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Biomedical subjects

Y Yabe

Publications and source records attributed to Y Yabe.

At least 37 records · Page 2Linked to original sources

Functional Anatomy of the Interosseous Membrane of the Forearm - Dynamic Changes During Rotation.

The functional anatomy of the interosseous membrane (IOM) of the forearm was studied in 15 fresh frozen cadavers. The IOM consisted of three components: the tendinous part; the membranous part; and the dorsal oblique accessory cord. The tendinous part was a thick and strong complex of three to ten bundles which run from the proximal one third of the radius to the distal quarter of the ulna. The membranous part was recognised as a soft and thin structure, adjacent proximal and distal to the tendinous part. The dorsal oblique cord was found as a single cord on the dorsal side of the IOM from the proximal quarter of the ulna to the middle region of the radius. This cord was distinct from the oblique cord, which existed on the palmar side of the forearm separated from the IOM. The IOM was flat in the neutral position, while it flexed along the rotation axis in pronation and supination. Since the prominence of the curvature in the IOM was almost in the same direction as the fibres of the tendinous part, the tendinous part demonstrated only bending, similar to partial bending of an elastic board. The bending position was changed with the forearm position and the tightened bundles in the tendinous part were altered during rotation.

Journal Article↗

Human osteoclast-like cells are formed from peripheral blood mononuclear cells in a coculture with SaOS-2 cells transfected with the parathyroid hormone (PTH)/PTH-related protein receptor gene.

Subclones of the human osteosarcoma cell line SaOS-2 were established by transfecting with an expression vector containing the human PTH/PTH-related protein (PTHrP) receptor, and their abilities to support osteoclast-like multinucleated cell (OCL) formation were examined in coculture with mouse or human hemopoietic cells. Of four subclones examined, SaOS-2/4 and SaOS-4/3 bound high levels of [125I]-PTH and produced a significant amount of cAMP in response to PTH. OCLs were formed in response to PTH in the cocultures of mouse bone marrow cells with either SaOS-2/4 cells or SaOS-4/3 cells. Human OCLs were also formed in response to PTH in the coculture of SaOS-4/3 cells and human peripheral blood mononuclear cells. Adding dexamethasone together with PTH greatly enhanced PTH-induced human OCL formation. Like mouse OCLs, human OCLs formed in response to PTH were tartrate-resistant acid phosphatase positive, expressed abundant calcitonin receptors and vitronectin receptors, and formed resorption pits on dentine slices. Other osteotropic factors such as 1alpha,25-dihydroxyvitamin D3, prostaglandin E2, and interleukin 6 plus soluble interleukin 6 receptors failed to induce mouse and human OCLs in cocultures with SaOS-4/3 cells. Both mouse and human OCL formation supported by SaOS-4/3 cells were inhibited by either adding an antibody against macrophage-colony stimulating factor or adding granulocyte/macrophage-colony stimulating factor. Thus, it is likely that human and mouse OCL formation supported by SaOS-4/3 cells are similarly regulated. These results indicate that the target cells of PTH for inducing osteoclast formation are osteoblast/stromal cells but not osteoclast progenitor cells in the coculture. This coculture model will be useful for investigating the abnormalities ofosteoclast differentiation and function in human metabolic bone diseases.

Acid Phosphatase↗

Targeted delivery and improved therapeutic potential of catalase by chemical modification: combination with superoxide dismutase derivatives.

Four types of bovine liver catalase (CAT) derivatives, succinylated (Suc-CAT), galactosylated (Gal-CAT), mannosylated (Man-CAT), and polyethylene glycol conjugate (PEG-CAT), were synthesized and their pharmacokinetics and therapeutic potential in a hepatic ischemia/reperfusion injury model were studied in mice. About 90% of the CAT enzymatic activity was retained after chemical modification. Biodistribution studies showed that 111indium (111In)-Gal-CAT accumulated selectively in the liver parenchymal cells as 111In-CAT, whereas an increased amount of 111In-Suc-CAT and 111In-Man-CAT was delivered to liver nonparenchymal cells. 111In-PEG-CAT exhibited prolonged retention in plasma. Pharmacokinetic analysis revealed that the hepatic uptake clearances of 111In-Suc-CAT, 111In-Gal-CAT, and 111In-Man-CAT were much greater than that of 111In-CAT, whereas that of 111In-PEG-CAT was very small. In the ischemia/reperfusion injury model, in which hepatic injury was induced by occlusion of the portal vein for 30 min followed by 1 h reperfusion, the elevation of plasma glutamic pyruvic transaminase and glutamic oxaloacetic transaminase levels was slightly inhibited by treatment with native CAT or Gal-CAT. PEG-CAT was less potent. In contrast, Suc-CAT and Man-CAT effectively suppressed the increase in plasma glutamic pyruvic transaminase and glutamic oxaloacetic transaminase. Coinjection of mannosylated superoxide dismutase marginally improved the inhibitory effects of CAT derivatives. These results demonstrate that targeted CAT delivery to liver nonparenchymal cells via chemical modification is a promising approach to prevent hepatic injuries caused by reactive oxygen species. The potential usefulness of combining of CAT and superoxide dismutase derivatives is also demonstrated.

Alanine Transaminase↗

Osteoclast differentiation factor (ODF) induces osteoclast-like cell formation in human peripheral blood mononuclear cell cultures.

We have reported that osteoclast differentiation factor (ODF) expressed on the plasma membrane of osteoblasts/ stromal cells is a ligand for osteoclastogenesis inhibitory factor (OCIF). A genetically engineered soluble form of ODF (sODF) induced osteoclast-like multinucleated cells (OCLs) in the presence of M-CSF in mouse spleen cell cultures. Osteoblasts/stromal cells were not required in this process. To elucidate the mechanism of human osteoclastogenesis, human peripheral blood mononuclear cells (PBMCs) were cultured for 7 days with sODF and human M-CSF in the presence or absence of dexamethasone. Treatment of human PBMCs with sODF together with M-CSF induced OCLs, which expressed tartrate-resistant acid phosphatase and vitronectin receptors, produced cAMP in response to calcitonin, and formed resorption pits on dentine slices. OCLs were also formed from the adherent cell population of human PBMCs. Dexamethasone was required for human OCL formation in culture of whole PBMCs but not in culture of the adherent cell population. OCL formation was strongly inhibited by OCIF simultaneously added. These results clearly indicate that like in mouse osteoclastogenesis, ODF is a critical factor for human osteoclastogenesis. The present study also indicates that OCIF acts as a naturally occurring decoy receptor for ODF in inhibiting signal transduction in human osteoclast formation.

Animals↗

Gene expression of noncollagenous bone matrix proteins in the limb joints and intervertebral disks of the twy mouse.

The twy (tiptoe walking Yoshimura) mouse is an autosomal recessive mutant manifesting multiple osteochondral lesions characterized by pathologic calcium deposition. To elucidate the pathophysiology of the limb joint lesions and the intervertebral disk lesions of the twy mouse, we assessed the mRNA expression of noncollagenous bone matrix proteins such as osteocalcin, osteonectin, osteopontin, and matrix Gla protein (MGP) by in situ hybridization, but only expression of MGP was observed in association with the pathologic calcium deposits in twy mice. Mild degeneration and abnormal growth of the cartilage in contact with the joint capsule was observed at 5 weeks in the articular cartilage of the ankle joint of the twy mouse, and MGP gene expression was observed at the same time. Simultaneous growth of synovial membrane cells and relatively undifferentiated articular cartilage cells in the knee joint, and of cartilage-like cells near the insertion of the cruciate ligament was observed in the twy mouse, and MGP gene expression was found to be present at the same time. Hypertrophy of abnormally proliferated chondrocyte-like cells, which are different from fibrocartilaginous cells of the annulus fibrosus, was observed in the intervertebral disks of the twy mouse at 3 weeks of age, and MGP gene expression was noted at the same time. These findings suggest that abnormal expression of MGP plays a major role in the pathologic calcification of the twy mouse.

Animals↗

Age-related changes in cortical bone in women: metacarpal bone mass measurement study.

The mechanism of age-related cortical bone loss was investigated in 229 Japanese women, 41-94 years of age, by metacarpal bone mass measurement. While no significant correlation was found between bone width and age, a significant increase in bone marrow width, and significant decreases in cortical bone density and total bone mass were observed in association with aging (P < 0.0001). There was a significant negative correlation between total bone mass and bone marrow width (r = -0.239; P < 0.0005), and significant positive correlations between both total bone mass and cortical bone density (r = 0.539; P < 0.0001) and cortical bone width (r = 0.839; P < 0.0001). The findings suggested that age-related cortical bone loss in middle-aged and elderly women resulted from two different factors; a decrease in cortical bone density caused by progression of intracortical porosity, and a decrease in cortical bone width as a result of bone loss on the endosteal surface. The latter had a greater influence on an age-related cortical bone loss than the former.

Absorptiometry, Photon↗

Structure-activity relationship of HIV-1 protease inhibitors containing AHPBA. Part III: Modification of P2 site.

The structure-activity relationship of HIV-1 protease (HIV-1 PR) inhibitors containing AHPBA (3-amino-2-hydroxy-4-phenylbutanoic acid) is discussed. In order to solve the problem of poor oral bioavailability, small-sized dipeptide HIV-1 protease inhibitors containing cyclic urethanes or benzamides at the P2 site were designed and prepared. The substitution patterns of the benzamides contributed significantly to their HIV-1 PR inhibitory activities, and it was shown that the choice of P2-residues was very important. Highly potent inhibitors possessing subnanomolar IC50 values and exhibiting good antiviral potency have been identified. In this class, inhibitor 18 was the most potent (IC90 (CEM/HIV-1 IIIB) 0.11 microM) and showed good oral bioavailability in dogs.

Animals↗

Selective neutrophil depletion with monoclonal antibodies attenuates ischemia/reperfusion injury in skeletal muscle.

The purpose of this study was to determine whether depletion of circulating neutrophils, using an antineutrophil monoclonal antibody (RP3), would attenuate ischemia/reperfusion injury in rat skeletal muscle. A 3- and 5-hr period of ischemia was induced unilaterally into the hindlimbs of rats; the isolated limbs were then reperfused for 24 hr after ischemia. The gastrocnemius muscle was then removed, and blood was taken simultaneously. The hematologic parameters were measured, muscle neutrophil sequestration was assessed by myeloperoxidase (MPO) activity, free radical production was evaluated by the tissue lipid peroxides (LPO) levels, muscle viability was assessed by tissue levels of adenosine triphosphate (ATP) and creatine phosphate (PCr) levels, and muscle wet/dry weights were determined. Treatment with RP3 selectively and sufficiently depleted the circulating neutrophil population, markedly reduced MPO, and significantly attenuated LPO and the tissue water content after both 3- and 5-hr of ischemia. After 3 hr of ischemia, ATP and PCr levels were significantly increased by neutrophil depletion; however, after 5 hr of ischemia, the same effect was not demonstrated. These results suggest that neutrophil depletion after 3 hr of ischemia restrains free radical production and edema formation, and also attenuates skeletal muscle ischemia reperfusion injury; however, after 5 hr of ischemia, ischemic damage was so severe, that neutrophil depletion did not reduce ischemia reperfusion injury.

Adenine Nucleotides↗

Multiple smooth muscle tumors arising in deep soft tissue of lower limbs with uterine leiomyomas.

A 40-year-old woman had multiple smooth muscle tumors in the left inguinal region, the bilateral thighs, the omentum, the peritoneum, and the right infundibulum pelvic ligament associated with uterine leiomyomas. She had a history of uterine leiomyomas, which were resected 13 years ago. Histopathologic evaluation revealed tumor masses composed of smooth muscle cells with relatively low cellularity, which were consistent with a diagnosis of leiomyoma. Tumor necrosis and nuclear atypia were absent. Mitotic figures were very scarce (less than 1 mitotic figure per 10 high-power fields). Immunohistochemical evaluation revealed a positive reaction of the tumor cells to muscle markers, estrogen receptors, and progesterone receptors. No pulmonary lesion was found. Similar instances of uterine leiomyomas with histologically benign extrauterine smooth muscle tumors have been reported. This curious condition has been referred to as "benign metastasizing leiomyoma," in which most of the reported cases involve the lungs. The distribution of extrauterine tumors in our case is very unusual and may be the first case with multiple leiomyomas in deep soft tissue of the limbs. Consideration was given to the concept that these may be of multifocal origin, rather than metastases.

Adult↗

Hepatic disposition characteristics of recombinant human interleukin-11 (rhIL-11) in the perfused rat liver.

The hepatic disposition characteristics of recombinant human interleukin-11 (rhIL-11) were investigated in perfused rat liver to clarify the mechanism of hepatic clearance which is a major contributor to the rapid clearance of rhIL-11 in vivo. We analyzed the disposition characteristics of [(111)In]-labeled rhIL-11 using a single-pass constant infusion mode at different concentrations of rhIL-11. The venous outflow rapidly reached a steady-state condition at every concentration. Liver extraction ratio at steady-state (Ess) was decreased with increase in the concentration, suggesting that there is a saturable interaction between the liver cells and rhIL-11 molecule. Cellular localization experiments demonstrated that rhIL-11 was taken up by both liver parenchymal and nonparenchymal cells depending on their surface area, suggesting that this uptake was mediated by electrostatic interaction due to cationic charges in the cytokine.

Animals↗

Structures of novel acidic galactooligosaccharides synthesized by Bacillus circulans beta-galactosidase.

The structures of acidic oligosaccharides synthesized by a transglycosylation reaction by Bacillus circulans beta-galactosidase, using lactose as the galactosyl donor, and N-acetylneuraminic acid (NeuAc) and glucuronic acid (GlcUA) as the acceptors were investigated. Acidic oligosaccharides thus synthesized were purified by anion exchange chromatography and charcoal chromatography. The MS and NMR studies indicated that the acidic oligosaccharides from NeuAc were Gal beta-(1-->8)-NeuAc, Gal beta-(1-->9)-NeuAc, and Gal beta-(1-->3)-Gal beta-(1-->8)-NeuAc, and those from GlcUA were Gal beta-(1-->3)-GlcUA and Gal beta-(1-->4)-Gal beta-(1-->3)-GlcUA. These are novel acidic galactooligosaccharides.

Bacillus↗

MRI of cervical intervertebral discs in asymptomatic subjects.

We studied degenerative changes in the cervical intervertebral discs of 497 asymptomatic subjects by MRI and evaluated disc degeneration by loss of signal intensity, posterior and anterior disc protrusion, narrowing of the disc space and foraminal stenosis. In each subject, five disc levels from C2-C3 to C6-C7 were evaluated. The frequency of all degenerative findings increased linearly with age. Disc degeneration was the most common observation, being present in 17% of discs of men and 12% of those of women in their twenties, and 86% and 89% of discs of both men and women over 60 years of age. We found significant differences in frequency between genders for posterior disc protrusion and foraminal stenosis. The former, with demonstrable compression of the spinal cord, was observed in 7.6% of subjects, mostly over 50 years of age. Our results should be taken into account when interpreting the MRI findings in patients with symptomatic disorders of the cervical spine.

Adolescent↗

Primary healing of physeal separation under rigid fixation.

We observed the healing process under rigid external fixation after Salter-Harris type-1 or type-2 physeal separation at the proximal tibia in immature rabbits. Metaphyseal vessels grew across the gap with little delay; the site of separation then came to lie in the metaphysis and was bridged by endochondral ossification. Union was achieved within two days in all rabbits. Progression of endochondral ossification repaired the separated physis, thus showing 'primary healing of physeal separation'. This depends on accurate reduction and stable fixation to allow the survival of vessels across the gap.

Animals↗

Effect of increased physical activity on bone mineral density in postmenopausal osteoporotic women.

The effect of increased physical activity on bone mineral density (BMD) of the lumbar vertebrae was examined in postmenopausal osteoporotic women. Thirty-five postmenopausal women, aged 53-77 years, whose BMD in the lumbar vertebrae (L2-L4) measured by dual energy x-ray absorptiometry (Norland XR-26) was below (> 30%) the young adult mean, were divided into two groups: a control group of 20 women and an exercise group of 15 women. The physical exercise consisted of daily outdoor walking and gymnastic training performed for 12 months. During the study period, all subjects were treated with calcium lactate, 2.0 g, and 1 alpha-hydroxyvitamin D3, 1 microgram, daily. Initial L2-L4 BMD was 0.611 +/- 0.045 (mean +/- SEM) g/cm2 in the control group and 0.606 +/- 0.066 g/cm2 in the exercise group (NS). In the control group, the BMD changes were -0.54 +/- 0.58% (mean +/- SEM) at 6 months and +1.00 +/- 1.29% at 12 months, compared to the baseline (P = 0.3424, by oneway ANOVA). In the exercise group, however, the changes were +1.78 +/- 0.90% and +4.48 +/- 0.93%, respectively (P = 0.0305, by two-way ANOVA). These data suggest that increased physical activity consisting of daily outdoor walking and gymnastic training can be useful in increasing lumbar BMD in postmenopausal osteoporotic women on calcium and vitamin D3 supplementation.

Aged↗

Preferential expression of alternatively spliced transcript of type II procollagen in the rabbit notochordal remnant and developing fibrocartilages.

Expression patterns for the two isoforms of alpha 1(II) mRNA in various cartilaginous tissues were examined using newly isolated cDNA clones encoding rabbit type II procollagen amino- and carboxy-terminal propeptide regions. In nonchondrogenic nucleus pulposus, the switching of the mRNA from the long form to the short form was accompanied by disc maturation after birth. Interestingly, the short transcript was also expressed preferentially in human chordoma tissues as aberrant chordal vestiges. These results suggest an abundance of the differentiated chondrocyte-like phenotype in the heterogeneous notochordal remnants.

Aged↗

Type-II collagen gene expression is transiently upregulated in experimentally induced degeneration of rabbit intervertebral disc.

To clarify phenotypic alterations of intervertebral disc cells during the repair process, we cloned partial type-II collagen cDNA from rabbits and analyzed the level of expression of type-II collagen mRNA in disc degeneration. An animal model was created by surgical denucleation of rabbit intervertebral discs through an extraperitoneal approach. Eight animals each from an experimental and a control group were killed at 2, 4, 8, or 16 weeks postoperatively, and the disc samples were used for this study. Round chondrocyte-like cells that filled the herniated space showed intense signal of type-II collagen mRNA and significant pericellular immunostaining of type-II collagen but no clear staining of type-I collagen. Northern blot analysis revealed that the expression of type-II collagen mRNA of the repair disc cells was transiently increased at 4 weeks postoperatively. The cells were able to change their morphology in response to mechanical stimulation by surgical denucleation and to induce a significant increase in the gene expression of type-II collagen at an early phase of disc degeneration. The present results indicate the transient enhancement of repair activity in the degenerative process of injured fibrocartilage.

Animals↗

Evaluation of left ventricular wall motion and function in patients with previous myocardial infarction by three-dimensional 99mTc-HSAD multigated cardiac pool imaging.

To evaluate left ventricular (LV) wall motion stereoscopically from all directions and to calculate the LV volume by three-dimensional (3D) imaging. 99mTc-DTPA human serum albumin-multigated cardiac pool-single photon emission computed tomography (99mTc-MUGA-SPECT) was performed. A new data processing program was developed with the Application Visualization System-Medical Viewer (AVS-MV) based on images obtained from 99mTc-MUGA-SPECT. In patients with previous myocardial infarction, LV function and LV wall motion were evaluated by 3D-99mTc-MUGA imaging. The LV end-diastolic volume (LVEDV) and end-systolic volume (LVESV) were obtained from 3D-99mTc-MUGA images by the surface rendering method, and the left ventricular ejection fraction (LVEF) was calculated at thresholds of 35% (T1), 40% (T2), 45% (T3), and 50% (T4). There was a strong correlation between the LV volume calculated by 3D-99mTc-MUGA imaging at a threshold of 40% and that determined by contrast left ventriculography (LVEDV: 194.7 +/- 36.0 ml vs. 198.7 +/- 39.1 ml, r = 0.791, p < 0.001; LVESV: 91.6 +/- 44.5 ml vs. 93.3 +/- 41.3 ml, r = 0.953, p < 0.001), respectively. When compared with the LVEF data obtained by left ventriculography, significant correlations were found for 3D images reconstructed at each threshold (T1: r = 0.966; T2: r = 0.962; T3: r = 0.958; and T4: r = 0.955). In addition, when LV wall motion obtained by 3D-99mTc-MUGA imaging (LAT and LAO views) was compared with the results obtained by left ventriculography (RAO and LAO views), there was good agreement. 3D-99mTc-MUGA imaging was superior in allowing evaluation of LV wall motion in all directions and in assessment of LV function, since data acquisition and image reconstruction could be done within a short time with the three-detector imaging system and AVS-MV. This method appears to be very useful for the observation of both LV wall motion and LV function in patients with ischemic heart disease, because it is a noninvasive examination.

Adult↗

A prospective, randomized, double-blind multicenter trial of a single bolus injection of the novel modified t-PA E6010 in the treatment of acute myocardial infarction: comparison with native t-PA. E6010 Study Group.

OBJECTIVES: This prospective, randomized, double-blind multicenter trial evaluated the efficacy and safety of a single bolus injection of the novel modified tissue-type plasminogen activator (t-PA) E6010 in the treatment of acute myocardial infarction compared with that of native t-PA. BACKGROUND: E6010 is a novel modified t-PA with a prolonged half-life (t1/2 alpha > or = 23 min) compared with native t-PA (t1/2 alpha = 4 min). E6010 can be administered in patients as a single intravenous bolus injection, and early recanalization can be expected. METHODS: The efficacy of E6010 was compared with that of native t-PA in 199 patients with acute myocardial infarction who were treated within 6 h of onset in a prospective, randomized, double-blind multicenter trial. Patients were given either 0.22 mg/kg body weight of E6010 intravenously over 2 min or native t-PA (tisokinase) 28.8 mg or 14.4 million IU (10% of the total dose over 1 to 2 min, the remainder infused over 60 min). RESULTS: The primary end point was the recanalization rate of the infarct-related coronary artery at 60 min after the start of treatment. Time to reperfusion was shorter in the E6010 group than in the native t-PA group. Thrombolysis in Myocardial Infarction flow grade 2 or 3 recanalization at 15, 30, 45 and 60 min after administration was observed in 37%, 62%, 74% and 79% (95% confidence interval [CI] 70% to 87%) of the E6010-treated patients and in 14%, 32%, 50% and 65% (95% CI 55% to 74%) of native t-PA-treated patients, respectively (p = 0.032 at 60 min). CONCLUSIONS: The present study indicates that, compared with native t-PA, a single bolus injection of E6010 over 2 min produces a higher rate of early recanalization of the infarct-related coronary artery without fatal bleeding complications.

Aged↗