collapse can be reliably selected during the early stages of ANFH.

Adrenal Cortex Hormones↗

[A case of unusual shaped pulmonary arteriovenous fistula].

Autopsy findings of pulmonary arteriovenous fistula (PAVF) was initially described by Churton in 1897. Since then, several hundreds of cases have been reported in Europe and the United States. In Japan, there has recently been an increase in case reports of PAVF. PAVF seems to be no longer a rare disorder in Japan. Several morphological classifications of PAVF have been reported. One of these classifies PAVF into 1) solitary types 2) multiple types and 3) diffuse telangiectasia. Another, for example, classifies the disorder into the following 3 types: 1) multiple telangiectasia 2) pulmonary arterial aneurysm and 3) pulmonary artery-left atrial communications. Many other classifications have been proposed. In the solitary type (PA aneurysmal type), fistulas are located at the relatively large, central vessels. Here we report a case of PAVF which presented not as a solitary aneurysm but rather as a distended and tortuous anomalous vessel.

Arteriovenous Fistula↗

[Two cases of aortoesophageal fistula due to ruptured thoracic aortic aneurysm].

Aortoesophageal fistula due to ruptured thoracic aortic aneurysm is uncommon, and exhibits extremely high mortality. We experienced two cases of such lesion. The first case showed aneurysm in the aortic arch closed with Dacron patch but leaving the esophageal defect. The patient died of an infection of the patch graft after oral feeding. The second case was demonstrated infected aneurysm of the descending aorta. The patient was rescued by primary operation, replacement of the aorta by an artificial graft and resection of the esophagus, and the secondary operation, reconstruction of the esophagus. We recommend resection of aneurysm and the esophagus as well in the aspect of lower post-operative infection in the graft and of the better prognosis of the lesion.

Aged↗

Partial activation of the pyruvate dehydrogenase kinase by the lipoyl domain region of E2 and interchange of the kinase between lipoyl domain regions.

The binding of the pyruvate dehydrogenase (E1) component and the E1-specific kinase to the core-forming dihydrolipoyl acetyltransferase (E2) component facilitates a severalfold enhancement in the rate at which the kinase phosphorylate E1 (i.e. versus free kinase phosphorylating free E1). The kinase and E1 associate with small exterior linker region-connected domains in the E2 structure. The kinase binds to one of two lipoyl domains, and the E1 component binds to a domain in E2"s structure between the lipoyl domain region and the inner domain. Sixty of the latter domains assemble to form a dodecahedron-shaped inner core. Binding of the kinase to a detached lipoyl domain region enhanced kinase activity. This bi-lipoyl domain fragment induced a 2-fold enhancement in the slow rate of phosphorylation of peptide substrate and intact E260 gave only a 50% higher rate. In contrast, the lipoyl domain fragment gave only a 40% enhancement in the faster rate of phosphorylation of E1; whereas the rate of phosphorylation of E1 was markedly increased (4-10-fold depending on conditions) by kinase interaction with the intact E2 core. Binding of E1 to an E2 structure lacking only the bi-lipoyl domain region did not enhance kinase activity. Thus, binding of the kinase to the lipoyl domain region elicits a structural change which enhances kinase activity; however, other processes are required to explain the very large enhancement in phosphorylation of E1 effected by intact E2 core. Among the latter is a need for a mechanism allowing one kinase molecule to phosphorylate many E1 tetramers, whereas both E1 and the kinase stay bound to the oligomeric E2 core (i.e. phosphorylation appears to be much faster than the dissociation of either the kinase or E1 tetramers from E260 core). Exposure of kinase bound to the lipoyl domain fragment to intact E2 core for 10 s allowed a transition to a maximal (7-fold) activation of the kinase. In the opposite direction, an increasing level of the free bi-lipoyl domain fragment rapidly reduced, in a concentration-dependent manner the activity of kinase bound initially to intact E2. The data strongly support kinase transfer between free lipoyl domains and the intact E2 core and fit about a 12-fold tighter binding of the kinase to intact E2 cores over binding to free lipoyl domains. Such an interchange of the kinase between these E2 structures was confirmed by sucrose gradient studies.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetyltransferases↗

Specific targeting and killing activities of anti-P-glycoprotein monoclonal antibody MRK16 directed against intrinsically multidrug-resistant human colorectal carcinoma cell lines in the nude mouse model.

Anti-P-glycoprotein (P-gp) monoclonal antibody, MRK16, and its F(ab')2 fragment were evaluated for its therapeutic efficacy to P-gp-mediated multidrug resistant human colorectal carcinoma cell lines in a nude mouse model. In a blood clearance experiment, 125I-labeled MRK16 had a half-life (16 h) 7 times longer than its F(ab')2 fragment (half-life of 1.8 h) in circulation in nude mice, and approximately 16 and 5% of MRK16 were retained on days 10 and 20 after injection, respectively. In biodistribution experiments using nude mice bearing HCT-15, an intrinsically resistant cell line, 125I-labeled MRK16 accumulated at the tumor site significantly higher than its F(ab')2 fragment as revealed by the percentage of injected dose/g of tissue values (7.4 versus 0.6%) on day 3 after injection. In contrast, the tissue to blood ratio at the tumor site of the MRK16 was significantly lower than that of its F(ab')2 fragment (1.2 versus 10.5). Specific targeting of the MRK16 F(ab')2 fragment to the P-gp-positive tumor (HCT-15) but not to the P-gp-negative tumor (COLO 205) was observed in the nude mice bearing both tumors. In the therapeutic efficacy tests, when administered i.v. 3 times on days 1, 4, and 7 after tumor s.c. inoculation, MRK16 alone showed the significant inhibition of tumor growth of P-gp-positive cell lines, HCT-15, DLD-1, SW480, and SW1417 in contrast to cases of P-gp-negative cell lines, COLO 205 and KM20L2. This inhibitory effect of MRK16 was enhanced in combination with Adriamycin, which alone hardly inhibited the tumor growth. However, MRK16 F(ab')2 fragment alone, even at 1 mg/mouse, had little inhibitory effect on the growth of HCT-15 in the same treatment schedule. When administered at early palpable stage, the degree of HCT-15 tumor growth suppression depended on the number of MRK16 injections. At more progressed stages, treatment with MRK16 alone showed little antitumor activity but when combined with Adriamycin resulted in significant suppression of tumor growth. The present results suggest that MRK16 may be useful for in vivo immunoscintigraphy and immunotherapy of multidrug-resistant colorectal carcinoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Clonal analysis for developmental potential of chick periosteum-derived cells: agar gel culture system.

The developmental potential of periosteum-derived cells was clonally assessed with an agar gel culture system. Morphologically, two types of colonies were predominantly observed. By immunocytochemical observation with antibodies against aggrecan or bone Gla protein, one type of colony was judged to be chondrogenic, and the other osteogenic. By chronological observation, each type of colony did not convert to the other. Supplementation with transforming growth factor (TGF)-beta 1 shortened the time course of chondrogenesis and also increased colony forming efficiency of chondrogenic colonies. On the other hand, colony forming efficiency of osteogenic colonies decreased with TGF-beta 1 treatment, whereas the time course of osteogenesis remained unaffected. These observations suggest that there are both committed osteoprogenitor and chondroprogenitor cells present in the periosteal cell population, and TGF-beta 1 stimulates proliferation and differentiation of chondrogenic cell population by its targeted action.

Agar↗

Aggressive pulmonary metastasectomy for soft tissue sarcomas.

BACKGROUND: To evaluate the efficacy of aggressive pulmonary metastasectomy for treating soft tissue sarcomas, the clinical data on the surgical management of 23 patients with extensive pulmonary metastases from soft tissue sarcomas were reviewed. METHODS: Between January 1973 and April 1991, 9 male patients and 14 female patients were treated. Their ages ranged from 13-68 years (median, 42 years). Twenty-one patients (91%) had bilateral and multiple metastases, and two patients had solitary metastasis. The number of resected metastatic nodules ranged from 1-110 (mean, 30.5). As an initial surgical approach, median sternotomy was used on 18 patients and lateral thoracotomy on 5 patients. Eleven patients underwent two or more explorations for recurrent metastases using lateral thoracotomy. The neodymium:yttrium-aluminum-garnet (Nd:YAG) laser was adopted in 10 patients since 1986. RESULTS: The actuarial 2-year and 5-year survival rates after the first pulmonary resection were 49.7% and 24.8%, respectively. Histologic type (alveolar soft part sarcoma versus synovial sarcoma, P < 0.025), histologic grade (G1 and G2 versus G3, P < 0.01), and metastatic localization (subpleural versus extrapleural, P < 0.005) were the most significant prognostic factors for aggressive pulmonary metastasectomy of soft tissue sarcomas. Application of laser surgery, absence of local recurrences, and absence of extrapulmonary metastases before pulmonary resection also correlated with better prognosis with borderline significance. CONCLUSIONS: Aggressive pulmonary metastasectomy for soft tissue sarcomas is a recommended procedure, even in the case of extensive metastases. The combination of median sternotomy and Nd:YAG laser-assisted surgery is a useful technique, especially in bilateral multiple pulmonary metastases.

Adolescent↗

Histologic grading in soft-tissue sarcomas. An analysis of 194 cases including AgNOR count and mast-cell count.

In order to establish a new histologic grading system for STS, we evaluated histologic prognostic factors. For this purpose, we selected 194 patients with STS: 31 in the upper extremities, 63 in the trunk, and 100 in lower extremities. All the patients were treated by surgery, followed by chemotherapy in 74 cases, radiotherapy in 11, chemotherapy and radiotherapy in 30, or no adjuvant treatment in 79. Histologic factors evaluated were mitotic count, extent of necrosis, cellularity, cellular pleomorphism, extent of myxoid change, sclerosis, non-specific histologic diagnosis, counting of reaction product in silver stain for nucleolar organizer regions (AgNOR) and mast-cell counts. Univariate analysis revealed mitotic count, necrosis, cellularity, cellular pleomorphism, non-specific histologic classification, AgNOR count and mast-cell count to be significantly related to prognosis. Multivariate analysis revealed that AgNOR count, cellularity and necrosis were independent prognostic factors. A new grading system was introduced: low-grade, intermediate-grade and high-grade. The survival between each group were significantly different; the 5-year-survival rate in patients of the low-, intermediate- and high-grade groups was 87%, 74% and 35% respectively. Our findings suggest that this histologic grading system may be useful for making therapeutic decisions.

Adolescent↗

Osteoarthritis associated with mild chondrodysplasia in transgenic mice expressing alpha 1(IX) collagen chains with a central deletion.

Type IX collagen, containing molecules of the three distinct polypeptides alpha 1(IX), alpha 2(IX), and alpha 3(IX), is an interesting hybrid extracellular matrix component in cartilage and eye tissues, with the properties of both a proteoglycan and a collagen. The alpha 1 (IX) chain has two forms, as a result of the tissue-specific utilization of two alternative promoters; the alpha 2(IX) chain carries a covalently attached glycosaminoglycan side chain. We have introduced a gene construct controlled by a tissue-specific promoter/enhancer and expressing a truncated alpha 1(IX) chain into mice. Examination of the offspring of two different founders revealed pathological changes similar to osteoarthritis in the articular cartilage of knee joints. In addition, mice homozygous for the transgene developed mild chondrodysplasia (i.e., mild dwarfism, anterior tonguing in the vertebral bodies, and ophthalmopathy). The relative ratio of transgene product to the endogenous alpha 1(IX) chain was approximately one in homozygotes and less than one in heterozygotes. Therefore, the phenotypic severity correlated well with the level of transgene expression. These findings suggest that mutations in type IX collagen genes may cause certain forms of osteoarthritis and chondrodysplasia in humans.

Animals↗

Critical role of a lipoyl cofactor of the dihydrolipoyl acetyltransferase in the binding and enhanced function of the pyruvate dehydrogenase kinase.

Mammalian pyruvate dehydrogenase kinase binds to the lipoyl domain region of the core structure forming dihydrolipoyl acetyltransferase (E2) subunits. The bound kinase has a greatly enhanced rate in phosphorylating E2-bound pyruvate dehydrogenase (E1) tetramers versus the rate at which resolved kinase phosphorylates dissociated E1. This E2-activated kinase function was completely prevented by selective alkylation of reduced lipoyl groups while kinase and E1 binding to the E2 core were retained. Selective removal of lipoyl cofactors from intact E2 by treatment with Enterococcus faecalis lipoamidase decreased kinase activity by 4-fold and caused selective release of a major portion of the kinase from E2 in a sucrose-step gradient procedure. Selective and reversible modification of the lipoyl groups of E2 subunits also allowed the kinase to be dissociated under mildly chaotropic conditions. Thus, the lipoyl prosthetic group on one of the two lipoyl domains of E2 subunits is critically important for maintaining E2-activated kinase function and contributes to binding of the kinase to E2. Since removal of the lipoyl group weakened kinase binding to E2 more than modifying lipoyl thiols, it is suggested that the hydrophobic inner portion of the lipoyl conjugate (i.e., lysine carbons and C1 to C5 of the lipoic acid) is important in the binding of the kinase.

Acetylation↗

Effects of solvent preservation with or without gamma irradiation on the material properties of canine tendon allografts.

We studied the effects of solvent preservation with and without gamma irradiation on the material properties and morphology of canine tendons. Twenty-four paired tendons were harvested from both hind limbs of eight dogs. The tendons from the right legs were divided into three treatment groups of eight tendons each. In the first group, the tendons were subjected to solvent preservation for sterilization and drying (solvent group). In the second group, the tendons were treated in the same manner and then were sterilized by gamma irradiation (solvent/gamma group). The same treatments were applied to the tendons in the third group but in reverse order (gamma/solvent group). Tendons from the contralateral left legs were frozen immediately for use as controls for each corresponding treatment group. Histologically, the tendons treated with solvent, with or without gamma irradiation, had a more prominent wavy pattern in the collagen fibers than the control tendons. Mechanically, the tangent moduli for the solvent, solvent/gamma, and gamma/solvent groups were 58, 53, and 99%, respectively, of each contralateral control. The respective tensile strengths were 85, 39, and 86% of that of the contralateral control. The tendons in the solvent/gamma group underwent the most severe changes in material properties; the tendons in the gamma/solvent group changed the least. This suggests that gamma irradiation followed by solvent drying is the procedure of choice for the preservation of tendon allografts.

Animals↗

Usefulness of argyrophilic nucleolar organizer staining for histologic grading of soft-tissue sarcomas.

Accurate histologic grading is essential for making a proper therapy decision in soft-tissue sarcomas (STS). The usefulness of the argyrophilic stain for nucleolar organizer region (AgNOR) in assessing the histologic grade of STS has been examined. One hundred and forty-two patients with STS confined to the extremity and trunk were selected. Tumors were classified based on the criteria of Enzinger and Weiss ["Soft-Tissue Tumors." St. Louis: C. V. Mosby, 1983]. In addition, non-specific classification was made based on the shape of proliferating cells occupying more than 50% of the field in the sections such as pleomorphic cell, small round cell, spindle cell, epithelioid cell, myxoid, and unclassified tumors. The mean number of AgNOR dots per nucleus of tumor cells was calculated in 200 cells (AgNOR count). Each category of non-specific classification was divided into a high-count group (< 8 AgNOR count) and a low-count group (> 8 NOR). The low-count group showed a significantly better prognosis than the high-count group in small round cell and spindle cell tumors (P < 0.007 and P < 0.0005, respectively). Similar results were obtained in pleomorphic cell tumors, though they were statistically not significant because of the relatively small number of examined cases. Most patients with epithelioid cell and myxoid tumors were in the low-count group. These findings suggest that the assessment of histologic grading of STS could be made effectively by the non-specific classification and the aid of AgNOR staining.

Actuarial Analysis↗

Gamma-aminobutyric acid (GABA) immunoreactivity in the mouse adrenal gland.

Gamma-aminobutyric acid (GABA) immunoreactivity was revealed by immunocytochemistry in the mouse adrenal gland at the light and electron microscopic levels. Groups of weakly or faintly GABA immunoreactive chromaffin cells were often seen in the adrenal medulla. By means of immunohistochemistry combined with fluorescent microscopy, these GABA immunoreactive chromaffin cells showed noradrenaline fluorescence. The immunoreaction product was seen mainly in the granular cores of these noradrenaline cells. These results suggest the co-existence of GABA and noradrenaline within the chromaffin granules. Sometimes thick or thin bundles of GABA immunoreactive nerve fibers with or without varicosities were found running through the cortex directly into the medulla. In the medulla, GABA immunoreactive varicose nerve fibers were numerous and were often in close contact with small adrenaline cells and large ganglion cells; a few, however, surrounded clusters of the noradrenaline cells, where membrane specializations were formed. Single GABA immunoreactive nerve fibers, and thin or thick bundles of the immunoreactive varicose nerve fibers ran along the blood vessels in the medulla. The immunoreaction deposits were observed diffusely in the axoplasm and in small agranular vesicles of the GABA immunoreactive nerve fibers. Since no ganglion cells with GABA immunoreactivity were found in the adrenal gland, the GABA immunoreactive nerve fibers are regarded as extrinsic in origin.

Adrenal Medulla↗